Eating a Weekly Serving of Walnuts Relates to Beneficial Brain Imaging Phenotypes in a Cohort at Increased Risk of Alzheimer’s Disease

Abstract

Abstract Objectives There is increasing evidence on the brain benefits of nut consumption. Magnetic resonance imaging (MRI) enables the detection of brain changes associated with neurodegenerative and vascular diseases. In middle-aged cognitively unimpaired subjects at increased risk of Alzheimer's disease (AD), we searched for cross-sectional associations between nut consumption and MRI-assessed brain phenotypes, including white matter hyperintensities (WMH, a marker of cerebral small vessel disease that confers increased risk of AD and stroke) and topographic patterns of gray matter volume (GMv). Methods We performed high-resolution structural MRI in 382 participants from the ALFA study (ALzheimer and FAmilies) cohort, which is enriched by family history of sporadic AD and APOE-ε4 carriership, the most prevalent genetic risk factor for AD. We assessed nut consumption by a food-frequency questionnaire containing five items related to nuts. WMH volume was normalized by intracranial volume (TIV) and rank-transformed. For WMH, we conducted univariate models with two factors: nut consumption (<1 and ≥1 serving/week) and being APOE-ε4 homozygote (yes/no), and their interaction, adjusting for age, gender, hypertension, hypercholesterolemia, and adherence to Mediterranean Diet. We also explored whether nut consumption related to differences in GMv using a voxel-based morphometry analysis corrected by age, gender, number of APOE-ε4 alleles, hypertension, hypercholesterolemia, adherence to Mediterranean Diet, and TIV. Results 187 participants reported nut consumption of ≥1 serving/week, 148 of whom disclosed walnut consumption. Nut (or walnut) consumption of ≥1 serving/week related to a significantly lower WMH volume (P ≤ 0.035, both). We found no statistically significant nut × APOE-ε4 interactions. Participants reporting consumption of ≥1 walnut serving/week showed significantly greater GMv in areas including the anterior/middle cingulate cortex, which is relevant for cognition and has been associated with successful aging. Conclusions Nut (in particular walnut) consumption relates to beneficial phenotypes of both cerebral vasculature and regional GMv. Funding Sources Instituto de Salud Carlos III, Spain; “la Caixa” Foundation; California Walnut Commission.