Cognitive Decline, Dementia, Alzheimer Disease, Vascular Dementia
Conditions
Brief summary
Phase III randomized controlled trial designed to test the effects of a 3-year intervention of the MIND diet (Mediterranean-DASH Intervention for Neurodegenerative Delay) on cognitive decline and brain neurodegeneration among 600 individuals 65+ years without cognitive impairment who are overweight and have suboptimal diets.
Detailed description
Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND) is a Phase III randomized controlled trial designed to test the effects of a 3-year intervention of a hybrid of the Mediterranean and DASH diets, called MIND, on cognitive decline among 600 individuals 65+ years without cognitive impairment who are overweight and have suboptimal diets. The proposed MIND diet is a hybrid of the Mediterranean and DASH diets but with selected modifications based on the most compelling evidence in the diet-dementia field. The MIND diet has the same basic components of the DASH and Mediterranean diets, such as emphasis on natural plant-based foods and limited animal and high saturated fat foods, but uniquely specifies green leafy vegetables and berries as well as food component servings that reflect the nutrition-dementia evidence. The trial will employ a parallel group design comparing the effects on cognitive outcomes of the MIND intervention diet plus mild caloric restriction for weight loss to the control diet, usual diet with mild caloric restriction for weight loss. Biological effects of the MIND diet will be assessed by measurement of brain macro- and micro-structural integrity in 300 randomly selected participants. Other biochemical markers will be assessed in the entire cohort of 600 participants, including: plasma Abeta 42/Abeta 40, brain-derived neurotrophic factor (BDNF) and plasma markers of oxidative stress and inflammation. In addition, the trial will examine potential effect mediators and modifiers by a number of cardiovascular risk factors, AD biomarkers, and biological mechanisms. The proposed study has two clinical sites, one in Chicago (Rush University) and one in Boston (Harvard University), and centralized laboratories for data coordinating and analyses (Brigham & Women's Hospital), neuroimaging analyses (Rush University), and specialized laboratories for tissue biochemical analyses.
Interventions
BEHAVIORALMIND Diet
3-year dietary counseling to adhere to the MIND diet and for mild weight loss
BEHAVIORALMild Weight Loss
3-year dietary counseling to reduce calorie intake by 250 kcal/day for mild weight loss
Sponsors
Harvard School of Public Health (HSPH)
Brigham and Women's Hospital
National Institute on Aging (NIA)
Rush University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to 84 Years
Healthy volunteers
Yes
Inclusion criteria
* family history of dementia * BMI \>=25 * suboptimal diet
Exclusion criteria
* heavy alcohol use * severe illness * cognitively impaired * psychiatric illness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in global cognitive function (composite score) | 3 years | Global cognitive function assessment is based on a battery of 12 cognitive tests \[1. Word list Memory; 2. Word List Recall; 3. Word List Recognition; 4. Logical Memory (East Boston Story Immediate Recall); 5. Logical Memory (East Boston Story Delayed Recall); 6. Verbal Fluency; 7. Multilingual Naming Test; 8. Trail A; 9. Trail B; 10. Flanker Inhibitory Control; 11. Oral Symbol Digit Modalities Test; and 12. Pattern Comparison. Individual test scores will be summarized by calculating the z-score for each test based on the mean and standard deviation of the sample distribution - averaging z-scores across tests will yield a composite score for global cognitive function. Cognitive function will be assessed at the baseline, 6, 12, 24, and 36 months to determine the time-course of cognitive change. |
| Change in specific cognitive domains | 3 years | Change in specific cognitive domains: episodic memory, semantic memory, perceptual speed, and executive function |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in brain MRI total brain /intracranial volume (cubic centimeters) and hippocampal/intracranial volume (cubic centimeters) | 3 years | Changes in brain MRI-derived normalized measures of total brain volume (cubic centimeters) and hippocampal volume (cubic centimeters) and white/gray matter, segmented gray matter regions, white matter lesions, and thickness of segmented cortical regions. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory aim 2c: Low-density lipoprotein (LDL) | 3 years | To evaluate the role of MIND diet on the change of LDL (mg/dL) in plasma from the baseline to 3 and 36 months. |
| Exploratory aim 2d: High-density lipoprotein (HDL) | 3 years | To evaluate the role of MIND diet on the change of HDL (mg/dL) in plasma from the baseline to 3 and 36 months. |
| Exploratory aim 2e: Hemoglobin A1c (HbA1c) | 3 years | To evaluate the role of MIND diet on the change of HbA1c levels in plasma from the baseline to 3 and 36 months. |
| Exploratory aim 3: Plasma amyloid beta (Abeta) | 3 years | To evaluate the role of MIND diet on the change of plasma Abeta 40 (pg/ml), Abeta42 (pg/ml), and ratio Abeta40/Abeta42 from the baseline to 3 and 36 months. |
| Exploratory aim 4a: C-Reactive Protein (CRP) | 3 years | To evaluate the role of MIND diet on the change of CRP (mg/L) levels in plasma from the baseline to 3 and 36 months. |
| Exploratory aim 1: Incidence of cardiovascular disease | 3 years | To evaluate the role of MIND diet on the risk of incident cardiovascular disease. Cardiovascular disease is defined as the presence of coronary heart disease, cerebrovascular disease, and/or heart failure. |
| Exploratory aim 4c: Oxidized LDL | 3 years | To evaluate the role of MIND diet on the change of oxidized LDL (mg/dl) in plasma from the baseline to 3 and 36 months. |
| Exploratory aim 4d: Estimated glomerular filtration rate (eGFR) | 3 years | To evaluate the role of MIND diet on the change of eGFR (mg/dL) from the baseline to 3 and 36 months. |
| Exploratory aim 4e: Brain-derived neurotrophic factor | 3 years | To evaluate the role of MIND diet on the change of plasma Brain-derived neurotrophic factor (pg/mL) from the baseline to 3 and 36 months. |
| Exploratory aim 4f: Adiponectin | 3 years | To evaluate the role of MIND diet on the change of plasma adiponectin (mg/L) levels from the baseline to 3 and 36 months. |
| Exploratory aim 4b: Interleukin 6 (IL-6) | 3 years | To evaluate the role of MIND diet on the change of plasma IL-6 (pg/mL) from the baseline to 3 and 36 months. |
| Exploratory aim 2a: Blood pressure | 3 years | To evaluate the role of MIND diet on the change of systolic and diastolic blood pressure (mmHg) from the baseline to 6, 12, 24, and 36 months |
| Exploratory aim 2b: Total cholesterol | 3 years | To evaluate the role of MIND diet on the change of total cholesterol (mg/dL), in plasma from the baseline to 3 and 36 months. |
Countries
United States
Outcome results
None listed