Journal of Alzheimer's Disease最新文献

{"title":"Role of subcortical iron in Parkinson's disease, prodromal-depression, and dementia: Comparative links to anemias and osteoporosis.","authors":"Jack T Rogers, Asif Mirza Maroof, Sanjan S Sarang, Gen Hamanaka, Changning Wang, Hyundae Cho, Tapan Parikh, Catherine M Cahill","doi":"10.1177/13872877261489296","DOIUrl":"https://doi.org/10.1177/13872877261489296","url":null,"abstract":"<p><p>Three reports employing Mendelian randomization and quantitative susceptibility mapping from 41,581-patients in the UK biobank provide evidence to support that excess subcortical iron accumulation causally accelerates Parkinson's disease (PD). While subcortical iron was not a significant driver of Alzheimer's disease (AD), neural shrinkage and ferroptosis in grey matter featured in vascular dementia. Subcortical iron was changed in depression, anemia and osteoporosis patients. Since iron chelators were not beneficial to either AD or PD patients in clinical trials, we propose that translational control of the iron-homeostatic protein α-synuclein (iron importer) could therapeutically normalize subcortical iron during PD progression.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261489296"},"PeriodicalIF":3.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136779","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":"Association between urinary metabolomics and cognitive performance in Asians with type 2 diabetes.","authors":"Serena Low, Huili Zheng, Angela Moh, Jian-Jun Liu, Sylvia Liu, Keven Ang, Ziliang Lim, Wern Ee Tang, Chee Fang Sum, Tavintharan Subramaniam, Su Chi Lim","doi":"10.1177/13872877261493174","DOIUrl":"https://doi.org/10.1177/13872877261493174","url":null,"abstract":"<p><p>BackgroundThere is an ongoing quest for novel biomarkers which may serve as therapeutic targets in cognitive impairment, alongside a growing appreciation of urinary metabolomics as a promising non-invasive approach to identify metabolic signature of Alzheimer's disease and other causes of dementia.ObjectiveWe studied whether urine metabolomics were associated with mild cognitive impairment (MCI) and cognitive performance in a diabetic milieu.MethodsWe implemented a cross-sectional study on 1053 patients who had Type 2 diabetes (T2D). Urinary metabolites were quantitated by nuclear magnetic resonance (NMR). We evaluated cognitive performance by administering Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Criteria for mild cognitive impairment (MCI) were met if patients scored > 1.5 standard deviations (SDs) less than the mean RBANS score for total index or any of the cognitive domains.ResultsThe average age was 65.1 ± 7.9. Four metabolites were associated with RBANS total score after multiple testing correction by Benjamini-Hochberg (BH) procedure in the adjusted analyses: sucrose (β = -1.17 (95%CI -1.71, -0.62)), 4-hydroxyhippurate (β = -0.92 (-1.42, -0.42)), trans-aconitate (β = -0.93 (-1.46, -0.40)), and tryptophan (β = -0.82 (-1.33, -0.32)). Sucrose was associated with MCI (OR = 2.19 (1.44, 3.32). Sucrose, trans-aconitate, 4-hydroxyhippurate, and 4-deoxythreonate were associated with delayed memory. Hypoxanthine, sucrose and tryptophan were related to visuo-spatial/constructional function.ConclusionsOur study identified several urinary metabolites which were differentially linked to cognitive performance in T2D. Future investigations are warranted to confirm the findings.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261493174"},"PeriodicalIF":3.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136711","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":"The impact of the COVID-19 pandemic on institutionalization and healthcare costs in memory clinic patients.","authors":"Els D Bakker, Pieter J van der Veere, Martijn W Heymans, Argonde C van Harten, Wiesje M van der Flier, Ingrid S van Maurik","doi":"10.1177/13872877261486732","DOIUrl":"https://doi.org/10.1177/13872877261486732","url":null,"abstract":"<p><p>BackgroundThe COVID-19 pandemic disrupted healthcare services and daily routines, which may have particularly affected individuals with cognitive impairment or dementia who rely on continuity of care. However, the impact of these disruptions on institutionalization and healthcare costs remains largely unknown.ObjectiveWe investigated the impact of COVID-19-pandemic on institutionalization and healthcare costs in a mixed memory clinic population, compared to a well-balanced historical control group.MethodsWe included memory clinic patients from the Amsterdam Dementia Cohort: 1) n = 911 pandemic-patients (baseline: 2017-2018, follow-up: until 2021), and 2) n = 821 well-balanced historical controls (baseline: 2015-2016, follow-up: until 2019). Time to institutionalization was analyzed using restricted mean survival time (RMST), and healthcare costs using linear regression with spline knot at 2 years.ResultsWe found no difference for time until institutionalization between groups for all diagnoses together. Stratified for syndrome diagnosis, we found that pandemic-patients with dementia (RMST between group contrast (BGC)[95%-CI] = -0.241 year[-0.456 - -0.026], i.e., -2.9 months) and another diagnosis (RMST BGC[95%-CI] = -0.214 year[-0.407 - -0.021], i.e., -2.6 months) had shorter time to institutionalization. Total healthcare costs did not differ between groups (<i>B</i> [95%-CI] = 302.12 [-1229.17-1833.40], <i>p</i> = 0.699).ConclusionsIn conclusion, we found no indications of a significantly decreased or increased healthcare consumption as a result of COVID-19 pandemic.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261486732"},"PeriodicalIF":3.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136877","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 randomized pilot trial of non-flickering 40 Hz light stimulation: EEG activity and cognitive outcomes in cognitively normal older adults.","authors":"Chia-Hsiung Cheng, Hsinjie Lu","doi":"10.1177/13872877261494219","DOIUrl":"https://doi.org/10.1177/13872877261494219","url":null,"abstract":"<p><p>BackgroundGamma-frequency (40 Hz) sensory stimulation is a promising non-pharmacological approach for modulating neural activity and cognitive function in aging and Alzheimer's disease. However, conventional flickering stimulation is often poorly tolerated, and evidence for non-flickering approaches remains limited.ObjectiveTo evaluate the neurophysiological and cognitive effects of 4-week (28-session) non-flickering 40 Hz light stimulation in cognitively normal older adults.MethodsIn this randomized, double-blind, active-controlled pilot trial, 33 cognitively normal older adults were assigned to receive either non-flickering 40 Hz light stimulation (n = 17) or a 70 Hz active-controlled condition (n = 16) over four weeks. Per-protocol analyses were conducted in 29 participants who completed the intervention. Resting-state electroencephalography (EEG) was acquired at baseline, immediately after the first intervention session, and after completion of the 4-week intervention. Neuropsychological assessments were performed at baseline and after the intervention. Prespecified primary outcomes were resting-state gamma-band power spectral density (PSD) and functional connectivity (FC).ResultsNo significant between-group differences were observed in resting-state gamma-band PSD or FC following either one-session or 28-session intervention. Unadjusted secondary analyses suggested potential improvements in selected episodic memory measures in the 40 Hz group. Exploratory analyses further identified a positive association between improvements in visuospatial memory and increases in occipital-temporal FC. Both interventions were well tolerated.ConclusionsA 28-session non-flickering 40 Hz light stimulation was well tolerated and may improve selected episodic memory measures in cognitively normal older adults. Although no measurable group-level EEG effects were observed, the exploratory cognitive findings warrant further investigation in larger randomized trials.ClinicalTrial.gov (ID: NCT06715995) https://clinicaltrials.gov/expert-search?term=NCT06715995.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261494219"},"PeriodicalIF":3.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136642","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":"Study on the global and national burden of Alzheimer's disease attributable to dietary fatty acids from 1990 to 2018: A combined analysis based on the global burden of disease and global dietary database.","authors":"Liuhui Zhu, Jie Liu, Jianzhun Chen, Longfeng Yang, Shimei Li, Xinglong Yang","doi":"10.1177/13872877261492342","DOIUrl":"https://doi.org/10.1177/13872877261492342","url":null,"abstract":"<p><p>BackgroundDespite the importance of fatty acids (FAs) for brain function, their association with the global burden of Alzheimer's disease (AD) remains unclear.ObjectiveUsing the Global Dietary Database and the Global Burden of Disease study (1990-2018), we examined global trends and projections of AD burden attributable to dietary saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs).MethodsWe analyzed global SFA/MUFA intake and age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and age-standardized disability-adjusted life year rate (ASDR) of FA-attributable AD. Spearman correlation analysis assessed associations with the Socio-demographic Index (SDI). Projections were extended to 2040.ResultsIn 2018, SFA intake was highest in Australia and France, while MUFA intake was highest in Russia and Sweden. For attributable burden, from 1990 to 2018, SFA-attributable ASDR ranked highest annually, peaking in 2010 then declining; MUFA-attributable burden showed no significant variation. In 2018, ASIR, ASMR, and ASDR attributable to both FAs were highest in adults ≥80 years. Females had higher burdens than males, with approximately 2-fold higher SFA-attributable rates. High SFA burden concentrated in high-SDI countries, while high MUFA burden shifted from low-middle to middle-high SDI regions. ASIR of SFA-attributable AD correlated positively with SDI in 1990 (cor = 0.41, <i>p</i> <i><</i> 0.001) and 2018 (cor = 0.5, <i>p</i> <i><</i> 0.001); a similar correlation was observed for MUFAs. Under the assumption of 3% annual growth, SFA- and MUFA-attributable ASIR would reach 57.8 and 19.7 per 100,000 by 2040.ConclusionsThis study links global SFA/MUFA intake to AD burden and projects future trends, supporting targeted prevention strategies.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261492342"},"PeriodicalIF":3.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136942","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":"Cerebrospinal fluid surfactant protein-G in neurodegenerative dementia: A comparative study with idiopathic normal-pressure hydrocephalus.","authors":"Stefania Cattaldo, Federica Scarpina, Elisa Prina, Paolo Piterà, Alessandra Milesi, Erica Sabattini, Matteo Bigoni, Corrado Azzaro, Luca Guglielmo Pradotto, Alessandro Mauro, Lorenzo Priano","doi":"10.1177/13872877261487596","DOIUrl":"10.1177/13872877261487596","url":null,"abstract":"<p><p>BackgroundSurfactant protein G (SP-G) is a recently characterized protein potentially involved in cerebrospinal fluid (CSF) dynamics. Its role in human neurodegenerative dementia remains unknown.ObjectiveTo investigate the potential clinical relevance of CSF SP-G levels in neurodegenerative dementia (ND; including Alzheimer's disease [AD] and frontotemporal dementia [FTD]), idiopathic normal-pressure hydrocephalus (iNPH), vascular dementia (VaD), and clinical controls (CTR).MethodsCSF SP-G levels were quantified in 94 individuals: 35 with ND (11 AD + 24 FTD), 19 with iNPH, 13 with VaD, and 27 CTR. Group differences were analyzed using ANOVA with post hoc tests. ANCOVA was performed to adjust for age.ResultsCSF SP-G levels differed significantly among groups in the primary analysis (ANOVA: F(3,90) = 3.862, p = 0.012), with higher levels in iNPH compared with ND (p = 0.012) and CTR (p = 0.026). No significant differences were observed between ND, VaD, and CTR groups. After adjustment for age, the group effect was no longer significant (F(3,89) = 2.253, p = 0.088).ConclusionsThis is the first study to investigate CSF SP-G levels in neurodegenerative dementia. Our findings suggest that SP-G is more closely related to altered CSF physiology in iNPH than to neurodegenerative pathology, although the influence of age indicates that these observations should be interpreted with caution. SP-G may represent a candidate marker of CSF homeostasis and fluid dynamics. Larger, age-matched studies integrating SP-G with established CSF biomarkers and neuroimaging are needed to clarify its diagnostic and pathophysiological significance.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261487596"},"PeriodicalIF":3.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of dementia severity on efficacy of brexpiprazole for agitation in Alzheimer's dementia: A post hoc analysis of a randomized, double-blind, placebo-controlled study in Japan.","authors":"Yu Nakamura, Yuta Seiyama, Koichi Shimizu, Yoshiyuki Shibasaki, Rikiya Toda, Norihiro Nakamichi, Jun Adachi, Naoki Hirota, Masami Nakai, Kaneyoshi Takahashi","doi":"10.1177/13872877261493010","DOIUrl":"10.1177/13872877261493010","url":null,"abstract":"<p><p>BackgroundThe impact of dementia severity on the efficacy of brexpiprazole for agitation associated with Alzheimer's disease in Japanese patients remains unclear.ObjectiveThis post hoc analysis aimed to further examine the efficacy of brexpiprazole with respect to the severity of Alzheimer's dementia (AD), determined using Mini-Mental State Examination (MMSE) score, in a randomized, double-blind, placebo-controlled study conducted in Japanese patients with agitation in AD (AAD).MethodsData from Japanese patients with AAD who received brexpiprazole 1 mg/day or 2 mg/day, or placebo for 10 weeks were analyzed. Changes from baseline in Cohen-Mansfield Agitation Inventory (CMAI) total score were evaluated according to severity of dementia (mild-to-moderate AD: MMSE 11-22; severe AD: MMSE 1-10). Changes from baseline in Clinical Global Impression-Severity of Illness (CGI-S) score were similarly assessed.ResultsAt Week 10, greater improvement was observed primarily with brexpiprazole compared with placebo, whereas efficacy in severe AD was limited with the 1 mg dose. Differences between brexpiprazole and placebo in the mean change from baseline in CMAI total score for mild-to-moderate and severe AD groups were -4.2 (p = 0.0306) and -2.9 (p = 0.2534) for brexpiprazole 1 mg, -7.0 (p = 0.0001) and -7.3 (p = 0.0024) for brexpiprazole 2 mg, respectively. Differences in CGI-S score were -0.3 (p = 0.0598) and -0.4 (p = 0.0762) in brexpiprazole 1 mg, -0.8 (p < 0.0001) and -0.7 (p = 0.0002) in brexpiprazole 2 mg, respectively.ConclusionsBrexpiprazole showed efficacy at the 2 mg dose in Japanese patients, supporting its effectiveness for AAD across AD severities; the effects of the 1 mg dose in severe AD were limited.ClinicalTrials.gov IdentifierNCT03620981 (trial registry name: Brexpiprazole for the Treatment of Patients With Agitation Associated With Dementia of the Alzheimer's Type).Available from https://www.clinicaltrials.gov/study/NCT03620981.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261493010"},"PeriodicalIF":3.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136707","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":"Multisystem aging discordance and cognitive decline in Chinese older adults: A longitudinal study from CHARLS.","authors":"Guanqun Hu, Ying Liu, Meiyun Zhang","doi":"10.1177/13872877261494123","DOIUrl":"https://doi.org/10.1177/13872877261494123","url":null,"abstract":"<p><p>BackgroundMultisystem aging discordance may represent an early risk factor for cognitive decline, but prospective evidence in Chinese older adults is limited.ObjectiveWe constructed a blood-based Aging Discordance Index (ADI) and examined its 3-year association with cognitive function in a nationally representative Chinese cohort. ADI was derived from five routine biomarkers (creatinine, total cholesterol, C-reactive protein, mean corpuscular volume, and glycated hemoglobin).MethodsData were from the China Health and Retirement Longitudinal Study (CHARLS). ADI was calculated as the standard deviation of age-adjusted Z-scores. Cognitive function was assessed via orientation, calculation, drawing, and equated word recall in 2018 data. Survey-weighted linear regression adjusted for baseline cognition, sociodemographic, lifestyle, and clinical covariates.ResultsAmong 1688 participants aged ≥60 years, higher ADI was independently associated with worse 3-year cognitive performance (fully adjusted β = -0.336, 95% CI: -0.598 to -0.075, p = 0.011) and greater cognitive decline (β = -0.326, 95% CI: -0.575 to -0.077, p = 0.010). To address potential bias due to loss to follow-up, we further applied linear mixed models (LMM) with random intercepts in an expanded sample of 2912 participants, which utilizes all available repeated measures. The ADI × time interaction remained significant (β = -0.346, 95% CI: -0.580 to -0.112, p = 0.004), confirming the robustness of the primary findings against attrition bias.ConclusionsA simple blood-based index of multisystem aging discordance independently predicts cognitive decline in Chinese older adults. ADI may offer a practical, low-cost tool for early risk stratification in community settings.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261494123"},"PeriodicalIF":3.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136773","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":"Acculturation is associated with cognitive performance but not changes in cognition among middle-aged and older Hispanic/Latino adults: Findings from the HCHS/SOL and SOL-INCA.","authors":"Ariana M Stickel, Wassim Tarraf, Sayaka Kuwayama, Yijia Xue, Jordana Breton, Luis D Medina, Alejandra Morlett Paredes, Linda C Gallo, Jianwen Cai, Melissa Lamar, Amber Pirzada, Martha L Daviglus, Carmen R Isasi, Robert Kaplan, Sylvia Wassertheil-Smoller, Hector M González","doi":"10.1177/13872877261492625","DOIUrl":"https://doi.org/10.1177/13872877261492625","url":null,"abstract":"<p><p>BackgroundHispanic/Latino adults are not a monolithic group. Individuals vary in a range of factors, including levels of acculturation (adoption of Anglo-American culture).ObjectiveTo investigate the relationships between acculturation with cognition, changes in cognition, and risk for mild cognitive impairment (MCI).MethodsWe included Hispanic/Latino adults (unweighted <i>n</i> = 5976) from the Study of Latinos - Investigation of Neurocognitive Aging (SOL-INCA), a Hispanic Community Health Study/Study of Latinos ancillary study. Three acculturation measures were collected at Visit 1 (Short Acculturation Scale for Hispanics (SASH) - Social and Language subscales and the MESA Acculturation score). Participants were grouped into quartiles per measure with higher scores reflecting greater acculturation. Outcomes included cognition and MCI prevalence 7-years after Visit 1 and 7-year change in cognition from Visit 1 to 2. Survey linear regressions were performed to model the associations between acculturation measures and cognitive outcomes, controlling for sociodemographic factors.ResultsThe lowest SASH Social and Language acculturation groups had lower global cognition scores than all other groups (all <i>p</i>-values<0.01). The lowest MESA Acculturation score group had lower global cognition scores relative to those in the highest quartile (<i>b</i> = 0.10; <i>SE</i> = 0.04; <i>p</i> < 0.05). However, there were no acculturation differences in cognitive change or MCI.ConclusionsThough low acculturation was associated with lower cognitive performance, it does not seem to be related to increased risk for cognitive decline or pathological cognitive aging (i.e., prevalent MCI).</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261492625"},"PeriodicalIF":3.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136675","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":"Temporal dysregulation of <i>PPARG-PRKAG2</i> co-localization in gray matter: Implications for cognitive decline and intervention targets in type 2 diabetes.","authors":"Shelli R Kesler, Kimberly A Lewis, Heather Cuevas, Elena Flowers","doi":"10.1177/13872877261493980","DOIUrl":"10.1177/13872877261493980","url":null,"abstract":"<p><p>BackgroundType 2 diabetes (T2DM) is associated with increased risk for neurodegeneration, including Alzheimer's disease.ObjectiveTo determine the differences in gray matter <i>PPARG</i> and <i>PRKAG2</i> co-localization in T2DM compared to non-diabetic controls.MethodsNeuroimaging was obtained for 1802 adults (66 ± 9 years, 47% male) of whom N = 271 had T2DM. We applied imaging transcriptomics to examine trajectories of <i>PPARG</i> and <i>PRKAG2</i> co-localization with gray matter volume.ResultsGene co-localization with gray matter was higher in early stages but weakened in later stages among T2DM compared to controls (χ² = 13.82, p = 0.001). Co-localization was significantly associated with cognitive function in controls (F = 3.17, p < 0.001) but not T2DM. Metformin use was associated with greater gene co-localization stability over time (χ² = 12.42, p = 0.006).Conclusions<i>PPARG</i>-mediated metabolic remodeling and <i>PRKAG2</i>/AMPK-driven energy sensing may act as neuroprotective mechanisms in response to both pathological (T2DM) and normative (aging) contexts. These processes appear to become dysregulated in T2DM, potentially resulting in cognitive decline and increased risk for dementia.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261493980"},"PeriodicalIF":3.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136906","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}