Aging brain最新文献

Subthreshold depressive symptoms are highly prevalent among older adults and are associated with numerous health risks including cognitive decline and decreased physical health. One brain region central to neuroanatomical models of depressive disorders is the anterior cingulate cortex (ACC). The rostral portion of the ACC—comprised of the pregenual ACC and subgenual ACC—is implicated in emotion control and reward processing. The goal of the current study was to examine how functional connectivity in subregions of the rostral ACC relate to depressive symptoms, measured by the Beck Depression Inventory-Second Edition, in an ethnically diverse sample of 28 community-dwelling older adults. Based on meta-analyses of previous studies in primarily young adults with clinical depression, we hypothesized that greater depressive symptoms would be associated with primarily increased resting-state functional connectivity from both the subgenual ACC and pregenual ACC to default mode network regions and the dorsolateral PFC. We instead found that higher depressive symptoms were associated with lower functional connectivity of the ACC to the dorsolateral PFC and regions within the default mode network, including from the subgenual ACC to the dorsolateral PFC and anterior cingulate and from the pregenual ACC to the middle cingulate gyrus. This preliminary study highlights brain alterations at subthreshold levels of depressive symptoms in older adults, which could serve as targets for interventions.

We quantified and investigated multimodal brain MRI measures in the LoCARPoN Study due to lack of normative data among Indians. A total of 401 participants (aged 50–88 years) without stroke or dementia completed MRI investigation. We assessed 31 brain measures in total using four brain MRI modalities, including macrostructural (global & lobar volumes, white matter hyperintensities [WMHs]), microstructural (global and tract-specific white matter fractional anisotropy [WM-FA] and mean diffusivity [MD]) and perfusion measures (global and lobar cerebral blood flow [CBF]). The absolute brain volumes of males were significantly larger than those of females, but such differences were relatively small (<1.2% of intracranial volume). With increasing age, lower macrostructural brain volumes, lower WM-FA, greater WMHs, higher WM-MD were found (P = 0.00018, Bonferroni threshold). Perfusion measures did not show significant differences with increasing age. Hippocampal volume showed the greatest association with age, with a reduction of approximately 0.48%/year. This preliminary study augments and provides insight into multimodal brain measures during the nascent stages of aging among the Indian population (South Asian ethnicity). Our findings establish the groundwork for future hypothetical testing studies.

Dietary self-control is associated with inter-individual differences in neuroanatomy. Yet, whether such inter-individual differences are also associated with healthier dietary patterns is yet to be determined. In this cross-sectional study, a total of 100 northern Portuguese older community-dwellers were assessed with regards to i) the adherence to a healthy dietary eating pattern – the Mediterranean diet (MedDiet), and ii) grey matter density (GMD) of brain regions associated with valuation and dietary self-regulation, the ventromedial (vmPFC) and dorsolateral prefrontal cortex (dlPFC), through voxel-based morphometry. Healthy food choices were ascertained through the Mediterranean Diet Adherence Screener (MEDAS) where higher scores indicated greater adherence to the MedDiet. Voxel-based morphometry showed that greater grey matter density in the dlPFC and vmPFC associated with a higher adherence to the MedDiet. These results replicate previous links between dietary decision-making measured under laboratory conditions and the neuroanatomy of the brain's valuation and self-control system. Importantly, they shed new light on the potential relevance of inter-individual differences in the neuroanatomy of these two brain regions for adhering to healthier dietary patterns in everyday life.

For quite a long time, researches on Alzheimer's disease (AD) primarily focused on the cortex and hippocampus, while the cerebellum has been ignored because of its abnormalities considered to appear in the late stage of AD. In recent years, increasing evidence suggest that the cerebellar pathological changes possibly occur in the preclinical phase of AD, which is also associated with sleep disorder. Sleep disturbance is a high risk factor of AD. However, the changes and roles of cerebellum has rarely been reported under conditions of AD accompanied with sleep disorders. In this study, using an amyloid-β oligomers (AβO)-induced rat model of AD subjected to sleep deprivation, combining with a 7.0 T animals structural magnetic resonance imaging (MRI), we assessed structural changes of cerebellum in MRI. Our results showed that sleep deprivation combined with AβO led to an increased FA value in the anterior lobe of cerebellum, decreased ADC value in the cerebellar lobes and cerebellar nuclei, and increased cerebellum volume. Besides that, sleep deprivation exacerbated the damage of AβO to the cerebellar structural network. This study demonstrated that sleep deprivation could aggravate the damage to cerebellum induced by AβO. The present findings provide supporting evidence for the involvement of cerebellum in the early pathology of AD and sleep loss. Our data would contribute to advancing the understanding of the mysterious role of cerebellum in AD and sleep disorders, as well as would be helpful for developing non-invasive MRI biomarkers for screening early AD patients with self-reported sleep disturbances.

To examine the relationships of retinal structural (optical coherence tomography) and visual functional (multifocal visual evoked potentials, mfVEP) indices with neuropsychological and brain structural measurements in healthy older subjects. 95 participants (mean (SD) age 68.1 (9.0)) years were recruited in the Optic Nerve Decline and Cognitive Change (ONDCC) study in this observational clinical investigation. OCT was conducted for retinal nerve fibre layer (RNFL) and mfVEP for amplitude and latency measurements. Participants undertook neuropsychological tests for cognitive performance and MRI for volumetric evaluation of various brain regions. Generalised estimating equation models were used for association analysis (p < 0.05). The brain volumetric measures including total grey matter (GM), cortex, thalamus, hippocampal and fourth ventricular volumes were significantly associated with global and sectoral RNFL. RNFL thickness correlated with delayed recalls of California verbal learning test (CVLT) and Rey complex figure test (RCFT). The mfVEP amplitudes associated with cerebral white matter (WM) and cingulate GM volumes in MRI and CVLT, RCFT and trail making test outcomes. A significant association of mfVEP latency with logical memory delayed recall and thalamus volume was also observed. Our results suggested significant association of specific RNFL and mfVEP measures with distinctive brain region volumes and cognitive tests reflecting performance in memory, visuospatial and executive functional domains. These findings indicate that the mfVEP and RNFL measurements may parallel brain structural and neuropsychological measures in the older population.

Some individuals maintain cognitive health despite neuropathology. Targets impacting “cognitive resilience” may provide interventions for preventing dementia without decreasing neuropathology. Neuroticism represents the tendency to experience negative emotions, and is related to worse cognitive resilience. Exploring proteins associated with cognitive resilience risk factors, such as neuroticism, could yield new protein targets. We used 355 postmortem prefrontal cortex from two cohorts to measure 8356 proteins. We identified (i) proteins associated with both neuroticism and cognitive resilience, and (ii) proteins statistically mediating relations of neuroticism to cognitive resilience. We found two proteins, 40S ribosomal proteinS3 (RPS3) and branched chain keto acid dehydrogenase E1, subunit beta (BCKDHB), ranked in the top 1% of smallest p-values in parallel linear regression models of neuroticism to protein levels, and protein levels to cognitive decline resilience. In mediation models, RPS3 and BCKDHB accounted for 25% (p = 0.005) of the relation of neuroticism to cognitive resilience. Our sample size is modest, thus results may be due to chance (p-values did not meet Bonferroni significance) and will require further confirmation; however, investigating biologic mediators of associations of risk factors to cognitive resilience may help discover targets to promote cognitive resilience and reduce dementia.

Older adults have been neglected in biobehavioral oxytocin research. Emerging research indicates that oxytocin signaling activity fluctuates over the lifespan, which suggests that results from studies investigating youth and young adults cannot be easily generalized to older adults. The recruitment of a wider age range of research participants using a variety of research tools is required to uncover the role of the oxytocin signaling system over the lifespan and may reveal novel treatment target candidates in older adults, beyond social cognition and behavior.

Aging leads to a complex pattern of structural and functional changes, gradually affecting sensorimotor, perceptual, and cognitive processes. These multiscale changes can hinder older adults’ interaction with their environment, progressively reducing their autonomy in performing tasks relevant to everyday life. Autonomy loss can further be aggravated by the onset and progression of neurodegenerative disorders (e.g., age-related macular degeneration at the sensory input level; and Alzheimer’s disease at the cognitive level). In this context, spatial cognition offers a representative case of high-level brain function that involves multimodal sensory processing, postural control, locomotion, spatial orientation, and wayfinding capabilities. Hence, studying spatial behavior and its neural bases can help identify early markers of pathogenic age-related processes. Until now, the neural correlates of spatial cognition have mostly been studied in static conditions thereby disregarding perceptual (other than visual) and motor aspects of natural navigation. In this review, we first demonstrate how visuo-motor integration and the allocation of cognitive resources during locomotion lie at the heart of real-world spatial navigation. Second, we present how technological advances such as immersive virtual reality and mobile neuroimaging solutions can enable researchers to explore the interplay between perception and action. Finally, we argue that the future of brain aging research in spatial navigation demands a widespread shift toward the use of naturalistic, ecologically valid experimental paradigms to address the challenges of mobility and autonomy decline across the lifespan.

The canonical role of Apolipoprotein E (ApoE) is related to lipid and cholesterol metabolism, however, additional functions of this protein have not been fully described. Given the association of ApoE with diseases such as Alzheimer’s Disease (AD), it is clear that further characterisation of its roles, especially within the brain, is needed.

Therefore, using protein and gene expression analyses of neonatal and 6-month old brain tissues from an ApoE knockout mouse model, we examined ApoE’s contribution to several CNS pathways, with an emphasis on those linked to AD. Early neonatal changes associated with ApoE−/− were observed, with decreased soluble phosphorylated tau (p-tau, –40 %), increased synaptophysin (+36 %) and microglial Iba1 protein levels (+25 %) vs controls. Progression of the phenotype was evident upon analysis of 6-month-old tissue, where decreased p-tau was also confirmed in the insoluble fraction, alongside reduced synaptic and increased amyloid precursor protein (APP) protein levels. An age comparison further underlined deviations from WT animals and thus the impact of ApoE loss on neuronal maturation.

Taken together, our data implicate ApoE modulation of multiple CNS roles. Loss of function is associated with alterations from birth, and include synaptic deficits, neuroinflammation, and changes to key AD pathologies, amyloid-β and tau.