Frontiers in Aging Neuroscience

Most evidence on age-related network topology derives from resting-state paradigms, leaving unclear how aging alters brain organization during naturalistic processing and whether graph-theoretical metrics relate to emotional and cognitive functioning in ecologically valid contexts. We analyzed movie-fMRI and behavioral data from 72 younger and 68 older adults, examining global (small-worldness, clustering coefficient, characteristic path length), network (participation coefficient), and nodal (degree centrality, betweenness centrality, nodal efficiency) properties. Regression models were used to test associations between nodal measures and both the Emotional Resilience Index (ERI) and the Cognitive Function Index (CFI), while mediation analyses were conducted to test whether nodal measures mediate the relationship between age and ERI. Older adults exhibited increased characteristic path length and clustering coefficient, indicating reduced global integration and greater local segregation. Although small-world organization was preserved in two groups, there was less pronounced small-world architecture in older adults compared to younger adults, suggesting a shift toward more regularized, locally clustered networks and reduced long-range connections during dynamic stimuli. Participation coefficient values were higher in the somatomotor, frontoparietal, and default mode networks, and lower in the subcortical network, among older adults reflecting greater between-network integration in cortical networks but diminished subcortical coordination in aging. Five key nodes, two thalamic regions, hippocampus, and two insular regions, showed reduced centrality and efficiency in older adults during the negative movie, indicating weakened dominance of subcortical hubs under emotional salience condition. Right thalamic nodal properties were negatively associated with ERI and CFI and served as mediators in the relationship between age and emotional resilience. These findings suggest that reduced thalamic hub centrality may reflect adaptive recalibration of salience emotional processing, linking network reorganization to improved emotional resilience in aging. Key pointsO_LIOlder adults showed higher path length and clustering, suggesting reduced integration. C_LIO_LIReduced small-worldness reflects weaker balance of segregation and integration with age. C_LIO_LIOlder adults showed higher cortical but lower subcortical participation coefficients. C_LIO_LIKey nodes showed reduced centrality during negative stimuli, indicating weaker hubs. C_LIO_LIRight thalamus changes linked to resilience, mediating age-emotion relationships. C_LI

Risky decision-making under uncertainty reflects complex cognitive processes supported by distributed brain networks that are vulnerable to aging. However, it remains unclear whether risk-taking behavior can serve as a behavioral marker of brain aging. In the present study, we combined behavioral tasks, computational modeling, and structural magnetic resonance imaging to investigate the relationship between risky decision-making, chronological age, and brain age. A total of 55 young adults and 112 healthy older adults completed the Iowa Gambling Task (IGT) and the Balloon Analogue Risk Task (BART), along with neuropsychological assessments and neuroimaging scanning. Decision processes were quantified using computational models, including the Value-Plus-Perseveration model and Exponential-Weight Mean-Variance. Brain age was estimated from gray matter volume. The results showed significant age-related alterations in parameters reflecting feedback sensitivity, learning rate, and loss aversion in both tasks. Within older adults, several decision parameters were significantly associated with both chronological age and brain age. Regression analyses further showed that computational parameters significantly predicted chronological age and brain age, whereas traditional cognitive screening measures did not show significant predictive effect. Structural brain analyses indicated that IGT-related parameters were primarily associated with the basal ganglia, while BART-related parameters were linked to a broader network including prefrontal, cingulate, and temporal regions. These findings suggest that computational markers of risk-taking behavior capture subtle age-related changes in cognitive processes and brain deterioration. Therefore, risk-taking parameters may serve as reliable functional markers of brain aging, providing critical insights into the mechanisms underlying successful aging.

Calcium dynamics controls learning and memory. Changes in calcium-induced calcium release (CICR), which is caused by opening ryanodine receptors (RyR) located on endoplasmic reticulum (ER) membrane, have been implicated in neurodegenerative disorders, such as Alzheimers disease (AD), manifesting with disruptions in calcium homeostasis and signaling. Calmodulin, one of the most abundant proteins in the brain, inhibits RyR2, expressed in the dendrites of hippocampal CA1 neurons, with several reported consequences: relieving of this inhibition is responsible for heart failure, and enhancing calmodulin to RyR binding [1] alleviates cell loss and AD-like neuronal hyperexcitability. To investigate the role of calmodulin in aging and AD, we built a sophisticated reaction-diffusion model of a dendritic branch with ER. We showed that relieving inhibition of RyR2 by calmodulin increased spatial and temporal spread of calcium transients in the dendrite. This effect was also visible in a model of old age, where disinhibition of RyR2 increased spatial spread of calcium transients by a factor of 2, and disinhibition of RyR2 combined with increased concentration of calcium buffering molecules increased duration of calcium transients, likely contributing to the deficits in learning and memory observed in old age. Lower activation of plasma membrane calcium ATPase (PMCA), which is also activated by calmodulin and inhibited by {beta}-Amyloid oligomers, and not RyR2 disinhibition, led to the increase resting intracellular calcium concentration observed in AD. Overall, our research demonstrates that changes in calmodulin that are associated with AD and aging, by regulation of RyR2 and PMCA, underlie changes in calcium dynamics that cause deficits in learning and memory. Author summaryCalcium dynamics controls learning and memory. In neurons calcium dynamics is regulated by a complex system including calcium-permeable channels and extrusion pumps. The components of this system are regulated by calmodulin, which is enriched in the brain. We show that relieving calmodulin inhibition of calcium permeable channels, which accompanies aging, decreases spatial and temporal specificity of calcium release contributing to the deficits in learning and memory observed in old age. In contrast, calcium extrusion pumps that are activated by calmodulin, are likely responsible for increased resting intracellular calcium concentration observed in Alzheimers disease. In consequence, a novel role emerges for calmodulin, which in the brain is primarily considered a fast-acting calcium buffering molecule, as an important regulator in neuronal calcium dynamics underlying pathology.

Cognitive flexibility is an executive function that enables adapting behaviour to a changing environment and is thus critical for daily life. The degree of its preservation upon healthy aging and the neural mechanisms underlying it are still a matter of debate. To investigate the electrophysiological correlates of cognitive flexibility in older age, we measured cognitive flexibility in 99 young (24.75 {+/-} 4.45 years) and 83 older adults (69.19 {+/-} 6.25) using electroencephalography (EEG). Compared to young adults, older adults showed a more conservative response pattern with longer reaction times, but lower error rates (speed-accuracy tradeoff). In the EEG, both age groups exhibited increased theta-power during set-shifting, with a fronto-central peak in the young, but a more fronto-lateral topography in older adults. Importantly, both groups displayed increases in theta coherence and global efficiency during set-shifting, but coherence modulations were restricted in frontocentral areas in the young but were diminished and distributed across the scalp in the older. Better set-shifting performance was most strongly associated with high coherence and global efficiency irrespective of age group. These results point to an age-related change of cortical processing underlying cognitive flexibility which involves the employment of more distributed neural resources for successful task completion.

Healthy aging is associated with progressive structural brain decline, yet the loss of functional abilities varies across individuals, which has been linked to reserve mechanisms. Within the framework of complex systems theory, reserve is thought to manifest as resilience when the system is challenged by stressors, such as increases in task difficulty. The cerebellum has been proposed as a potential source of motor reserve, but empirical evidence linking cerebellar structure, function, and resilience remains limited. We conducted a cross-sectional study including 50 young, 80 older, and 30 older-old adults to examine resilience to increasing task demands across cerebellar-specific and general outcomes. Participants completed three motor tasks (pure elbow motion, motor timing, postural stability) and two cognitive tasks (mental rotation, spatial working memory). Structural MRI was acquired to quantify cerebellar grey matter volume within functionally defined regions. Cerebellar-specific motor measures (anticipatory muscle activation and timing variability) were preserved across age groups and remained resilient under increased task demands, including in adults over 80 years of age. In contrast, general sensorimotor performance (postural sway) declined with age and showed reduced resilience. Within the cognitive domain, both cerebellar-specific and general measures showed comparable age-related declines and reduced resilience. Resilience measures were not correlated across tasks, indicating that resilience is task- and domain-specific. Furthermore, cerebellar grey matter volume did not predict resilience in motor or cognitive outcomes. These findings support the cerebellar motor reserve hypothesis, suggesting that cerebellar-dependent motor processes remain resilient despite age-related structural decline. However, resilience appears to be function-specific rather than a generalized individual trait. Overall, the results highlight dissociations between brain structure, function, and resilience, underscoring the selective contribution of the cerebellum to motor preservation in healthy aging.

Meningeal lymphatic vessels (mLV) play essential roles in draining cerebrospinal fluid (CSF) into peripheral blood. The mLVs are hypothesized to be supportive structures to the glymphatic system, which is thought to remove metabolic byproducts from brain parenchyma and has been most directly studied in rodent models. Previous rodent studies have indicated a correlation between mLV function and cognitive performance, but this relationship in humans remains unexplored. Age-related declines in glymphatic system efficiency in humans and cognitive performance have been observed separately. This study investigates age- and sex-related differences in CSF production via choroid plexus volumes, mLV characteristics, and glymphatic system efficiency, overall elucidating the implication of cerebral lymphatic function on cognition. We recruited 26 healthy adults from Dallas-Fort Worth and acquired magnetic resonance images. mLVs along the sagittal sinus were visualized and segmented from T2-FLAIR images. The glymphatic system was evaluated by measuring diffusivity along the perivascular space. Choroid plexus volume and brain volume were estimated from T1-MPRAGE. Neuropsychological tests were conducted to assess cognitive function. Our findings indicate that glymphatic function diminishes with age, while mLV and choroid plexus volumes increase. Males displayed greater mLV volume than females, yet no sex differences were found in glymphatic function or choroid plexus volume. Notably, mLV volume increased as glymphatic function declined, independent of age. Moreover, a glymphatic-mLV latent variable significantly predicted processing speed, underscoring the influence of cerebral lymphatics on cognition. In conclusion, this study highlights a decline in glymphatic function with age, accompanied by increased mLV volumes and altered processing speed. These lymphatic system changes may underlie or contribute to the cognitive declines observed in healthy and pathological aging. Significance StatementThe glymphatic system and meningeal lymphatic vessels play crucial roles in removing brain cell waste. The relationship between these systems and their effect on human cognition, particularly processing speed, is unknown. We demonstrate that these systems change with advancing age. Variations in cerebral lymphatic function contribute to differences in processing speed independent of age, ultimately affecting higher-order cognitive function. The findings presented have implications for cognitive function in both healthy and diseased states.

Sarcopenia is a geriatric condition characterized by the loss of muscle strength, muscle mass, and physical performance, yet its neural mechanisms remain insufficiently understood. This study aimed to identify cortical indicators of motor and cognitive functioning in individuals with sarcopenia using functional near-infrared spectroscopy (fNIRS), along with electromyography (EMG) and hand dynamometer measurements. 30 sarcopenia patients (age 67.33 {+/-} 7.48, F/M: 22/8) and 38 healthy controls (age 65.37 {+/-} 4.18, F/M: 29/9) participated in three experimental sessions designed to probe different neural systems: a Hand Grip task to assess motor function, an N-Back task to evaluate working memory, and an Oddball task to measure attention and inhibitory control. fNIRS measurements were carried out during all experimental sessions, while EMG and force output were extracted from the Hand Grip task. Group differences and neural-behavioral relationships were examined using t-tests, correlations, and repeated measures analyses. Participants with sarcopenia demonstrated significantly reduced EMG activity and force production. Although motor cortex responses during the Hand Grip task were similar between groups, the N-Back task revealed lower activation in the precentral, middle frontal, and superior frontal regions in the sarcopenia group. In contrast, the Oddball task showed increased right-hemisphere activation in sarcopenic individuals, suggesting compensatory recruitment. Significant correlations between cortical activity, grip strength, and Chair Stand Test performance indicated shared neural pathways linking motor and cognitive function. These findings highlight altered neural processing in sarcopenia and emphasize the importance of integrating neuroimaging with clinical measures to advance early detection and targeted intervention strategies. HighlightsO_LIfNIRS assessed motor and cognitive cortical activity in sarcopenia. C_LIO_LISarcopenia showed lower EMG amplitude and grip force output. C_LIO_LINo group difference in motor cortex activation during hand grip. C_LIO_LIN-back revealed lower frontal and precentral activation in sarcopenia. C_LIO_LIOddball showed higher right-hemisphere activation in sarcopenia. C_LI

As cognitive decline progresses, older adults may self-regulate their driving. Avoidance of left turns across traffic is observable in naturalistic driving data but rarely self-reported. We studied 106 older adults using baseline and one-year follow-up neuropsychological assessments. In-vehicle sensors passively recorded driving behavior over 12 weeks. We identified 295,112 turns from vehicle heading changes. We used mixed-effects logistic regression to model the odds of turning left, with cognitive status category change from baseline to one-year follow-up as the predictor. Greater cognitive impairment, represented by movement to a more severe cognitive status category at one-year follow-up, was associated with reduced odds of turning left (odds ratio = 0.984, 95% confidence interval = 0.969-0.999; P value = .037). Left-turn avoidance may be a behavioral marker of early cognitive decline. Passive driving data could help detect functional changes, enabling intervention to preserve mobility and independence. Further research is needed to establish a clinical threshold of concern for decreasing trends in left turn frequency in older drivers.

Emerging preclinical and clinical evidence suggests that low frequency hemodynamic oscillations drive CSF flow, which in turn mediates glymphatic clearance. The current study investigated whether CO2-induced low frequency hemodynamic oscillations during magnetic resonance imaging would increase clearance of proteins (glial fibrillary acidic protein, neurofilament light chain, ptau217 and brain-derived tau) from brain to blood, and temporarily improve cognitive performance in individuals with chronic traumatic brain injury (TBI) and age/sex-matched healthy controls. Results indicated that cerebrovascular reactivity, normalized CSF volume, and predicted brain age significantly differed between chronic TBI and controls, while bulk CSF flow differed only at trend levels. Multiple protein concentrations were significantly increased at [~]45 minutes post-hypercapnia, decreased at [~]90 minutes, and returned to pre-hypercapnia levels by [~]150 minutes. Protein efflux was more strongly associated with total CSF volume and total white matter volume rather than cerebrovascular reactivity or bulk CSF flow. Both groups exhibited reduced cognitive interference post-hypercapnia, and hypercapnia associated symptoms quickly returned to baseline levels. In conclusion, hypercapnia temporarily increases clearance of multiple neural abundant proteins into blood, and this effect is moderated by atrophy. Current results suggest that hypercapnia may therapeutically combat pathological protein aggregation post-trauma, and prophylactically during normal aging.

Insulin-like growth factor-1 (IGF-1) plays a critical role in neuronal signaling. Disrupted insulin/IGF-1 signaling is implicated in Alzheimers disease, among other conditions, yet its specific influence on glutamate receptor-mediated calcium responses remains unclear. We examined the impacts of IGF-1 on glutamate receptor function in primary rat neurons monitored for intraneuronal calcium following stimulation with glutamate, AMPA, or NMDA/glycine. Pharmacological blockers (CNQX for AMPA receptors, APV for NMDA receptors, and nimodipine for L-type calcium channels) were applied to define receptor-specific contributions. In hippocampal neurons, IGF-1 and insulin altered responses to glutamate in different directions, with IGF-1 tending to evoke and enhanced response. In neocortical neurons, by contrast, IGF-1 consistently reduced glutamate- and AMPA-evoked calcium peaks, suggesting an inhibitory effect on AMPA receptors. To rule out effects on voltage-gated calcium channels downstream of AMPA receptors, we tested effects of IGF-1 on depolarization with potassium chloride; calcium elevation in this case was unaffected by IGF-1. Likewise, IGF-1 did not inhibit responses to NMDA/glycine; and IGF-1 did not affect glutamate responses in the presence of CNQX, a selective AMPA receptor blocker. These findings, combined with the observation that IGF-1 effects persisted in the presence of APV (an NMDA receptor antagonist), indicate that the inhibition of glutamate responses by IGF-1 is mediated by suppression of AMPA receptor activity. IGF-1 may thus contribute to normal neurophysiology, and given the role that glutamate receptors play in excitotoxicity, IGF-1 may confer neuroprotection in the neocortex. Disruption of IGF-1 signaling, as seen in states resembling insulin resistance, may therefore worsen glutamate-driven excitotoxicity and contribute to adverse outcomes.

Ageing is associated with declines in mobility and balance that threaten independence and increase fall risk. Although these changes are often attributed to deterioration of muscular and sensory systems, growing evidence suggests that age-related alterations in cognitive control also contribute to postural instability and gait impairments. Here, we examined whether shifts in cognitive control strategy underlie impaired gait initiation in older adults by modelling how individuals update beliefs about upcoming actions. Older and younger adults performed a choice-stepping go/no-go task in which step likelihood was manipulated across trials. We measured anticipatory postural adjustments (APAs), the preparatory weight shifts preceding stepping and modelled age-related differences in APA onset using a hierarchical Bayesian framework. Older adults initiated slower APAs, particularly after repeated go trials. Computational modelling revealed reduced learning rates and heightened sensitivity to uncertainty in older adults, identifying altered belief updating as a cognitive mechanism shaping age-related changes in adaptive stepping.

Alzheimers disease (AD), a neurodegenerative disorder associated with amyloid beta (A{beta}) plaque deposition, leads to cognitive decline in affected individuals. Vision changes are some of the first reported symptoms in AD with studies showing both decline in functions performed by the visual system as well as associations between vision loss and cognitive impairment in AD patients. Due to the increasing number of individuals diagnosed with AD and its early impact on vision, we sought to provide an in-depth analysis using immunohistochemistry and 2-photon imaging techniques in the 5xFAD mouse model of amyloidosis to examine specifically how A{beta}, a primary pathology typically preceding many other AD-associated pathologies, affects visual regions of the brain and how microglia, key immune regulators of the brains environment, respond to this AD-like pathology. We found that in the pathway for image-forming vision, including the dorsolateral geniculate nucleus (dLGN) and the primary visual cortex (V1), there was significant A{beta} pathology and shifts in microglial morphology to an amoeboid state and increased phagocytic activity. However, in non-image-forming visual brain regions such as the superior colliculus (SC) and suprachiasmatic nucleus (SCN), there was minimal A{beta} pathology, ramified microglial morphology, and minimal phagocytic activity. Overall, visual brain regions associated with A{beta} plaque deposition experience significant microglial polarization when examining both morphology and function.

Tauopathies, including Alzheimers disease, are age-related neurodegenerative disorders characterized by abnormal phosphorylation and buildup of microtubule-associated protein tau. Gene expression dysregulation is a key molecular feature of tauopathies, but how aging and disease interact to disrupt crucial transcriptional regulators and pathways remains largely unknown. Here, we examined how pathological tau affects gene expression programs in age-related neurodegenerative disease using a well-established Drosophila melanogaster tauopathy model with neuronal expression of the toxic human tauR406W. Transcriptomic analysis of tau-expressing fly heads showed a preferential downregulation of long neuronal genes with long introns. Notably, we found that these downregulated genes in the tauopathy model are marked by increased accumulation of initiating RNA polymerase II (RNAP II) near the transcription start site and reduced elongating RNAP II within gene bodies, indicating a problem with the transition from initiation to elongation. By calculating an RNAP II Pause Index (PI) for each gene, we identified a strong link between promoter-proximal RNAP II stalling, gene expression deficits, and gene length in the tauopathy model. Overall, we have uncovered the genomic and transcriptomic features of tau-dependent downregulated genes and identified increased RNAP II promoter-proximal stalling as a significant mechanism of transcription stress in tauopathy.

Background and ObjectivesAlzheimers disease (AD) is characterized by early disruptions in brain connectivity. However, how genetic and biological markers of AD risk relate to dynamic functional connectivity (dFC) remains unclear. This study examined whether AD-related pathology, genetic risk, and blood-based biomarkers (BBMs) of neurodegeneration are associated with local and distant resting-state dFC patterns, and whether these relate to cognitive performance in cognitively normal older adults. Research Design and MethodsWe analyzed baseline data from 86 cognitively normal older adults (71.6 {+/-} 3.9 years; 60.5% female) enrolled in the AGUEDA trial (NCT05186090). Participants underwent A{beta}-PET imaging, APOE4 genotyping, and plasma quantification of BBMs (A{beta}42/40, BD-tau, GFAP, NfL, p-tau181, p-tau217). Resting-state fMRI was used to compute voxel-wise local and distant dFC using a stepwise connectivity framework. General linear models tested associations between AD pathology, APOE4 status, and BBMs with dFC, adjusting for age, sex, and education. Additional models examined links between dFC and six cognitive domains ResultsA{beta}-positive individuals and APOE4 carriers showed lower local connectivity in frontal regions, while APOE4 carriers exhibited higher distant connectivity in the superior motor area, inferior frontal gyrus, and anterior insula. Among BBMs, only neurofilament light chain (NfL) was associated with both lower local (insula, cingulate) and higher distant (precuneus, putamen, thalamus, supramarginal, superior motor area) connectivity. Regions showing higher distant connectivity related to APOE4 or NfL were associated with poorer cognitive performance. Discussion and ImplicationsDynamic functional connectivity reveals early network alterations in AD risk, characterized by reduced local and elevated distant connectivity--patterns linked to poorer cognition and potential early neurofunctional vulnerability in aging.

Age and coronary artery disease (CAD) are known risk factors for cognitive decline and dementia, in which cerebral blood flow (CBF) has as a key role. Cardiorespiratory fitness (CRF) has shown consistent links with brain health and dementia, though its association with CBF and whether it differs depending on age or disease status remains limited. The main aim of this study was to examine the association of CRF, assessed through the six-minute walk test (6MWT) and peak oxygen uptake (VO2peak), with CBF in cognitively normal older adults and individuals with CAD. We hypothesized that CRF will be positively associated with global and regional CBF. Seventy-nine cognitively normal older adults from the AGUEDA trial and 84 individuals with CAD from the Heart-Brain trial were included in this cross-sectional analysis. Participants underwent 6MWT, and a 3D arterial spin labelling magnetic resonance imaging scan to assess global and regional CBF. In the Heart-Brain project, participants additionally conducted a cardiopulmonary exercise test from which VO2peak was determined. In the Heart-Brain sample, after adjusting for age, sex, education, mean arterial pressure and APOE4, CRF was positively associated with global CBF (6MWT: {beta}=0.26, P=0.04; VO2peak: {beta}=0.33, P=0.02). At a regional level, CRF was positively associated with CBF in the posterior cingulate cortex (6MWT: {beta}=0.26, P=0.04; VO2peak: {beta}=0.31, P=0.02), the anterior cingulate cortex (6MWT: {beta}=0.29, P=0.02), the precuneus (6MWT: {beta}=0.28, P=0.02; VO2peak: {beta}=0.32, P=0.01) and the hippocampus (VO2peak: {beta}=0.29, P=0.03). No significant associations were observed in the AGUEDA sample (all P>0.05). When adding body mass index (BMI) to the models, the associations were no longer statistically significant in either sample. The association between VO2peak and CBF was significantly mediated (i.e. indirect effect) by BMI (Indirect effect: {beta}=0.250 (95% CI 0.02;0.486), percentage of mediation=72.67%). CRF was positively associated with CBF in individuals with CAD, but not in cognitively normal older adults. Interestingly, the association of CRF with CBF was largely explained and mediated by BMI. Further studies are warranted to clarify the role of CRF and BMI in relation to CBF, the mechanisms involved and the implications for dementia risk prevention in older adults and individuals with CAD.

Healthy aging is accompanied by subtle difficulties in language production. While behavioral and neuroimaging studies suggest that older adults rely on acute semantic access to maintain language abilities, the underlying neurophysiological mechanisms remain poorly understood. In particular, it is still unclear how large-scale brain dynamics reorganize to support naturalistic sentence generation with age. In this study, we investigated the spatiotemporal brain-state dynamics during covert sentence generation (GE2REC protocol) in younger and older adults using magnetoencephalography (MEG). Source-reconstructed MEG signals were analyzed using a Hidden Markov Model which identified five recurrent brain states, encompassing language-semantic, language-control, sensorimotor, and visual domains. Latent modeling was then used to relate the spectral and temporal properties of these brain states to age and language performance. Spectrally, older adults appear to redistribute oscillatory activity from sensorimotor-related states toward semantic-related states across alpha, beta, and low-gamma frequency bands. Temporally, older adults exhibit a more segmented processing sequence between semantic and sensorimotor processing which interfaces with visuo-posterior processing. These changes robustly covaried with age and better verbal fluency (semantic & lexical). Taken together, these results suggest that the older adult brain undergoes a coordinated time-frequency reorganization to support sentence production. Individuals likely establish an embodied semantic strategy in aging that involves "chunking" the processing stages of sentence production via visuo-posterior information processing. We speculate that this may help shape a resource-efficient, predictive route for complex cognition in older adulthood.

Aging affects cerebellar structure, yet the regional specificity of this decline and its relationship to sensorimotor function remain unclear. In this study, we quantified age-related gray matter differences in 50 young and 80 older adults using both anatomically defined cerebellar parcellations and a functionally defined cerebellar atlas. Across both anatomical and functional parcellations, older adults showed robust reductions in gray matter volume relative to young adults. However, contrary to prior reports of region-specific vulnerability, age effects did not differ significantly across regions: both datasets demonstrated remarkably uniform gray matter decline. Structural covariance analyses revealed that correlations between cerebellar regions were determined primarily by spatial proximity and, to a lesser extent, by medial-lateral (vermis-hemisphere) organization or functional similarity. Importantly, the topological organization of the cerebellum remained stable across age groups, indicating preserved structural coordination despite widespread gray matter loss. Finally, despite substantial interindividual variability in behavioral, regional cerebellar gray matter volumes, whether anatomically or functionally defined, did not predict inter-individual variability for any of our eight cerebellum-dependent outcomes. This absence of structure-function relationships suggests that behavioral performance is maintained through compensatory mechanisms or microstructural features not captured by regional gray matter volume. Together, the results demonstrate uniform age-related cerebellar degeneration alongside preserved topological organization and no measurable impact on cerebellar sensorimotor function, supporting the notion of a robust cerebellar reserve throughout healthy aging.

Disruptions in large-scale electroencephalography dynamics are a hallmark of Alzheimers disease. However, conventional microstate analyses rely primarily on amplitude-based features and may overlook phase-related alterations in network organization. This study examined whether integrating instantaneous frequency and instantaneous amplitude into a unified microstate framework could better characterize AD-related EEG dynamics. Resting-state electroencephalography data were recorded from 16 patients with Alzheimers disease and 18 healthy controls using 16 scalp electrodes. Instantaneous frequency and instantaneous amplitude were derived via the Hilbert transformation in the theta to alpha band, ranging from 4 to 13 Hz, spatially normalized, and jointly clustered using the k-means algorithm with k equal to 4 to define the integrated frequency and amplitude microstates. Temporal properties, including dwell time, fractional occurrence, and transition probabilities, were compared between groups. The analysis identified recurrent instantaneous frequency and instantaneous amplitude microstates. Patients with Alzheimers disease showed a reduced occurrence of the occipital-leading state with frontal amplitude enhancement and an increased occurrence of the frontal-leading, frontal-amplified state, while transition probabilities did not differ significantly. These findings suggest that impairments related to Alzheimers disease are reflected in the altered prevalence of integrated phase and amplitude brain states, supporting integrated instantaneous frequency and instantaneous amplitude microstates as a complementary approach based on electroencephalography for probing neurodegenerative network dysfunction.

The aim of this study was to investigate the effects of cognitive dual-tasking on low-frequency oscillations during quiet standing in older adults. Thirty-two older adults (age 71{+/-}8 yrs) were categorized into high- and low-risk fall groups. Both groups performed three trials each of the following tasks: 1) quiet standing with eyes open - on a force plate; 2) quiet standing with eyes open and verbal memory encoding task - on a force plate; and 3) quiet sitting with eyes open and verbal memory encoding task - not on a force plate. We found that: A) older adults at high fall risk exhibit greater postural sway when compared with older adults at low fall risk, B) most of the absolute and normalized wavelet power from 0-4 Hz is concentrated within the 0-1 Hz frequency band across all directions, and C) the absolute change in wavelet power in the 0-1 Hz band from single to dual-task is associated with increased total COP sway displacement irrespective of fall risk group. Based on these findings, it is concluded that nonlinear postural sway measures provide valuable insights into age-associated changes in fall risk and dual-task performance. Focusing on low-frequency oscillations, particularly in the 0-1 Hz band, could enable the earlier identification of individuals at high risk of falls and a better understanding of how the dual-tasking paradigm challenges the aging population.

Amygdala-related functional connectivity plays a crucial role in human emotion, cognition, and mental well-being. The amygdala is a highly heterogeneous structure, with subregions that have both distinct and overlapping functions. However, the connectivity patterns of different amygdala subregions--and how these associations vary with age--remain poorly understood. Functional MRI data were analyzed from 68 younger adults and 66 older adults during movie watching in a 7T MRI scanner. Partial least squares (PLS) analysis was used to identify latent variables capturing variance associated with age-related differences in the functional connectivity patterns of three amygdala subregions: the basolateral (BLA), centromedial (CMA), and superficial (SFA) nuclei. In addition, covariance between behavioral measures, such as emotional resilience and cognitive function, and functional connectivity of these subregions was examined. We further explored the associated cognitive processes, correspondence with large-scale brain networks, and the underlying chemoarchitecture of the identified connectivity patterns of the BLA, CMA, and SFA. Multivariate analyses revealed age-related and subregion-specific functional connectivity patterns. Functional connectivity patterns of amygdala subregions were further associated with emotional resilience, which largely overlapped across widespread brain regions; however, their associations differed by age. Stronger coupling of amygdala subregions predicted higher resilience in older adults but lower resilience in younger adults. The identified connectivity patterns were linked to the salience, control, and default mode networks and showed spatial correspondence with mGluR5 and 5-HT6 receptor distributions. These findings highlight age-dependent reorganization of amygdala-related networks that support emotional resilience and provide novel insights into how functional and neurochemical changes of the amygdala subregions contribute to adaptive emotional and cognitive functions in aging.