Brain Energy for Amyloid Transformation in Alzheimer's Disease Study

This study will examine the effects of a 4-month Modified Mediterranean-Ketogenic Diet compared with an American Heart Association Diet (AHAD - a regimen that has been shown to reduce the risk for cardiovascular disease). We will investigate diet effects on AD biomarkers, on cognition, and on neuroimaging measures of blood flow. Our study will extend previous findings in several important ways by: 1) using a Modified Mediterranean-Ketogenic Diet rather than a traditional Ketogenic Diet, which has the potential for greater long-term compliance and health benefits; 2) increasing the sample size and duration of the diet intervention; 3) examining potential mechanisms of diet effects that may result in new biomarkers and therapeutic targets; and 4) examining key treatment response variables such as Apolipoprotein E (ApoE) genotype, amyloid positivity and metabolic status that could inform precision medicine approaches to dietary prescription.

Adults with amnestic mild cognitive impairment (MCI) will be randomized on a 1:1 schedule to receive either a 4-month Modified Mediterranean-Ketogenic Diet (MMKD) or American Heart Association Diet (AHAD) intervention. Diet interventions will be equicaloric with participants' normal diets. Personalized nutritional guidance and menus will be provided, and compliance will be assessed by a registered dietitian. The principal investigator will be responsible for the overall monitoring of the data and safety of study participants, with assistance by members of the study staff, and the Data and Safety Monitoring Board (DSMB), which will be responsible for monitoring the safety of research participants.

Inclusion criteria

• Diagnosis of amnestic mild cognitive impairment
• An informant (study partner) able to provide collateral information on the participant
• Stable medical condition (generally 3 months prior to screening visit) at the discretion of study physician
• Stable on medications (generally 4 weeks prior to screening visit) at the discretion of study physician
• Able to complete baseline assessments

Exclusion criteria

• Diagnosis of neurodegenerative illness (except for MCI);
• History of a clinically significant stroke
• Current evidence or history in past year of focal brain lesion, head injury with loss of consciousness or DSM-IV criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse
• Sensory impairment (i.e.: visual or auditory) that would preclude the participant from participating in the protocol
• Diabetes that requires current use of diabetes medications
• Clinically significant elevations in liver function tests
• Active neoplastic disease (stable prostate cancer and non-melanoma skin cancer is permissible)
• History of epilepsy or seizure within past year
• Contraindications for MRI (claustrophobia, craniofacial metal implants, pacemakers)
• Significant medical illness or organ failure, such as uncontrolled hypertension or cardiovascular disease, chronic obstructive pulmonary disease, liver disease, or kidney disease