Age is the strongest risk factor for Alzheimer’s disease (AD), yet the neurobiological trajectories distinguishing normal from pathological aging remain poorly understood.

Nonhuman primates (NHPs) offer important opportunities to longitudinally characterize brain aging processes that may parallel humans.

Here, we examined the main and interactive effects of age and longitudinal aging on neuroanatomy in female vervet monkeys, a well-validated NHP model of aging and early AD-like neuropathology.

 

Regions of Interest: cerebrospinal fluid (CSF), cortical gray matter, deep gray matter, total gray matter, white matter, cerebellum, and brainstem

Statistical Approach: Linear mixed-effects models with main effect of age, main effect of longitudinal aging & interaction term: age-by-aging; ICV as a covariate in models to control for inter-individual variation in head size; Random effect: ID to control for repeated measures

 

Results

Figure 1. Main effects of age on global brain volumes. Age was negatively associated with cortical gray matter (p<0.001) and white matter volumes (p=0.049) and positively associated with deep-gray matter volumes (p<0.001). Total gray matter (p=0.268), CSF (p=0.222), cerebellar (p=0.485), and brain stem volumes (p=0.297) were unrelated to age.

Figure 2. Significant age x aging interaction effects on global brain volumes: deep gray matter (p<0.001), white matter (p=0.034), and brainstem (p=0.016). These interactions illustrate how age and aging interact in complex, region-specific ways to shape neuroanatomical trajectories in female vervets.

Conclusions:

Considering both age & longitudinal aging is critical for characterizing changes relevant to AD. NHPs may differ from humans in some brain aging trajectories. Vervets remain useful translational models for investigating vulnerability to AD-associated neuropathology.