TREAD: Time Restricted Eating Intervention for Alzheimer's Disease

The goal of this clinical trial is to learn if restricting the time of eating to allow for prolonged fasting at night may reduce sleep disturbances, cognitive decay, and pathology in patients diagnosed with Mild Cognitive Impairment (MCI) or early to moderate Alzheimer's disease (AD). It will also learn about the feasibility of practicing 14 h of nightly fasting in this group of older adults. The main questions it aims to answer are:

• Does prolonged nightly fasting of 14 h can reduce markers of AD pathology and aging and reduce cognitive and sleep alterations in MCI and AD patients?
• Can patients with MCI and early /moderate AD sustain time-restricted eating for 6 to 12 months? Researchers will compare participants who fast for 14 h per night during 6 months to those who fast for less than 10 h/night. Researchers will also compare participants that fast for 6 months to those who fast during 12 months, to determine the effective duration of the intervention. Finally, researchers will evaluate whether following the time-restricted eating diet alongside a partner actively following the same diet, will increase adherence to the protocol compared to subjects that fast alone.

Participants will:

• Fast for 14 h a night (stop eating at 8 pm and start eating the following morning at 10 am) for 6 or 12 months
• Visit the clinic three times (at the beginning of the study, 6 and 12 months later)
• Provide blood samples and take a cognitive test during clinic visits
• Keep a diary (or use an app on a smart phone) to record time of eating
• Wear an activity tracker watch

Study Description: Our overarching hypothesis is that circadian alignment of food intake and biological clocks can reduce pathology and improve cognitive function in Alzheimer's disease (AD) patients. The rationale for this proposal is that the prolonged nightly fasting form of Time-restricted eating (TRE) aligns food intake with the daytime "wake phase" of the biological clock, optimizing nutrient processing, and may modulate disease trajectory in AD. This Pilot study will test the feasibility and safety of TRE, consisting of 14 hours of night fasting for 6 or 12 months, in patients along the AD continuum and will explore the outcomes of this intervention on markers of aging and AD pathology. Results from this study will provide a strong scientific justification and will optimize the methods for a larger trial to determine the clinical efficacy of TRE to mitigate disease progression in AD and related dementias.

Objectives:

Primary Objective: Test the feasibility of a TRE intervention (TREAD) among patients with Mild Cognitive Impairment (MCI) or AD.

Secondary Objectives: Explore the effects of TRE on metabolic and pathological markers in MCI/AD patients.

Endpoints:

Primary Endpoint: Feasibility, safety, cognition, and metabolic indicators. Secondary Endpoints: Biomarkers of AD pathology, sleep and activity, and markers of epigenetic aging.

Study Population:

Adult subjects (female and males, ≥65 years old) with normal cognition or with a clinical diagnosis of MCI/AD (meeting research consensus criteria for probable MCI or dementia due to AD, and positive for AD biomarkers).

Phase: Early phase 1

Description of Sites/Facilities Enrolling Participants:

Shiley-Marcos Alzheimer's disease Research Center (SMARDC) at the University of California San Diego (UCSD) La Jolla campus.

Description of Study Intervention: The investigators will enroll older-adult participants (>65 years old) clinically diagnosed with MCI or early to moderate AD (n=20 subjects) and 20 dyads of participants (n=40 subjects) composed of an MCI/AD patient and a cognitively normal living partner (age-matched); for a total enrollment of 60 subjects. All participants must have a baseline nightly fasting of <10 h. Individual participants and dyads will be randomized into the Intervention group (INT) or the Delayed Start Intervention group (DS-INT). The intervention will involve prolonged nightly fasting of 14 hours (TRE). The INT group will follow the TRE regimen for 12 months. The DS-INT group will practice their regular eating pattern for 6 months (nightly fasting <10 h) followed by 6 months of TRE. All participants will have study visits, outcome assessments, and biospecimen collections at baseline, 6, and 12 months.

Study Duration: Two years Participant Duration: 12 months