Neurobiology of Aging最新文献

{"title":"Gender-related facilitators and barriers to participation in research on aging using fuzzy cognitive mapping","authors":"Vasvi Dhir ,&nbsp;Ivan Sarmiento ,&nbsp;Isabel McDonald ,&nbsp;Maude Gélinas Faucher ,&nbsp;Stéfanie A. Tremblay ,&nbsp;Mark J. Yaffe ,&nbsp;Neil Andersson ,&nbsp;Maiya R. Geddes","doi":"10.1016/j.neurobiolaging.2026.01.009","DOIUrl":"10.1016/j.neurobiolaging.2026.01.009","url":null,"abstract":"<div><div>In the context of cognitive neuroscience research on aging, older women are often overrepresented in observational research, whereas men are overrepresented in clinical trials. Factors underlying the selection bias between and across genders in research on aging are currently poorly understood. Addressing this knowledge gap is critical to provide guidance on how we might mitigate selection bias and improve the generalizability, robustness, and reproducibility of our findings. We aimed to identify the barriers and facilitating factors that older adults perceive when considering participation in cognitive neuroscience research that were shared across, or that differed between, older women and men. We employed fuzzy cognitive mapping (FCM), a method that facilitates participation in research and action. Maps were co-created individually with research participants to identify factors, and their inter-relationships, that encouraged or hindered their participation in research. These factors were then standardized across maps, categorized through thematic analysis, and organized into group-level causal networks using graph theory methods. Our results indicated that both older women and men perceived individual psychological motivators, the quality of communication with the research team, logistic considerations and research-specific practices as key factors that influenced their participation in research. Dissociable factors between genders were also identified: Prior personal and professional experiences facilitated research engagement in women, whereas willingness to return benefits to the general population encouraged men’s research participation. These findings provide insights to guide the development of sampling strategies that enable equitable access to research and enhanced sample representativeness among women and men in research on aging.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"162 ","pages":"Pages 1-13"},"PeriodicalIF":3.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146161783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frontal white matter hyperintensity burden predicts cognitive response to N-acetylcysteine and exercise in vascular mild cognitive impairment","authors":"Ethan Mah ,&nbsp;Damien Gallagher ,&nbsp;Fuqiang Gao ,&nbsp;Joel Ramirez ,&nbsp;Jennifer S. Rabin ,&nbsp;Kate Survilla ,&nbsp;Danielle Vieira ,&nbsp;Jinghan Jenny Chen ,&nbsp;Yejin Kang ,&nbsp;Ana Andreazza ,&nbsp;Nathan Herrmann ,&nbsp;Alex Kiss ,&nbsp;Susan Marzolini ,&nbsp;Paul Oh ,&nbsp;Walter Swardfager ,&nbsp;Sandra E. Black ,&nbsp;Krista L. Lanctôt","doi":"10.1016/j.neurobiolaging.2026.01.005","DOIUrl":"10.1016/j.neurobiolaging.2026.01.005","url":null,"abstract":"<div><div>Vascular mild cognitive impairment (vaMCI) is a prodromal stage of dementia defined by cognitive deficits due to cerebrovascular disease. Increased white matter hyperintensity (WMH) volume has been associated with reduced executive function (EF). We explored whether lower baseline frontal and global WMH volume predicted an improvement in EF in vaMCI participants treated with N-acetylcysteine (NAC) and exercise as compared to placebo and exercise. Fifty-eight individuals with vaMCI received exercise therapy and were randomized to NAC or placebo. EF was assessed using the Trail Making Test Part B (TMT-B), Digit Symbol-Coding Test (DSCT), and a test of phonemic fluency, at baseline, 3 months, and 6 months. WMH volumes were measured from baseline magnetic resonance imaging scans. Linear mixed models were used. All participants improved on TMT-B (β = –0.185, SE = 0.046, p &lt; 0.001) and phonemic fluency (β = 4.440, SE = 0.911, p &lt; 0.001) over 6 months. A significant three-way interaction between baseline frontal WMH volume, treatment group, and timepoint predicted TMT-B performance at 3 months (β = 0.160, SE = 0.076, p = 0.039), but not at 6 months. No significant interactions were found for DSCT or phonemic fluency. Global WMH did not predict treatment response. Participants demonstrated improvement in EF regardless of treatment group and WMH volume. Lower frontal WMH volume predicted a greater improvement in TMT-B performance at 3 months in those treated with NAC versus placebo. These findings underscore the importance of considering participant heterogeneity in trials for vaMCI.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"161 ","pages":"Pages 39-46"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146036054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ABCA7 rs115550680 risk allele carriers have lower medial temporal lobe dynamic network flexibility than APOE-ε4 allele carriers among older African Americans","authors":"Miray Budak ,&nbsp;Bernadette A. Fausto ,&nbsp;Victoria Paruzel ,&nbsp;Payton White ,&nbsp;Martina Ishaq ,&nbsp;Soodeh Moallemian ,&nbsp;Kelly N. Nudelman ,&nbsp;Mark A. Gluck","doi":"10.1016/j.neurobiolaging.2026.01.008","DOIUrl":"10.1016/j.neurobiolaging.2026.01.008","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) pathology disrupts functional brain connectivity long before symptoms emerge. African Americans face elevated AD risk, yet underlying mechanisms remain unclear. Genetic risk differs by ancestry: <em>APOE-ε4</em> strongly predicts late-onset AD in European ancestry, whereas <em>ABCA7 rs115550680</em> confers substantial risk in African ancestry. Yet, how these variants influence neural function in African Americans is unclear. The medial temporal lobe (MTL) is an early target of AD pathology and resting-state functional Magnetic Resonance Imaging (rs-fMRI) measures of dynamic network connectivity (hereafter “flexibility”), the brain’s capacity to dynamically reconfigure connectivity, provide a sensitive metric of network adaptability, potentially preceding structural decline. However, comparative influence of <em>APOE-ε4</em> and <em>ABCA7 rs115550680</em> on MTL flexibility and subregional volumes in this population is unknown. 146 older African Americans (<em>Mean</em>_<em>Age</em>=69.71 <em>Mean</em>_<em>SD</em>=6.29) were genotyped for <em>APOE-ε4</em> and <em>ABCA7 rs115550680</em> via saliva samples. Rs-fMRI was used to calculate MTL flexibility and T1-weighted MRI quantified MTL subregional volumes. ANCOVAs controlled for age, sex, and education, and <em>APOE-ε4</em> when <em>ABCA7 rs115550680</em> was the predictor. <em>ABCA7 rs115550680</em> risk allele carriers exhibited lower MTL flexibility than non-carriers (<em>p = .042</em>) and <em>APOE-ε4</em> allele carriers (<em>p = .030</em>). They also showed hypertrophy in left anterior hippocampus (<em>p = .049</em>), bilateral entorhinal cortex (ERC) (right <em>p = .048</em>; left <em>p = .020</em>) compared to non-carriers, and greater left ERC volume than <em>APOE-ε4</em> allele carriers (<em>p</em> = .027). <em>APOE-ε4</em> or interaction effects were not significant (<em>p &gt; .05</em>). These findings provide preliminary evidence that <em>ABCA7 rs115550680</em> risk allele, but not <em>APOE-ε4</em> allele, is linked to reduced MTL flexibility and subregional hypertrophy in older African Americans, suggesting ancestry-specific mechanisms of early AD risk.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"161 ","pages":"Pages 64-72"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha band activity mediates age-related effects on three distinct aspects of working memory dynamics","authors":"Charlotte Pscherer ,&nbsp;Moritz Mückschel ,&nbsp;Christian Beste","doi":"10.1016/j.neurobiolaging.2026.01.001","DOIUrl":"10.1016/j.neurobiolaging.2026.01.001","url":null,"abstract":"<div><div>Working memory (WM) processes decline with increasing age. According to recent concepts, it is necessary to differentiate between dynamically changing ‘WM states’ which are regulated via gating mechanisms. We investigated which neural oscillatory processes underlying WM gating and updating are affected by age with a focus on alpha and theta band activity. With an EEG beamforming approach, we examined the data of N = 132 healthy individuals aged 18–76 years who performed the reference-back paradigm. Using mediation analyses we analyzed whether alpha and theta band activity can explain age-related effects on WM gate opening, gate closing, and updating processes at the behavioral level. The data showed that alpha band activity mediated the relationship between age and all three core WM processes, primarily reflected in slower and less efficient switching among WM states with increasing age. Theta band effects did not mediate age-related effects on WM dynamics. The likely reason why alpha band activity is particularly involved in age-related effects on WM functions may lie in its superordinate role, which facilitates the coordination of suppressing distractions and maintaining relevant information in the WM. Alpha band activity might therefore be mechanistically relevant for counteracting WM decline during aging.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"161 ","pages":"Pages 1-13"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concurrent associations between visit-to-visit changes in actigraphy-based physical activity and cognitive aging in older adults","authors":"Ranjani P. Shankar,&nbsp;Rowan Saloner,&nbsp;Coty Chen,&nbsp;Claire Cadwallader,&nbsp;Anna M. VandeBunte,&nbsp;Valentina Diaz,&nbsp;Lana Callies,&nbsp;Carina Lo,&nbsp;Sophia Licata,&nbsp;Jessica Buxton,&nbsp;Albert Pham,&nbsp;Molly Olzinski,&nbsp;Yann Cobigo,&nbsp;Adam M. Staffaroni,&nbsp;Gil D. Rabinovici,&nbsp;Joel H. Kramer,&nbsp;Kaitlin B. Casaletto,&nbsp;Emily W. Paolillo","doi":"10.1016/j.neurobiolaging.2026.01.004","DOIUrl":"10.1016/j.neurobiolaging.2026.01.004","url":null,"abstract":"<div><div>Physical activity (PA) is associated with lower dementia risk, yet few studies examine objectively measured PA with concurrently measured brain and cognitive aging outcomes longitudinally, leaving a gap in knowledge regarding temporality of these brain-behavior associations. We examined how longitudinal within-person changes in average daily step count track with changes in memory, executive function, hippocampal volumes, white matter hyperintensities (WMH), and depressive symptoms over time. 107 older adults completed neuropsychological testing and brain magnetic resonance imaging, followed by 30-day Fitbit monitoring at two or more annual study visits at the UCSF Memory and Aging Center. Linear mixed-effects models examined each brain health outcome as a function of visit-to-visit PA, time (years since baseline), baseline age, sex, education, and total intracranial volume (neuroimaging models only). Within-person increases in daily step count were most strongly associated with within-person increases in executive functioning (Std. β = 0.128, 95 %CI [0.056, 0.200], p ≤ 0.001) and decreases in depressive symptoms (Std. β = −0.201, 95 %CI [-0.284, −0.119], p ≤ 0.001). Longitudinal PA associations with memory, hippocampal volumes, and WMH did not reach statistical significance. Findings suggest that within-person changes in PA may reduce real-time risk of cognitive decline; additionally, real-world monitoring of movement via actigraphy may be sensitive to early and subtle aspects of neurobehavioral declines with aging.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"161 ","pages":"Pages 31-38"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human in vitro and rodent in vivo models highlight progressive mitochondrial dysfunction as a starting point of cerebral amyloidosis","authors":"Zahra Motamed ,&nbsp;Gisela Novack ,&nbsp;Daniel Heutschi ,&nbsp;Carine Gaiser ,&nbsp;Corina Garcia ,&nbsp;Sonia Do Carmo ,&nbsp;A. Claudio Cuello ,&nbsp;Laura Morelli ,&nbsp;Laura Suter-Dick","doi":"10.1016/j.neurobiolaging.2026.01.006","DOIUrl":"10.1016/j.neurobiolaging.2026.01.006","url":null,"abstract":"<div><div>Mitochondrial dysfunction is a well-established hallmark of Alzheimer’s disease (AD), particularly in the context of amyloid-beta (Aβ) accumulation. Here, we explored the progression of mitochondrial impairment associated with cerebral amyloidosis in human and rodent systems expressing AD-relevant APP mutations. We investigated mitochondrial function, dynamics, and degradation in human neural progenitor cells differentiated for two and six weeks, carrying the APP (Swedish/London) mutations. These analyses were complemented by studies in 3- and 9-month-old McGill-R-Thy1-APP transgenic (Tg) rats expressing the APP (Swedish/Indiana) mutations. We observed a consistent accumulation of pathogenic Aβ species associated with mitochondrial damage. <em>In vitro</em>, early indicators of oxidative stress and initial alterations in mitochondrial network dynamics were evident, including increased mitochondrial reactive oxygen species and elevated total DRP1 levels. Later, after 6 weeks of differentiation, significant mitochondrial dysfunction emerged, including reduced membrane potential, increased mitochondrial network fragmentation, and decreased GSH/GSSG ratio. Mitophagy was also disrupted, as evidenced by reduced localization of TOMM20 to the lysosomes, suggesting impaired mitochondrial clearance. Similarly, hippocampal mitochondria fraction of 9-month-old Tg rats showed elevated fission markers, nitrosative stress, and mitochondrial p62 accumulation, which were absent in 3-month-old Tg animals. Hence, we identified both early and late molecular alterations in mitochondrial homeostasis revealing accumulation of mitochondrial stress, altered dynamics, and mitophagy failure in response to sustained Aβ release. Our results underscore mitochondrial vulnerability during early amyloidosis, identifying it as a potential therapeutic target at initial disease stages. It also reinforces the utility of in vitro models for studying cerebral amyloid pathologies.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"161 ","pages":"Pages 47-63"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood biomarkers of frailty and cognition: A scoping review","authors":"Maddison L. Hodgins ,&nbsp;Selena P. Maxwell ,&nbsp;Susan E. Howlett ,&nbsp;Kenneth Rockwood","doi":"10.1016/j.neurobiolaging.2026.01.003","DOIUrl":"10.1016/j.neurobiolaging.2026.01.003","url":null,"abstract":"<div><div>Frailty increasingly is recognized as a factor that modifies the relationship between disease biomarkers, including neuropathology, and dementia expression. The mechanisms underlying the relationship between frailty and dementia remain unclear, but blood biomarkers can offer insight into these mechanisms. We completed a scoping review of research examining the associations between blood biomarkers, frailty, and cognition. Three online databases were searched to identify original research examining blood biomarkers in the context of frailty and/or cognitive decline that accounted for the other condition in the analysis through stratification or inclusion in the model. Five of the 76 unique biomarkers identified —A disintegrin and Metalloproteinase 10 (ADAM10), fibrinogen, interleukin (IL)-6, neurofilament light chain (NfL) and vitamin D— were significantly and independently associated with both frailty and cognition. All five biomarkers could contribute to aging mechanisms, including disrupted proteostasis, chronic inflammation, dysregulated metabolism and/or deregulated nutrient sensing. These biomarkers could thus be common pathways of frailty and cognitive decline. Despite the Alzheimer-defining roles of β-amyloid and phosphorylated tau, these biomarkers typically are reported without considering the degree of frailty. Future biomarker research in cognitive decline and frailty should seek a clearer understanding of their relationship.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"161 ","pages":"Pages 14-30"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantifying calretinin-labeled afferent terminals in vestibular sensory epithelia of young and older gerbils","authors":"Anna Dondzillo ,&nbsp;Tyler Bauer ,&nbsp;Kathryn King ,&nbsp;Anthony Peng ,&nbsp;Katherine J. Rennie","doi":"10.1016/j.neurobiolaging.2026.01.007","DOIUrl":"10.1016/j.neurobiolaging.2026.01.007","url":null,"abstract":"<div><div>Vestibular dysfunction becomes increasingly prevalent with aging and it is estimated that more than 80 % of people over 80 years old experience balance problems linked to vestibular dysfunction. Within the peripheral vestibular organs, sensory hair cells transform hair bundle motion into receptor potentials and information is next relayed to the brain by electrical activity in vestibular afferent nerves. There are three types of vestibular afferents: <em>calyx-only</em> afferents innervate one or more type I hair cells; <em>bouton</em> dendrites innervate type II hair cells and <em>dimorphic</em> afferents contact both hair cell types. Calyx-only afferents are found solely in central areas of vestibular neuroepithelia and have distinct physiological characteristics. Previous studies have shown changes in vestibular-mediated responses with aging in addition to age-related degeneration of afferent synapses in rodent inner ear epithelia. However, whether calyx-only afferent synapses are lost with aging in vestibular epithelia remains unresolved. Here we used an antibody to the Ca^2 + -binding protein calretinin as a marker of calyx-only afferent terminals in gerbil vestibular epithelia at different ages. We used fluorescent immunohistochemistry and confocal imaging to identify afferent neurons in the utricle and cristae of young (1–2 months), adult (1–2 years), and older adult (≥3 years) gerbils. Counts were made of single, double and triple calretinin-positive calyx terminals in central regions of vestibular epithelia. Overall, a mild decrease in numbers occurred with aging between adult and older adult animals suggesting that aging-related decline in vestibular function can be linked to partial loss of calretinin-positive calyx-only afferent terminals.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"161 ","pages":"Pages 73-82"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regional growth rates of white matter hyperintensities are associated with beta-amyloid burden","authors":"Jeremy F. Strain ,&nbsp;Maryam Rahmani ,&nbsp;Chia-Ling Phuah ,&nbsp;Donna Dierker ,&nbsp;Jingqin Luo ,&nbsp;Christopher Owen ,&nbsp;Andrei G. Vlassenko ,&nbsp;Hussain Jafri ,&nbsp;Pierreck Bourgeat ,&nbsp;Jurgen Fripp ,&nbsp;Liang Jin ,&nbsp;Krista Moulder ,&nbsp;Tammie Benzinger ,&nbsp;Chengjie Xiong ,&nbsp;Jin-Moo Lee ,&nbsp;Michael Weiner ,&nbsp;Colin L. Masters ,&nbsp;John C. Morris ,&nbsp;Kyle Womack ,&nbsp;Manu S. Goyal","doi":"10.1016/j.neurobiolaging.2025.12.006","DOIUrl":"10.1016/j.neurobiolaging.2025.12.006","url":null,"abstract":"<div><div>There is increasing evidence for an association between white matter hyperintensities (WMH) and brain beta-amyloid deposition. How WMH are longitudinally associated with brain beta-amyloid burden requires further investigation, particularly with respect to co-existent vascular risk factors and differences across white matter regions. We measured WMH on MRI and vascular risk factors in a combined neuroimaging data set of cognitively normal and individuals with dementia comprised of the ADNI, AIBL and OASIS3 studies, which includes harmonized centiloid estimates of beta-amyloid burden from PET imaging. WMH were measured using the TrUE-Net algorithm. Vascular risk factors were extracted from provided clinical data and used to calculate individual revised Framingham Stroke Risk Profile (FSRP) scores. Linear mixed effects modelling was used to determine the relationship between the growth rate of WMH and baseline beta-amyloid burden, controlling for age, sex, APOE4 status, and vascular risk factors. 1243 participants [49 % female, mean age 71.7 y (SD 7.6 y)] had at least 3 brain MRIs. Linear mixed models demonstrate robust independent cross-sectional relationships between WMH and baseline beta-amyloid burden (beta coefficient=0.27, p &lt; 0.001), age (beta coefficient=0.04, p &lt; 0.001) and vascular risk factors (beta coefficient=0.25, p &lt; 0.001). Growth rates of WMH increased with baseline beta-amyloid burden (slope=0.021, p &lt; 0.001) and decreased with anti-hypertensive medications (slope=-0.019, p = 0.002), above and beyond age, APOE4 status, and other vascular risk factors. The longitudinal association for beta-amyloid burden persisted in a similar analysis for parietal WM. Our study suggests that in Alzheimer disease research cohorts, WMH progression is associated with age and beta-amyloid burden, particularly in parietal white matter, and slowed by anti-hypertensive treatment.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"160 ","pages":"Pages 22-32"},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A timeline of structural and functional consequences to ipRGCs in a mouse model of Alzheimer’s disease","authors":"Brandy S. Recio ,&nbsp;William A. Pérez ,&nbsp;Ruth Tjondropurnomo ,&nbsp;Jenibelle Hsu ,&nbsp;Simrah Ahmed ,&nbsp;Sachin Parikh ,&nbsp;Jake Sun ,&nbsp;Sreya Mitra ,&nbsp;Rajesh Kumar Goit ,&nbsp;Nicholas C. Brecha ,&nbsp;Nimesh Patel ,&nbsp;Anna Matynia ,&nbsp;Luis Pérez de Sevilla Müller","doi":"10.1016/j.neurobiolaging.2025.12.007","DOIUrl":"10.1016/j.neurobiolaging.2025.12.007","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that affects cognitive, sensory and motor systems, including the visual system and has a significant impact on autonomy and quality of life. Emerging evidence suggests that visual system abnormalities may enable early detection and monitoring for AD, appearing before cognitive symptoms. Intrinsically photosensitive retinal ganglion cells (ipRGCs or mRGCs) are among the first neurons affected in AD. This study investigates the structural and functional changes in ipRGCs during aging. ipRGC and retinal ganglion cell (RGC) degeneration were assessed using immunohistological analyses of retinal wholemounts of the 3xTg-AD mouse model. Behavioral changes were analyzed using light aversion with and without pupil dilation, contrast sensitivity function across five spatial frequencies, and pupillary light reflex (PLR) at three light levels. Changes in ipRGC dendritic varicosities begin between 4–8 months followed by degeneration of other RGC types by 12–16 months of age. Alterations in light aversion were observed at both 6 and 12 months with no alterations in contrast sensitivity function or PLR. Sex-specific differences in disease progression were detected in RGC degeneration. Our findings support the hypothesis that ipRGC dysfunction occurs early in AD and precedes cognitive decline. These findings are similar to ipRGC degeneration previously observed in postmortem human AD retinas, and thus provides a valuable model for studying the mechanism of degeneration and identifying potential behavior changes that might serve as early biomarkers in AD.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"160 ","pages":"Pages 47-63"},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}