Modifiable Risk Factors and Brain Positron Emission Tomography Measures of Amyloid and Tau in Nondemented Adults with Memory Complaints

Abstract

Objective: Exercise and diet impact body composition, but their age-related brain effects are unclear at the molecular imaging level. To address these issues, the authors determined whether body mass index (BMI), physical activity, and diet relate to brain positron emission tomography (PET) of amyloid plaques and tau tangles using 2-(1-(6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl)ethylidene)malononitrile (FDDNP).

Methods: Volunteers (N = 44; mean age: 62.6 ± 10.7 years) with subjective memory impairment (N = 24) or mild cognitive impairment (MCI; N = 20) were recruited by soliciting for memory complaints. Levels of physical activity and extent of following a Mediterranean-type diet were self-reported. FDDNP-PET scans assessed plaque/tangle binding in Alzheimer disease-associated regions (frontal, parietal, medial and lateral temporal, posterior cingulate). Mixed models controlling for known covariates examined BMI, physical activity, and diet in relation to FDDNP-PET.

Results: MCI subjects with above normal BMI (>25) had higher FDDNP-PET binding compared with those with normal BMI (1.11(0.03) versus 1.08(0.03), ES = 1.04, t(35) = 3.3, p = 0.002). Greater physical activity was associated with lower FDDNP-PET binding in MCI subjects (1.07(0.03) versus 1.11(0.03), ES = 1.13, t(35) = -3.1, p = 0.004) but not in subjects with subjective memory impairment (1.07(0.03) versus 1.07(0.03), ES = 0.02, t(35) = -0.1, p = 0.9). Healthier diet related to lower FDDNP-PET binding, regardless of cognitive status (1.07(0.03) versus 1.09(0.02), ES = 0.72, t(35) = -2.1, p = 0.04).

Conclusion: These preliminary findings are consistent with a relationship between risk modifiersand brain plaque/tangle deposition in nondemented individuals and supports maintenance of normal body weight, regular physical activity, and healthy diet to protect the brain during aging. (clinicaltrials.gov; NCT00355498).

Keywords: Alzheimer disease; FDDNP; PET; exercise.

Conflict of interest statement

Financial Disclosures: Dr. Merrill reports having received lecture fees from Assurex Health. Dr. Barrio and Dr. Small co-inventors of FDDNP-PET, which UCLA has licensed to TauMark, LLC. Dr. Barrio and Dr. Small have a financial interest in TauMark, LLC. Dr. Small reports having served as a consultant and/or having received lecture fees from Novartis, Forum Pharmaceuticals, Lily and Herbalife; grants from POM Wonderful; and writing fees from Herbalife, Newsmax Media, and Workman Publishing. Dr. Lavretsky reports having received grant support from Forest Research Institute and the Alzheimer’s Research and Prevention Foundation and consulting fees from Eli Lilly. Drs. Siddarth, Raji, Ercoli, Miller, Harris, Burggren, Bookheimer, Mrs. Emerson, and Ms. Rueda have no financial conflicts of interest.

Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1. Relation of FDDNP-PET Binding Levels to Diet, Physical Activity, and Body Mass Index Groups

Histograms represent mean FDDNP-PET binding levels (with standard deviation bars) in relation to lifestyle measures in MCI and subjective memory impairment groups. Lower FDDNP-PET binding was present in both MCI and subjective memory impairment subjects adhering ‘often’ to a healthy diet (A) when compared to those ‘rarely’ adherent to a healthy diet. In contrast, MCI but not subjective memory impairment subjects differed in FDDNP-PET binding levels based on categorization of both higher vs. lower physical activity levels (B) and normal BMI vs. above normal BMI status (C). Abbreviations: MCI: mild cognitive impairment; FDDNP: 2-(1-(6-[(2-[F18]fluoroethyl)(methyl)amino]-2-naphthyl)ethylidene)malononitrile; PET: positron emission tomography; SMI: subjective memory impairment.