Aging brain最新文献

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.

We explored the effects of parietal damage on inhibitory effects of visuospatial attention, inhibition of return (IOR) and inhibitory tagging (IT), in the vertical meridian. We combined a vertical spatial cue paradigm with a Stroop task employing three different temporal intervals between the spatial cue and the target (700, 1200 and 2000 ms) in two groups of patients, one with damage to the parietal cortex and underlying white matter (the parietal patients group) and the other with damage in other brain areas not including the parietal lobe (the control patient group), and a healthy control group. Healthy controls showed the expected inhibitory effects, IOR at the 700 and 1200 intervals and IT at the 1200 interval (as evidenced in a reduction in the magnitude of Stroop interference at the cued location). On the other hand, only the group of parietal patients showed delayed onset of inhibitory effects, IOR and IT appeared at the 1200 ms and 2000 ms intervals, respectively. These findings provide evidence for a role of the parietal cortex, and the underlying fibre tracts, in inhibitory processing in the vertical meridian, with damage to the parietal cortex altering the time course of attention-dependent inhibition.

Sleep plays a major role in brain health, and cognition. Disrupted sleep is a well-described symptom of Alzheimer’s disease (AD). However, accumulating evidence suggests suboptimal sleep also increases AD risk. The deacetylase Sirtuin 1 (Sirt 1), encoded by the SIRT1 gene, impacts sleep via its relationship to wake-sleep neurotransmitters and somnogens. Evidence from animal and human studies supports a significant and complex relationship between sleep, Sirt 1/ SIRT1 and AD. Numerous hypotheses attempt to explain the critical impact of Sirt 1/ SIRT1 on wake- and sleep- promoting neurons, their related mechanisms and neurotransmitters. However, there is a paucity of studies assessing the interaction between sleep and Sirt 1/ SIRT1, as a principal component of sleep regulation, on AD pathology. In this review, we explore the potential association between Sirt 1/ SIRT1, sleep, and AD aetiology. Given sleep is a likely modifiable risk factor for AD, and recent studies suggest Sirt 1/ SIRT1 activation can be modulated by lifestyle or dietary approaches, further research in this area is required to explore its potential as a target for AD prevention and treatment.

A critical challenge in current research on Alzheimer’s disease (AD) is to clarify the relationship between network dysfunction and the emergence of subtle memory deficits in itspreclinical stage. The AppNL-F/MAPT double knock-in (dKI) model with humanized β-amyloid peptide (Aβ) and tau was used to investigate both memory and network dysfunctions at an early stage. Young male dKI mice (2 to 6 months) were tested in three tasks taxing different aspects of recognition memory affected in preclinical AD. An early deficit first appeared in the object-place association task at the age of 4 months, when increased levels of β-CTF and Aβ were detected in both the hippocampus and the medial temporal cortex, and tau pathology was found only in the medial temporal cortex. Object-place task-dependent c-Fos activation was then analyzed in 22 subregions across the medial prefrontal cortex, claustrum, retrosplenial cortex, and medial temporal lobe. Increased c-Fos activation was detected in the entorhinal cortex and the claustrum of dKI mice. During recall, network efficiency was reduced across cingulate regions with a major disruption of information flow through the retrosplenial cortex. Our findings suggest that early perirhinal-entorhinal pathology is associated with abnormal activity which may spread to downstream regions such as the claustrum, the medial prefrontal cortex and ultimately the key retrosplenial hub which relays information from frontal to temporal lobes. The similarity between our findings and those reported in preclinical stages of AD suggests that the AppNL-F/MAPT dKI model has a high potential for providing key insights into preclinical AD.

Introduction

The typical spatial pattern of amyloid-β (Aβ) in diagnosed Alzheimer’s disease (AD) is that of a symmetrical hemispheric distribution. However, Aβ may be asymmetrically distributed in early stages of AD. Aβ distribution on PET has previously been explored in MCI and AD, but it has yet to be directly investigated in preclinical AD (pAD). We examined how Aβ was distributed in individuals with pAD and MCI using ¹¹C-Pittsburgh Compound B (PiB) PET.

Methods

In this PET study, 79 subjects were retrospectively enrolled, including 34 controls, 24 pAD, and 21 MCI. All subjects underwent APOE genotyping, ¹¹C-PiB PET, MRI, and cognitive testing. We explored differences in Aβ load, Aβ lateralisation, and Aβ distribution, as well as associations between Aβ distribution and cognition.

Results

The Aβ asymmetry index (AI) differed between groups, with pAD having the highest Aβ AI as compared to both controls and MCI. There was no clear Aβ lateralisation in pAD, but there was a non-significant trend towards Aβ being more left-lateralised in MCI. There were no correlations between the cognitive scores and Aβ AI or Aβ lateralisation in pAD or MCI.

Conclusion

The distribution of Aβ is most asymmetrical in pAD, as Aβ first starts accumulating, and it then becomes less asymmetrical in MCI, when Aβ has spread further, suggesting that more pronounced asymmetrical Aβ distribution may be a distinguishing factor in pAD. Longitudinal studies examining the distribution of Aβ across the AD continuum are needed.

Background

Healthy aging can include declines in processing speed and executive function. Further research is needed to characterize the neurobiological underpinnings of these cognitive changes in older adulthood. The current study used functional near infrared spectroscopy (fNIRS), an optical neuroimaging technique, to examine differences in cerebral oxygenation between healthy older adults (OA) and younger adults (YA) during a measure of cognitive interference.

Methods

Thirty-four participants were sampled from two age groups: YA (mean age = 28.1 years, SD = 2.8, F = 9) and OA (mean age = 70.9 years, SD = 5.4, F = 9). Participants completed the Multi-Source Interference Task (MSIT), a measure of executive function with high and low-demand conditions, while undergoing fNIRS recordings using a TechEn CW6 system with 34-source-detector channels, situated over the prefrontal cortex. Functional activation patterns, accuracy, and reaction time were compared between and within groups for each condition.

Results

Behaviourally, during the control condition, OA and YA had comparable accuracy, although OA had significantly slower reaction times than YA. During the interference condition, OA had significantly lower accuracy and slower reaction times than YA. Results demonstrated a significant difference between groups with an age-related increase in HbO for OA in both conditions (p < 0.05). Within groups, OA showed greater activation during the control condition, while YA demonstrated greater activation during the interference condition.

Conclusions

The findings suggest that OA recruit additional neural resources to achieve similar behavioural performance during low-level cognitive interference, but that compensation in OA may be insufficient to support behavioural performance at higher levels of interference.