Cognitive decline is a common but not inevitable consequence of normal aging. Age-related declines in cognitive ability have been linked to neurobiological changes in specific brain areas that affect synaptic communication, restrict the capacity of information processing, and interfere with memory formation and retrieval. Moreover, these changes in neural function may render neurons more vulnerable to degeneration. Thus, good synaptic health may not only promote preservation of cognitive function into advanced age but also protect against neurodegenerative diseases that increase in prevalence with aging.
Two schematic illustrations of dendritic segments from the dorsolateral prefrontal cortex show thin (purple), mushroom (red), and stubby (blue) spine morphologies. The segment on the left illustrates good synaptic health, indicated by a high density of thin spines. The magnified mushroom spine shows straight mitochondria (green) in the presynaptic bouton apposed to the spine as well as synaptic vesicles (small circles) abutting the active zone of the presynaptic membrane, ready for release. The segment on the right illustrates poor synaptic health, indicated by a reduction in the number of thin spines, donut-shaped abnormal mitochondria in presynaptic boutons apposed to the mushroom spines, a reduction in the size of the synapse, and a reduction in the number of synaptic vesicles docked at the active zone. The synaptic profile on the left is associated with good working memory, whereas the profile on the right is associated with poor working memory. Cyclicity of estradiol levels, either from natural ovarian cycles or exogenous administration on a cyclic schedule, is associated with good synaptic health and good working memory, whereas estrogen deficiency is associated with poor synaptic health and poor working memory.
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