Abstract
Increased physical activity and higher adherence to a Mediterranean-type diet (MeDi) have been independently associated with reduced risk of Alzheimer’s disease (AD). Their association has not been investigated with the use of biomarkers. This study examines whether, among cognitively normal (NL) individuals, those who are less physically active and show lower MeDi adherence have brain biomarker abnormalities consistent with AD.MethodsForty-five NL individuals (age 54 ± 11, 71% women) with complete leisure time physical activity (LTA), dietary information, and cross-sectional 3D T1-weigthed MRI, 11C-Pittsburgh Compound B (PiB) and 18F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) scans were examined. Voxel-wise multivariate partial least square (PLS) regression was used to examine the effects of LTA, MeDi and their interaction on brain biomarkers. Age, gender, ethnicity, education, caloric intake, BMI, family history of AD, Apolipoprotein E (APOE) genotype, presence of hypertension and insulin resistance were examined as confounds. Subjects were dichotomized into more and less physically active (LTA+ vs. LTA−; n = 21 vs. 24), and into higher vs. lower MeDi adherence groups (n = 18 vs. 27) using published scoring methods. Spatial patterns of brain biomarkers that represented the optimal association between the images and the groups were generated for all modalities using voxel-wise multivariate Partial Least Squares (PLS) regression.ResultsGroups were comparable for clinical and neuropsychological measures. Independent effects of LTA and MeDi factors were observed in AD-vulnerable brain regions for all modalities (p < 0.001). Increased AD-burden (in particular higher Aβ load and lower glucose metabolism) were observed in LTA− compared to LTA+ subjects, and in MeDi− as compared to MeDi+ subjects. A gradient effect was observed for all modalities so that LTA−/MeDi− subjects had the highest and LTA+/MeDi+ subjects had the lowest AD-burden (p < 0.001), although the LTA × MeDi interaction was significant only for FDG measures (p < 0.03). Adjusting for covariates did not attenuate these relationships.ConclusionLower physical activity and MeDi adherence were associated with increased brain AD-burden among NL individuals, indicating that lifestyle factors may modulate AD risk. Studies with larger samples and longitudinal evaluations are needed to determine the predictive power of the observed associations
Highlights
Alzheimer’s disease (AD) is the most common cause of dementia and a major public health problem
Among a larger pool of clinically and cognitively normal (NL) individuals participating in longitudinal brain imaging studies at New York University (NYU) Langone School of Medicine, this study was based on a sub-set of 62 NL participants who participated in a lifestyle survey between 2013-2014
The remaining 15 subjects reported taking either or a combination of the following medications: high blood pressure medications and/or statins (16%), anti-depressants/SSRI (4%; note: all subjects washed off anti-depressants for at least 2 weeks before FDG-Positron Emission Tomography (PET)), prostate medications (4%), hormone replacement therapy (9%)
Summary
Alzheimer’s disease (AD) is the most common cause of dementia and a major public health problem. There is growing evidence to suggest that diet and physical activity, two major targetable lifestyle factors, may play a role in modulating risk of AD. AD is characterized by the gradual accumulation of amyloid-beta (Aβ) plaques, neurofibrillary tangles and neuronal loss in selectively vulnerable brain regions, which takes place over decades [3]. These changes can be visualized in vivo by means of brain imaging [3]. Imaging-based AD biomarkers offer a unique opportunity to understand how lifestyle can promote healthy brain aging prior to symptoms onset
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