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Age-related cerebral atrophy in nonhuman primates predicts cognitive impairments.

ABSTRACT: In humans, but not in nonhuman primates, a clear relationship has been established between age-associated cognitive decline and atrophy of specific brain regions. We evaluated age-related cerebral atrophy and cognitive alterations in mouse lemur primates. Cerebral atrophy was evaluated by in vivo magnetic resonance imaging in 34 animals aged from 1.9 to 11.8 years. The caudate and splenium were atrophied in most older animals, whereas shrinkage of the hippocampus, entorhinal cortex, and septal region was identified in a subgroup of the older animals. The temporal and cingulate cortex also exhibited a severe atrophy, whereas frontal and parietal areas were spared. Measures of cognitive ability in 16 animals studied by magnetic resonance imaging (MRI) showed that both executive functions and spatial memory declined with aging. Impairment of executive functions in older animals was associated with atrophy of the septal region while spatial memory performance was related to atrophy of the hippocampus and entorhinal cortex. Mouse lemurs are the first nonhuman primates in which a clear relationship is established between age-associated cognitive alteration and cerebral atrophy.

SUBMITTER: Picq JL

PROVIDER: S-EPMC3381737 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Age-related cerebral atrophy in nonhuman primates predicts cognitive impairments.

Picq Jean-Luc JL Aujard Fabienne F Volk Andreas A Dhenain Marc M

Neurobiology of aging 20101022 6

In humans, but not in nonhuman primates, a clear relationship has been established between age-associated cognitive decline and atrophy of specific brain regions. We evaluated age-related cerebral atrophy and cognitive alterations in mouse lemur primates. Cerebral atrophy was evaluated by in vivo magnetic resonance imaging in 34 animals aged from 1.9 to 11.8 years. The caudate and splenium were atrophied in most older animals, whereas shrinkage of the hippocampus, entorhinal cortex, and septal r ...[more]

PMID: 20970891

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Project description:The hypothalamic-pituitary-adrenal (HPA) axis is a key adaptive neuroendocrine system, dysfunction of which plays an important role in the increasing incidence of stress-dependent age-related pathology. Among the environmental factors effecting increase age-related diseases, great importance is given to disturbances of the light-dark schedule, particularly with increased illumination at night. While disruption of the light-dark schedule has long been recognized as a powerful behavioral stressor, little is known regarding stress reactivity of the HPA under constant light (CL) conditions, especially with aging and depending on the features of stress behavior. The purpose of this investigation was to study the age-related and individual features of the HPA axis response to acute stress exposure (ASE) under chronic CL in nonhuman primates that are known to differ in behavioral responsiveness to stress. Young and old female rhesus monkeys (with control standard behavior or anxiety and depression-like behavior) were exposed to CL (24 h light/day, 330-400 lux for 4 to 8 weeks). Control young and old monkeys were exposed to standard lighting (SL) with natural light during the day and darkness at night. All animals were subjected to ASE (restriction of mobility for 2 hours), functional tests with corticotrophin-releasing hormone and arginine-vasopressin, and study of circadian rhythms of cortisol and pineal melatonin secretion. For the first time an inhibitory effect of CL on the reaction of the adrenal cortex to ASE was revealed in all individuals, regardless of age and preexisting behavior stress reactivity, the mechanisms of which were age-dependent: due to inhibition of the pituitary ACTH secretion in young animals and mainly not affecting the ACTH secretion in old individuals. There were no significant changes in melatonin secretion both in young and old animals. The observed CL inhibition of adrenal cortical reactivity to ASE may be useful to correct increased vulnerability to ASE observed in individuals with preexisting anxiety and depression-like stress behaviors. On the other hand, the CL induced decrease in adrenal stress reactivity of behaviorally normal animals suggests a potential risk of reducing the adaptive capacity of the organism under conditions of continuous light exposure.

Project description:Preclinical studies demonstrate that generalized endothelial cell dysfunction and microvascular impairment are potentially reversible causes of age-related vascular cognitive impairment and dementia (VCID). The present study was designed to test the hypothesis that severity of age-related macro- and microvascular dysfunction measured in the peripheral circulation is an independent predictor of cognitive performance in older adults. In this study, we enrolled 63 healthy individuals into young (< 45 years old) and aged (> 65 years old) groups. We used principal component analysis (PCA) to construct a comprehensive peripheral vascular health index (VHI) encompassing peripheral microvascular reactivity, arterial endothelial function, and vascular stiffness, as a marker of aging-induced generalized vascular dysfunction. Peripheral macrovascular and microvascular endothelial function were assessed using flow-mediated dilation (FMD) and laser speckle contrast imaging tests. Pulse waveform analysis was used to evaluate the augmentation index (AIx), a measure of arterial stiffness. Cognitive function was measured using a panel of CANTAB cognitive tests, and PCA was then applied to generate a cognitive impairment index (CII) for each participant. Aged subjects exhibited significantly impaired macrovascular endothelial function (FMD, 5.6 ± 0.7% vs. 8.3 ± 0.6% in young, p = 0.0061), increased arterial stiffness (AIx 29.3 ± 1.8% vs 4.5 ± 2.6% in young, p < 0.0001), and microvascular dysfunction (2.8 ± 0.2 vs 3.4 ± 0.1-fold change of perfusion in young, p = 0.032). VHI showed a significant negative correlation with age (r = - 0.54, p < 0.0001) and CII significantly correlated with age (r = 0.79, p < 0.0001). VHI significantly correlated with the CII (r = - 0.46, p = 0.0003). A decline in peripheral vascular health may reflect generalized vascular dysfunction and predict cognitive impairment in older adults.

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Age-related cerebral atrophy in nonhuman primates predicts cognitive impairments.

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Age-related cerebral atrophy in nonhuman primates predicts cognitive impairments.

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