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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: It is demonstrated that a loss of cholinergic integrity in the CNS, indexed by longitudinal decreases of basal forebrain volume, interacts with multiple biomarkers of inflammation in cognitively normal older adults with abnormal amyloid and tau pathology.
Abstract: Cholinergic inputs originating from the peripheral nervous system regulate the inflammatory immune responses of macrophages during clearance of blood-based pathogens. Because microglia are involved in clearing amyloid and tau pathology from the central nervous system, we hypothesized that cholinergic input originating from the basal forebrain might similarly regulate inflammatory immune responses to these pathologies in the aging brain. To explore this hypothesis, we leveraged the Alzheimer's Disease Neuroimaging Initiative dataset. Cognitively normal older male and female human adults were differentiated according to the relative concentration of phosphorylated tau and amyloid in their cerebrospinal fluid, yielding neurotypical and preclinical, cognitively healthy, subgroups. We then tracked these two groups longitudinally with structural MRI and biomarkers of inflammation, including soluble sTREM2 levels in the CSF and complement C3 expression in the blood transcriptome. Longitudinal loss of basal forebrain volume was larger in the preclinical compared with the neurotypical subgroup. Across preclinical adults, loss of basal forebrain volume was associated with greater longitudinal accumulation of sTREM2 and higher peripheral blood C3 expression. None of these relationships were attributable to degeneration in the whole-brain gray matter volume. Preclinical APOE e4 carriers exhibited the largest loss of basal forebrain volume and highest C3 expression. Consistent with the known anti-inflammatory influence of the peripheral cholinergic pathways on macrophages, our findings indicate that a loss of central cholinergic input originating from the basal forebrain might remove a key check on microglial inflammation induced by amyloid and tau accumulation.SIGNIFICANCE STATEMENT In the peripheral nervous system, cholinergic modulation holds the reactivity of macrophages to blood-based pathogens in check, promoting clearance while preventing runaway inflammation and immune-triggered cell death. Microglia are the brain's resident macrophages and play an important role in clearing accumulated amyloid and tau from neurons. Here, we demonstrate that a loss of cholinergic integrity in the CNS, indexed by longitudinal decreases of basal forebrain volume, interacts with multiple biomarkers of inflammation in cognitively normal older adults with abnormal amyloid and tau pathology. These interactions were not detected in cognitively normal older adults with "neurotypical" levels of amyloid and tau. An age-related loss of cholinergic neuromodulation may remove key checks on microglial reactivity to amyloid and tau.
26 citations
TL;DR: The lack of senescence-related differences in these biochemical markers does not preclude the possibility of functional changes in the NMDA receptor with aging.
26 citations
26 citations
Journal Article•
TL;DR: As a consequence of the estrogen deficiency state of the postmenopausal woman, brain aging may be accelerated, resulting in the greater incidence of injurious falls and accidental injuries in women than in men of the same age.
Abstract: There is a growing appreciation of the role of ovarian hormones as modulators of neuronal function within the central nervous system. Ovarian failure has long been known to result in reversible changes in mental function, affect, and behavior. Only recently have we begun to appreciate the potential role of these hormones, specifically estrogen, in the aging of the brain and in the expression of Alzheimer's disease. As a consequence of the estrogen deficiency state of the postmenopausal woman, brain aging may be accelerated, resulting in the greater incidence of injurious falls and accidental injuries in women than in men of the same age. This sex steroid deficiency in postmenopausal women may also account for the earlier expression of Alzheimer's disease in women.
26 citations
TL;DR: Grey matter loss in the frontal lobe was among the most widespread of all brain regions across the comparison groups that showed significant age-related changes in grey matter for both males and females.
Abstract: Previous and more recent work of analyzing structural changes in the brain suggest that certain brain regions such as the frontal lobe are among the brain regions profoundly affected by the aging process across males and females. Also, a unified model of structural changes in a normally aging brain is still lacking. The present study investigated age-related structural brain changes in gray matter from young to early middle-age adulthood for males and females. Magnetic resonance images of 215 normal and healthy participants between the ages of 21-45 years were acquired. Changes in gray matter were assessed using voxel-based morphometry and gray matter volumetric analysis. The results showed significant decrease in gray matter volume between the youngest and oldest groups in the following brain regions: frontal, temporal, and parietal lobes. Grey matter loss in the frontal lobe was among the most widespread of all brain regions across the comparison groups that showed significant age-related changes in grey matter for both males and females. This work provides a unique pattern of age-related decline of normal and healthy adult males and females that can aid in the future development of a unified model of normal brain aging.
26 citations