Abstract
The aging of brain cells and synaptic loss are the major underlying pathophysiological processes contributing to the progressive decline in cognitive functions and Alzheimer’s disease. The difference in cognitive performances observed between adult and aged subjects across species highlights the decline of brain systems with age. The inflection point in age-related cognitive decline is important for our understanding of the pathophysiology of neurodegenerative diseases and for timing therapeutic interventions. Humans and nonhuman primates share many similarities including age-dependent changes in gene expression and decline in neural and immune functions. Given these evolutionary conserved organ systems, complex human-like behavioral and age-dependent changes may be modeled and monitored longitudinally in nonhuman primates. We integrated three clinically relevant outcome measures to investigate the effect of age on cognition, motor function and diurnal activity in aged baboons. We provide evidence of a naturally-occurring age-dependent precipitous decline in movement planning, in learning novel tasks, in simple discrimination and in motivation. These results suggest that baboons aged ~20 years (equivalent to ~60 year old humans) may offer a relevant model for the prodromal phase of Alzheimer’s disease and related dementias to investigate mechanisms involved in the precipitous decline in cognitive functions and to develop early therapeutic interventions
Highlights
Aging is currently an irreversible biological process characterized by a gradual deterioration in general health and function along side an increase in risk of disease and death [1]
The response latency (Figure 1F, 1G) revealed that adult subjects exhibited a heightened attentional performance reflected by significantly better response accuracy and latency (Figure 1D, 1G)
nonhuman primates (NHP) models have played a vital role in aging research as they manifest many of the structural and physiological modifications in the brain linked to chronological aging
Summary
Aging is currently an irreversible biological process characterized by a gradual deterioration in general health and function along side an increase in risk of disease and death [1]. The loss of neurons and changes in dendritic arborization, spines, and density of synapses have been attributed to grey matter shrinkage [9,10,11,12]; whereas degeneration or lesions due to ischemic injury are contributing factors to age-related changes in white matter [13, 14]. These changes to the brain are region specific. Age-associated changes in PFC function can impair cognitive functions, learning and memory [20,21,22,23,24,25,26]
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