Feasibility and Efficacy of Dietary Interventions for Older Adults With Subjective Cognitive Decline

This study aims to assess if/how dietary interventions (i.e., the Modified Atkins Diet (MAD) and/or the Mediterranean-Dietary Approaches to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay (MIND)) might prevent, delay onset, alleviate symptoms, or otherwise alter the course of subjective cognitive decline (SCD) likely due to Alzheimer's disease (AD).

We hypothesize that participants will tolerate both diets well and that the MAD will result in more favorable changes in cognition and other functioning.

Specific aims are to 1) to establish the feasibility of implementing the MAD in older adults with subjective cognitive decline (SCD) likely due to AD, 2) to examine whether changes in participants' cognition, mood, or other functioning are more favorable in patients using the MAD than in patients using the MIND diet, 3) to assess the role of Apolipoprotein E (ApoE) epsilon 4 genotype in response to the MAD in individuals with SCD. We hypothesize that 1) participants will be able to adhere to and tolerate the MAD and the MIND, determined by review of patients' food records and urine ketone production, 2) participants who adhere to the MAD will demonstrate a more favorable change on neuropsychological tests than participants on the MIND diet, and 4) the neuropsychological effects of the MAD will be greatest in those participants without a ε4 allele of the ApoE gene.

Eligibility Criteria:
Inclusion Criteria:

* Self-experienced persistent decline in cognitive capacity compared with a previously normal status that is unrelated to an acute event and that is not explained by a psychiatric disorder or neurological disease apart from Alzheimer's disease, medical disorder, medication, or substance use, with the onset of decline no longer than 5 years prior to study participation
* Clinical Dementia Rating (CDR) score equal to 0
* Montreal Cognitive Assessment (MoCA) equal to or greater than 26
* Age 60 years or older
* Personal physician clearance
* Willing to comply with all requirements of the study protocol and provide informed consent

Exclusion Criteria:

* Diagnosis of mild cognitive impairment (MCI), Alzheimer's disease (AD), or other dementia
* Current psychiatric diagnosis
* Unstable metabolic condition (documented on screening laboratory studies performed within the past year)
* persistent hyponatremia (sodium \< 130 mg/dL twice within the past year)
* severe hypernatremia (sodium \> 150 mg/dL twice within the past year)
* hypoglycemia (glucose \< 50 mg/dL)
* hypocalcemia (albumin-corrected calcium \< 8 mg/dL)
* Type-I diabetes
* Type-2 diabetes requiring any medication other than metformin. (Please note that patients with type-2 diabetes may require medication adjustment if on the very low-carb modified Atkins diet.)
* Liver failure
* Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or ammonia \> 5x upper limits of normal
* hyperbilirubinemia
* total bilirubin \> 15 mg/dL
* direct bilirubin \> 5 mg/dL
* Hypercholesterolemia (on medication, if needed)
* fasting total cholesterol \> 300 mg/dL
* fasting LDL cholesterol \> 200 mg/dL
* Known fatty acid oxidation disorder or pyruvate carboxylase deficiency
* Body mass index \< 18.5
* History of ischemic or hemorrhagic stroke
* History of nephrolithiasis
* History of myocardial infarction or known coronary artery disease
* Acute pancreatitis
* Multiple food allergies or strict dietary requirements
* Any other concerns about nutritional status (e.g., recent unexplained weight loss, difficulty swallowing)