Dietary Treatments for Cognitive Impairment in Older Adults

This trial seeks to establish the feasibility of implementing a ketogenic, modified Atkins diet (MAD) to older adults with mild cognitive impairment (MCI) or early Alzheimer's disease (AD) living in the community. A secondary aim is to determine whether adherence to the MAD results in better cognitive test scores than adherence to a non-ketogenic control diet. A final aim is to determine the role of apolipoprotein E (ApoE) genotype in participants' response to the MAD. Participants will be randomly assigned to a 12-week trial of either the MAD or a placebo diet based on the National Institute on Aging's recommendations for senior nutrition.

It is well established that Alzheimer's disease (AD) is associated with insulin resistance and, hence, abnormal glucose metabolism. In fact, abnormalities in the brain's uptake of glucose can be observed on PET imaging in advance of clinical symptoms. In patients with established dementia due to AD, the severity of cognitive impairment is strongly correlated with the decrease in glucose uptake. Ketone bodies, the products of fat metabolism, can serve as a "backup" fuel when glucose is unavailable. Ketone body metabolism appears to bypass the metabolic processes that are abnormal in AD and may provide better nourishment for neurons. As a result, ketone body metabolism may slow cognitive decline or even improve cognition in patients with AD. Participants will be 60 people, age 60 or older, with MCI or mild probable AD and without significant cardiovascular disease. They will be required to obtain the consent of their primary care physicians for their participation. Each patient will have a study partner who is cognitively healthy, lives with the participant, and can help him/her adhere to the diet. A research dietitian will teach participants and partners the new diet and monitor participants' adherence with food logs, in-person assessments, and urine ketone testing. After an initial baseline visit, participants will complete four in-person assessments during which adherence to the diet will be assessed and neurocognitive tests will be administered. It is hypothesized that the MAD will be feasible and well tolerated by seniors with MCI and AD. It is further hypothesized that adherence to the MAD will be associated with a greater increase (or less decline) in cognitive test scores than the placebo diet, particularly for those participants who do not carry an ApoE ε4 allele.

Inclusion Criteria: diagnosis of mild cognitive impairment or Alzheimer's disease availability of cohabitating study partner without cognitive impairment consent of primary care physician Exclusion Criteria: history of stroke history of coronary artery disease history of pancreatitis untreated hypothyroidism or B12 deficiency history of renal disease or recurrent kidney stones history of liver disease insulin-dependent diabetes body mass index <18.5 multiple food allergies follow strict diet (e.g., vegetarian, gluten-free)