TREAD: Time Restricted Eating Intervention for Alzheimer's Disease

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 3 or 6 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, ≥60 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).

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 (>60 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 (> 18 years old ); for a total enrollment of 60 subjects. All participants must have a baseline nightly fasting of <12 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 3 months (nightly fasting <12 h) followed by 3 months of TRE. All participants will have study visits, outcome assessments, and biospecimen collections at baseline, 3, and 6 months.

Study Duration: Two years Participant Duration: 6 months

Provision of signed and dated informed consent form. Stated willingness to comply with all study procedures and availability for the duration of the study.

Inclusion criteria

• Persons, aged ≥60 years
• In good general health as evidenced by medical history or diagnosed with clinical diagnosis of MCI/AD: meeting research consensus criteria for probable MCI or dementia due to AD, requiring positive amyloid biomarkers in brain or cerebrospinal fluid (CSF) obtained at their regular point of care or study referral no longer than 3 months prior to screening.
• Ability and willingness to complete cognitive evaluations, blood draw, actigraphy monitoring and to record fasting times daily.
• Daily night fasting <12h at baseline. Ability and willingness to follow an eating protocol of prolonged night fasting for 14 h
• For cognitively normal living partners in the dyads group, scores >26 in the Montreal Cognitive Assessment (MoCA) test administered at screening.

Exclusion criteria

• Clinical diagnosis with a neurodegenerative condition other than MCI/AD.
• Presenting cognitive impairment not due to AD.
• Clinical diagnoses of diabetes.
• Actively using insulin in the past 6 months.
• Started a new medication (or changed doses) indicated for the treatment of MCI/AD in the last three months prior to enrollment.
• Currently taking any medication known to affect appetite, inlcuding but not limited to GLP-1 agonists.
• Any history of disordered eating, including difficulty swallowing and refusal to eat.
• Currently engaged in shift work.
• In treatment with another investigational drug.
• Body Mass Index (BMI) <20. or >35