Alzheimer's Disease, Diabetes Mellitus, Obesity
Conditions
Keywords
Biomarkers, Diabetes, Obesity, Dementia of the Alzheimer Type, Functional Magnetic Resonance Imaging (fMRI)
Brief summary
Background: \- Insulin removes sugar from the blood to use for energy. Insulin resistance means that cells may not respond to insulin normally. It can lead to serious diseases. Researchers want to see how diet affects insulin resistance, weight, and brain chemicals related to Alzheimer s disease. Objectives: \- To compare two forms of diet and their effects on insulin resistance and the brain. Eligibility: \- Women ages 55 70 with insulin resistance. Design: * This study requires 6 clinic visits over 9 12 weeks. Participants must fast before visits. * Visit 1, screening: * Medical history, physical exam, and blood and urine tests. * Participants will get a wrist device to wear for 4 days. * Visit 2: * Weight and waist measurement. * Blood drawn. * Questionnaires and thinking tests. * Lumbar puncture. Skin will be numbed and a needle inserted between bones in the back will remove \<TAB\>fluid. * Participants will drink a nutrition shake. Blood will be taken 12 times over 4 \<TAB\>hours through a thin tube in \<TAB\>the arm. * Brain MRI. Participants will lie on a table that slides in and out of a cylinder in a strong magnetic field. \<TAB\>They will have a coil on their head and may do tasks. * Participants will get advice about healthy eating and be randomly put in one of 2 groups. One group will get \<TAB\>nutrition shakes to drink. * Visits 3 5: * Weight and waist measurements, vital signs, blood draw, and questionnaires. * Between visits, participants will get a call or email to check how they are doing. * Visit 6: Repeat of visit 1. * Participants will wear the wrist device for 4 more days, have a follow-up contact, then the study is finished.
Detailed description
Being overweight or obese can cause insulin resistance (IR), which is defined as reduced responsiveness to insulin by the cells of various tissues or organs. IR at midlife increases the risk of developing Alzheimer s disease (AD). We recently discovered novel biomarkers of brain IR (altered Tyr and Ser phosphorylated forms of insulin receptor substrate 1; IRS-1) in plasma exosomes enriched for neuronal origin. Moreover, IR is associated with AD biomarkers including deficits in resting state brain activity and cognitive performance. Calorie restriction is defined as consuming fewer calories than what is considered normal without a lack of nutrients. A certain type of calorie restriction, in which one consumes 500-600 calories a day for two consecutive days, followed by non-restricted eating for 5 days (5-2 CR), has been shown to lower peripheral insulin resistance effectively. Effects of CR and lowering peripheral IR on brain IR and cognition are unknown. The goal of this exploratory pilot study is to provide proof-of-concept that 5-2 CR at midlife can reverse brain IR, lower peripheral IR, improve cognitive performance, and increase brain activation at rest and during tasks. Specifically, we will study the effects of 8 weeks of 5-2 CR versus a control dietary intervention on brain and peripheral IR, memory and executive function, resting state default mode network activity, brain metabolism, and AD biomarkers. Forty overweight to obese women and men (between 55 and 70 years of age) will be randomized 1:1 into 5-2 CR and control groups. In the 5-2 CR group, participants will be offered healthy living dietary counseling at baseline, which they will be instructed to implement for five days/week. For each of the other two consecutive days/week, they will consume two shakes (Boost , CWI Medical), providing a total of 480 Kcal/day. In the control group, participants will be offered healthy living dietary counseling at baseline, which they will be asked to implement for every day of the week. Participants will undergo screening including a history and physical examination, calculation of Body Mass Index (BMI, which must be greater than or equal to 27) and a blood draw for insulin and glucose to determine whether they have insulin resistance. If participants meet eligibility criteria, they will continue with a baseline visit involving anthropometric measures, questionnaires, tests of cognitive function, brain MRI, blood draws for plasma and peripheral blood mononuclear cells, and lumbar puncture for cerebrospinal fluid biomarkers of AD. After 8 weeks, we will collect the same measures. To assess and reinforce compliance with their respective diet, participants will come into the clinic every 2 weeks to discuss compliance, measure their body weight and perform blood draws for measurement of ketones to objectively confirm energy restriction for the 5-2 CR group. We will also contact participants every week to further ensure compliance. To assess the effects of the diets on physical activity, participants will be asked to wear an accelerometer for 96 hours before and after they are on the diet.
Interventions
OTHERBoost (R) 5-2 diet
Regular diet for 5 days/week; Calorie Restriction (480 Kcal in the form of a shake) for 2 days/week. Supplement providing 240 Kcal per shake. Participant takes 2 shakes per calorie restriction day.
OTHERHealthy Living Diet
Counseling and educational material on diet portion, consistency
Sponsors
National Institute on Aging (NIA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* INCLUSION CRITERIA: * BMI greater than or equal to 27; in addition, weight less than or equal to 350 lbs (weight limit for MRI scanner); * Age of 55-70 years; * HOMA-IR greater than or equal to 1.8; * MMSE greater than or equal to 26 EXCLUSION CRITEIRA: * History of clinically significant cardiovascular disease for the purpose of this study, such as chronic heart failure, coronary disease, cardiomyopathy, clinically significant cardiac valvular disease or clinically significant peripheral vascular disease. Cardiovascular conditions that are clinically non-significant for the purpose of this study, such as controlled hypertension, minor EKG abnormalities, mitral valve prolapse or benign murmurs are permissible; * History of clinically significant stroke or other neurological disease of the central nervous system; * History of substance abuse in the past 6 months or positive urine drug screen; * History of clinically significant endocrine disorders (common mild endocrine disorders, such as untreated subclinical hypothyroidism with TSH \< 10 mU/l or successfully treated hypothyroidism may be allowed); * History of eating disorders, significant GI disorders or malabsorption disorders; * History of type 2 diabetes; and/or use of anti-diabetes medications or insulin; and/or type 2 diabetes diagnosed during the screening visit based on fasting glucose \> 125 mg/dL; * History of hypoglycemia; and/or a fasting glucose \< 70 mg/dL during the screening visit. * Current use of systemic corticosteroids; * Positive screening tests for HIV, HCV or HBV; * Hematocrit less than 35% or hemoglobin less than 11 mg/dL; * ALT or AST \> 1.5 times the upper normal limit; * Contraindications for MRI (pacemakers, ferrous metal implants or shrapnel in or around the head, etc.). * Contraindications to LP, such as Coumadin, coagulopathy (international normalized ratio, or INR \> 1.5; prothrombin time (PT), partial prothrombin time (PTT) \> 1.5 x upper normal limit). Aspirin 81 mg qd is allowed. Aspirin up to 325 mg qd is allowed, if withheld for 7 days prior to the LP. * Pregnancy or nursing. * Refusal to consent to genetic testing for APOE.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Serine312-insulin Receptor Substrate-1 (pS312-IRS-1) | Week 0, Week 4, Week 8 | IRS-1 is an intracellular adaptor molecule that is being recruited and activated by the binding of insulin and insulin-like growth factor to their respective receptors and in insulin resistance (IR) it shows aberrant phosphorylation in serine residues resulting in impaired downstream signal propagation. pS312-IRS-1 is considered an index of brain insulin resistance and a therapeutic response biomarker for interventions targeting brain IR. A decrease in its levels indicates target engagement with the intervention and improvement in brain IR. |
| Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) P-pan-Tyrosine-IRS-1 (pY-IRS-1) | Week 0, Week 4, Week 8 | IRS-1 is an intracellular adaptor molecule that is being recruited and activated by the binding of insulin and insulin-like growth factor to their respective receptors and in insulin resistance (IR) it shows aberrant phosphorylation in tyrosine residues resulting in impaired downstream signal propagation. pY-IRS-1 is considered an index of brain insulin resistance and a therapeutic response biomarker for interventions targeting brain IR. A decrease in its levels indicates target engagement with the intervention and improvement in brain IR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Waist Circumference | Week 0, Week 8 | — |
| Mean Change in Fasting Glucose | Week 0, Week 8 | — |
| Mean Change in Fasting Insulin | Week 0, Week 8 | — |
| Mean Change in Homeostatic Model Assessment of Insulin Resistance 2 (HOMA2-IR) | Week 0, Week 8 | Homeostatic Model Assessment of Insulin Resistance Index 2 (HOMA2-IR) is a marker of peripheral insulin resistance and is calculated by fasting insulin (μIU/L) multiplied by fasting glucose (mg/dL), and divided by a constant (405). A higher score indicates higher insulin resistance. A cut-off of 1.8 was used to indicate peripheral insulin resistance. |
| Mean Change in Glycosylated Hemoglobin (HbA1c) | Week 0, Week 8 | — |
| Mean Change in White Blood Cells (WBCs) | Week 0, Week 8 | — |
| Mean Change in Red Blood Cells (RBCs) | Week 0, Week 8 | — |
| Mean Change in Platelets | Week 0, Week 8 | — |
| Mean Change in Hemoglobin | Week 0, Week 8 | — |
| Mean Change in Hematocrit | Week 0, Week 8 | — |
| Mean Change in International Normalized Ratio (INR) | Week 0, Week 8 | The International Normalized Ratio (INR) is derived from prothrombin time (PT) which is calculated as a ratio of the patient's PT to a control PT standardized for the potency of the thromboplastin reagent developed by the World Health Organization (WHO) using the following formula: INR = Patient PT ÷ Control PT. The higher the INR, the longer it takes for blood to clot. |
| Mean Change in Serum Beta-Hydroxybutyrate (bHB) | Week 0, Week 8 | — |
| Mean Change in Serum Acetoacetate (AcAc) | Week 0, Week 8 | — |
| Mean Change in Serum Non-Esterified Fatty Acids (NEFA) | Week 0, Week 8 | — |
| Mean Change in Serum Cortisol | Week 0, Week 8 | — |
| Mean Change in Creatinine | Week 0, Week 8 | — |
| Mean Change in Blood Urea Nitrogen (BUN) | Week 0, Week 8 | — |
| Mean Change in Alanine Aminotransferase (ALT) | Week 0, Week 8 | — |
| Mean Change in Aspartate Aminotransferase (AST) | Week 0, Week 8 | — |
| Mean Change in Total Cholesterol | Week 0, Week 8 | — |
| Mean Change in HDL Cholesterol | Week 0, Week 8 | — |
| Mean Change in LDL Cholesterol | Week 0, Week 8 | — |
| Mean Change in Triglycerides | Week 0, Week 8 | — |
| Mean Change in Cerebrospinal Fluid (CSF) Amyloid Beta 42 | Week 0, Week 8 | — |
| Mean Change in Cerebrospinal Fluid (CSF) Amyloid Beta 40 | Week 0, Week 8 | — |
| Mean Change in Cerebrospinal Fluid (CSF) Amyloid Beta 42 / Amyloid Beta 40 Ratio | Week 0, Week 8 | — |
| Mean Change in Cerebrospinal Fluid (CSF) Total Tau | Week 0, Week 8 | — |
| Mean Change in Cerebrospinal Fluid (CSF) p181-Tau | Week 0, Week 8 | — |
| Mean Change in Cerebrospinal Fluid (CSF) Neurogranin | Week 0, Week 8 | — |
| Mean Change in Cerebrospinal Fluid (CSF) Light Chain Neurofilaments (Nf-L) | Week 0, Week 8 | — |
| Mean Change in Cerebrospinal Fluid (CSF) Glial Fibrillary Acidic Protein (GFAP) | Week 0, Week 8 | — |
| Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Amyloid Beta 42 | Week 0, Week 4, Week 8 | — |
| Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Amyloid Beta 40 | Week 0, Week 4, Week 8 | — |
| Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Amyloid Beta 42 / Amyloid Beta 40 Ratio | Week 0, Week 4, Week 8 | — |
| Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Total Tau | Week 0, Week 4, Week 8 | — |
| Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) p181-Tau | Week 0, Week 4, Week 8 | — |
| Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) p231-Tau | Week 0, Week 4, Week 8 | — |
| Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Akt | Week 0, Week 4, Week 8 | Akt (or protein kinase B) is an insulin signaling cascade mediator. An increase in its levels indicates an improvement in brain insulin resistance. |
| Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Serine473-Akt (pS473-Akt) | Week 0, Week 4, Week 8 | pS473-Akt is an insulin signaling cascade mediator. An increase in its levels indicates activation of downstream insulin signaling pathway. |
| Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Serine473-Akt (pS473-Akt) / Akt Ratio | Week 0, Week 4, Week 8 | — |
| Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Extracellular Signal-regulated Kinase 1/2 (pERK1/2) | Week 0, Week 4, Week 8 | pERK1/2 is an insulin signaling cascade mediator. An increase in its levels indicates activation of downstream insulin signaling pathway. |
| Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated c-Jun N-terminal Kinase (pJNK) | Week 0, Week 4, Week 8 | JNK is an insulin signaling cascade mediator. Activated JNK (pJNK) inhibits insulin signaling. An increase in pJNK levels indicates inhibition of downstream insulin signaling pathway. |
| Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated p38 (pp38) | Week 0, Week 4, Week 8 | p38 is an insulin signaling cascade mediator. Activated p38 (pp38) inhibits insulin signaling. An increase in pp38 levels indicates inhibition of downstream insulin signaling pathway. |
| Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) proBDNF | Week 0, Week 4, Week 8 | — |
| Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) BDNF | Week 0, Week 4, Week 8 | — |
| Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Neurogranin | Week 0, Week 4, Week 8 | — |
| Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Heavy Chain Neurofilaments (Nf-H) | Week 0, Week 4, Week 8 | — |
| Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) A-synuclein | Week 0, Week 4, Week 8 | — |
| Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) TAR DNA-binding Protein 43 (TDP-43) | Week 0, Week 4, Week 8 | — |
| Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Monocarboxylate Transporter 1 (MCT1) | Week 0, Week 4, Week 8 | — |
| Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Monocarboxylate Transporter 2 (MCT2) | Week 0, Week 4, Week 8 | — |
| Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Mitochondrial Complex IV Quantity | Week 0, Week 4, Week 8 | Complex IV is part of the mitochondrial electron transport chain. Decreased complex IV levels in NDEVs have been found in patients with Alzheimer's disease. A decrease in its levels may indicate decreased ability of neurons for ATP production and energy crisis. |
| Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Mitochondrial Complex V Quantity | Week 0, Week 4, Week 8 | Complex V is part of the mitochondrial electron transport chain. Decreased complex V levels in NDEVs have been found in patients with Alzheimer's disease. A decrease in its levels may indicate decreased ability of neurons for ATP production and energy crisis. |
| Mean Change in Glucose by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | Week 0, Week 8 | Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Glucose concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Glucose relative ratio to creatine was quantified. |
| Mean Change in N-acetyl-aspartate by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | Week 0, Week 8 | Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) N-acetyl-aspartate concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. N-acetyl-aspartate relative ratio to creatine was quantified. |
| Mean Change in Lactate by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | Week 0, Week 8 | Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Lactate concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Lactate relative ratio to creatine was quantified. |
| Mean Change in Glutamate by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | Week 0, Week 8 | Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Glutamate concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Glutamate relative ratio to creatine was quantified. |
| Mean Change in Gamma-Aminobutyric Acid (GABA) by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | Week 0, Week 8 | Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Gamma-Aminobutyric Acid (GABA) concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Gamma-Aminobutyric Acid (GABA) relative ratio to creatine was quantified. |
| Mean Change in Glutamine by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | Week 0, Week 8 | Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Glutamine concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Glutamine relative ratio to creatine was quantified. |
| Mean Change in Glutathione by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | Week 0, Week 8 | Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Glutathione concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Glutathione relative ratio to creatine was quantified. |
| Mean Change in Myo-Inositol by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | Week 0, Week 8 | Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Myo-Inositol concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Myo-Inositol relative ratio to creatine was quantified. |
| Mean Change in N-acetyl-aspartyl-glutamate by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | Week 0, Week 8 | Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) N-acetyl-aspartyl-glutamate concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. N-acetyl-aspartyl-glutamate relative ratio to creatine was quantified. |
| Mean Change in Ascorbate by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | Week 0, Week 8 | Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Ascorbate concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Ascorbate relative ratio to creatine was quantified. |
| Mean Change in Alanine by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | Week 0, Week 8 | Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Alanine concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Alanine relative ratio to creatine was quantified. |
| Mean Change in Scyllo-Inositol by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | Week 0, Week 8 | Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Scyllo-Inositol concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Scyllo-Inositol relative ratio to creatine was quantified. |
| Mean Change in Glucose by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | Week 0, Week 8 | Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Glucose concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Glucose relative ratio to creatine was quantified. |
| Mean Change in Lactate by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | Week 0, Week 8 | Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Lactate concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Lactate relative ratio to creatine was quantified. |
| Mean Change in Glutamate by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | Week 0, Week 8 | Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Glutamate concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Glutamate relative ratio to creatine was quantified. |
| Mean Change in Glutamine by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | Week 0, Week 8 | Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Glutamine concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Glutamine relative ratio to creatine was quantified. |
| Mean Change in Glutathione by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | Week 0, Week 8 | Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Glutathione concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Glutathione relative ratio to creatine was quantified. |
| Mean Change in Myo-Inositol by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | Week 0, Week 8 | Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Myo-Inositol concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Myo-Inositol relative ratio to creatine was quantified. |
| Mean Change in N-acetyl-aspartyl-glutamate by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | Week 0, Week 8 | Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) N-acetyl-aspartyl-glutamate concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. N-acetyl-aspartyl-glutamate relative ratio to creatine was quantified. |
| Mean Change in Ascorbate by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | Week 0, Week 8 | Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Ascorbate concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Ascorbate relative ratio to creatine was quantified. |
| Mean Change in Alanine by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | Week 0, Week 8 | Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Alanine concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Alanine relative ratio to creatine was quantified. |
| Mean Change in Scyllo-Inositol by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | Week 0, Week 8 | Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) glucose concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Glucose relative ratio to creatine was quantified. |
| Mean Change in Executive Function Composite | Week 0, Week 8 | Executive function was assessed with the National Institutes of Health (NIH) Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER) battery that comprises written, verbal, and computerized tasks that test working memory, inhibition, set shifting, fluency, planning, insight, and social cognition and behavior. The Executive function Composite is a computerized score calculated based on the individual tests. It ranges between 0 and 10. Higher score values indicate better performance. |
| Mean Change in California Verbal Learning Test (CVLT) | Week 0, Week 8 | California Verbal Learning Test (CVLT) assesses verbal memory for unstructured information. Examinees are asked to recall words on a 16-item list after each of 5 learning trials (Immediate Free Recall; range 0-80 \[5 x 0-16\]). After a distractor list, participants are again asked to recall words spontaneously (Short Delay Free Recall; range 0-16) and with category cueing (Short Delay Cued Recall; range 0-16). Spontaneous recall (Long Delay Free Recall; range 0-16) and category cueing (Long Delay Cued Recall; range 0-16) are repeated after a 20-minute delay. Following the longer delay, participants also complete a yes/no recognition trial during which they need to discriminate between the target words and 32 distractor words (Long Delay Recognition; range 0-48 \[0-16 true positive target words + 0-32 true negative distractor words\]). Higher scores indicate better performance. |
| Mean Change in Logical Memory (LM) Test | Week 0, Week 8 | Logical Memory (LM) test assesses verbal memory for structured information. It consists of two thematically independent narrative stories. Each story has 25 items, which the examinee has to recall with as much detail and precision as possible. Each item is scored the same regardless of importance level, and all correct items are summed giving a maximum score of 25 for each story. Verbatim recall score only includes the items that are recalled exactly and with detailed information, whereas gist recall score includes both the verbatim recall and the items that are recalled with only the essential elements of the information. The examinee has to recall the two stories twice, immediately after their initial administration (immediate recall) and after a 20 to 30-minute delay (delayed recall). Total maximum score for each of the subtests is 50 (25 items x 2 stories) and the minimum score is 0. Higher scores indicate better performance. |
| Mean Change in Body Weight | Week 0, Week 8 | — |
| Mean Change in the Short Form 36-item Health Survey (SF-36) | Week 0, Week 8 | Short Form 36-item Health Survey (SF-36) is a gauge of physical and psychosocial effects of the interventions. It consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability; the higher the score the less disability. |
| Mean Change in Total Energy Expenditure | Week 0, Week 8 | Physical activity was monitored with an Actigraph GT3X-BT accelerometer device which measures accelerations in vertical, horizontal, and anterior-posterior directions. |
| Mean Change in Daily Energy Expenditure | Week 0, Week 8 | Physical activity was monitored with an Actigraph GT3X-BT accelerometer device which measures accelerations in vertical, horizontal, and anterior-posterior directions. |
| Mean Change in Hourly Energy Expenditure | Week 0, Week 8 | Physical activity was monitored with an Actigraph GT3X-BT accelerometer device which measures accelerations in vertical, horizontal, and anterior-posterior directions. |
| Mean Change in Metabolic Rate | Week 0, Week 8 | Physical activity was monitored with an Actigraph GT3X-BT accelerometer device which measures accelerations in vertical, horizontal, and anterior-posterior directions. |
| Mean Change in Time in Activity | Week 0, Week 8 | Physical activity was monitored with an Actigraph GT3X-BT accelerometer device which measures accelerations in vertical, horizontal, and anterior-posterior directions. |
| Mean Change in Total Steps | Week 0, Week 8 | Physical activity was monitored with an Actigraph GT3X-BT accelerometer device which measures accelerations in vertical, horizontal, and anterior-posterior directions. |
| Mean Change in Steps Per Minute | Week 0, Week 8 | Physical activity was monitored with an Actigraph GT3X-BT accelerometer device which measures accelerations in vertical, horizontal, and anterior-posterior directions. |
| Mean Change in Total Sedentary Bouts | Week 0, Week 8 | Physical activity was monitored with an Actigraph GT3X-BT accelerometer device which measures accelerations in vertical, horizontal, and anterior-posterior directions. |
| Change in the Positive and Negative Affect Schedule (PANAS) | Week 0, Week 8 | Positive and Negative Affect Schedule (PANAS) is a 20-item self-report measure to assess positive and negative affect and is an index of emotional state. For positive affect, score can range from 10 - 50, with higher scores representing higher levels of positive affect. For negative affect, score can range from 10 - 50, with lower scores representing lower levels of negative affect. |
| Mean Change in Body Mass Index (BMI) | Week 0, Week 8 | — |
Countries
United States
Participant flow
Recruitment details
Recruitment took place between 22 June 2015 and 23 December 2022.
Pre-assignment details
129 participants underwent screening; 80 were not eligible, 3 withdrew prior to randomization, and 46 participants were randomized, 22 to 5-2 CR and 24 to HL.
Participants by arm
| Arm | Count |
|---|---|
| 5-2 CR Healthy living diet for 5 days/week; Calorie Restriction (480 Kcal in the form of a shake) for 2 days/week.
Boost (R) 5-2 diet: Regular diet for 5 days/week; Calorie Restriction (480 Kcal in the form of a shake) for 2 days/week. Supplement providing 240 Kcal per shake. Participant takes 2 shakes per calorie restriction day. | 20 |
| Healthy Living Diet Healthy living diet for 7 days/week
Healthy Living Diet: Counseling and educational material on diet portion, consistency | 20 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | 5-2 CR | Healthy Living Diet | Total |
|---|---|---|---|
| Age, Continuous | 63.5 years STANDARD_DEVIATION 4.2 | 63.0 years STANDARD_DEVIATION 6.1 | 63.2 years STANDARD_DEVIATION 5.2 |
| ApoE ε4 carrier status Carrier | 3 Participants | 8 Participants | 11 Participants |
| ApoE ε4 carrier status Non-carrier | 17 Participants | 12 Participants | 29 Participants |
| Body Mass Index (BMI) | 35.0 kg/m^2 STANDARD_DEVIATION 4 | 33.8 kg/m^2 STANDARD_DEVIATION 3.1 | 34.4 kg/m^2 STANDARD_DEVIATION 3.6 |
| Body weight | 99.0 kg STANDARD_DEVIATION 16 | 95.4 kg STANDARD_DEVIATION 10.7 | 97.2 kg STANDARD_DEVIATION 13.6 |
| Height | 168.0 cm STANDARD_DEVIATION 9.2 | 168.0 cm STANDARD_DEVIATION 9.5 | 168.0 cm STANDARD_DEVIATION 9.2 |
| Homeostatic Model Assessment of Insulin Resistance 2 (HOMA2-IR) | 2.4 (μU/mmol/L)2 STANDARD_DEVIATION 0.7 | 2.3 (μU/mmol/L)2 STANDARD_DEVIATION 1 | 2.3 (μU/mmol/L)2 STANDARD_DEVIATION 0.9 |
| Mini-Mental State Examination (MMSE) score | 29.7 units on a scale STANDARD_DEVIATION 0.6 | 29.3 units on a scale STANDARD_DEVIATION 0.8 | 29.5 units on a scale STANDARD_DEVIATION 0.7 |
| Race/Ethnicity, Customized Black/African American | 6 Participants | 8 Participants | 14 Participants |
| Race/Ethnicity, Customized Hispanic | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White/Caucasian | 14 Participants | 11 Participants | 25 Participants |
| Sex: Female, Male Female | 13 Participants | 11 Participants | 24 Participants |
| Sex: Female, Male Male | 7 Participants | 9 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 8 / 20 | 2 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Serine312-insulin Receptor Substrate-1 (pS312-IRS-1)
IRS-1 is an intracellular adaptor molecule that is being recruited and activated by the binding of insulin and insulin-like growth factor to their respective receptors and in insulin resistance (IR) it shows aberrant phosphorylation in serine residues resulting in impaired downstream signal propagation. pS312-IRS-1 is considered an index of brain insulin resistance and a therapeutic response biomarker for interventions targeting brain IR. A decrease in its levels indicates target engagement with the intervention and improvement in brain IR.
Time frame: Week 0, Week 4, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Serine312-insulin Receptor Substrate-1 (pS312-IRS-1) | Week 4 - Week 0 | 79.01 pg/mL | Standard Error 287.16 |
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Serine312-insulin Receptor Substrate-1 (pS312-IRS-1) | Week 8 - Week 4 | -337.70 pg/mL | Standard Error 256.08 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Serine312-insulin Receptor Substrate-1 (pS312-IRS-1) | Week 8 - Week 4 | -608.92 pg/mL | Standard Error 269.84 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Serine312-insulin Receptor Substrate-1 (pS312-IRS-1) | Week 4 - Week 0 | 443.72 pg/mL | Standard Error 182.56 |
Primary
Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) P-pan-Tyrosine-IRS-1 (pY-IRS-1)
IRS-1 is an intracellular adaptor molecule that is being recruited and activated by the binding of insulin and insulin-like growth factor to their respective receptors and in insulin resistance (IR) it shows aberrant phosphorylation in tyrosine residues resulting in impaired downstream signal propagation. pY-IRS-1 is considered an index of brain insulin resistance and a therapeutic response biomarker for interventions targeting brain IR. A decrease in its levels indicates target engagement with the intervention and improvement in brain IR.
Time frame: Week 0, Week 4, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) P-pan-Tyrosine-IRS-1 (pY-IRS-1) | Week 4 - Week 0 | 5.05 Arbitrary Units (AU) | Standard Error 10.43 |
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) P-pan-Tyrosine-IRS-1 (pY-IRS-1) | Week 8 - Week 4 | -24.72 Arbitrary Units (AU) | Standard Error 10.76 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) P-pan-Tyrosine-IRS-1 (pY-IRS-1) | Week 4 - Week 0 | 33.88 Arbitrary Units (AU) | Standard Error 32.28 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) P-pan-Tyrosine-IRS-1 (pY-IRS-1) | Week 8 - Week 4 | -54.23 Arbitrary Units (AU) | Standard Error 31.72 |
Secondary
Change in the Positive and Negative Affect Schedule (PANAS)
Positive and Negative Affect Schedule (PANAS) is a 20-item self-report measure to assess positive and negative affect and is an index of emotional state. For positive affect, score can range from 10 - 50, with higher scores representing higher levels of positive affect. For negative affect, score can range from 10 - 50, with lower scores representing lower levels of negative affect.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Change in the Positive and Negative Affect Schedule (PANAS) | Positive Affect | -2.45 units on a scale | Standard Error 1.34 |
| 5-2 CR | Change in the Positive and Negative Affect Schedule (PANAS) | Negative Affect | 0.51 units on a scale | Standard Error 0.65 |
| Healthy Living Diet | Change in the Positive and Negative Affect Schedule (PANAS) | Positive Affect | -1.35 units on a scale | Standard Error 0.96 |
| Healthy Living Diet | Change in the Positive and Negative Affect Schedule (PANAS) | Negative Affect | -0.06 units on a scale | Standard Error 0.57 |
Secondary
Mean Change in Alanine Aminotransferase (ALT)
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Alanine Aminotransferase (ALT) | -2.33 IU/L | Standard Error 1.45 |
| Healthy Living Diet | Mean Change in Alanine Aminotransferase (ALT) | -0.77 IU/L | Standard Error 1.49 |
Secondary
Mean Change in Alanine by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC)
Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Alanine concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Alanine relative ratio to creatine was quantified.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Metabolite measurements with Cramer-Rao lower bounds (CRLBs) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Alanine by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | -0.009 Ratio | Standard Error 0.022 |
| Healthy Living Diet | Mean Change in Alanine by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | 0.001 Ratio | Standard Error 0.021 |
Secondary
Mean Change in Alanine by Proton J-PRESS MRS of Posteromedial Cortex (PMC)
Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Alanine concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Alanine relative ratio to creatine was quantified.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Metabolite measurements with Cramer-Rao lower bounds (CRLBs) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Alanine by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | -0.006 Ratio | Standard Error 0.01 |
| Healthy Living Diet | Mean Change in Alanine by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | -0.017 Ratio | Standard Error 0.01 |
Secondary
Mean Change in Ascorbate by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC)
Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Ascorbate concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Ascorbate relative ratio to creatine was quantified.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Metabolite measurements with Cramer-Rao lower bounds (CRLBs) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Ascorbate by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | -0.039 Ratio | Standard Error 0.075 |
| Healthy Living Diet | Mean Change in Ascorbate by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | 0.006 Ratio | Standard Error 0.078 |
Secondary
Mean Change in Ascorbate by Proton J-PRESS MRS of Posteromedial Cortex (PMC)
Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Ascorbate concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Ascorbate relative ratio to creatine was quantified.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Metabolite measurements with Cramer-Rao lower bounds (CRLBs) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Ascorbate by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | -0.107 Ratio | Standard Error 0.05 |
| Healthy Living Diet | Mean Change in Ascorbate by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | -0.076 Ratio | Standard Error 0.033 |
Secondary
Mean Change in Aspartate Aminotransferase (AST)
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Aspartate Aminotransferase (AST) | 0.87 IU/L | Standard Error 1.7 |
| Healthy Living Diet | Mean Change in Aspartate Aminotransferase (AST) | 2.95 IU/L | Standard Error 2.49 |
Secondary
Mean Change in Blood Urea Nitrogen (BUN)
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Blood Urea Nitrogen (BUN) | -0.72 mg/dL | Standard Error 1.04 |
| Healthy Living Diet | Mean Change in Blood Urea Nitrogen (BUN) | -0.55 mg/dL | Standard Error 1.03 |
Secondary
Mean Change in Body Mass Index (BMI)
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Body Mass Index (BMI) | -1.41 kg/m^2 | Standard Error 0.26 |
| Healthy Living Diet | Mean Change in Body Mass Index (BMI) | -0.80 kg/m^2 | Standard Error 0.2 |
Secondary
Mean Change in Body Weight
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Body Weight | -4.06 kg | Standard Error 0.72 |
| Healthy Living Diet | Mean Change in Body Weight | -2.33 kg | Standard Error 0.62 |
Secondary
Mean Change in California Verbal Learning Test (CVLT)
California Verbal Learning Test (CVLT) assesses verbal memory for unstructured information. Examinees are asked to recall words on a 16-item list after each of 5 learning trials (Immediate Free Recall; range 0-80 \[5 x 0-16\]). After a distractor list, participants are again asked to recall words spontaneously (Short Delay Free Recall; range 0-16) and with category cueing (Short Delay Cued Recall; range 0-16). Spontaneous recall (Long Delay Free Recall; range 0-16) and category cueing (Long Delay Cued Recall; range 0-16) are repeated after a 20-minute delay. Following the longer delay, participants also complete a yes/no recognition trial during which they need to discriminate between the target words and 32 distractor words (Long Delay Recognition; range 0-48 \[0-16 true positive target words + 0-32 true negative distractor words\]). Higher scores indicate better performance.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in California Verbal Learning Test (CVLT) | Immediate Free Recall | 4.55 units on a scale | Standard Error 1.26 |
| 5-2 CR | Mean Change in California Verbal Learning Test (CVLT) | Short Delay Free Recall | 0.75 units on a scale | Standard Error 0.49 |
| 5-2 CR | Mean Change in California Verbal Learning Test (CVLT) | Short Delay Cued Recall | 0.85 units on a scale | Standard Error 0.33 |
| 5-2 CR | Mean Change in California Verbal Learning Test (CVLT) | Long Delay Free Recall | 0.90 units on a scale | Standard Error 0.48 |
| 5-2 CR | Mean Change in California Verbal Learning Test (CVLT) | Long Delay Cued Recall | 1.40 units on a scale | Standard Error 0.37 |
| 5-2 CR | Mean Change in California Verbal Learning Test (CVLT) | Long Delay Recognition | 0.75 units on a scale | Standard Error 0.58 |
| Healthy Living Diet | Mean Change in California Verbal Learning Test (CVLT) | Long Delay Cued Recall | 0.25 units on a scale | Standard Error 0.44 |
| Healthy Living Diet | Mean Change in California Verbal Learning Test (CVLT) | Immediate Free Recall | 4.55 units on a scale | Standard Error 1.13 |
| Healthy Living Diet | Mean Change in California Verbal Learning Test (CVLT) | Long Delay Free Recall | 0.10 units on a scale | Standard Error 0.46 |
| Healthy Living Diet | Mean Change in California Verbal Learning Test (CVLT) | Short Delay Free Recall | 1.40 units on a scale | Standard Error 0.65 |
| Healthy Living Diet | Mean Change in California Verbal Learning Test (CVLT) | Long Delay Recognition | -0.35 units on a scale | Standard Error 0.49 |
| Healthy Living Diet | Mean Change in California Verbal Learning Test (CVLT) | Short Delay Cued Recall | 0.75 units on a scale | Standard Error 0.48 |
Secondary
Mean Change in Cerebrospinal Fluid (CSF) Amyloid Beta 40
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Measurements with coefficient of variation (CV) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Cerebrospinal Fluid (CSF) Amyloid Beta 40 | -608.42 pg/mL | Standard Error 434.48 |
| Healthy Living Diet | Mean Change in Cerebrospinal Fluid (CSF) Amyloid Beta 40 | -117.75 pg/mL | Standard Error 565.04 |
Secondary
Mean Change in Cerebrospinal Fluid (CSF) Amyloid Beta 42
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Measurements with coefficient of variation (CV) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Cerebrospinal Fluid (CSF) Amyloid Beta 42 | -43.56 pg/mL | Standard Error 27.59 |
| Healthy Living Diet | Mean Change in Cerebrospinal Fluid (CSF) Amyloid Beta 42 | -30.16 pg/mL | Standard Error 36.7 |
Secondary
Mean Change in Cerebrospinal Fluid (CSF) Amyloid Beta 42 / Amyloid Beta 40 Ratio
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Measurements with coefficient of variation (CV) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Cerebrospinal Fluid (CSF) Amyloid Beta 42 / Amyloid Beta 40 Ratio | -0.0005 Ratio | Standard Error 0.001 |
| Healthy Living Diet | Mean Change in Cerebrospinal Fluid (CSF) Amyloid Beta 42 / Amyloid Beta 40 Ratio | -0.004 Ratio | Standard Error 0.002 |
Secondary
Mean Change in Cerebrospinal Fluid (CSF) Glial Fibrillary Acidic Protein (GFAP)
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Measurements with coefficient of variation (CV) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Cerebrospinal Fluid (CSF) Glial Fibrillary Acidic Protein (GFAP) | 1748.07 pg/mL | Standard Error 1303.72 |
| Healthy Living Diet | Mean Change in Cerebrospinal Fluid (CSF) Glial Fibrillary Acidic Protein (GFAP) | 627.26 pg/mL | Standard Error 624.3 |
Secondary
Mean Change in Cerebrospinal Fluid (CSF) Light Chain Neurofilaments (Nf-L)
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Measurements with coefficient of variation (CV) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Cerebrospinal Fluid (CSF) Light Chain Neurofilaments (Nf-L) | 134.31 pg/mL | Standard Error 72.6 |
| Healthy Living Diet | Mean Change in Cerebrospinal Fluid (CSF) Light Chain Neurofilaments (Nf-L) | 30.23 pg/mL | Standard Error 26.86 |
Secondary
Mean Change in Cerebrospinal Fluid (CSF) Neurogranin
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Measurements with coefficient of variation (CV) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Cerebrospinal Fluid (CSF) Neurogranin | 16.32 pg/mL | Standard Error 9.25 |
| Healthy Living Diet | Mean Change in Cerebrospinal Fluid (CSF) Neurogranin | 2.70 pg/mL | Standard Error 6.86 |
Secondary
Mean Change in Cerebrospinal Fluid (CSF) p181-Tau
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Measurements with coefficient of variation (CV) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Cerebrospinal Fluid (CSF) p181-Tau | -5.23 pg/mL | Standard Error 10.67 |
| Healthy Living Diet | Mean Change in Cerebrospinal Fluid (CSF) p181-Tau | -1.82 pg/mL | Standard Error 8.77 |
Secondary
Mean Change in Cerebrospinal Fluid (CSF) Total Tau
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Measurements with coefficient of variation (CV) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Cerebrospinal Fluid (CSF) Total Tau | -13.45 pg/mL | Standard Error 7.95 |
| Healthy Living Diet | Mean Change in Cerebrospinal Fluid (CSF) Total Tau | -3.61 pg/mL | Standard Error 4.12 |
Secondary
Mean Change in Creatinine
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Creatinine | -0.01 mg/dL | Standard Error 0.02 |
| Healthy Living Diet | Mean Change in Creatinine | -0.02 mg/dL | Standard Error 0.02 |
Secondary
Mean Change in Daily Energy Expenditure
Physical activity was monitored with an Actigraph GT3X-BT accelerometer device which measures accelerations in vertical, horizontal, and anterior-posterior directions.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Daily Energy Expenditure | -18.76 kilocalories/day | Standard Error 106.75 |
| Healthy Living Diet | Mean Change in Daily Energy Expenditure | -175.79 kilocalories/day | Standard Error 113.5 |
Secondary
Mean Change in Executive Function Composite
Executive function was assessed with the National Institutes of Health (NIH) Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER) battery that comprises written, verbal, and computerized tasks that test working memory, inhibition, set shifting, fluency, planning, insight, and social cognition and behavior. The Executive function Composite is a computerized score calculated based on the individual tests. It ranges between 0 and 10. Higher score values indicate better performance.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Executive Function Composite | 0.23 units on a scale | Standard Error 0.05 |
| Healthy Living Diet | Mean Change in Executive Function Composite | 0.07 units on a scale | Standard Error 0.08 |
Secondary
Mean Change in Fasting Glucose
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Fasting Glucose | 0.57 mg/dL | Standard Error 1.64 |
| Healthy Living Diet | Mean Change in Fasting Glucose | 2.16 mg/dL | Standard Error 1.64 |
Secondary
Mean Change in Fasting Insulin
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Fasting Insulin | -4.48 μIU/mL | Standard Error 1.08 |
| Healthy Living Diet | Mean Change in Fasting Insulin | -2.87 μIU/mL | Standard Error 1.52 |
Secondary
Mean Change in Gamma-Aminobutyric Acid (GABA) by Proton J-PRESS MRS of Posteromedial Cortex (PMC)
Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Gamma-Aminobutyric Acid (GABA) concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Gamma-Aminobutyric Acid (GABA) relative ratio to creatine was quantified.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Metabolite measurements with Cramer-Rao lower bounds (CRLBs) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Gamma-Aminobutyric Acid (GABA) by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | 0.002 Ratio | Standard Error 0.023 |
| Healthy Living Diet | Mean Change in Gamma-Aminobutyric Acid (GABA) by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | 0.020 Ratio | Standard Error 0.016 |
Secondary
Mean Change in Glucose by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC)
Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Glucose concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Glucose relative ratio to creatine was quantified.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Metabolite measurements with Cramer-Rao lower bounds (CRLBs) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Glucose by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | -0.002 Ratio | Standard Error 0.059 |
| Healthy Living Diet | Mean Change in Glucose by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | 0.065 Ratio | Standard Error 0.04 |
Secondary
Mean Change in Glucose by Proton J-PRESS MRS of Posteromedial Cortex (PMC)
Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Glucose concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Glucose relative ratio to creatine was quantified.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Metabolite measurements with Cramer-Rao lower bounds (CRLBs) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Glucose by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | -0.086 Ratio | Standard Error 0.034 |
| Healthy Living Diet | Mean Change in Glucose by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | -0.013 Ratio | Standard Error 0.023 |
Secondary
Mean Change in Glutamate by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC)
Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Glutamate concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Glutamate relative ratio to creatine was quantified.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Metabolite measurements with Cramer-Rao lower bounds (CRLBs) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Glutamate by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | 0.010 Ratio | Standard Error 0.108 |
| Healthy Living Diet | Mean Change in Glutamate by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | -0.088 Ratio | Standard Error 0.056 |
Secondary
Mean Change in Glutamate by Proton J-PRESS MRS of Posteromedial Cortex (PMC)
Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Glutamate concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Glutamate relative ratio to creatine was quantified.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Metabolite measurements with Cramer-Rao lower bounds (CRLBs) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Glutamate by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | -0.014 Ratio | Standard Error 0.046 |
| Healthy Living Diet | Mean Change in Glutamate by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | 0.008 Ratio | Standard Error 0.047 |
Secondary
Mean Change in Glutamine by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC)
Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Glutamine concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Glutamine relative ratio to creatine was quantified.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Metabolite measurements with Cramer-Rao lower bounds (CRLBs) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Glutamine by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | -0.042 Ratio | Standard Error 0.046 |
| Healthy Living Diet | Mean Change in Glutamine by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | -0.048 Ratio | Standard Error 0.043 |
Secondary
Mean Change in Glutamine by Proton J-PRESS MRS of Posteromedial Cortex (PMC)
Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Glutamine concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Glutamine relative ratio to creatine was quantified.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Metabolite measurements with Cramer-Rao lower bounds (CRLBs) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Glutamine by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | -0.052 Ratio | Standard Error 0.029 |
| Healthy Living Diet | Mean Change in Glutamine by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | -0.004 Ratio | Standard Error 0.024 |
Secondary
Mean Change in Glutathione by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC)
Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Glutathione concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Glutathione relative ratio to creatine was quantified.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Metabolite measurements with Cramer-Rao lower bounds (CRLBs) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Glutathione by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | -0.011 Ratio | Standard Error 0.014 |
| Healthy Living Diet | Mean Change in Glutathione by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | 0.030 Ratio | Standard Error 0.018 |
Secondary
Mean Change in Glutathione by Proton J-PRESS MRS of Posteromedial Cortex (PMC)
Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Glutathione concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Glutathione relative ratio to creatine was quantified.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Metabolite measurements with Cramer-Rao lower bounds (CRLBs) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Glutathione by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | -0.010 Ratio | Standard Error 0.01 |
| Healthy Living Diet | Mean Change in Glutathione by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | -0.018 Ratio | Standard Error 0.015 |
Secondary
Mean Change in Glycosylated Hemoglobin (HbA1c)
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Glycosylated Hemoglobin (HbA1c) | -0.20 percentage | Standard Error 0.08 |
| Healthy Living Diet | Mean Change in Glycosylated Hemoglobin (HbA1c) | -0.02 percentage | Standard Error 0.06 |
Secondary
Mean Change in HDL Cholesterol
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in HDL Cholesterol | -3.11 mg/dL | Standard Error 1.34 |
| Healthy Living Diet | Mean Change in HDL Cholesterol | -4.01 mg/dL | Standard Error 1.45 |
Secondary
Mean Change in Hematocrit
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Hematocrit | -1.08 percentage | Standard Error 0.49 |
| Healthy Living Diet | Mean Change in Hematocrit | -0.20 percentage | Standard Error 0.39 |
Secondary
Mean Change in Hemoglobin
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Hemoglobin | -0.29 g/dL | Standard Error 0.18 |
| Healthy Living Diet | Mean Change in Hemoglobin | -0.143 g/dL | Standard Error 0.15 |
Secondary
Mean Change in Homeostatic Model Assessment of Insulin Resistance 2 (HOMA2-IR)
Homeostatic Model Assessment of Insulin Resistance Index 2 (HOMA2-IR) is a marker of peripheral insulin resistance and is calculated by fasting insulin (μIU/L) multiplied by fasting glucose (mg/dL), and divided by a constant (405). A higher score indicates higher insulin resistance. A cut-off of 1.8 was used to indicate peripheral insulin resistance.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Homeostatic Model Assessment of Insulin Resistance 2 (HOMA2-IR) | -0.49 μIU/L*mg/dL | Standard Error 0.12 |
| Healthy Living Diet | Mean Change in Homeostatic Model Assessment of Insulin Resistance 2 (HOMA2-IR) | -0.33 μIU/L*mg/dL | Standard Error 0.18 |
Secondary
Mean Change in Hourly Energy Expenditure
Physical activity was monitored with an Actigraph GT3X-BT accelerometer device which measures accelerations in vertical, horizontal, and anterior-posterior directions.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Hourly Energy Expenditure | 0.23 kilocalories/hour | Standard Error 5.64 |
| Healthy Living Diet | Mean Change in Hourly Energy Expenditure | -9.17 kilocalories/hour | Standard Error 5.86 |
Secondary
Mean Change in International Normalized Ratio (INR)
The International Normalized Ratio (INR) is derived from prothrombin time (PT) which is calculated as a ratio of the patient's PT to a control PT standardized for the potency of the thromboplastin reagent developed by the World Health Organization (WHO) using the following formula: INR = Patient PT ÷ Control PT. The higher the INR, the longer it takes for blood to clot.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in International Normalized Ratio (INR) | 0.02 Ratio | Standard Error 0.01 |
| Healthy Living Diet | Mean Change in International Normalized Ratio (INR) | 0.02 Ratio | Standard Error 0.01 |
Secondary
Mean Change in Lactate by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC)
Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Lactate concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Lactate relative ratio to creatine was quantified.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Metabolite measurements with Cramer-Rao lower bounds (CRLBs) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Lactate by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | 0.012 Ratio | Standard Error 0.019 |
| Healthy Living Diet | Mean Change in Lactate by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | -0.017 Ratio | Standard Error 0.02 |
Secondary
Mean Change in Lactate by Proton J-PRESS MRS of Posteromedial Cortex (PMC)
Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Lactate concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Lactate relative ratio to creatine was quantified.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Metabolite measurements with Cramer-Rao lower bounds (CRLBs) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Lactate by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | -0.016 Ratio | Standard Error 0.016 |
| Healthy Living Diet | Mean Change in Lactate by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | -0.012 Ratio | Standard Error 0.012 |
Secondary
Mean Change in LDL Cholesterol
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in LDL Cholesterol | -18.31 mg/dL | Standard Error 5.82 |
| Healthy Living Diet | Mean Change in LDL Cholesterol | -11.59 mg/dL | Standard Error 3.71 |
Secondary
Mean Change in Logical Memory (LM) Test
Logical Memory (LM) test assesses verbal memory for structured information. It consists of two thematically independent narrative stories. Each story has 25 items, which the examinee has to recall with as much detail and precision as possible. Each item is scored the same regardless of importance level, and all correct items are summed giving a maximum score of 25 for each story. Verbatim recall score only includes the items that are recalled exactly and with detailed information, whereas gist recall score includes both the verbatim recall and the items that are recalled with only the essential elements of the information. The examinee has to recall the two stories twice, immediately after their initial administration (immediate recall) and after a 20 to 30-minute delay (delayed recall). Total maximum score for each of the subtests is 50 (25 items x 2 stories) and the minimum score is 0. Higher scores indicate better performance.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Logical Memory (LM) Test | Immediate Verbatim Recall | 1.60 units on a scale | Standard Error 0.78 |
| 5-2 CR | Mean Change in Logical Memory (LM) Test | Immediate Gist Recall | 1.65 units on a scale | Standard Error 0.85 |
| 5-2 CR | Mean Change in Logical Memory (LM) Test | Delayed Verbatim Recall | 1.30 units on a scale | Standard Error 0.92 |
| 5-2 CR | Mean Change in Logical Memory (LM) Test | Delayed Gist Recall | 1.95 units on a scale | Standard Error 0.74 |
| Healthy Living Diet | Mean Change in Logical Memory (LM) Test | Delayed Gist Recall | 3.00 units on a scale | Standard Error 1.35 |
| Healthy Living Diet | Mean Change in Logical Memory (LM) Test | Immediate Verbatim Recall | 1.10 units on a scale | Standard Error 0.95 |
| Healthy Living Diet | Mean Change in Logical Memory (LM) Test | Delayed Verbatim Recall | 2.80 units on a scale | Standard Error 1.26 |
| Healthy Living Diet | Mean Change in Logical Memory (LM) Test | Immediate Gist Recall | 1.75 units on a scale | Standard Error 1.04 |
Secondary
Mean Change in Metabolic Rate
Physical activity was monitored with an Actigraph GT3X-BT accelerometer device which measures accelerations in vertical, horizontal, and anterior-posterior directions.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Metabolic Rate | 0.01 Watts/sec | Standard Error 0.04 |
| Healthy Living Diet | Mean Change in Metabolic Rate | -0.07 Watts/sec | Standard Error 0.04 |
Secondary
Mean Change in Myo-Inositol by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC)
Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Myo-Inositol concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Myo-Inositol relative ratio to creatine was quantified.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Metabolite measurements with Cramer-Rao lower bounds (CRLBs) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Myo-Inositol by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | 0.001 Ratio | Standard Error 0.036 |
| Healthy Living Diet | Mean Change in Myo-Inositol by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | -0.006 Ratio | Standard Error 0.035 |
Secondary
Mean Change in Myo-Inositol by Proton J-PRESS MRS of Posteromedial Cortex (PMC)
Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Myo-Inositol concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Myo-Inositol relative ratio to creatine was quantified.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Metabolite measurements with Cramer-Rao lower bounds (CRLBs) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Myo-Inositol by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | -0.046 Ratio | Standard Error 0.031 |
| Healthy Living Diet | Mean Change in Myo-Inositol by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | -0.012 Ratio | Standard Error 0.028 |
Secondary
Mean Change in N-acetyl-aspartate by Proton J-PRESS MRS of Posteromedial Cortex (PMC)
Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) N-acetyl-aspartate concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. N-acetyl-aspartate relative ratio to creatine was quantified.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Metabolite measurements with Cramer-Rao lower bounds (CRLBs) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in N-acetyl-aspartate by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | -0.028 Ratio | Standard Error 0.034 |
| Healthy Living Diet | Mean Change in N-acetyl-aspartate by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | 0.054 Ratio | Standard Error 0.029 |
Secondary
Mean Change in N-acetyl-aspartyl-glutamate by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC)
Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) N-acetyl-aspartyl-glutamate concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. N-acetyl-aspartyl-glutamate relative ratio to creatine was quantified.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Metabolite measurements with Cramer-Rao lower bounds (CRLBs) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in N-acetyl-aspartyl-glutamate by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | 0.001 Ratio | Standard Error 0.04 |
| Healthy Living Diet | Mean Change in N-acetyl-aspartyl-glutamate by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | 0.042 Ratio | Standard Error 0.026 |
Secondary
Mean Change in N-acetyl-aspartyl-glutamate by Proton J-PRESS MRS of Posteromedial Cortex (PMC)
Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) N-acetyl-aspartyl-glutamate concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. N-acetyl-aspartyl-glutamate relative ratio to creatine was quantified.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Metabolite measurements with Cramer-Rao lower bounds (CRLBs) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in N-acetyl-aspartyl-glutamate by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | -0.038 Ratio | Standard Error 0.015 |
| Healthy Living Diet | Mean Change in N-acetyl-aspartyl-glutamate by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | 0.013 Ratio | Standard Error 0.016 |
Secondary
Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Akt
Akt (or protein kinase B) is an insulin signaling cascade mediator. An increase in its levels indicates an improvement in brain insulin resistance.
Time frame: Week 0, Week 4, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Akt | Week 4 - Week 0 | 1.30 Arbitrary Units (AU) | Standard Error 2.79 |
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Akt | Week 8 - Week 4 | -2.15 Arbitrary Units (AU) | Standard Error 2.04 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Akt | Week 4 - Week 0 | -3.27 Arbitrary Units (AU) | Standard Error 2.38 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Akt | Week 8 - Week 4 | -0.48 Arbitrary Units (AU) | Standard Error 2.93 |
Secondary
Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Amyloid Beta 40
Time frame: Week 0, Week 4, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Amyloid Beta 40 | Week 4 - Week 0 | -16.92 pg/mL | Standard Error 23.41 |
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Amyloid Beta 40 | Week 8 - Week 4 | 11.47 pg/mL | Standard Error 20.42 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Amyloid Beta 40 | Week 4 - Week 0 | -4.84 pg/mL | Standard Error 15.8 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Amyloid Beta 40 | Week 8 - Week 4 | 15.14 pg/mL | Standard Error 20.2 |
Secondary
Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Amyloid Beta 42
Time frame: Week 0, Week 4, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Amyloid Beta 42 | Week 4 - Week 0 | -10.82 pg/mL | Standard Error 25.178 |
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Amyloid Beta 42 | Week 8 - Week 4 | -0.62 pg/mL | Standard Error 22.71 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Amyloid Beta 42 | Week 4 - Week 0 | -9.58 pg/mL | Standard Error 15.11 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Amyloid Beta 42 | Week 8 - Week 4 | 10.61 pg/mL | Standard Error 17.28 |
Secondary
Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Amyloid Beta 42 / Amyloid Beta 40 Ratio
Time frame: Week 0, Week 4, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Amyloid Beta 42 / Amyloid Beta 40 Ratio | Week 4 - Week 0 | 0.01 Ratio | Standard Error 0.02 |
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Amyloid Beta 42 / Amyloid Beta 40 Ratio | Week 8 - Week 0 | -0.02 Ratio | Standard Error 0.02 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Amyloid Beta 42 / Amyloid Beta 40 Ratio | Week 4 - Week 0 | -0.03 Ratio | Standard Error 0.02 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Amyloid Beta 42 / Amyloid Beta 40 Ratio | Week 8 - Week 0 | 0.01 Ratio | Standard Error 0.02 |
Secondary
Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) A-synuclein
Time frame: Week 0, Week 4, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) A-synuclein | Week 4 - Week 0 | -4.21 pg/mL | Standard Error 18.18 |
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) A-synuclein | Week 8 - Week 4 | 1.57 pg/mL | Standard Error 13.87 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) A-synuclein | Week 4 - Week 0 | -27.97 pg/mL | Standard Error 9.23 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) A-synuclein | Week 8 - Week 4 | 17.06 pg/mL | Standard Error 14.77 |
Secondary
Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) BDNF
Time frame: Week 0, Week 4, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Measurements with coefficient of variation (CV) ≥ 20% were excluded from the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) BDNF | Week 4 - Week 0 | 0.01 pg/mL | Standard Error 1.22 |
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) BDNF | Week 8 - Week 4 | 0.98 pg/mL | Standard Error 1.51 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) BDNF | Week 4 - Week 0 | 1.07 pg/mL | Standard Error 2.37 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) BDNF | Week 8 - Week 4 | 0.65 pg/mL | Standard Error 3.09 |
Secondary
Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Heavy Chain Neurofilaments (Nf-H)
Time frame: Week 0, Week 4, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Measurements with coefficient of variation (CV) ≥ 20% were excluded from the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Heavy Chain Neurofilaments (Nf-H) | Week 4 - Week 0 | -25.12 pg/mL | Standard Error 47.07 |
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Heavy Chain Neurofilaments (Nf-H) | Week 8 - Week 4 | -1.59 pg/mL | Standard Error 45.27 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Heavy Chain Neurofilaments (Nf-H) | Week 4 - Week 0 | 4.80 pg/mL | Standard Error 39.04 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Heavy Chain Neurofilaments (Nf-H) | Week 8 - Week 4 | 54.71 pg/mL | Standard Error 56.18 |
Secondary
Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Mitochondrial Complex IV Quantity
Complex IV is part of the mitochondrial electron transport chain. Decreased complex IV levels in NDEVs have been found in patients with Alzheimer's disease. A decrease in its levels may indicate decreased ability of neurons for ATP production and energy crisis.
Time frame: Week 0, Week 4, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Mitochondrial Complex IV Quantity | Week 4 - Week 0 | 0.00037 Arbitrary Units (AU) | Standard Error 0.00076 |
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Mitochondrial Complex IV Quantity | Week 8 - Week 4 | -0.00051 Arbitrary Units (AU) | Standard Error 0.00047 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Mitochondrial Complex IV Quantity | Week 4 - Week 0 | -0.00006 Arbitrary Units (AU) | Standard Error 0.00035 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Mitochondrial Complex IV Quantity | Week 8 - Week 4 | -0.00002 Arbitrary Units (AU) | Standard Error 0.00051 |
Secondary
Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Mitochondrial Complex V Quantity
Complex V is part of the mitochondrial electron transport chain. Decreased complex V levels in NDEVs have been found in patients with Alzheimer's disease. A decrease in its levels may indicate decreased ability of neurons for ATP production and energy crisis.
Time frame: Week 0, Week 4, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Mitochondrial Complex V Quantity | Week 4 - Week 0 | 0.000082 Arbitrary Units (AU) | Standard Error 0.0002 |
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Mitochondrial Complex V Quantity | Week 8 - Week 4 | 0.00006 Arbitrary Units (AU) | Standard Error 0.00013 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Mitochondrial Complex V Quantity | Week 4 - Week 0 | 0.00019 Arbitrary Units (AU) | Standard Error 0.0001 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Mitochondrial Complex V Quantity | Week 8 - Week 4 | -0.000074 Arbitrary Units (AU) | Standard Error 0.00036 |
Secondary
Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Monocarboxylate Transporter 1 (MCT1)
Time frame: Week 0, Week 4, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Monocarboxylate Transporter 1 (MCT1) | Week 4 - Week 0 | 158.32 ng/mL | Standard Error 153.93 |
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Monocarboxylate Transporter 1 (MCT1) | Week 8 - Week 4 | -5.01 ng/mL | Standard Error 139.56 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Monocarboxylate Transporter 1 (MCT1) | Week 8 - Week 4 | -141.72 ng/mL | Standard Error 159.49 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Monocarboxylate Transporter 1 (MCT1) | Week 4 - Week 0 | -104.39 ng/mL | Standard Error 167.54 |
Secondary
Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Monocarboxylate Transporter 2 (MCT2)
Time frame: Week 0, Week 4, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Monocarboxylate Transporter 2 (MCT2) | Week 4 - Week 0 | 1.27 ng/mL | Standard Error 1.14 |
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Monocarboxylate Transporter 2 (MCT2) | Week 8 - Week 4 | -0.67 ng/mL | Standard Error 0.78 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Monocarboxylate Transporter 2 (MCT2) | Week 4 - Week 0 | -1.72 ng/mL | Standard Error 0.72 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Monocarboxylate Transporter 2 (MCT2) | Week 8 - Week 4 | 1.86 ng/mL | Standard Error 1.37 |
Secondary
Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Neurogranin
Time frame: Week 0, Week 4, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Measurements with coefficient of variation (CV) ≥ 20% were excluded from the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Neurogranin | Week 4 - Week 0 | 5.69 pg/mL | Standard Error 12.14 |
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Neurogranin | Week 8 - Week 4 | -5.43 pg/mL | Standard Error 12.5 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Neurogranin | Week 4 - Week 0 | 1.08 pg/mL | Standard Error 14.91 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Neurogranin | Week 8 - Week 4 | 4.07 pg/mL | Standard Error 16.84 |
Secondary
Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) p181-Tau
Time frame: Week 0, Week 4, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) p181-Tau | Week 4 - Week 0 | 1.70 pg/mL | Standard Error 15.72 |
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) p181-Tau | Week 8 - Week 4 | -1.65 pg/mL | Standard Error 15.11 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) p181-Tau | Week 4 - Week 0 | 1.01 pg/mL | Standard Error 8.94 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) p181-Tau | Week 8 - Week 4 | 9.90 pg/mL | Standard Error 12.26 |
Secondary
Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) p231-Tau
Time frame: Week 0, Week 4, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) p231-Tau | Week 4 - Week 0 | -3.47 pg/mL | Standard Error 7.78 |
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) p231-Tau | Week 8 - Week 4 | -2.12 pg/mL | Standard Error 7.1 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) p231-Tau | Week 4 - Week 0 | -5.60 pg/mL | Standard Error 4.71 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) p231-Tau | Week 8 - Week 4 | 0.13 pg/mL | Standard Error 5.09 |
Secondary
Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated c-Jun N-terminal Kinase (pJNK)
JNK is an insulin signaling cascade mediator. Activated JNK (pJNK) inhibits insulin signaling. An increase in pJNK levels indicates inhibition of downstream insulin signaling pathway.
Time frame: Week 0, Week 4, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated c-Jun N-terminal Kinase (pJNK) | Week 4 - Week 0 | 2.91 Arbitrary Units (AU) | Standard Error 2.72 |
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated c-Jun N-terminal Kinase (pJNK) | Week 8 - Week 4 | -1.44 Arbitrary Units (AU) | Standard Error 3.08 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated c-Jun N-terminal Kinase (pJNK) | Week 4 - Week 0 | -2.88 Arbitrary Units (AU) | Standard Error 3.3 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated c-Jun N-terminal Kinase (pJNK) | Week 8 - Week 4 | 8.44 Arbitrary Units (AU) | Standard Error 7.93 |
Secondary
Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Extracellular Signal-regulated Kinase 1/2 (pERK1/2)
pERK1/2 is an insulin signaling cascade mediator. An increase in its levels indicates activation of downstream insulin signaling pathway.
Time frame: Week 0, Week 4, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Extracellular Signal-regulated Kinase 1/2 (pERK1/2) | Week 4 - Week 0 | 4.66 Arbitrary Units (AU) | Standard Error 3.05 |
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Extracellular Signal-regulated Kinase 1/2 (pERK1/2) | Week 8 - Week 4 | -2.66 Arbitrary Units (AU) | Standard Error 2.9 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Extracellular Signal-regulated Kinase 1/2 (pERK1/2) | Week 4 - Week 0 | -2.23 Arbitrary Units (AU) | Standard Error 2.82 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Extracellular Signal-regulated Kinase 1/2 (pERK1/2) | Week 8 - Week 4 | 0.37 Arbitrary Units (AU) | Standard Error 3.52 |
Secondary
Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated p38 (pp38)
p38 is an insulin signaling cascade mediator. Activated p38 (pp38) inhibits insulin signaling. An increase in pp38 levels indicates inhibition of downstream insulin signaling pathway.
Time frame: Week 0, Week 4, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated p38 (pp38) | Week 4 - Week 0 | 5.76 Arbitrary Units (AU) | Standard Error 7.1 |
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated p38 (pp38) | Week 8 - Week 4 | -12.20 Arbitrary Units (AU) | Standard Error 7.64 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated p38 (pp38) | Week 4 - Week 0 | -1.39 Arbitrary Units (AU) | Standard Error 9.26 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated p38 (pp38) | Week 8 - Week 4 | 21.81 Arbitrary Units (AU) | Standard Error 25.47 |
Secondary
Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Serine473-Akt (pS473-Akt)
pS473-Akt is an insulin signaling cascade mediator. An increase in its levels indicates activation of downstream insulin signaling pathway.
Time frame: Week 0, Week 4, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Serine473-Akt (pS473-Akt) | Week 4 - Week 0 | -1.73 Arbitrary Units (AU) | Standard Error 1.8 |
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Serine473-Akt (pS473-Akt) | Week 8 - Week 4 | -3.33 Arbitrary Units (AU) | Standard Error 3.02 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Serine473-Akt (pS473-Akt) | Week 4 - Week 0 | -5.13 Arbitrary Units (AU) | Standard Error 3.78 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Serine473-Akt (pS473-Akt) | Week 8 - Week 4 | -0.93 Arbitrary Units (AU) | Standard Error 4 |
Secondary
Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Serine473-Akt (pS473-Akt) / Akt Ratio
Time frame: Week 0, Week 4, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Serine473-Akt (pS473-Akt) / Akt Ratio | Week 4 - Week 0 | -0.02 Ratio | Standard Error 0.02 |
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Serine473-Akt (pS473-Akt) / Akt Ratio | Week 8 - Week 4 | -0.01 Ratio | Standard Error 0.02 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Serine473-Akt (pS473-Akt) / Akt Ratio | Week 4 - Week 0 | -0.01 Ratio | Standard Error 0.02 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Phosphorylated Serine473-Akt (pS473-Akt) / Akt Ratio | Week 8 - Week 4 | -0.003 Ratio | Standard Error 0.02 |
Secondary
Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) proBDNF
Time frame: Week 0, Week 4, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) proBDNF | Week 4 - Week 0 | -723.76 pg/mL | Standard Error 814.01 |
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) proBDNF | Week 8 - Week 4 | 531.01 pg/mL | Standard Error 646.66 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) proBDNF | Week 4 - Week 0 | -91.37 pg/mL | Standard Error 593.83 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) proBDNF | Week 8 - Week 4 | -388.59 pg/mL | Standard Error 984.13 |
Secondary
Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) TAR DNA-binding Protein 43 (TDP-43)
Time frame: Week 0, Week 4, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) TAR DNA-binding Protein 43 (TDP-43) | Week 4 - Week 0 | -443.207 pg/mL | Standard Error 324.78 |
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) TAR DNA-binding Protein 43 (TDP-43) | Week 8 - Week 4 | 64.67 pg/mL | Standard Error 265.15 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) TAR DNA-binding Protein 43 (TDP-43) | Week 4 - Week 0 | 67.84 pg/mL | Standard Error 185.71 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) TAR DNA-binding Protein 43 (TDP-43) | Week 8 - Week 4 | 89.56 pg/mL | Standard Error 258.47 |
Secondary
Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Total Tau
Time frame: Week 0, Week 4, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Total Tau | Week 4 - Week 0 | -3.05 pg/mL | Standard Error 25.93 |
| 5-2 CR | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Total Tau | Week 8 - Week 4 | 8.00 pg/mL | Standard Error 24.48 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Total Tau | Week 4 - Week 0 | -5.33 pg/mL | Standard Error 19.79 |
| Healthy Living Diet | Mean Change in Neuron-Derived Extracellular Vesicle (NDEV) Total Tau | Week 8 - Week 4 | 20.31 pg/mL | Standard Error 26.43 |
Secondary
Mean Change in Platelets
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Platelets | 2.18 cells x 10^3/L | Standard Error 5.15 |
| Healthy Living Diet | Mean Change in Platelets | 8.07 cells x 10^3/L | Standard Error 4.1 |
Secondary
Mean Change in Red Blood Cells (RBCs)
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Red Blood Cells (RBCs) | -0.12 cells x 10^12/L | Standard Error 0.06 |
| Healthy Living Diet | Mean Change in Red Blood Cells (RBCs) | -0.04 cells x 10^12/L | Standard Error 0.05 |
Secondary
Mean Change in Scyllo-Inositol by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC)
Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) glucose concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Glucose relative ratio to creatine was quantified.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Metabolite measurements with Cramer-Rao lower bounds (CRLBs) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Scyllo-Inositol by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | -0.002 Ratio | Standard Error 0.008 |
| Healthy Living Diet | Mean Change in Scyllo-Inositol by Proton J-PRESS MRS of Medial Prefrontal Cortex (MPFC) | 0.004 Ratio | Standard Error 0.004 |
Secondary
Mean Change in Scyllo-Inositol by Proton J-PRESS MRS of Posteromedial Cortex (PMC)
Proton J-PRESS Magnetic Resonance Spectroscopy (MRS) Scyllo-Inositol concentrations were determined using the Prior-Knowledge Fitting Procedure (ProFit), which fits linear combinations of simulated two-dimensional basis metabolite spectra. Scyllo-Inositol relative ratio to creatine was quantified.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population). Metabolite measurements with Cramer-Rao lower bounds (CRLBs) ≥ 20% were excluded from the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Scyllo-Inositol by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | 0.002 Ratio | Standard Error 0.003 |
| Healthy Living Diet | Mean Change in Scyllo-Inositol by Proton J-PRESS MRS of Posteromedial Cortex (PMC) | 0.004 Ratio | Standard Error 0.004 |
Secondary
Mean Change in Serum Acetoacetate (AcAc)
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Serum Acetoacetate (AcAc) | 0.03 mmol/L | Standard Error 0.01 |
| Healthy Living Diet | Mean Change in Serum Acetoacetate (AcAc) | 0.01 mmol/L | Standard Error 0.01 |
Secondary
Mean Change in Serum Beta-Hydroxybutyrate (bHB)
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Serum Beta-Hydroxybutyrate (bHB) | 0.06 mmol/L | Standard Error 0.03 |
| Healthy Living Diet | Mean Change in Serum Beta-Hydroxybutyrate (bHB) | 0.03 mmol/L | Standard Error 0.02 |
Secondary
Mean Change in Serum Cortisol
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Serum Cortisol | 22.89 ng/mL | Standard Error 15.55 |
| Healthy Living Diet | Mean Change in Serum Cortisol | 25.04 ng/mL | Standard Error 12.63 |
Secondary
Mean Change in Serum Non-Esterified Fatty Acids (NEFA)
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Serum Non-Esterified Fatty Acids (NEFA) | 0.09 mEq/L | Standard Error 0.07 |
| Healthy Living Diet | Mean Change in Serum Non-Esterified Fatty Acids (NEFA) | 0.07 mEq/L | Standard Error 0.04 |
Secondary
Mean Change in Steps Per Minute
Physical activity was monitored with an Actigraph GT3X-BT accelerometer device which measures accelerations in vertical, horizontal, and anterior-posterior directions.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Steps Per Minute | -0.13 steps/minute | Standard Error 0.52 |
| Healthy Living Diet | Mean Change in Steps Per Minute | -1.20 steps/minute | Standard Error 0.67 |
Secondary
Mean Change in the Short Form 36-item Health Survey (SF-36)
Short Form 36-item Health Survey (SF-36) is a gauge of physical and psychosocial effects of the interventions. It consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability; the higher the score the less disability.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in the Short Form 36-item Health Survey (SF-36) | Physical functioning | 2.50 units on a scale | Standard Error 2.49 |
| 5-2 CR | Mean Change in the Short Form 36-item Health Survey (SF-36) | Role limitations due to physical health | 1.25 units on a scale | Standard Error 3.74 |
| 5-2 CR | Mean Change in the Short Form 36-item Health Survey (SF-36) | Role limitations due to emotional problems | -5.00 units on a scale | Standard Error 3.56 |
| 5-2 CR | Mean Change in the Short Form 36-item Health Survey (SF-36) | Energy/fatigue | 4.50 units on a scale | Standard Error 3.35 |
| 5-2 CR | Mean Change in the Short Form 36-item Health Survey (SF-36) | Emotional well-being | 1.00 units on a scale | Standard Error 1.09 |
| 5-2 CR | Mean Change in the Short Form 36-item Health Survey (SF-36) | Social functioning | 1.88 units on a scale | Standard Error 2.21 |
| 5-2 CR | Mean Change in the Short Form 36-item Health Survey (SF-36) | Pain | 3.00 units on a scale | Standard Error 3.96 |
| 5-2 CR | Mean Change in the Short Form 36-item Health Survey (SF-36) | General health | -2.25 units on a scale | Standard Error 1.56 |
| Healthy Living Diet | Mean Change in the Short Form 36-item Health Survey (SF-36) | General health | -2.50 units on a scale | Standard Error 1.79 |
| Healthy Living Diet | Mean Change in the Short Form 36-item Health Survey (SF-36) | Physical functioning | 2.00 units on a scale | Standard Error 1.52 |
| Healthy Living Diet | Mean Change in the Short Form 36-item Health Survey (SF-36) | Emotional well-being | 3.20 units on a scale | Standard Error 1.73 |
| Healthy Living Diet | Mean Change in the Short Form 36-item Health Survey (SF-36) | Role limitations due to physical health | 0.00 units on a scale | Standard Error 5.59 |
| Healthy Living Diet | Mean Change in the Short Form 36-item Health Survey (SF-36) | Pain | 3.38 units on a scale | Standard Error 3.19 |
| Healthy Living Diet | Mean Change in the Short Form 36-item Health Survey (SF-36) | Role limitations due to emotional problems | 0.00 units on a scale | Standard Error 2.36 |
| Healthy Living Diet | Mean Change in the Short Form 36-item Health Survey (SF-36) | Social functioning | 0.00 units on a scale | Standard Error 3.54 |
| Healthy Living Diet | Mean Change in the Short Form 36-item Health Survey (SF-36) | Energy/fatigue | 3.75 units on a scale | Standard Error 2.29 |
Secondary
Mean Change in Time in Activity
Physical activity was monitored with an Actigraph GT3X-BT accelerometer device which measures accelerations in vertical, horizontal, and anterior-posterior directions.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5-2 CR | Mean Change in Time in Activity | Time in moderate physical activity | 0.005 percentage of time | Standard Error 0.009 |
| 5-2 CR | Mean Change in Time in Activity | Sedentary time | -0.013 percentage of time | Standard Error 0.023 |
| 5-2 CR | Mean Change in Time in Activity | Time in light physical activity | 0.008 percentage of time | Standard Error 0.014 |
| 5-2 CR | Mean Change in Time in Activity | Time in moderate-to-vigorous physical activity | 0.005 percentage of time | Standard Error 0.009 |
| Healthy Living Diet | Mean Change in Time in Activity | Time in moderate-to-vigorous physical activity | -0.015 percentage of time | Standard Error 0.01 |
| Healthy Living Diet | Mean Change in Time in Activity | Time in moderate physical activity | -0.015 percentage of time | Standard Error 0.01 |
| Healthy Living Diet | Mean Change in Time in Activity | Time in light physical activity | -0.019 percentage of time | Standard Error 0.012 |
| Healthy Living Diet | Mean Change in Time in Activity | Sedentary time | 0.033 percentage of time | Standard Error 0.021 |
Secondary
Mean Change in Total Cholesterol
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Total Cholesterol | -23.16 mg/dL | Standard Error 6.17 |
| Healthy Living Diet | Mean Change in Total Cholesterol | -16.29 mg/dL | Standard Error 4.6 |
Secondary
Mean Change in Total Energy Expenditure
Physical activity was monitored with an Actigraph GT3X-BT accelerometer device which measures accelerations in vertical, horizontal, and anterior-posterior directions.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Total Energy Expenditure | -538.44 kilocalories | Standard Error 626.72 |
| Healthy Living Diet | Mean Change in Total Energy Expenditure | -302.86 kilocalories | Standard Error 649.62 |
Secondary
Mean Change in Total Sedentary Bouts
Physical activity was monitored with an Actigraph GT3X-BT accelerometer device which measures accelerations in vertical, horizontal, and anterior-posterior directions.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Total Sedentary Bouts | -17.69 sedentary bouts | Standard Error 6.44 |
| Healthy Living Diet | Mean Change in Total Sedentary Bouts | 13.41 sedentary bouts | Standard Error 5.49 |
Secondary
Mean Change in Total Steps
Physical activity was monitored with an Actigraph GT3X-BT accelerometer device which measures accelerations in vertical, horizontal, and anterior-posterior directions.
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Total Steps | -4821.93 steps | Standard Error 2993.63 |
| Healthy Living Diet | Mean Change in Total Steps | -2937.65 steps | Standard Error 2362.82 |
Secondary
Mean Change in Triglycerides
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Triglycerides | -9.61 mg/dL | Standard Error 6.72 |
| Healthy Living Diet | Mean Change in Triglycerides | -6.61 mg/dL | Standard Error 10.03 |
Secondary
Mean Change in Waist Circumference
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in Waist Circumference | -2.84 cm | Standard Error 0.63 |
| Healthy Living Diet | Mean Change in Waist Circumference | -1.64 cm | Standard Error 0.82 |
Secondary
Mean Change in White Blood Cells (WBCs)
Time frame: Week 0, Week 8
Population: FAS (full analysis set) is all randomized participants who completed 8 weeks of diet (per protocol population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5-2 CR | Mean Change in White Blood Cells (WBCs) | -0.31 cells x 10^9/L | Standard Error 0.23 |
| Healthy Living Diet | Mean Change in White Blood Cells (WBCs) | -0.23 cells x 10^9/L | Standard Error 0.2 |