Aging brain最新文献

Previous studies have often reported timing deficits in older adults with different degrees of cognitive decline, however, the exact nature of impairments in time perception is still to be elucidated. In particular, it is unclear if the deficits are more pronounced for short or long intervals, consistent with notions that different cognitive processes and neuroanatomical areas are involved in the processing of durations of different ranges. The present study aims to further investigate timing abilities in amnestic mild cognitive impairment (aMCI) patients and age-matched controls. Participants were asked to decide whether an acoustic event occurred within the first or the second half of a reference duration. The results revealed a bias towards larger PSE values and reduced precision in aMCI patients compared to healthy controls. Further analyses showed that the bias towards larger PSE values correlated with memory performance, especially when sub-second durations were tested. Overall, the results demonstrate that memory deficits in aMCI patients coincide with changes in time perception in the sub-second interval range.

Aging leads to response slowing but the underpinning cognitive and neural mechanisms remain elusive. We modelled older and younger adults’ response times (RT) from a flanker task with a diffusion drift model (DDM) and employed diffusion-weighted magnetic resonance imaging and spectroscopy to study neurobiological predictors of DDM components (drift-rate, boundary separation, non-decision time). Microstructural indices were derived from white matter pathways involved in visuo-perceptual and attention processing [optic radiation, inferior and superior longitudinal fasciculi (ILF, SLF), fornix]. Estimates of metabolite concentrations [N-acetyl aspartate (NAA), glutamate (Glx), and γ-aminobutyric acid (GABA), creatine (Cr), choline (Cho), myoinositol (mI)] were measured from occipital (OCC), anterior cingulate (ACC) and posterior parietal cortices (PPC). Age-related increases in RT, boundary separation, and non-decision time were observed with response conservatism acounting for RT slowing. Aging was associated with reductions in white matter microstructure (lower fractional anisotropy and restricted signal fraction, larger diffusivities) and in metabolites (NAA in ACC and PPC, Glx in ACC). Regression analyses identified brain regions involved in top-down (fornix, SLF, ACC, PPC) and bottom-up (ILF, optic radiation OCC) processing as predictors for DDM parameters and RT. Fornix FA was the strongest predictor for increases in boundary separation (beta = −0.8) and mediated the effects of age on RT. These findings demonstrate that response slowing in visual discrimination is driven by the adoption of a more conservative response strategy. Age-related fornix decline may result in noisier communication of contextual information from the hippocampus to anterior decision-making regions and thus contribute to the conservative response strategy shift.

Defective brain glucose utilization is a hallmark of Alzheimer’s disease (AD) while Type II diabetes and elevated blood glucose escalate the risk for AD in later life. Isolating contributions of normal aging from coincident metabolic or brain diseases could lead to refined approaches to manage specific health risks and optimize treatments targeted to susceptible older individuals. We evaluated metabolic, neuroendocrine, and neurobiological differences between young adult (6 months) and aged (24 months) male rats. Compared to young adults, blood glucose was significantly greater in aged rats at the start of the dark phase of the day but not during the light phase. When challenged with physical restraint, a potent stressor, aged rats effected no change in blood glucose whereas blood glucose increased in young adults. Tissues were evaluated for markers of oxidative phosphorylation (OXPHOS), neuronal glucose transport, and synapses. Outright differences in protein levels between age groups were not evident, but circadian blood glucose was inversely related to OXPHOS proteins in hippocampal synaptosomes, independent of age. The neuronal glucose transporter, GLUT3, was positively associated with circadian blood glucose in young adults whereas aged rats tended to show the opposite trend. Our data demonstrate aging increases daily fluctuations in blood glucose and, at the level of individual differences, negatively associates with proteins related to synaptic OXPHOS. Our findings imply that glucose dyshomeostasis may exacerbate metabolic aspects of synaptic dysfunction that contribute to risk for age-related brain disorders.

There exists a group of older individuals who appear to be resistant to age-related memory decline. These “SuperAgers” have been shown to demonstrate preservation of cortical thickness and functional connectivity strength across the cortex which positively correlates with memory performance. Over the last decade, roughly 30 articles have been published regarding SuperAgers; however, to our knowledge, no replications of these studies have been published. The current study sought to conceptually replicate Zhang and colleagues’ (2020) findings that SuperAgers demonstrate stronger intrinsic functional connectivity within the default mode (DMN) and salience networks (SN), and that connectivity strength within these networks correlates with memory performance. We identified 20 SuperAgers and 20 matched Normal Agers in the control cohort of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. We compared the functional connectivity strength of the DMN and SN between these groups, and used the Rey Auditory Verbal Learning Test (RAVLT) to evaluate correlations between functional connectivity and memory performance. Our results did not replicate Zhang and colleagues’ (2020) results, as we found negligible differences between SuperAgers and Normal Agers in the DMN and SN, and no significant correlations between functional connectivity and memory performance after accounting for multiple comparisons. More replications are needed to confirm existing work. In addition, more research with larger SuperAger samples and more consistent definitions of SuperAging is needed, so that we can better understand this remarkable group of older adults.

Older adults with impairment in contrast sensitivity (CS), the ability to visually perceive differences in light and dark, are more likely to demonstrate limitations in mobility function, but the mechanisms underlying this relationship are poorly understood. We sought to determine if functional brain networks important to visual processing and mobility may help elucidate possible neural correlates of this relationship. This cross-sectional analysis utilized functional MRI both at rest and during a motor imagery (MI) task in 192 community-dwelling, cognitively-unimpaired older adults $\ge$ 70 years of age from the Brain Networks and Mobility study (B-NET). Brain networks were partitioned into network communities, groups of regions that are more interconnected with each other than the rest of the brain, the spatial consistency of the communities for multiple brain subnetworks was assessed. Lower baseline binocular CS was significantly associated with degraded sensorimotor network (SMN) community structure at rest. During the MI task, lower binocular CS was significantly associated with degraded community structure in both the visual (VN) and default mode network (DMN). These findings may suggest shared neural pathways for visual and mobility dysfunction that could be targeted in future studies.

Background

Advanced maternal age (AMA), commonly defined as pregnancy at or above 35 years old. Based on the evidence, this trend has raised concerns about potential health consequences for mothers, particularly in relation to ischemic stroke. Studies suggest that AMA may be associated with a higher risk of ischemic stroke in women due to physiological changes that impact vascular health and increase cardiovascular risk factors. The aim of this study was to investigate the effect of AMA on the extent of damage after ischemic stroke in aged rats.

Methods

Female rats that gave birth at an old age (10 months) and at a young age (4 months) were subjected to ischemic stroke in old age (20 months) and subsequently compared.

We assessed neurological deficits, infarct volume, blood–brain barrier (BBB) permeability, TNF-alpha levels, total oxidant capacity, and gene expressions that play a role in BBB integrity (VEGF, Occludin, and MMP-9) following ischemic stroke.

Results

There were significantly elevated levels of MMP-9 expression and reduced levels of occludin in AMA rats. Additionally, AMA rats had significantly higher levels of TNF-alpha and total oxidant capacity after experiencing an ischemic stroke. AMA rats showed significantly higher brain water content (BBB permeability), infarct volume, and neurological deficits compared to young-aged pregnancies.

Discussion

Complex relationship between pregnancy-related physiological changes, aging, vascular gene expression, and inflammatory factors may play a role in the increased vulnerability observed in older pregnant rats. The similarities between pregnancy-related alterations and aging highlight the influence of advanced maternal age on susceptibility to ischemic stroke.

We investigated age-related trends in the topology and hierarchical organization of brain structural and functional networks using diffusion-weighted imaging and resting-state fMRI data from a large cohort of healthy aging adults. At the cross-modal level, we explored age-related patterns in the RC involvement of different functional subsystems using a high-resolution functional parcellation. We further assessed age-related differences in the structure–function coupling as well as the network vulnerability to damage to rich club connectivity.

Regardless of age, the structural and functional brain networks exhibited a rich club organization and small-world topology. In older individuals, we observed reduced integration and segregation within the frontal-occipital regions and the cerebellum along the brain's medial axis. Additionally, functional brain networks displayed decreased integration and increased segregation in the prefrontal, centrotemporal, and occipital regions, and the cerebellum. In older subjects, structural networks also exhibited decreased within-network and increased between-network RC connectivity. Furthermore, both within-network and between-network RC connectivity decreased in functional networks with age. An age-related decline in structure–function coupling was observed within sensory-motor, cognitive, and subcortical networks. The structural network exhibited greater vulnerability to damage to RC connectivity within the language-auditory, visual, and subcortical networks. Similarly, for functional networks, increased vulnerability was observed with damage to RC connectivity in the cerebellum, language-auditory, and sensory-motor networks. Overall, the network vulnerability decreased significantly in subjects older than 70 in both networks. Our findings underscore significant age-related differences in both brain functional and structural RC connectivity, with distinct patterns observed across the adult lifespan.