Diet, psychosocial stress, and Alzheimer’s disease-related neuroanatomy in female nonhuman primates

INTRODUCTION Associations between diet, psychosocial stress, and neurodegenerative disease, including Alzheimer’s disease (AD), have been reported, but causal relationships are difficult to determine in human studies. METHODS We used structural magnetic resonance imaging in a well-validated nonhuman primate model of AD-like neuropathology to examine the longitudinal effects of diet (Mediterranean versus Western) and social subordination stress on brain anatomy, including global volumes, cortical thicknesses and volumes, and twenty individual regions of interest (ROIs). RESULTS Western diet resulted in greater cortical thicknesses, total brain volumes and gray matter, and diminished cerebrospinal fluid and white matter volumes. Socially stressed subordinates had smaller whole brain volumes but larger ROIs relevant to AD than dominants. DISCUSSION The observation of increased size of AD-related brain areas is consistent with similar reports of mid-life volume increases predicting increased AD risk later in life. While the biological mechanisms underlying the findings require future investigation, these observations suggest that Western diet and psychosocial stress instigate pathologic changes that increase risk of AD-associated neuropathologies, whereas Mediterranean diet may protect the brain. RESEARCH IN CONTEXT Systematic review: The authors reviewed the literature with PubMed and Google Scholar and found a number of publications which are cited that suggest that AD pathogenesis begins well before the onset of symptoms. Interpretation: Our findings support the hypothesis that Western diet and psychosocial stress may instigate neuroinflammatory responses that increase risk of later developing AD-like neuropathologies, whereas the structural stasis in the Mediterranean diet group may represent a resilient phenotype. Future directions: The manuscript serves as a critical first step in describing risk and resilient phenotypes during middle age in a nonhuman primate model of AD-like neuropathology. This report lays the groundwork for ongoing efforts to determine whether neuroinflammatory profiles differed across diet and stress groups. Future studies should aim to understand the temporal emergence of functional disparities associated with the changes in brain structure observed here. HIGHLIGHTS Global brain volumes changed in response to Western, but not Mediterranean, diet. Western diet increased cortical thickness in multiple regions relevant to AD. Mediterranean diet did not alter cortical thicknesses relevant to AD. Brain regions associated with AD risk differed between low and high stress monkeys. Psychosocial stress may modulate the effects of diet on the brain.