Time Restricted Eating for Metabolic and Psychological Optimization

Assessing the Feasibility and Acceptability of a Time Restricted Feeding Intervention Among Older Adults With Mild Cognitive Impairment

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.

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'.

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).