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

IntroductionAge-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. MethodsUsing 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. ResultsWe 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]). DiscussionCortical 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.

Automated summary

This study examined the relationship between age, cognitive performance, and neuroanatomy in vervet monkeys. The results showed that age was negatively associated with cortical gray matter volume and temporal-parietal cortical thickness. Additionally, cortical gray matter volumes predicted working memory performance. This study provides a foundation for future investigations into the early diagnosis and treatment of Alzheimer's disease.