DNC Alterations Underlying Age-related Cognitive Decline

Prefrontal cortical functions weaken with advancing age in both animals and humans. There is an increase in Ca²⁺-cAMP signaling in PFC that correlates with cognitive deficits, and a selective loss of long, thin spines from the monkey dlPFC. Physiological recordings have shown that the persistent firing needed for working memory markedly declines with age, and is restored by inhibiting Ca²⁺-cAMP signaling, e.g. with guanfacine. Understanding these mechanisms may allow us to treat age-related cognitive deficits that afflict the association cortices.

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