Mild Cognitive Impairment, Obesity
Conditions
Brief summary
Obesity and related metabolic comorbidities have been associated with more than a 4-fold increased risk of incident cognitive impairment, including Alzheimer's disease and related dementias (ADRD). Dysfunctional metabolic flexibility is increasingly recognized as a critical mechanism linking metabolic risk factors to risk of cognitive impairment, although few studies portable behavioral strategies to enhance metabolic function among individuals at risk for ADRD. The present study will examine the feasibility and acceptability of a 12-week time restricted feeding intervention among individuals with mild cognitive impairment (MCI). Changes in cognitive and metabolic function will also be examined.
Detailed description
Obese older adults with mild cognitive impairment with mild cognitive impairment will be asked to participate in a 12 week time restricted fasting intervention. Working with a behavioral psychologist, they will adapt the timing their eating patterns to incorporate 2-3 days per week with a 16 hour fasting period, typically lasting from after dinner to lunch the next day. The behavioral intervention will titrate fasting using established behavioral change techniques, with early phase sessions focusing on organizational principles to prepare for weekly fasting scheduling and acceptance-based psychological coping skills, including the ability to tolerate symptoms of hunger and discomfort that may accompany fasting. After treatment initiation, sessions will focus on broadening fasting behaviors for flexible adoption across different contexts and to enhance maintenance of fasting patterns. At baseline and following treatment, participants will undergo tests of cognitive and metabolic function to assess memory, executive function, metabolic flexibility, and inflammation. At both time points, participants will also undergo an abbreviated assessment of cognitive and metabolic function under fasting conditions to assess for any cognitive weaknesses unmasked during periods of brief metabolic 'stress'.
Interventions
BEHAVIORALTime restricted eating
Participants will work with a psychologist towards achieving a 16 hour fasting period, 2-3 days per week. The intervention will last 12 weeks, with different intervention materials gradually introduced over the course of the 12 weeks.
Sponsors
University of North Carolina, Chapel Hill
Duke University
National Institute on Aging (NIA)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Assessors will be blinded to the participant's intervention fidelity and engagement.
Eligibility
Sex/Gender
ALL
Age
65 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Subjects will include those men and women: * aged 65-80 years, * with amnestic Mild Cognitive Impairment (Montreal Cognitive Assessment Battery score \[MoCA\] total score 19-25 or a phonemic fluency score of =\<12 (with MoCA \>25) or semantic fluency score of =\<15 (with MoCA \>15); and score of \> 1.0 on the Mail-in Cognitive Function Screening Instrument), * obese (body mass index 27.5-40 kg/m\^2), * sedentary, and * willing to participate in all aspects of the proposed intervention.
Exclusion criteria
Reasons for participant exclusion will include: * secondary causes of obesity, * evidence of clinical dementia (MoCA score \< 18), severe chronic kidney disease (eGFR \<45 ml/min/1.73m\^2), * heart failure, * high grade arrhythmias, * severe valvular heart disease, * severe asthma or chronic obstructive lung disease, * diabetes requiring insulin, * musculoskeletal or neurologic problems that would preclude participation in aerobic exercise training, * a major psychiatric disorder, * a history of drug abuse, * alcohol consumption \>14 drinks/week, * gastric bypass surgery, * non-English speaking, or * a life-limiting comorbid medical condition (e.g. cancer).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Memory Composite Rank | Baseline, 12 Weeks | Participants completed two assessments of learning and memory at each time point. The Hopkins Verbal Learning Test Revised (HVLT-R) was used to assess verbal memory and the Brief Visual Memory Test - Revised (BVMT-R) was used to assess visual memory. Both the HVLT-R and the BVMT-R provide three separate scores that reflect total learning, retention of information, and recognition of learned items following a delay. In order to create a single Memory performance score, each of these six scores were ranked at each time point and a mean rank was created, with higher scores reflecting higher Memory performance. The mean rank for Memory performance at 12 weeks was used as the outcome, controlling for baseline Memory performance. Larger mean ranks at 12 weeks indicate greater improvements. As a rank-based outcome, values have no fixed theoretical upper or lower bound. |
| Change in Executive Function Composite Rank | Baseline, 12 Weeks | Participants underwent multiple assessments of Executive Functioning at each time point. Specifically, participants completed the Trail Making Test Parts A \& B, the Digit Span Forwards and Backwards Tasks, the Digit Symbol Substitution Test, the Controlled Oral Word Association Test, the Animal Naming Test, and the Stroop Word and Color-Word Interference Tests at both pre-and-post treatment. In order to create a single Executive Function score, each of these nine measures were ranked at each time point and a mean rank was created, with higher scores reflecting higher Executive Function performance. The mean rank for Executive Function performance at 12 weeks was used as the outcome, controlling for baseline Executive Function performance, with larger 12-week mean ranks indicating greater improvements compared to baseline. As a rank-based outcome, values have no fixed theoretical upper or lower bound. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Metabolic Function Composite Rank | Baseline, 12 Weeks | Participants underwent assessments of multiple metabolic markers at each time point. Metabolic biomarkers included glucose, β-hydroxybutyrate, adiponectin, lactate, leptin, non-esterified fatty acids (NEFAs), and fibroblast growth factor-21. In order to create a single measure of Metabolic Function, each of these seven metabolic biomarkers were ranked at each time point and a mean rank was created, with higher scores reflecting better Metabolic Function. The mean rank for Metabolic Function at 12 weeks was used as the outcome, controlling for baseline Metabolic Function. If time restricted fasting was effective in improving Metabolic Function, then the mean rank composite score should be larger at 12 weeks compared to baseline. As a rank-based outcome,values have no fixed theoretical upper or lower bound. |
| Change in Inflammatory Function Composite Rank | Baseline, 12 Weeks | Participants underwent assessments of multiple inflammatory markers at each time point. Inflammatory biomarkers included interleukin-6, high-sensitivity C-reactive protein, vascular cell adhesion molecule, intracellular adhesion molecule, interleukin-10, tumor necrosis factor-alpha, tumor necrosis factor receptor type I, and tumor necrosis factor receptor type II. In order to create a single measure of Inflammatory Function, each of these seven inflammatory biomarkers were ranked at each time point and a mean rank was created, with higher scores reflecting higher Inflammatory Function. The mean rank for Inflammatory Function at 12 weeks was used as the outcome, controlling for baseline Inflammatory Function. Smaller values at 12 weeks compared to baseline were indicative of reduced inflammation. As a rank-based outcome, values have no fixed theoretical upper or lower bound. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORPatrick J Smith, PhD, MPH
University of North Carolina, Chapel Hill
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 74.2 Years STANDARD_DEVIATION 5.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 29 Participants |
| Region of Enrollment United States | 33 Participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 33 |
| other Total, other adverse events | 0 / 33 |
| serious Total, serious adverse events | 0 / 33 |
Outcome results
None listed