Topic
Aging brain
About: Aging brain is a research topic. Over the lifetime, 1255 publications have been published within this topic receiving 66405 citations.
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TL;DR: The new evidence that suggests an age-related increase in brain IL-6 and the impact this inflammatory cytokine may have on "successful" aging are discussed.
162 citations
TL;DR: A deeper understanding of the underlying pathways responsible for APOE4 toxicity is needed so that more tractable pathways and drug targets can be identified to reduceAPOE4-mediated disease risk.
Abstract: APOE4 is the greatest genetic risk factor for late-onset Alzheimer's disease (AD), increasing the risk of developing the disease by 3-fold in the 14% of the population that are carriers. Despite 25 years of research, the exact mechanisms underlying how APOE4 contributes to AD pathogenesis remain incompletely defined. APOE in the brain is primarily expressed by astrocytes and microglia, cell types that are now widely appreciated to play key roles in the pathogenesis of AD; thus, a picture is emerging wherein APOE4 disrupts normal glial cell biology, intersecting with changes that occur during normal aging to ultimately cause neurodegeneration and cognitive dysfunction. This review article will summarize how APOE4 alters specific pathways in astrocytes and microglia in the context of AD and the aging brain. APOE itself, as a secreted lipoprotein without enzymatic activity, may prove challenging to directly target therapeutically in the classical sense. Therefore, a deeper understanding of the underlying pathways responsible for APOE4 toxicity is needed so that more tractable pathways and drug targets can be identified to reduce APOE4-mediated disease risk.
161 citations
TL;DR: The role of heat shock expression on aging-induced changes in mitochondrial and antioxidant redox status and a significant positive correlation between decrease in GSH and increase in Hsp72 was observed in all brain regions examined during aging.
160 citations
TL;DR: The data suggest that WMH in the parietal lobe are chiefly responsible for reduced balance and postural support compared with the other 3 lobes and may alter integration of sensory information via parietal lobes dysfunction in the aging brain.
Abstract: Objective To investigate the impact white matter hyperintensities (WMH) detected on magnetic resonance imaging have on motor dysfunction and cognitive impairment in elderly subjects without dementia. Design Cross-sectional study. Setting Population-based study on the incidence and prevalence of cognitive impairment in Olmsted County, Minnesota. Participants A total of 148 elderly subjects (65 men) without dementia ranging in age from 73 to 91 years. Main Outcome Measures We measured the percentage of the total white matter volume classified as WMH in a priori–defined brain regions (ie, frontal, temporal, parietal, occipital, periventricular, or subcortical). Motor impairment was evaluated qualitatively using the Unified Parkinson's Disease Rating Scale summary measures of motor skills and quantitatively using a digitized portable walkway system. Four cognitive domains were evaluated using z scores of memory, language, executive function, and visuospatial reasoning. Results A higher WMH proportion in all regions except the occipital lobe was associated with lower executive function z score ( P value P value P value Conclusions We conclude that executive function is the primary cognitive domain affected by WMH burden. The data suggest that WMH in the parietal lobe are chiefly responsible for reduced balance and postural support compared with the other 3 lobes and may alter integration of sensory information via parietal lobe dysfunction in the aging brain. Parietal white matter changes were not the predominant correlate with motor speed, lending evidence to a global involvement of neural networks in gait velocity.
159 citations