Cognitive decline

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

A prospective study of cognitive impairment in ALS.

Abstract: Objective: To characterize prospectively the cognitive profile in ALS. Methods: Clinically definite ALS patients (11 men, 2 women), age 39.9 to 74.0 years (mean age, 54.2 ± 9.6 years; mean disease duration, 21.1 ± 10.5 months) underwent neuropsychologic, language, and speech testing followed by MR 1H spectroscopy (4 T). Five spousal control subjects completed an identical protocol. Eight ALS patients participated in follow-up studies at a 6-month interval. Results: Relative to control subjects, ALS patients showed mild impairment in word generation, recognition memory (faces), and motor-free visual perception. Bulbar-onset patients showed greater impairment in a number of measures (working memory, problem solving/cognitive flexibility, visual perception, and recognition memory for words and faces), and cognitive impairment appeared more progressive over time. ALS patients demonstrated anomia on a confrontation naming test, with no significant problems following commands or repeating. Speech motor performance scores and intelligibility scores were not significantly different. No significant declines in forced vital capacity, forced expiratory volume, or peak expiratory flow rates were observed. Although normal at initial testing (T1), MR 1H spectroscopy demonstrated a reduction of the N-acetylaspartate/creatine (NAA/Cr) ratio in the nondominant precentral motor strip across the two testing intervals. In contrast, the NAA/Cr ratio obtained from the anterior cingulate gyrus at T1 was already reduced in bulbar-onset patients (p Conclusions: Bulbar-onset ALS patients with cognitive impairments and neuronal loss in the anterior cingulate gyrus subsequently developed more profound neuropsychological dysfunction whereas both language and speech capabilities remained relatively preserved. Of note, the absence of bulbar signs did not predict an absence of cognitive decline.

High fat diet increases hippocampal oxidative stress and cognitive impairment in aged mice: implications for decreased Nrf2 signaling

Abstract: Long term consumption of a high fat diet (HFD) contributes to increased morbidity and mortality. Yet the specific effects of HFD consumption on brain aging are poorly understood. In the present study 20-month old male C57Bl/6 mice were fed either 'western diet' (41% fat), very high fat lard diet (60% fat), or corresponding control diets for 16 weeks and then assessed for changes in metabolism and brain homeostasis. Although both HFDs increased adiposity and fasting blood glucose, only the high fat lard diet increased age-related oxidative damage (protein carbonyls) and impaired retention in the behavioral test. This selective increase in oxidative damage and cognitive decline was also associated with a decline in NF-E2-related factor 2 (Nrf2) levels and Nrf2 activity, suggesting a potential role for decreased antioxidant response. Taken together, these data suggest that while adiposity and insulin resistance following HFD consumption are linked to increased morbidity, the relationship between these factors and brain homeostasis during aging is not a linear relationship. More specifically, these data implicate impaired Nrf2 signaling and increased cerebral oxidative stress as mechanisms underlying HFD-induced declines in cognitive performance in the aged brain.

Epidemiological studies of the effect of stroke on incident dementia: a systematic review.

Abstract: Background and Purpose— Stroke is implicated in the incidence of dementia, and the risk of poststroke dementia is well characterized, but the excess risk of dementia in those with stroke compared with those without stroke is not well known. Methods— We conducted a systematic review of the excess risk of incident dementia conferred by stroke. Studies of the risk of incident dementia in the population with stroke compared with the population without stroke were identified and compared. Results— Sixteen studies were identified with all but one conducted in a community setting. A history of stroke doubles the risk of incident dementia in the older population. This increase is not explained by demographic or cardiovascular risk factors or by prestroke cognitive decline. The excess risk of incident dementia diminishes with time after stroke and may be higher in those without an APOE e4 allele. There is no excess risk of incident dementia in those aged >85 years with a history of stroke compared to those aged >8...

Telomere length predicts poststroke mortality, dementia, and cognitive decline

Abstract: Objective Long-term cognitive development is variable among stroke survivors, with a high proportion developing dementia. Early identification of those at risk is highly desirable to target interventions for secondary prevention. Telomere length in peripheral blood mononuclear cells was tested as prognostic risk marker. Methods A cohort of 195 nondemented stroke survivors was followed prospectively from 3 months after stroke for 2 years for cognitive assessment and diagnosis of dementia and for 5 years for survival. Telomere lengths in peripheral blood mononuclear cells were measured at 3 months after stroke by in-gel hybridization. Hazard ratios for survival in relation to telomere length and odds ratios for dementia were estimated using multivariate techniques, and changes in Mini-Mental State Examination scores between baseline and 2 years were related to telomere length using multivariate linear regression. Results Longer telomeres at baseline were associated with reduced risk for death (hazard ratio for linear trend per 1,000bp = 0.52; 95% confidence interval, 0.28–0.98; p = 0.04, adjusted for age) and dementia (odds ratio for linear trend per 1,000bp = 0.19; 95% confidence interval, 0.07–0.54; p = 0.002) and less reduction in Mini-Mental State Examination score (p = 0.04, adjusted for baseline score). Interpretation Telomere length is a prognostic marker for poststroke cognitive decline, dementia, and death. Ann Neurol 2006

Cognitive decline in Alzheimer's disease is associated with selective changes in calcineurin/NFAT signaling.

Abstract: Upon activation by calcineurin, the nuclear factor of activated T-cells (NFAT) translocates to the nucleus and guides the transcription of numerous molecules involved in inflammation and Ca(2+) dysregulation, both of which are prominent features of Alzheimer's disease (AD). However, NFAT signaling in AD remains relatively uninvestigated. Using isolated cytosolic and nuclear fractions prepared from rapid-autopsy postmortem human brain tissue, we show that NFATs 1 and 3 shifted to nuclear compartments in the hippocampus at different stages of neuropathology and cognitive decline, whereas NFAT2 remained unchanged. NFAT1 exhibited greater association with isolated nuclear fractions in subjects with mild cognitive impairment (MCI), whereas NFAT3 showed a strong nuclear bias in subjects with severe dementia and AD. Similar to NFAT1, calcineurin-Aalpha also exhibited a nuclear bias in the early stages of cognitive decline. But, unlike NFAT1 and similar to NFAT3, the nuclear bias for calcineurin became more pronounced as cognition worsened. Changes in calcineurin/NFAT3 were directly correlated to soluble amyloid-beta (Abeta((1-42))) levels in postmortem hippocampus, and oligomeric Abeta, in particular, robustly stimulated NFAT activation in primary rat astrocyte cultures. Oligomeric Abeta also caused a significant reduction in excitatory amino acid transporter 2 (EAAT2) protein levels in astrocyte cultures, which was blocked by NFAT inhibition. Moreover, inhibition of astrocytic NFAT activity in mixed cultures ameliorated Abeta-dependent elevations in glutamate and neuronal death. The results suggest that NFAT signaling is selectively altered in AD and may play an important role in driving Abeta-mediated neurodegeneration.