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

Abstract

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 non-human primate model of AD-like neuropathology to examine the longitudinal effects of diet (Mediterranean vs Western) and social subordination stress on brain anatomy, including global volumes, cortical thicknesses and volumes, and 20 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 neuropathology, whereas the Mediterranean diet may protect the brain.

Keywords: Alzheimer's disease; diet; magnetic resonance imaging; non-human primate; psychological stress.

FIGURE 1

Changes in global brain volumes during experiment. Global brain volumes changed in the Western group, whereas Mediterranean volumes remained stable over time. In the Western group, total brain volume (TBV) and gray matter volume (GM) increased significantly, whereas the volumes of cerebrospinal fluid (CSF) and white matter (WM) significantly decreased. Percent changes in volumes from Baseline to the Experimental time points are shown for each region of interest (ROI). Significant differences (P ≤ .05) indicated by (*)

FIGURE 2

Social status differences in global brain volumes. Socially subordinate monkeys had smaller (A) intracranial volumes (ICVs) and (B) total brain volumes (TBVs) than dominants. In contrast, subordinate monkeys had larger volumes than dominants in the following regions of interest (ROIs): (C) middle temporal gyri, (D) left inferior temporal gyri, and (E) left meta‐ROI. Adjusted means and standard errors are shown

FIGURE 3

Anatomical map of cortical thickness changes in Alzheimer's disease (AD) “signature” regions. Cortical thicknesses in regions of interest for AD‐like neuropathology increased in animals consuming Western, but not Mediterranean diets. Orange and yellow tones indicate increases in cortical thicknesses, and pink tones indicate decreases in cortical thicknesses. Anterior (left) to posterior (right) coronal sections are shown

FIGURE 4

Diet‐group differences of cortical thicknesses in AD “signature” regions. Following dietary intervention, Western group cortices were significantly thicker than Mediterranean cortices for every AD‐signature region of interest (ROI) except the right entorhinal cortex. Individual values for the ROIs are indicated by the gray points. Adjusted means and standard errors for each diet group are indicated by the solid dots and lines, respectively

FIGURE 5

Diet‐group differences in caudate volumes. Analysis of covariance (ANCOVA) controlling for baseline volumes showed that caudate volumes were smaller in the Mediterranean diet group (377 ± 2.71 mm ³ ) than in the Western diet group (385 ± 2.40 mm ³ ) (F(1,33) = 4.254; P = .047). Individual data points are indicated in gray, and adjusted means and standard errors are represented by solid dots and lines, respectively

FIGURE 6

Social status differences in left frontal volumes. In animals consuming Western diets, left frontal volumes were indistinguishable by social status. In contrast, within the Mediterranean diet group, subordinates had significantly larger left frontal volumes than did dominant monkeys (Tukey = 0.039). Adjusted means and standard errors after adjusting for baseline volumes are shown