Journal of Alzheimer's Disease最新文献

{"title":"Education as a domain-specific moderator: Shaping the impact of cerebral structural changes on clinical manifestations in Alzheimer's disease.","authors":"Tianqing Deng, Jingxi Duan, Wuhan Yu, Zhangjing Deng, Qi Tian, Xintong Liu, Jianwei Shou, Ting Tang, Weihua Yu, Yang Lü","doi":"10.1177/13872877251379078","DOIUrl":"https://doi.org/10.1177/13872877251379078","url":null,"abstract":"<p><p>BackgroundGlobal cognitive performance is influenced by change in cerebral structure and educational background. However, little is known about how education moderates the impact of cerebral structural changes on different cognitive domains and other non-cognitive dysfunction across the clinical stages of Alzheimer's disease (AD).ObjectiveTo explore the moderating effect of education on relationship between cerebral structure and various clinical manifestations across the AD continuum, ranging from mild cognitive impairment (MCI) to AD.MethodsThis cross-sectional study included data of 570 patients diagnosed with MCI or AD. The total years of education were used as a moderating variable, and AD-related cerebral structure changes were assessed through visual ratings on magnetic resonance imaging (MRI). Multiple linear regressions were performed to examine whether education moderated the association between cerebral structure and clinical characteristics at different diagnostic stages of AD.ResultsPatients with higher levels of education demonstrated better cognitive ability, enhanced activities of daily living, and milder neuropsychiatric symptoms. The moderating effect of education was most prominent during the MCI or early AD stages, showing cognitive domain-specific effects. In these stage, education alleviated the negative impacts of neurostructural changes on immediate learning but exacerbated the detrimental effects of cerebral structural changes on speed/executive function, language, and episodic memory.ConclusionsEducation serve as a moderator in relationship between cerebral structure and various clinical characteristics. The moderating effect of education is domain-specific and most noticeable in the early stage of AD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251379078"},"PeriodicalIF":3.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080765","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":"Identifying differential brain structures and genetic mechanisms between Alzheimer's disease and idiopathic normal pressure hydrocephalus.","authors":"Wencai Wang, Hui Liu, Yinuo Chen, Zijie Xiong, Menghao Liu, Zun Wang, Wei Ye, Xianfeng Li","doi":"10.1177/13872877251379046","DOIUrl":"https://doi.org/10.1177/13872877251379046","url":null,"abstract":"<p><p>BackgroundIdiopathic normal pressure hydrocephalus (INPH) is a reversible neurological disorder presenting with cognitive decline, urinary incontinence, and gait disturbance, yet it is often misdiagnosed as Alzheimer's disease (AD) due to overlapping features. Magnetic resonance imaging (MRI) highlights structural differences, but their causal links to disease manifestations remain unclear.ObjectiveTo investigate the causal relationships between brain structures and INPH/AD through Mendelian randomization (MR) and to explore genetic mechanisms underlying structural variations.MethodsWe analyzed 83 brain phenotypes from the UK Biobank and INPH/AD data from the FinnGen cohort using bidirectional MR. Differentially expressed genes (DEGs) in MR-identified brain regions were obtained from the Allen Human Brain Atlas and examined via bioinformatics analyses.ResultsMR revealed 12 brain structures associated with INPH and 5 with AD, identifying 13 distinct regions differentiating the two disorders across temporal, frontal, occipital, and parietal lobes, as well as the basal ganglia and limbic system. Genetic analyses identified 205 DEGs linked to these regions, enriched in pathways regulating neurodevelopment, neuronal differentiation, and synaptic plasticity. Notably, the neuroactive ligand-receptor interaction pathway was significantly implicated, suggesting a mechanism contributing to cerebrospinal fluid circulation abnormalities in INPH.ConclusionsThis study integrates MR and bioinformatics to reveal structural and genetic factors distinguishing INPH from AD. These findings provide new insights into the pathogenesis of INPH, improve diagnostic precision, and may inform targeted therapeutic strategies.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251379046"},"PeriodicalIF":3.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080322","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":"Sex-specific brain atrophy patterns associated with the motoric cognitive risk syndrome.","authors":"Helena M Blumen, Natalie Delpratt, Olivier Beauchet, Michele L Callisaya, Takehiko Doi, Vg Pradeep Kumar, Richard B Lipton, Sofiya Milman, Hiroyuki Shimada, Velandai Srikanth, Joe Verghese","doi":"10.1177/13872877251378656","DOIUrl":"https://doi.org/10.1177/13872877251378656","url":null,"abstract":"<p><p>BackgroundFemales are twice as likely to be diagnosed with Alzheimer's disease (AD) as males, but the underlying mechanisms of this sex difference are not well-understood. The motoric cognitive risk (MCR) syndrome is characterized by slow gait and subjective cognitive concerns and predicts both AD and vascular dementia (VaD). The prevalence of MCR is typically similar in females and males. We have previously shown that MCR is associated with cortical atrophy in frontal, parietal, and temporal regions.ObjectiveThe current study examined sex-specific, cortical (frontal), and subcortical (hippocampal) atrophy patterns associated with MCR.MethodsFrontal cortical thicknesses (in 11 frontal regions) and hippocampal volumes (in 12 hippocampal subfields) were quantified in 940 females (<i>M</i> Age = 71.03 years) and 1108 males (<i>M</i> Age = 71.07 years). Sex-stratified linear models were used to examine frontal cortical thicknesses and hippocampal volumes as a function of MCR-after adjusting for age, education, total intracranial volume, study site, vascular comorbidities, white matter lesion burden, and multiple comparisons (with the false discovery rate).ResultsMCR-related frontal atrophy was observed (in pars orbitalis and caudal middle frontal) in males but not in females. MCR-related hippocampal atrophy (in CA1, molecular layer, GCMLDG, and Fimbria) was observed in females but not in males.ConclusionsThere are sex-specific patterns of atrophy associated with MCR. Females with MCR display brain atrophy patterns more consistent with early AD, while males with MCR display atrophy patterns more consistent with VaD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251378656"},"PeriodicalIF":3.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080485","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":"Impact of socio-economic and patient-centered characteristics on access to Alzheimer's disease medication in primary care: A population-based study in the Stockholm county, Sweden.","authors":"Ayda Shaker, Gunnar Ljunggren, Laura E Vossen, Dorota Religa, Pauline Raaschou","doi":"10.1177/13872877251375900","DOIUrl":"https://doi.org/10.1177/13872877251375900","url":null,"abstract":"<p><p>BackgroundDespite treatment guidelines for Alzheimer's disease (AD), access to AD medications varies significantly within the same health care setting.ObjectivePredictors influencing access to AD medication were assessed in a retrospective cohort study comprising most individuals diagnosed with AD in Stockholm 2013-2021.Methods14,884 individuals were included, with an incident AD diagnosis between 2013-2021 in Stockholm, Sweden. The primary outcome was the dispensation of AD-specific drugs (cholinesterase inhibitors or memantine) within 90 days before to 180 days after AD diagnosis. We used a generalized linear mixed-effects model (GLMM). Variables included patient-centered characteristics such as age and comorbidities, and characteristics of the primary care centers (PCC) where the individuals were listed, including Care Need Index (CNI).ResultsOverall, 77% of diagnosed patients were dispensed AD medications. Individuals listed at PCCs with high CNI score, indicative of lower socio-economic resources of the area, were less likely to receive a dispensation of any AD medication compared with low CNI score (76.2% versus 84.8%; OR 0.65, 95% CI 0.50-0.86). The association between CNI score and likelihood of receiving AD medication was attenuated in subgroup analysis of individuals living in nursing homes. Also associated with lower likelihood of receiving AD medications were age ≥85 years (OR 0.25, 95% CI 0.21-0.28), nursing home residency (OR 0.37, 95% CI 0.34-0.41), and comorbidity (OR 0.63, 95% CI 0.57-0.70).ConclusionsSocio-economic factors strongly influenced the likelihood of receiving AD medication, in addition to more established factors such as age and comorbidities. Interventions are needed to eliminate barriers to equal drug treatment in AD, particularly those related to socio-economic disadvantages.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251375900"},"PeriodicalIF":3.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075345","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":"Environmental noise exposure and a new biomarker of Alzheimer's disease: A pilot study.","authors":"Jonghun Lee, Cheol-Woon Kim, Youjin Kim, Seunghyun Lee, Joon Yul Choi, Wanhyung Lee","doi":"10.1177/13872877251376920","DOIUrl":"https://doi.org/10.1177/13872877251376920","url":null,"abstract":"<p><p>BackgroundEnvironmental noise pollution is increasingly recognized as a contributor to neurodegenerative processes, yet its relationship with early Alzheimer's disease biomarkers remains unclear.ObjectiveThis pilot study aimed to assess the feasibility of using gray-to-white matter signal intensity contrast (GWC) as a potential biomarker to explore associations between environmental noise exposure and early neurodegenerative changes.MethodsA total of 106 participants (mean age 35.97 ± 9.21 years, range 20-55), without cognitive impairment or neurological disorders, were included. Environmental noise levels were estimated using spatial interpolation from the National Noise Information System. Based on WHO guidelines (>60 dB daytime or >55 dB nighttime), participants were categorized into high- and low-noise groups. Whole-brain and regional GWC values were derived from 3D T1-weighted MRI using FreeSurfer. Correlations between noise exposure and GWC were analyzed with Pearson's correlation.ResultsThe high-noise group exhibited elevated whole-brain GWC values (20.11 ± 0.93) compared with the low-noise group (19.68 ± 0.96; p = 0.036). Regional analyses revealed higher GWC in the superior frontal gyrus, precentral gyrus, and paracentral lobules (all p < 0.05, FDR corrected). Nighttime noise exposure correlated more strongly with increased GWC (r = 0.203, p = 0.037) than daytime exposure.ConclusionsThis pilot study provides preliminary evidence of an association between environmental noise-particularly nighttime exposure-and subtle structural brain changes, as indicated by elevated GWC values. These findings suggest a potential neurobiological pathway linking noise exposure to early markers of neurodegeneration, warranting validation in larger, longitudinal studies.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251376920"},"PeriodicalIF":3.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075324","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":"Efficacy of AD04, an aluminum-based vaccine adjuvant, in patients with early Alzheimer's disease: Post hoc analysis of AFF006 (NCT01117818), a proof-of-concept, phase 2 randomized controlled trial.","authors":"Benjamin Haaland, Samuel P Dickson, Agustin Fernández Santana, Rudolph E Tanzi, Bruno Dubois, Oliver Peters, Timo Grimmer, Joshua Christensen, Craig Mallinckrodt, Achim Schneeberger, Suzanne B Hendrix","doi":"10.1177/13872877251375985","DOIUrl":"https://doi.org/10.1177/13872877251375985","url":null,"abstract":"<p><p>BackgroundThe AFF006 trial (NCT01117818) provided unexpected evidence of benefits of the vaccine adjuvant AD04 (aluminum oxyhydroxide) in patients with early Alzheimer's disease (AD), compared with AD02, a vaccine consisting of a peptide that mimics the N-terminal region of human amyloid-β (Aβ) conjugated with keyhole limpet hemocyanin.ObjectiveThe objective of this post hoc analysis was to assess whether this unexpected benefit of AD04 was an artifact of multiple testing (i.e., type I error inflation) or a robust result.MethodsIn this post hoc assessment, we used permutation testing to estimate type I error inflation due to the evaluation of multiple outcomes in AFF006. Efficacy was assessed using a patient-level global statistical test combining composite endpoints of cognition, function, and global AD. In addition, we examined the observed treatment benefits of AD04 in the context of effects observed in trials of aducanumab, donanemab, and lecanemab, monoclonal anti-Aβ antibodies that received regulatory approval for AD.ResultsThe global statistical test suggested a treatment benefit of AD04 versus ineffective AD02 arms, even after accounting for multiplicity (primary methodology p-value, 0.03; permutation test p-value, 0.02). The observed effect estimates for AD04 compared favorably with approved monoclonal antibodies.ConclusionsPost-hoc analyses are hypothesis generating rather than confirmatory. Adjusting for multiplicity using permutation testing can determine whether post-hoc effects are worth pursuing, or unlikely to be confirmed. These analyses have motivated a follow-up prospective randomized controlled trial, ADVANCE (EudraCT 2022-003532-73), in which optimized AD04 dosing will be compared to placebo in early AD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251375985"},"PeriodicalIF":3.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069573","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":"Development of a risk prediction model for Alzheimer's disease based on the UK Biobank prospective study.","authors":"Huilin Li, Yiwen Wu, Ting Huang, Yue Sun, Zixuan Lu, Musu Li, Hongmei Wo, Fang Shao, Shaowen Tang, Yang Zhao, Juncheng Dai, Honggang Yi","doi":"10.1177/13872877251375473","DOIUrl":"https://doi.org/10.1177/13872877251375473","url":null,"abstract":"<p><p>BackgroundEarly prevention and intervention for Alzheimer's disease (AD) are critical due to the absence of effective therapeutic treatment. However, a widely accepted risk prediction model for AD has yet to be established.ObjectiveTo develop a novel risk prediction model for AD by leveraging recent advances in identifying risk factors, focusing on multi-omics data.MethodsGenetic data from the UK Biobank were employed to calculate the polygenic risk score (PRS) using the clumping and thresholding (C + T) method. Univariate Cox regression and Elastic Net Cox models were utilized to identify significant predictors in the training cohort. Subsequently, a multivariate Cox regression model was developed to construct the prediction model, which was visualized using a nomogram. The performance of the model was evaluated through calibration curves, receiver operating characteristic (ROC) curves, and the Hosmer-Lemeshow test.ResultsTen risk factors, including age, education, family history of dementia, diabetes, depression, hypertension, anemia, coronary heart disease (CAD), falls and PRS, were identified as significant predictors through Cox regression and Elastic Net Cox model. The model demonstrated strong predictive performance, with area under the curves (AUCs) of 0.864 [95% CI: (0.814, 0.911)], 0.860 [95% CI: (0.842, 0.876)], and 0.842 [95% CI: (0.819, 0.863)] at 5, 10, and 14 years, respectively, in the validation cohort.ConclusionsIncorporating colocalized single nucleotide polymorphisms (SNPs) into the PRS derived using the C + T method significantly enhances predictive accuracy. This study highlights the importance of integrating multimodal patient data, including colocalized genetic information, to refine AD risk prediction.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251375473"},"PeriodicalIF":3.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069505","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":"Melatonin alleviates cognitive impairment via modulating NLRP3/Caspase 1 pathway in db/db mice.","authors":"Ming Gao, Jinting Chen, Beiyao Zhang, Jie Li, Jiadong Lang, Xin Zhao, Qiangqiang Zhang","doi":"10.1177/13872877251375479","DOIUrl":"https://doi.org/10.1177/13872877251375479","url":null,"abstract":"<p><p>BackgroundActivation of NLRP3 inflammasome has been implicated in cognitive impairment. Melatonin, known for its anti-inflammatory properties and traditional use in regulating circadian rhythms, is the focus of this study. This study intended to investigate the role of melatonin in diabetic cognitive impairment model.ObjectiveThe present study aimed to investigate the underlying mechanism of melatonin in alleviating diabetic cognitive impairment by suppressing NLRP3/Caspase 1 signaling pathway.MethodsCognitive function was assessed using Morris water maze test and Novel Object Recognition test. Apoptosis rate of hippocampal neurons was evaluated by TUNEL staining. Western blot was used to evaluate NLRP3/Caspase 1 pathway expression. Double immunofluorescence labelling of GFAP, Iba-1 or NeuN with NLRP3 respectively showed the localization of NLRP3 in hippocampus of db/db mice. In vitro, HT-22 cells treated with high glucose as cellular model were transfected with pc-DNA3.1-mNLRP3 or co-cultured with NLRP3 inhibitor MCC950 to elucidate NLRP3/Caspase 1 pathway in neuronal apoptosis regulation.ResultsMelatonin treatment improved cognitive function and morphologic abnormalities of hippocampal neurons. The double immunofluorescence labelling revealed melatonin inhibited NLRP3 inflammasome activation in hippocampal neurons rather than microglia or astrocytes. TUNEL staining and western blot showed melatonin markedly reversed the upregulation of NLRP3/Caspase 1 signaling pathway against neuronal apoptosis.ConclusionsMelatonin attenuates diabetic cognitive impairment in db/db mice with down-regulation of NLRP3/Caspase 1 signaling pathway. In vivo and vitro studies supported that NLRP3 activation in hippocampal neurons was associated with diabetic cognitive impairment progression.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251375479"},"PeriodicalIF":3.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069542","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":"Long-term predictive accuracy of the 'mild cognitive impairment due to Alzheimer's disease' criteria.","authors":"Sandra Cardoso, Alexandre Montalvo, João Maroco, Dina Silva, Luísa Alves, Manuela Guerreiro, Alexandre de Mendonça","doi":"10.1177/13872877251375927","DOIUrl":"https://doi.org/10.1177/13872877251375927","url":null,"abstract":"<p><p>BackgroundThe development and clinical use of biomarkers has dramatically changed the framework of Alzheimer's disease (AD) management, allowing the diagnosis at the mild cognitive impairment (MCI) stage. In 2015 we compared the prevalence and prognosis of AD at the MCI stage according to different criteria available at that time, and we found that the National Institute of Aging-Alzheimer Association (NIA-AA) criteria provided higher predictive accuracy for AD dementia after 3 years. Since then, we adopted these criteria in clinical practice.ObjectiveTo evaluate the long-term predictive accuracy of the 'MCI due to AD - high likelihood' criteria by taking advantage from an extended follow-up in a memory clinic setting.MethodsPatients were diagnosed according to the 'MCI due to AD - high likelihood' criteria and followed up until conversion to dementia.ResultsOne hundred and fourteen patients with 'MCI due to AD - high likelihood' were enrolled in the study and followed-up for 3.0 ± 1.8 [0.4-8.3] years. During the follow-up 106 (93.0%) patients progressed to dementia, 2 (1.8%) had stroke, 6 (5.3%) died, and none remained in MCI or reverted to normal cognitive status. The average survival time remaining in MCI, analyzed with Kaplan-Meier curve, was 3.2 (95% CI 2.9-3.6) years. Using a multivariate Cox proportional hazards regression model, patients with higher Mini-Mental State Examination kept the MCI status longer.ConclusionsThe diagnostic criteria of NIA-AA 'MCI due to AD - high likelihood' have an excellent long-term predictive accuracy in a memory clinic setting.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251375927"},"PeriodicalIF":3.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069518","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":"Impaired parasympathetic network function confers susceptibility to neurodegeneration and memory impairment in older adults with elevated beat-to-beat blood pressure variability.","authors":"Trevor Lohman, Isabel Sible, Arunima Kapoor, Allison C Engstrom, Fatemah Shenasa, John Paul M Alitin, Aimee Gaubert, Kathleen E Rodgers, David Bradford, Mara Mather, S Duke Han, Elizabeth Head, Lorena Sordo, Julian F Thayer, Daniel A Nation","doi":"10.1177/13872877251376715","DOIUrl":"https://doi.org/10.1177/13872877251376715","url":null,"abstract":"<p><p>BackgroundBlood pressure variability (BPV) is associated with neurodegeneration and cognitive decline independent of average pressure. The effect of parasympathetic central autonomic network (CAN) impairment on this relationship has not been assessed.ObjectiveDetermine whether parasympathetic CAN network function affects the relationship between BPV and neurodegenerative markers.Methods100 independently living older adults (55-89 years) underwent continuous blood pressure monitoring, neuropsychological testing, venipuncture, and brain MRI. Hippocampal volumes and entorhinal cortex thicknesses were assessed. Functional connectivity within a parasympathetic cardiovascular control network was used as a measure of parasympathetic CAN function. Plasma glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) were used as measures of glial and neuronal injury, respectively.ResultsElevated BPV was associated with left hippocampal atrophy (p <i>=</i> 0.03) and elevated plasma GFAP (p <i>=</i> 0.005) independent of age, sex, vascular risk factor burden, total intracranial volume (when applicable) and average blood pressure. These relationships were not mediated by parasympathetic central autonomic network impairment. Instead, parasympathetic CAN impairment conferred a vulnerability to elevated BPV. In participants with decreased parasympathetic CAN connectivity elevated BPV was associated with left entorhinal cortex atrophy (p <i>=</i> 0.0001), elevated plasma GFAP (p <i>=</i> 0.0001), elevated plasma NfL (p <i>=</i> 0.001), and memory impairment (p <i>=</i> 0.007).ConclusionsFindings suggest elevated beat-to-beat BPV is directly related to brain injury, and this effect is not mediated by CAN dysfunction. Instead, CAN impairment may confer a susceptibility to glial and neuronal injury in older adults with elevated beat-to-beat blood pressure variability. Mechanisms underlying increased susceptibility to BPV elevation in those with CAN dysfunction warrants further study.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251376715"},"PeriodicalIF":3.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069570","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}