Biology subjects

Ances, B. M.

Publications and source records attributed to Ances, B. M..

4 recordsLinked to original sources

bioRxiv2026

Structural Brain Indicators of Cognitive Performance in Middle and Late Adulthood: The Human Connectome Project in Aging/Aging Adult Brain Connectome Cohort

IntroductionSignificant effort has been put towards mapping patterns of atrophy in the cerebral cortex that are related to pathological aging, including the characteristic patterns of neurodegeneration in Alzheimers disease (AD). In contrast, brain structural patterns that support preserved or even exceptional cognition throughout the adult age-span and especially in later life are much less known. It is possible that superior cognitive performance in late life is supported by a preservation of brain structures vulnerable to typical aging. Alternatively, elevated performance could be related to preservation of brain regions vulnerable to age-associated pathology. Examination of individuals that exhibit superior cognition throughout the adult lifespan may provide unique insights into neural mechanisms that support cognitive resilience in late life. MethodsWe examined cross-sectional associations between cortical brain structure and cognitive performance across three stages of adulthood: midlife (36-59), young-old (60-79), and older adults (80+) in typically aging individuals enrolled as part of the Human Connectome Project Lifespan-Aging (HCP-A)/Aging Adult Brain Connectome (AABC) studies. Participants were considered generally healthy and excluded for significant and/or atypical health conditions for their demographic category, including a clinical diagnosis of cognitive impairment or dementia. Domain-specific cognitive factor scores representing memory, fluid intelligence, and crystalized intelligence were sex-stratified and residualized relative to age, and participants were classified as high, middle, or low performers based on their unique performance relative to the study sample. ResultsIn the full sample, high performers demonstrated greater cortical thickness in regions of somatomotor, visual, and auditory cortices, as well as cortical areas in the frontal, parietal, and insular cortices (e.g., 5m, LIPv, MBelt). We also found associations between medial temporal and cingulate cortical thickness and cognitive performance, but only for select analyses. Group differences in cortical thickness were greatest when contrasting high and low performers for fluid intelligence compared to the other cognitive factors and were most prominent in the midlife participants compared to the other age strata. These group differences were primarily driven by reduced cortical thickness in the low performing individuals in the younger age bins relative to the typically performing sample. Effects were rather limited when contrasting high and low performers in the 80+ age group. The cortical areas of high statistical significance appeared to show a cross-sectional convergence effect, such that the differences in cortical thickness between high vs. low cognitive performance groups diminished with increasing age. Despite lower statistical power, effect sizes were greatest when contrasting individuals at the extremes of performance (e.g., top 10% vs. bottom 10% performers). These effects were robust to subsample replications using longitudinally defined cognitive classifications. DiscussionElevated cognitive performance was cross-sectionally associated with increased regional cortical thickness and effects were most prominent in mid-life compared to later ages. Notably, contrary to brain regions that may be expected to support such high-order cognitive performance, a significant portion of primary sensory, motor, and insular cortical areas exhibited group differences between the high- and low-performing groups in this relatively younger age group. Group differences were due to lower thickness in these regions in the low performing group relative to the typical performers. In contrast to the younger portion of the sample, regions typically considered vulnerable to Alzheimers disease (i.e., regions in the medial temporal lobe) were only infrequently implicated. These results suggest that specific patterns of cortical brain structural integrity including preserved thickness of primary motor and sensory cortical regions may be a necessary but not sufficient mechanism supporting superior cognitive abilities in earlier adulthood, while alternate neural mechanisms may support cognitive resilience later in life. These results must be interpreted with caution given the cross-sectional nature of this study. Cognitive capacity can only be estimated from a single timepoint, and several factors contribute to inter-individual variation that will not be accounted for in the models applied here. Longitudinal assessment of cognitive resilience in the HCP-A/AABC cohort will be performed in future work.

neuroscience↗

bioRxiv2023

Increasing hub disruption parallels dementia severity in autosomal dominant Alzheimer disease

Hub regions in the brain, recognized for their roles in ensuring efficient information transfer, are vulnerable to pathological alterations in neurodegenerative conditions, including Alzheimer Disease (AD). Given their essential role in neural communication, disruptions to these hubs have profound implications for overall brain network integrity and functionality. Hub disruption, or targeted impairment of functional connectivity at the hubs, is recognized in AD patients. Computational models paired with evidence from animal experiments hint at a mechanistic explanation, suggesting that these hubs may be preferentially targeted in neurodegeneration, due to their high neuronal activity levels--a phenomenon termed "activity-dependent degeneration". Yet, two critical issues were unresolved. First, past research hasnt definitively shown whether hub regions face a higher likelihood of impairment (targeted attack) compared to other regions or if impairment likelihood is uniformly distributed (random attack). Second, human studies offering support for activity-dependent explanations remain scarce. We applied a refined hub disruption index to determine the presence of targeted attacks in AD. Furthermore, we explored potential evidence for activity-dependent degeneration by evaluating if hub vulnerability is better explained by global connectivity or connectivity variations across functional systems, as well as comparing its timing relative to amyloid beta deposition in the brain. Our unique cohort of participants with autosomal dominant Alzheimer Disease (ADAD) allowed us to probe into the preclinical stages of AD to determine the hub disruption timeline in relation to expected symptom emergence. Our findings reveal a hub disruption pattern in ADAD aligned with targeted attacks, detectable even in pre-clinical stages. Notably, the disruptions severity amplified alongside symptomatic progression. Moreover, since excessive local neuronal activity has been shown to increase amyloid deposition and high connectivity regions show high level of neuronal activity, our observation that hub disruption was primarily tied to regional differences in global connectivity and sequentially followed changes observed in A{beta} PET cortical markers is consistent with the activity-dependent degeneration model. Intriguingly, these disruptions were discernible 8 years before the expected age of symptom onset. Taken together, our findings not only align with the targeted attack on hubs model but also suggest that activity-dependent degeneration might be the cause of hub vulnerability. This deepened understanding could be instrumental in refining diagnostic techniques and developing targeted therapeutic strategies for AD in the future.

neuroscience↗

bioRxiv2022

Neuroimaging within the Dominantly Inherited Alzheimer's Network (DIAN): PET and MRI

The Dominantly Inherited Alzheimer Network (DIAN) Observational Study is an international collaboration studying autosomal dominant Alzheimer disease (ADAD). This rare form of Alzheimer disease (AD) is caused by mutations in the presenilin 1 (PSEN1), presenilin 2 (PSEN2), or amyloid precursor protein (APP) genes. As individuals from these families have a 50% chance of inheriting the familial mutation, this provides researchers with a well-matched cohort of carriers vs non-carriers for case-control studies. An important trait of ADAD is that the age at symptom onset is highly predictable and consistent for each specific mutation, allowing researchers to estimate an individuals point in their disease time course prior to symptom onset. Although ADAD represents only a small proportion (approximately 0.1%) of all AD cases, studying this form of AD allows researchers to investigate preclinical AD and the progression of changes that occur within the brain prior to AD symptom onset. Furthermore, the young age at symptom onset (typically 30-60 years) means age-related comorbidities are much less prevalent than in sporadic AD, thereby allowing AD pathophysiology to be studied independent of these confounds. A major goal of the DIAN Observational Study is to create a global resource for AD researchers. To that end, the current manuscript provides an overview of the DIAN magnetic resonance imaging (MRI) and positron emission tomography (PET) protocols and highlights the key imaging results of this study to date.

neuroscience↗

bioRxiv2019

Smaller limbic structures are associated with greater immunosuppression in over 1000 HIV-infected adults across five continents: Findings from the ENIGMA-HIV Working Group

BackgroundHuman immunodeficiency virus type-1 (HIV) infection can be controlled with combination antiretroviral therapy (cART), but neurocognitive impairment remains common even in chronic and treated HIV-infected (HIV+) cohorts. Identifying the neuroanatomical pathways associated with infection has the potential to delineate novel neuropathological processes underlying persisting deficits, yet individual neuroimaging studies have yielded inconsistent findings. The ENIGMA-HIV Working Group was established to harmonize data from diverse studies to identify the common effects of HIV-infection on brain structure.\n\nMethodsData were pooled from 12 independent neuroHIV studies from Africa, Asia, Australia, Europe, and North America. Volume estimates for eight subcortical brain regions were extracted from T1-weighted MRI from 1,044 HIV+ adults (aged 22-81 years; 72.4% on cART; 70.3% male; 41.6% with detectable viral load (dVL)), to identify associations with plasma markers reflecting current immunosuppression (CD4+ T-cell count) or dVL. Follow-up analyses stratified data by cART status and sex. Bonferroni correction was used to determine statistical significance.\n\nFindingsLower current CD4+ count was associated with smaller hippocampal ({beta} = 20.3 mm3 per 100 cells/mm3; p = 0.0001) and thalamic volumes ({beta} = 29.3; p = 0.003); in the subset of participants not on cART, it was associated with smaller putamen volumes ({beta} = 65.1; p = 0.0009). On average, a dVL was associated with smaller hippocampal (Cohens d = 0.24; p = 0.0003) and amygdala volumes (d = 0.18; p = 0.0058).\n\nInterpretationIn HIV+ individuals across five continents, smaller limbic volumes were consistently associated with current plasma markers. As we assessed cohorts with different inclusion/exclusion criteria and demographic distributions, these deficits may represent a generalizable brain-signature of HIV infection in the cART era. Our findings support the importance of achieving viral suppression and immune restoration for maintaining brain health.\n\nFundingThis work was supported, in part, by NIH grant U54 EB020403.\n\nResearch in ContextO_ST_ABSEvidence before this studyC_ST_ABSHIV type-1 infection can be managed with antiretroviral therapy, however neurocognitive impairment persists even in treated HIV+ individuals. Given the challenges associated with standardized cognitive testing, there is a need to identify quantitative markers of central nervous system impairment. A number of neuroimaging studies have reported brain abnormalities in HIV-infected patients; however, prior studies investigating associations between CD4+ T-cell count or HIV viral load and subcortical brain volume report variable effect sizes and regional distributions of effects, limiting the generalizability of the conclusions drawn to date. We have conducted a literature search for reports in English language journals published until June 2019, using the following search terms: HIV AND subcortical AND neuroimaging AND brain AND viral load AND RNA AND CD4. After removing studies that were not applicable, there were 30 studies investigating CD4+ T-cell count and viral load associations with subcortical brain structure.\n\nAdded value of the studyThe aim of the current study was to investigate structural brain associations with two biomarkers universally used to monitor immune function and treatment response, namely plasma RNA viral load and CD4+ T-cell counts. Prior analyses have been performed in smaller, heterogeneous cohorts, but by combining data across cohorts, we can identify consistent associations between brain volume and indicators of HIV infection across cohorts. The ENIGMA-HIV Working Group was established to identify common neurobiological signatures of the HIV-infected brain by harmonizing data analysis from HIV neuroimaging studies worldwide. The value of this dataset is that it is well-powered and representative of many HIV+ people living in the cART era.\n\nImplications of all the available evidenceOur results provide robust evidence that despite demographic and clinical heterogeneity among HIV-infected individuals, brain abnormalities are consistently linked to HIV viral load and immunosuppression. This supports the importance of achieving viral suppression and immune system restoration in maintaining brain health in people living with HIV. The vulnerability of limbic regions, found in this study, extends beyond the classically implicated regions of the basal ganglia; this suggests that these regions remain an important target of cART era HIV research, especially given their heightened vulnerability to age-associated atrophy and neurodegeneration.

neuroscience↗