Low, Audrey

Objective Magnetic resonance imaging (MRI)‐visible enlarged perivascular spaces (PVS) are markers of cerebral small vessel disease (SVD) and aging, processes implicated in both neurodegenerative and cerebrovascular pathologies. However, longitudinal positron emission tomography (PET) studies examining PVS as a mechanism underlying Alzheimer's disease (AD) pathophysiological progression are lacking. Our overall objective was to investigate the associations of baseline PVS burden with white matter hyperintensity (WMH) volume, amyloid‐PET, and tau‐PET, both cross‐sectionally and longitudinally. Methods We examined 2,229 participants across the aging‐AD spectrum from the Mayo Clinic Study of Aging (MCSA) and the Mayo Alzheimer's Disease Research Center (ADRC) (mean age = 68.59 ± 12.70 and 48.94% women). PVS and WMH were quantified using a novel in‐house algorithm. Amyloid on [ 11 C]Pittsburgh Compound B (PiB)‐PET and tau on AV1451‐PET were measured. Cross‐sectional regional and global associations were examined using canonical correlation analysis (CCA). Longitudinal associations were examined using age‐ and sex‐adjusted linear mixed effect (LME) models with natural splines and subject‐wise 10‐fold cross‐validation. Result Three distinct associations were observed: (1) PVS in the basal ganglia (PVS‐BG) was associated with greater WMH volume both cross‐sectionally and longitudinally; (2) PVS‐BG covaried with higher PiB standardized uptake value ratio (SUVR) cross‐sectionally, with longitudinal trajectory associations limited to amyloid‐negative individuals; (3) PVS in the centrum semiovale (PVS‐CSO) was not associated with amyloid or tau, but was associated with occipital WMH, a pattern characteristic of CAA. Interpretation Findings lend support for PVS‐BG as an early indicator of small vessel dysfunction and WMH pathogenesis. Individuals with higher PVS‐BG burden exhibited higher WMH burden and faster WMH progression, suggesting that PVS‐BG may identify individuals at increased risk of progressive SVD. Evidence linking PVS to downstream AD biomarker progression was weaker. Findings support the relevance of PVS‐CSO to CAA, suggesting that they may reflect changes occurring early in the disease process. ANN NEUROL 2026

Abstract INTRODUCTION Women are increasingly entering the dementia research workforce, but they frequently fail to attain senior leadership positions in academia. Discrepancies in academic research outputs were investigated to guide equity‐focused policy recommendations. METHODS Bibliometrics was conducted on 400,482 original research articles (2003–2022) followed by surveying the AD/ADRD research community, to quantitatively and qualitatively evaluate discrepancies in publication and authorship trends. In addition, an unsupervised learning algorithm was developed to analyze underlying relationships between author groups. RESULTS Male author gender was consistently predictive of better publication and citation metrics across all bibliometrics outcomes, with senior male authors outperforming all other subgroups and fewer senior female authors in most research areas. Female survey respondents reported more barriers, but comparable productivity and citation strategies as male authors. DISCUSSION Multi‐pronged approaches by stakeholders across institutions, funders, and journals are necessary to provide career support for early‐career scientists working to transition to senior research roles.

Abstract Different MRI image contrasts are designed to highlight various tissue properties and combining them allows extension of probabilistic segmentation beyond the commonly used “gray-white-CSF” models. This work describes a fully automated method that combines T1-weighted, T2-FLAIR, and conventional T2-weighted images to provide internal consistency across prediction of tissue segmentations including segmentation of superficial and deep gray matter, white matter hyperintensities, and MR-visible perivascular spaces. Results from 773 imaging datasets from 403 participants in the Mayo Clinic Study of Aging and Mayo Clinic Alzheimer’s Disease Research Center (ADRC) are presented.

Abstract Dementia is associated with altered resting-state connectivity, measures of which could aid in its early detection and monitoring. High-density diffuse optical tomography (HD-DOT) is well suited to detect these alterations at scale due to its numerous practical advantages, but it has not yet been applied to dementia. In this study, we investigated resting-state functional connectivity across the prefrontal cortex in individuals with mild cognitive impairment (MCI, n = 22), Alzheimer’s disease (AD, n = 21), and in healthy controls (n = 22). A graph theoretical approach was taken to characterise both global and local patterns of prefrontal connectivity over a 5-minute resting period. We found that individuals with MCI exhibited denser and stronger networks with shorter path lengths, which normalised in AD, accompanied by a redistribution of network hubs that were less stable. These results perhaps reflect the recruitment of additional connections in the early stages of pathology to maintain short-term network stability, which is ultimately associated with less efficient and more fragmented network organisation in later stages. Following the demonstration of HD-DOT’s capacity to detect differences between healthy ageing and AD-type cognitive impairment, this work opens up new possibilities for the use of optical imaging in the study of this clinical population and HD-DOT’s potential for scalable clinical use.

Abstract Background Individuals living in socioeconomically disadvantaged areas are disproportionately affected by dementia. However, the pathway leading from neighbourhood deprivation to cognitive symptoms is not well understood. To test our hypothesis that this relationship is associated with cerebral small vessel disease (SVD), we examined (1) whether neighbourhood deprivation related to midlife SVD burden and cognition, and (2) whether these links can be explained by modifiable lifestyle risk factors. Method In this multi‐centre cross‐sectional study, 514 cognitively healthy midlife participants aged 40‐59 years (median 52 years, 64.6% female) underwent clinical assessment and 3T MRI. Postcode data were used to obtain national indices of neighbourhood deprivation. To quantify SVD, we assessed white matter hyperintensities (WMH), perivascular spaces, cerebral microbleeds, and lacunes. Cognition was assessed using the Computerized Assessment of Information Processing (COGNITO) battery. Lifestyle risk factors were evaluated based on clinical data. Using multivariate statistics like structural equation modelling (SEM) and canonical correlation analysis (CCA), we examined associations between these constructs both globally and at the item‐level (i.e., distinction between domains of cognition/deprivation), to shed light on specific domains that could inform targeted prevention strategies. Result Neighbourhood deprivation related to greater prevalence of lifestyle risk factors ( r = 0.36, p < .001), greater SVD burden (b=0.18, p = .01; Figure 1), and greater cognitive impairment ( r = 0.36, p < .001), independent of educational attainment, sex, and age. These links with neighbourhood deprivation were largely driven by lifestyle factors relating to vascular health (sleep, physical activity, obesity, hypertension) (Figure 2), and cognitive deficits consistent with SVD (processing speed, visuospatial) (Figure 3). Residents of deprived neighbourhoods displayed greater prevalence of lifestyle risk factors, except alcohol consumption. Lower cognitive scores were most closely associated with deprivation domains of Crime and Living Environment (Figure 3). The DEPRIVATION→SVD path was mediated by lifestyle risk factors (z=2.57, p = .010), and the DEPRIVATION→COGNITION path was mediated by SVD (z=‐2.14, p = .032) (global SVD & hypertensive subtype, but not CAA‐SVD). Conclusion The pathway linking neighbourhood disadvantage to cognitive impairment at midlife is influenced by vascular risk factors and cerebrovascular burden. Tailored strategies could promote resilience against dementia by promoting health behaviours aligned with the community's unique needs.

ABSTRACT INTRODUCTION Neighborhood deprivation increases dementia risk, although mechanisms remain unclear. We tested a framework in which modifiable risk factors and cerebral small vessel disease (SVD) mediate the link between neighborhood deprivation and cognition. METHODS In 585 cognitively healthy midlife adults (ages 40–59), neighborhood deprivation was derived from postcodes, cognition was assessed using the COGNITO, lifestyle risk factors were measured using clinical assessments, and SVD (white matter hyperintensities, lacunes, microbleeds, perivascular spaces) was assessed on 3T magnetic resonance imaging. Multivariate analyses examined association pathways among these variables. RESULTS Neighborhood deprivation was associated with poorer cognition ( r = 0.36, p < 0.001), greater prevalence of modifiable risk factors ( r = 0.36, p < 0.001), and greater SVD burden ( β = 0.18, p = 0.008). Serial mediation showed that the effects of deprivation on cognition were indirect, possibly operating via lifestyle risk and SVD, explaining 20% of the total effect, whereas SVD alone explained 28%. DISCUSSION Neighborhood disadvantage relates to poorer cognition, possibly mediated through vascular risk factors and cerebrovascular disease. Highlights Neighborhood deprivation linked to poorer cognition in healthy midlife adults Deprivation linked to small vessel disease (SVD) and modifiable risk factors (chiefly cardiovascular risk) Association between deprivation and cognition mediated by modifiable risk and SVD Mediation was exclusive to hypertensive SVD, but not cerebral amyloid angiopathy (CAA)‐related SVD

Background Sex affects the prevalence of atherosclerotic cardiovascular disease (ASCVD) risk factors but whether sex differences exist in the associations between ASCVD risk burden and cognitive function is unclear. Methods This cross‐sectional study included participants from a population‐based cohort study in China that recruited community‐dwelling adults aged 50 to 75 years without baseline cardiovascular disease and stroke. The 10‐year ASCVD risk burden was quantified with 3 multivariate risk prediction equations. Cognitive domains of memory, attention, visuospatial function, executive function, and processing speed were assessed. Multivariable linear regression models were used to examine the interaction terms between sex and ASCVD risk scores on cognition. Results The final analytical sample included 2180 participants. Mean±SD age was 60.14 (6.38) and 52.1% were women. Men showed significantly higher ASCVD risk burden than women at baseline but the effect of ASCVD risk on 2‐year cognition were amplified in women compared with men, for the domains of memory (eg, β=−0.20 [95% CI, –0.26 to −0.13] versus β=−0.11 [95% CI, –0.16 to −0.07]), executive function (eg, β=−0.23 [95% CI, –0.31 to −0.16] versus β=−0.16 [95% CI, –0.21 to −0.10]), and processing speed (eg, β=−0.33 [95% CI, –0.39 to −0.27] versus β=−0.17 [95% CI, –0.21 to −0.13]). Sex‐stratified analyses showed different neuropsychological profiles at moderate ASCVD risk burden levels, suggesting sex‐specific ASCVD‐risk related cognitive phenotypes. Conclusions Sex differences in cognitive health affected by ASCVD risk underscore the importance of sex‐specific cognitive monitoring during ASCVD risk management and better vascular risk control in women to prevent cognitive decline.