Cognitive decline

About: Cognitive decline is a research topic. Over the lifetime, 29308 publications have been published within this topic receiving 1174689 citations.

Neuronal basis of age-related working memory decline

Abstract: Many of the cognitive deficits of normal ageing (forgetfulness, distractibility, inflexibility and impaired executive functions) involve prefrontal cortex (PFC) dysfunction. The PFC guides behaviour and thought using working memory, which are essential functions in the information age. Many PFC neurons hold information in working memory through excitatory networks that can maintain persistent neuronal firing in the absence of external stimulation. This fragile process is highly dependent on the neurochemical environment. For example, elevated cyclic-AMP signalling reduces persistent firing by opening HCN and KCNQ potassium channels. It is not known if molecular changes associated with normal ageing alter the physiological properties of PFC neurons during working memory, as there have been no in vivo recordings, to our knowledge, from PFC neurons of aged monkeys. Here we characterize the first recordings of this kind, revealing a marked loss of PFC persistent firing with advancing age that can be rescued by restoring an optimal neurochemical environment. Recordings showed an age-related decline in the firing rate of DELAY neurons, whereas the firing of CUE neurons remained unchanged with age. The memory-related firing of aged DELAY neurons was partially restored to more youthful levels by inhibiting cAMP signalling, or by blocking HCN or KCNQ channels. These findings reveal the cellular basis of age-related cognitive decline in dorsolateral PFC, and demonstrate that physiological integrity can be rescued by addressing the molecular needs of PFC circuits.

Neuronal depletion of calcium-dependent proteins in the dentate gyrus is tightly linked to Alzheimer's disease-related cognitive deficits

Abstract: Transgenic mice expressing human amyloid precursor proteins (hAPP) and amyloid-beta peptides (Abeta) in neurons develop phenotypic alterations resembling Alzheimer's disease (AD). The mechanisms underlying cognitive deficits in AD and hAPP mice are largely unknown. We have identified two molecular alterations that accurately reflect AD-related cognitive impairments. Learning deficits in mice expressing familial AD-mutant hAPP correlated strongly with decreased levels of the calcium-binding protein calbindin-D28k (CB) and the calcium-dependent immediate early gene product c-Fos in granule cells of the dentate gyrus, a brain region critically involved in learning and memory. These molecular alterations were age-dependent and correlated with the relative abundance of Abeta1-42 but not with the amount of Abeta deposited in amyloid plaques. CB reductions in the dentate gyrus primarily reflected a decrease in neuronal CB levels rather than a loss of CB-producing neurons. CB levels were also markedly reduced in granule cells of humans with AD, even though these neurons are relatively resistant to AD-related cell death. Thus, neuronal populations resisting cell death in AD and hAPP mice can still be drastically altered at the molecular level. The tight link between Abeta-induced cognitive deficits and neuronal depletion of CB and c-Fos suggests an involvement of calcium-dependent pathways in AD-related cognitive decline and could facilitate the preclinical evaluation of novel AD treatments.

Exercise enhances and protects brain function

Abstract: Physical activity, in the form of voluntary wheel running, induces gene expression changes in the brain. Animals that exercise show an increase in brain-derived neurotrophic factor, a molecule that increases neuronal survival, enhances learning, and protects against cognitive decline. Microarray analysis of gene expression provides further support that exercise enhances and supports brain function.

Alcohol, dementia and cognitive decline in the elderly: a systematic review

Abstract: Background: dementia and cognitive decline have been linked to cardiovascular risk. Alcohol has known negative effects in large quantities but may be protective for the cardiovascular system in smaller amounts. Effect of alcohol intake may be greater in the elderly and may impact on cognition. Methods: to evaluate the evidence for any relationship between incident cognitive decline or dementia in the elderly and alcohol consumption, a systematic review and meta-analyses were carried out. Criteria for inclusion were longitudinal studies of subjects aged ≥65, with primary outcomes of incident dementia/cognitive decline. Results: 23 studies were identified (20 epidemiological cohort, three retrospective matched case-control nested in a cohort). Meta-analysessuggestthatsmallamountsofalcoholmaybeprotectiveagainstdementia(randomeffectsmodel,riskratio[RR] 0.63; 95% CI 0.53‐0.75) and Alzheimer’s disease (RR 0.57; 0.44‐0.74) but not for vascular dementia (RR 0.82; 0.50‐1.35) or cognitive decline (RR 0.89; 0.67‐1.17) However, studies varied, with differing lengths of follow up, measurement of alcohol intake, inclusion of true abstainers and assessment of potential confounders. Conclusions: because of the heterogeneity in the data these findings should be interpreted with caution. However, there is some evidence to suggest that limited alcohol intake in earlier adult life may be protective against incident dementia later.