Individual differences in neurocognitive aging of the medial temporal lobe

Abstract

A wide spectrum of outcomes in the cognitive effects of aging is routinely observed in studies of the elderly. Individual differences in neurocognitive aging are also a characteristic of other species, such as rodents and non-human primates. In particular, investigations at behavioral, brain systems, cellular and molecular levels of analysis have provided much information on the basis for individual differences in neurocognitive aging among healthy outbred rats. These findings are likely to be relevant to an understanding of the effects of aging on the brain, apart from neurodegenerative conditions, such as Alzheimer's disease, which do not naturally occur in rodents. Here we review and integrate those findings in a model supporting the concept that certain features of cognitive decline are caused by distributed alterations in the medial temporal lobe, which alter the information processing functions of the hippocampal formation. An additional emerging concept from this research is that preserved abilities at older ages may depend on adaptive changes in the hippocampal system that distinguish successful aging.

Integrating new findings and examining clinical applications of pattern separation

“…Convergent data across animal and human studies have suggested that a key neural substrate for this decline is a shift in hippocampal network dynamics away from pattern separation and toward pattern com- pletion 72 , which appears to be mediated by CA3 hyperactivity 35,73–76 and representational rigidity 35,72,75,77 —a failure to remap or manifest a novelty signal when stimuli are similar but not identical. These alterations may be closely linked to changes in the perforant path 78–81 and to disinhibition in the DG and CA3 subregions resulting from the loss of inhibitory tone in GABAergic interneurons 72,82 .…”

Functional connectivity with the retrosplenial cortex predicts cognitive aging in rats

“…4A, where the loss of the anticorrelated FC is represented as a net positive shift). A growing body of evidence suggests that successful cognitive outcomes in aging arise from active neurobiological adaption (42), perhaps comprising the substrates of cognitive resilience and reserve. Here, the affected network in AU rats involved frontoinsular circuitry implicated in switching between the DMN and executive control networks (41).…”

Late enrichment maintains accurate recent and remote spatial memory only in aged rats that were unimpaired when middle aged

“…Exposure to an enriched environment during adulthood modifies many aspects of rodent behavior and improves learning and memory in a variety of tasks, especially those assessing spatial memory (e.g., Schrijver et al 2002;Leggio et al 2005;Birch et al 2013;Mora-Gallegos et al 2015). Evaluation of the effects of environmental enrichment on spatial memory is especially relevant in the context of physiological aging, as enrichment was shown to stimulate neuroplasticity in brain areas playing a major role in this cognitive domain (e.g., Faherty et al 2003;Leggio et al 2005;Birch et al 2013;, which is particularly sensitive to aging (Gallagher et al 2006). Several studies using cross-sectional experimental designs showed that spatial memory progressively declines during adulthood.…”

“…For this longitudinal study, middle-aged (17 mo) rats were trained in a first reference memory task in a Morris water maze (i.e., finding an escape platform located in a fixed position in a pool), a place-learning task widely used to distinguish individuals with or without impaired learning and memory during aging (e.g., Gallagher et al 2006;Cassel et al 2007). Similar number of rats thereby classified as either unimpaired or impaired were subsequently housed for 6 mo in enriched environment (EE) or standard conditions (SC).…”