Sex and APOE4-specific links between cardiometabolic risk factors and white matter alterations in individuals with a family history of Alzheimer's disease

Neurobiology of Aging, Год журнала: 2025, Номер 150, С. 80 - 96

Опубликована: Март 8, 2025

Early detection of pathological changes in Alzheimer's disease (AD) has garnered significant attention the last few decades as interventions aiming to prevent progression will likely be most effective when initiated early. White matter (WM) alterations are among earliest AD, yet limited work comprehensively characterized effects AD risk factors on WM. In older adults with a family history we investigated sex-specific and APOE genotype-related relationships between WM microstructure factors. Multiple MRI-derived metrics were integrated using multivariate approach based Mahalanobis distance (D2). To uncover specific biological underpinnings these alterations, then extracted contribution each MRI feature D2 clusters. Lastly, links cognition explored. several regions was associated high systolic blood pressure, BMI, glycated hemoglobin, low cholesterol, both males females. APOE4 + displayed distinct pattern, LDL-cholesterol having detrimental effect only carriers, this pattern linked immediate memory performance. Myelination main mechanism underlying alterations. Our findings reveal that combined exposure multiple cardiometabolic negatively impacts microstructural health, which may subsequently affect cognition. Notably, carriers exhibited different especially role LDL, suggesting mechanisms group.

Язык: Английский

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Reply to Lockhart et al.: Advancing the understanding of sex differences in functional brain organization with innovative AI tools

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(2)

Опубликована: Янв. 2, 2025

Emotions coordinate our behavior and physiological states during survival-salient events pleasurable interactions. Even though we are often consciously aware of current emotional state, such as anger or happiness, the mechanisms giving ...Emotions felt in body, somatosensory feedback has been proposed to trigger conscious experiences. Here reveal maps bodily sensations associated with different emotions using a unique topographical self-report method. In ...

Язык: Английский

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Role of Sex in Shaping Brain Network Organization During Reading in Developmental Dyslexia

Children, Год журнала: 2025, Номер 12(2), С. 207 - 207

Опубликована: Фев. 10, 2025

Background/Methods: The influence of sex on brain organization was investigated in functional reading networks 8-year-old children, those typically developing and with developmental dyslexia (DD), utilizing the minimum spanning tree model. Results: word task revealed subtle differences connectivity highlighted even small individual variations characteristics, particularly among boys DD. In girls, significantly stronger connections core hubs were identified within between motor, parietal, visual posterior regions both hemispheres, θ (dyslexics) δ (normolexics) frequency bands. contrast, showed a more diffuse pattern, predominantly left hemisphere, encompassing anterior heteromodal sensorimotor networks. Girls exhibited greater network complexity (bigger leaf fraction, kappa, hierarchy), bands, while DD increased efficiency, except for γ2 band (smaller diameter bigger fraction). Therefore, gender-specific may affect development dyslexia. While development, its impact frontoparietal children is relatively limited. Significant observed only subset primarily higher (β2-γ2) Conclusions: Interindividual evident DD, impacting association Different rates cortical maturation sexes during childhood contribute to associated disruptions fundamental like network.

Язык: Английский

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“Precision Medicine” and the Failed Search for Binary Brain Sex Differences to Address Gender Behavioral Health Disparities

American Journal of Human Biology, Год журнала: 2025, Номер 37(4)

Опубликована: Апрель 1, 2025

ABSTRACT Human brain imaging took off in the 1980s and has since flooded zone analysis of gender differences behavior mental health. Couched aims “precision medicine,” vast majority this research taken a binary approach, dividing participants according to M/F box at intake asserting that sex found neuroimaging will lead important advances for treating neuropsychiatric disorders. However, actual findings from 40‐year project have not lived up its promise, part because over‐binarization general ignorance as complex variable influencing human function. This paper reviews history failed claims about male–female difference modern era, illuminates deep‐pocketed incentives driving such research, examines limitations approach understanding gender‐related health disparities. It then considers more recent efforts “break binary” by using measures “gender” addition “sex” an independent studies. Given multidimensional nature gender—as identity, expression, roles relations—this is challenging implement, with initial producing little substance. Better approaches addressing disparities require focusing on specific behaviors (e.g., anxiety, risk‐taking, verbal memory, spatial navigation) components body size, hormone levels, gene caregiver role, financial independence, discrimination) when seeking brain‐behavior correlates diverse population.

Язык: Английский

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Characterizing the Effects of Age, Puberty, and Sex on Variability in Resting-State Functional Connectivity in Late Childhood and Early Adolescence

NeuroImage, Год журнала: 2025, Номер unknown, С. 121238 - 121238

Опубликована: Апрель 1, 2025

Understanding the relative influences of age, pubertal development, and sex assigned at birth on brain development is a key priority developmental neuroscience given complex interplay these factors in onset psychopathology. Previous research has investigated how relate to static (time-averaged) functional connectivity (FC), but little known about their relationship with dynamic (time-varying) FC. The present study aimed investigate unique overlapping roles FC children aged approximately 9 14 ABCD Study using sample 5,122 low-motion resting-state scans (from 4,136 participants). Time-varying correlations frontolimbic, default mode, dorsal ventral corticostriatal networks, estimated Dynamic Conditional Correlations (DCC) method, were used calculate variability within- between-network graph theoretical measures segregation integration. We found decreased global efficiency across age range, increased within frontolimbic network driven primarily by those female (AFAB). AFAB youth specifically also showed several other networks. Controlling for both advanced being associated all segregation. These results potentially suggest maturation youth, particularly networks related psychopathology, lay foundation future investigations

Язык: Английский

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Sex differences in the executive and behavioral reserve of autosomal dominant frontotemporal dementia

Alzheimer s & Dementia, Год журнала: 2025, Номер 21(4)

Опубликована: Апрель 1, 2025

Abstract INTRODUCTION Self‐reported sex influences brain resilience, but its role in genetic frontotemporal dementia (FTD) remains unclear. METHODS We analyzed 394 genetic‐FTD patients and 279 controls from the ALLFTD consortium, assessing annual neuropsychological performance MRI‐based cortical thickness. Clinical characteristics thickness were compared between sexes. used residuals of linear regression models, which predict each participant's cognitive behavioral levels relative to thickness, as a proxy for reserve. then modeled differences longitudinal trajectories with mixed‐effects models. RESULTS Symptomatic females FTD had lower frontal than males, C9orf72 subgroup showed lower‐than‐expected given level executive functioning. Differences reserve sexes peaked near symptom onset diminished thereafter. DISCUSSION Females higher suggesting that self‐reported modulates resilience neurodegeneration. Highlights males. Those particularly pronounced GRN subgroups. The declined disease progressed.

Язык: Английский

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Neuroanatomy Reflects Individual Variability in Impulsivity in Youth

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 23, 2025

A bstract Individual differences in neural circuits underlying emotional regulation, motivation, and decision-making are implicated many psychiatric illnesses. Interindividual variability these may manifest, at least part, as individual impulsivity both normative clinically significant levels. Impulsivity reflects a tendency towards rapid, unplanned reactions to internal or external stimuli without considering potential negative consequences coupled with difficulty inhibiting responses. Here, we use multivariate brain-based predictive models explore the bases of across multiple behavioral scales, neuroanatomical features (cortical thickness, surface area, gray matter volume), sexes (females males) large sample youth from Adolescent Brain Cognitive Development (ABCD) Study baseline (n=9,099) two-year follow-up (n=6,432). is significantly associated variability, associations vary scales features. broadly maps onto cortical thickness dispersed regions (e.g., inferior frontal, lateral occipital, superior entorhinal), well area volume specific medial parahippocampal, cingulate) polar frontal temporal) territories. Importantly, while relationships stable time points, others sex-specific dynamic. These results highlight complexity between neuroanatomy features, sexes, points youth. findings suggest that neuroanatomy, combination other biological environmental factors, key driver As such, markers help identify increased risk for developing impulsivity-related Furthermore, this work emphasizes importance adopting multidimensional approach neuroimaging research.

Язык: Английский

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Longitudinal development of sex differences in the limbic system is associated with age, puberty and mental health

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 30, 2025

Abstract Sex differences in mental health become more evident across adolescence, with a two-fold increase of prevalence mood disorders females compared to males. The brain underpinnings remain understudied. Here, we investigated the role age, puberty and determining longitudinal development sex structure. We captured limbic non-limbic structures using machine learning models trained cross-sectional imaging data 1132 youths, yielding estimates sex. Applied two independent samples (total: 8184 youths), our revealed pronounced structure increasing age. For females, was sensitive pubertal (menarche) over time and, for structures, mood-related health. Our findings highlight system as key contributor potential classification investigate sex-specific processes relevant

Язык: Английский

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Influences of sex and gender on the associations between risk and protective factors, brain, and behavior

Biology of Sex Differences, Год журнала: 2024, Номер 15(1)

Опубликована: Ноя. 26, 2024

Abstract Risk and protective factors for psychiatric illnesses are linked to distinct structural functional changes in the brain. Further, prevalence of these varies across sexes genders, yet joint effects sex gender this context have not been extensively characterized. This suggests that risk may map onto brain uniquely influence individuals genders. Here, we review how specific (childhood maltreatment, COVID-19 pandemic, experiences racism), (social support psychological resilience) distinctly We also discuss role compounding interdependent influences factors. As such, call on researchers consider when researching illnesses, provide concrete recommendations account them future research. Considering alongside research acknowledging differences will enable us establish sex- gender-specific brain-behavior relationships. subsequently inform development targeted prevention intervention strategies which lacking. To achieve equality mental health, potential lead a better understanding men women, males females, make more vulnerable or resilient psychopathology.

Язык: Английский

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Considering the interconnected nature of social identities in neuroimaging research

Nature Neuroscience, Год журнала: 2024, Номер unknown

Опубликована: Дек. 27, 2024

Язык: Английский

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