Neurobiology of Aging最新文献

{"title":"Editorial Advisory Board","authors":"","doi":"10.1016/S0197-4580(25)00158-7","DOIUrl":"10.1016/S0197-4580(25)00158-7","url":null,"abstract":"","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"155 ","pages":"Page IFC"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145003754","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":"Hypothalamic imaging in Alzheimer’s disease and Lewy body dementia: A systematic review and meta-analysis","authors":"Axel AS Laurell ,&nbsp;Sita N. Shah ,&nbsp;Masoud Rahmati ,&nbsp;John T. O’Brien ,&nbsp;Benjamin R. Underwood","doi":"10.1016/j.neurobiolaging.2025.07.011","DOIUrl":"10.1016/j.neurobiolaging.2025.07.011","url":null,"abstract":"<div><div>Symptoms related to sleep, weight, and endocrine dysfunction are common in Alzheimer’s disease (AD) and Lewy body dementia (LBD). The cause of these symptoms is not known, but they may be related to hypothalamic neurodegeneration. We performed a systematic search of MEDLINE and EMBASE for studies using MRI or PET imaging to examine the hypothalamus in AD or LBD. The Newcastle-Ottawa scale was used to assess the risk of bias. A random-effects meta-analysis was conducted using the standardised mean difference (SMD) in hypothalamic volume, and a narrative synthesis was used to examine associations between hypothalamic imaging and sleep, weight, and endocrine function. We screened 8891 articles which identified 22 studies for inclusion in the narrative synthesis of which 6 were suitable for meta-analysis. 86 % had a low to moderate risk of bias. People with mild-moderate AD had a smaller hypothalamus compared to controls (SMD=-0.49[-0.86,-0.13],p = 0.018;I²=67 %[21.5 %-86.1 %];n = 454(AD),715(controls)), and had differences in hypothalamic metabolism and connectivity. Two studies in LBD found lower grey matter and serotonin transporter binding in the hypothalamus compared to controls. Hypothalamic differences in AD were associated with male sex, worse sleep, lower bone mineral density and plasma levels of sex hormones. Body mass index was not associated with hypothalamic volume in AD, although further studies are needed. Lower hypothalamic volume is seen in AD and this may influence sleep and endocrine function. A better understanding of hypothalamic degeneration may help elucidate how pathology relates to symptoms in AD and LBD and reveal new targets for intervention.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"155 ","pages":"Pages 87-99"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724423","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 oxygenation level-dependent responses in neuromodulatory nuclei and their associations with attention and memory across age groups","authors":"Elizabeth Riley,&nbsp;Nicholas Cicero,&nbsp;Khena Swallow,&nbsp;Adam Anderson,&nbsp;Eve De Rosa","doi":"10.1016/j.neurobiolaging.2025.07.010","DOIUrl":"10.1016/j.neurobiolaging.2025.07.010","url":null,"abstract":"<div><div>Using multi-echo blood oxygenation level-dependent (BOLD) neuroimaging, we examined lifespan differences in three subcortical nuclei important to the neuromodulation of cognition and target sites for early Alzheimer’s pathogenesis in the isodendritic core: the locus coeruleus (LC) the major source of noradrenaline, the nucleus basalis of Meynert (NBM) the major source of acetylcholine, and the ventral tegmental area (VTA) the major source of dopamine. Seventy-one participants, from 19 to 86 years old (young n = 29, middle-aged, n = 18, and older n = 24), were tasked with memorizing visual images while monitoring auditory tones for a predefined target to assess attentional modulation of subsequent memory for the images. Young adults demonstrated a memory advantage for images paired with a target tone relative to no tone, which was diminished in middle age, and absent in older adults. Elevated NBM and VTA BOLD responses to subsequently remembered target-paired images were present in all groups but were selectively absent in the LC of older adults. Moreover, only LC activity explained individual variation in subsequent memory performance. Even though activity in multiple modulatory nuclei contributed, age-related change in the attentional boosting of memory was specifically tied to altered LC activity.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"155 ","pages":"Pages 24-34"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144632968","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":"Serum HDL-cholesterol is associated with the clinical-biological profile of early-stage Parkinson’s disease patients independently of APOE","authors":"Davide Mascioli ,&nbsp;Matteo Conti ,&nbsp;Jacopo Bissacco ,&nbsp;Roberta Bovenzi ,&nbsp;Clara Simonetta ,&nbsp;Veronica Buttarazzi ,&nbsp;Maria Mancini ,&nbsp;Silvio Bagetta ,&nbsp;Giulia Maria Sancesario ,&nbsp;Daniela Maftei ,&nbsp;Federica Veltri ,&nbsp;Enrica Marchionni ,&nbsp;Alessandro Stefani ,&nbsp;Nicola Biagio Mercuri ,&nbsp;Massimo Pieri ,&nbsp;Tommaso Schirinzi","doi":"10.1016/j.neurobiolaging.2025.07.004","DOIUrl":"10.1016/j.neurobiolaging.2025.07.004","url":null,"abstract":"<div><div>Emerging evidence highlights a possible interplay between serum lipid profiles and Parkinson’s disease (PD), but the biological underpinnings remain largely unexplored. In this cross-sectional study, we investigated whether serum lipid levels (total cholesterol, high-density lipoprotein cholesterol (HDL), non-high-density lipoprotein cholesterol, and triglycerides) were associated with clinical severity and cerebrospinal fluid (CSF) biomarkers in early-stage PD patients. A cohort of 90 PD patients and 74 matched controls underwent serum lipid and CSF biomarker assessment and <em>APOE</em> genotyping. While serum lipid levels did not differ significantly between groups, PD patients showed reduced CSF α-synuclein. Notably, higher HDL levels correlated with higher CSF α-synuclein and amyloid-β42 (Aβ42) concentrations and milder motor impairment, independent of <em>APOE</em> ε4 status. <em>APOE</em> ε4 carriers displayed increased CSF phosphorylated tau and reduced Aβ42/Aβ40 ratio, but <em>APOE</em> genotype did not modify the observed HDL associations. These findings suggest that higher circulating HDL levels are associated with a milder clinical phenotype and a more favorable CSF biomarker profile in early-stage PD, potentially reflecting a protective role independent of <em>APOE</em> genotype. Further studies are warranted to validate these observations and to assess their therapeutic implications.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"155 ","pages":"Pages 1-7"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144581375","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":"Comparison of CSF neurofilament light chain and total tau as neurodegeneration markers: Associations with synaptic markers and cognitive outcomes","authors":"Grit Richter ,&nbsp;Bjørn-Eivind Kirsebom ,&nbsp;Jonas Alexander Jarholm ,&nbsp;Lene Pålhaugen ,&nbsp;Berglind Gísladóttir ,&nbsp;Dag Aarsland ,&nbsp;Gøril Rolfseng Grøntvedt ,&nbsp;Ragnhild Eide Skogseth ,&nbsp;Knut Waterloo ,&nbsp;Tormod Fladby ,&nbsp;Kaja Nordengen","doi":"10.1016/j.neurobiolaging.2025.07.005","DOIUrl":"10.1016/j.neurobiolaging.2025.07.005","url":null,"abstract":"<div><div>Clinically, Alzheimer's disease (AD) is characterized by progressive cognitive decline due to neuronal and synaptic degeneration. Neurofilament light chain (NfL) and total tau (T-tau) reflect neurodegeneration, NfL putatively more related to white and T-tau to grey matter. This study examines how cerebrospinal fluid (CSF) neurodegeneration markers (T-tau, NfL or both) are correlated with synaptic markers and clinical progression. We included 331 individuals with (n = 212) and without (n = 119) pathological CSF Aβ42/40 ratios. Associations between CSF NfL, T-tau, and the synaptic biomarkers neurogranin and BACE1 were assessed using Pearson’s correlation. Group differences in synaptic marker levels were evaluated using linear regression comparing individuals with isolated pathological T-tau, NfL, or both, versus biomarker-negative individuals. Clinical progression to MCI or dementia was assessed using a Cox proportional hazards model (n = 257; mean follow-up = 3.75 years). Linear regression and Cox proportional hazards models included age, sex, and dichotomized <em>APOE</em>-ε4 carriership as covariates. T-tau had a stronger correlation with neurogranin(r = 0.84) and BACE1(r = 0.73) than NfL(r = 0.51 and 0.48; p &lt; 0.001). Group-wise comparisons confirmed this, showing that only individuals with pathological T-tau—alone or with NfL—had significantly higher synaptic marker levels (p &lt; 0.001). Only the combination of pathological T-tau and NfL was associated with a significantly increased risk of clinical progression(HR=6.79; <em>p</em> &lt; 0.001). These findings suggest that T-tau is more closely related to early synaptic dysfunction in AD than NfL. The combined elevation of both biomarkers, linked to greater clinical decline, supports a dual contribution of grey- and white matter degeneration to disease progression.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"155 ","pages":"Pages 13-23"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144632514","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":"Integrating plasma, MRI, and cognitive biomarkers for personalized prediction of decline across cognitive domains","authors":"Elaheh Moradi ,&nbsp;Robert Dahnke ,&nbsp;Vandad Imani ,&nbsp;Christian Gaser ,&nbsp;Alina Solomon ,&nbsp;Jussi Tohka ,&nbsp;Alzheimer’s Disease Neuroimaging Initiative","doi":"10.1016/j.neurobiolaging.2025.06.010","DOIUrl":"10.1016/j.neurobiolaging.2025.06.010","url":null,"abstract":"<div><div>Plasma biomarkers are associated with cognitive performance and decline in Alzheimer’s disease, making them promising for early detection. This study investigates their predictive value, combined with non-invasive measures, in forecasting cognitive decline in individuals without dementia. We developed a multimodal machine-learning approach incorporating plasma biomarkers (Amyloid<span><math><mi>β</mi></math></span>42/40 (A<span><math><mi>β</mi></math></span>42/40), p-tau181, NfL), MRI, demographics, APOE4, and cognitive assessments to predict the rate of cognitive decline. Various models were designed to predict decline rates across cognitive domains (memory, executive function, language, and visuospatial abilities) and assess their relevance in predicting dementia progression. Cross-validated correlations between predicted and actual cognitive decline rates were 0.50 for memory, 0.49 for language, 0.42 for executive function, and 0.44 for visuospatial ability. MRI showed greater predictive importance than plasma biomarkers. Among plasma biomarkers, NfL and p-tau181 outperformed A<span><math><mi>β</mi></math></span>42/40. Predicting cognitive decline and progression to MCI/dementia was most accurate in the memory domain, where plasma biomarkers (A<span><math><mi>β</mi></math></span>42/40, p-tau181, NfL) added significant value to predictive models, likely due to their AD-specific nature. Plasma biomarkers contributed less to predictions in other cognitive domains. The results indicate that plasma biomarkers, particularly when combined with MRI, demographics, APOE4, and cognitive measures, have significant potential for predicting memory decline and assessing the risk of dementia progression, even in cognitively unimpaired individuals.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"155 ","pages":"Pages 53-65"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695114","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":"2988Multi-omic derived cell-type specific Alzheimer disease polygenic risk scores","authors":"Nicholas O’Neill ,&nbsp;Nuzulul Kurniansyah ,&nbsp;Congcong Zhu ,&nbsp;Oluwatosin A. Olayinka ,&nbsp;Richard Mayeux ,&nbsp;Jonathan L. Haines ,&nbsp;Margaret A. Pericak-Vance ,&nbsp;Li-San Wang ,&nbsp;Gerard D. Schellenberg ,&nbsp;Lindsay A. Farrer ,&nbsp;Xiaoling Zhang","doi":"10.1016/j.neurobiolaging.2025.07.009","DOIUrl":"10.1016/j.neurobiolaging.2025.07.009","url":null,"abstract":"<div><div>Alzheimer disease (AD) polygenic risk scores (ADPRS) built from cell-type (ct) specific genetic variants can be used to infer cell-type contributions to AD. We derived two ct-ADPRSs using variants near single-nuclei RNA-seq (snRNA) derived cell-type specific genes or on single-nuclei ATAC-seq (snATAC) derived cell-type specific accessible chromatin regions. We generated a multi-omic ct-ADPRS for eight neuron subtypes using both single-nuclei datasets. SnATAC-derived ct-ADPRSs demonstrated considerably lower correlations among cell types (average r = 0.071) than snRNA-derived ct-ADPRSs (average r = 0.19), indicating their heightened cell-type specificity. The association of these ct-ADPRSs with AD endophenotypes was evaluated using logistic and linear regression models. Tau tangle burden was associated with astrocyte (AST) ct-ADPRS derived from snATAC (β=0.82, FDR=0.0013) and snRNA (β=0.60, FDR=0.045) as well as microglia (MIC) ct-ADPRS from both (snATAC: β=0.75, FDR=0.0047) (snRNA: β=0.63, FDR=0.028). AST ct-ADPRS was significantly associated with Mini-Mental State Examination score only when derived from snATAC data (β=-0.82, FDR=0.011). SST expressing GABAergic neuron ADPRS was strongly associated ct-ADPRS with neuritic plaque burden (β=0.087, FDR=0.0014) and the only neuron subtype ct-ADPRS significantly associated with AD endophenotypes. We investigated 1954 SNPs contributing to this ct-ADPRS and found the strongest association with variants upstream of the neuropeptide Y gene, <em>NPY</em>, particularly rs3940268 (β=-0.13, P = 8.2x10⁻⁵). This association is significant even after adjusting for diffuse plaque (β=-0.12, P = 1.5x10⁻⁴) or neurofibrillary tangle burden (β=-0.08, P = 3.9x10⁻³). <em>NPY</em> was expressed in a small subset of neurons, and these findings suggest its strong impact on the association of SST+ GABAergic neurons with early AD pathology.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"155 ","pages":"Pages 44-52"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695113","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":"Epigenetic age is associated with regional brain aging along the sensorimotor-to-association axis of cortical organization","authors":"Nicholas Riccardi ,&nbsp;Carolyn Banister ,&nbsp;Natalie Busby ,&nbsp;Sarah Newman-Norlund ,&nbsp;Roger Newman-Norlund ,&nbsp;Ida Rangus ,&nbsp;Alex Teghipco ,&nbsp;Chris Roden ,&nbsp;Julius Fridriksson ,&nbsp;Leonardo Bonilha","doi":"10.1016/j.neurobiolaging.2025.07.006","DOIUrl":"10.1016/j.neurobiolaging.2025.07.006","url":null,"abstract":"<div><div>Brain age and epigenetic age (DNAmAge) are ‘biological clocks’ independently linked to health outcomes. However, the relationship between brain and epigenetic age remains unclear. We used path analysis to investigate relationships between chronological age, DNAmAge, and brain age and explored whether advanced aging in specific brain regions relates to DNAmAge. BrainAge (global and regional) was estimated from brain MRI in 149 participants (ages 20–80). From whole blood, four DNAmAges were calculated: Pheno, Hannum, Horvath, and SkinBlood. Mediation was used to test the indirect effect of DNAmAge on global BrainAge, as well as the reverse, with chronological age as the independent variable. Correlations between accelerated region-specific BrainAge and DNAmAge were also examined. DNAmPhenoAge mediated the relationship between chronological age and global BrainAge. DNAmPhenoAge was related to advanced BrainAge of regions higher on the sensorimotor-to-association axis of cortical organization (F(1104) = 17.5, R² = .15, p &lt; .001). DNAmPhenoAge age may uniquely capture cellular aging processes that are related to brain health across the adult lifespan. Region-based results suggest that biological aging in higher-order association cortices is related to epigenetic aging.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"155 ","pages":"Pages 8-12"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144588310","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":"White matter hyperintensities contribute to early cortical thinning in addition to tau in aging","authors":"Riccardo Leone ,&nbsp;Xenia Kobeleva ,&nbsp;for the Alzheimer's Disease Neuroimaging Initiative","doi":"10.1016/j.neurobiolaging.2025.07.007","DOIUrl":"10.1016/j.neurobiolaging.2025.07.007","url":null,"abstract":"<div><div>White matter hyperintensities (WMH) are associated with cortical thinning in distant brain regions. However, it is currently unclear how WMH affect neurodegeneration in early Alzheimer’s disease (AD). Here, we investigated associations between WMH and cortical thickness in temporal regions involved in early AD (AD cortical signature), while correcting for regional amyloid and tau accumulation assessed by PET. We performed cross-sectional (n = 551), and longitudinal (n = 125) analyses in older adults without dementia, also stratified by amyloid positivity. We evaluated WMH volume - as a measure of the global burden of WMH-related cerebrovascular pathology (GB-WMH) - and investigated the role of deep versus periventricular WMH. We also tested whether a higher focal burden of WMH in specific tracts connected to AD signature regions (FB-WMH) would lead to greater cortical thinning than expected solely from GB-WMH. We performed exploratory analyses in other brain regions to check the specificity of our findings to the temporal AD signature. GB-WMH damage, especially involving periventricular WMH, was cross-sectionally (not longitudinally) associated with cortical thinning in the fusiform, inferior and middle temporal gyri. Stronger associations were found in amyloid-positive individuals, including for the entorhinal cortex. Effects were mostly confined to regions of the temporal AD signature. FB-WMH did not yield higher cortical thinning than expected solely by GB-WMH. Cerebrovascular disease is associated with cortical thinning of temporal regions involved in early AD. Interventions aimed at improving cerebrovascular health might help to mitigate neurodegeneration in these regions.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"155 ","pages":"Pages 66-77"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703718","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":"Neural network mechanisms of emotional dysregulation in cerebral small vessel disease","authors":"Olga R. Dobrushina ,&nbsp;Larisa A. Dobrynina ,&nbsp;Galina A. Arina ,&nbsp;Evgenia S. Novikova ,&nbsp;Mariia M. Tsypushtanova ,&nbsp;Angelina G. Makarova ,&nbsp;Mariia V. Gubanova ,&nbsp;Viktoriya V. Trubitsyna ,&nbsp;Vlada V. Kolomoitseva ,&nbsp;Daria A. Kazantseva ,&nbsp;Elena I. Kremneva ,&nbsp;Marina V. Krotenkova","doi":"10.1016/j.neurobiolaging.2025.07.013","DOIUrl":"10.1016/j.neurobiolaging.2025.07.013","url":null,"abstract":"<div><div>Cerebral small vessel disease (CSVD) is a prevalent age-related disorder that leads to progressive white matter damage, resulting in cognitive decline and depression. This study explored the neural network mechanisms of emotional dysregulation in CSVD, focusing on both depression and alexithymia and considering the broader context of studies on emotional cardiovascular risk factors. Study participants (n = 196, age 37–75) were assessed for CSVD, arterial hypertension, depressive symptoms, and alexithymia. Emotional dysregulation, defined by depression and alexithymia, was estimated using a structural equation model accounting for the potential of bidirectional links with CSVD. To investigate the connectivity of networks involved in emotional processing, 167 participants underwent resting-state functional MRI. The study showed that emotional dysregulation was associated with reduced functional connectivity between the salience and language networks and within the language network. Age was associated with reduced functional connectivity within the salience and language networks, suggesting a possibility of synergistic deleterious effects. The revealed alterations in brain connectivity might reflect the dysfunction of the system of allostasis, explaining the observed symptoms of depression and alexithymia, as well as the previous findings on emotional cardiovascular risk factors.</div></div>","PeriodicalId":19110,"journal":{"name":"Neurobiology of Aging","volume":"155 ","pages":"Pages 78-86"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703719","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}