Early Alzheimer's disease-like reductions in gray matter and cognitive function with aging in nonhuman primates

Abstract

Introduction: Age-related neuropathology associated with sporadic Alzheimer's disease (AD) often develops well before the onset of symptoms. Given AD's long preclinical period, translational models are needed to identify early signatures of pathological decline. Methods: Using structural magnetic resonance imaging and cognitive assessments, we examined the relationships among age, cognitive performance, and neuroanatomy in 48 vervet monkeys (Chlorocebus aethiops sabaeus) ranging from young adults to very old. Results: We found negative associations of age with cortical gray matter volume (P =.003) and the temporal-parietal cortical thickness meta-region of interest (P =.001). Additionally, cortical gray matter volumes predicted working memory at approximately 1-year follow-up (correct trials at the 20s delay [P =.008]; correct responses after longer delays [P =.004]). Discussion: Cortical gray matter diminishes with age in vervets in regions relevant to AD, which may increase risk of cognitive impairment. This study lays the groundwork for future investigations to test therapeutics to delay or slow pathological decline.