Journal of Alzheimer's Disease最新文献

{"title":"Association between insomnia and its symptoms and cognitive impairment in community-dwelling older adults in China: A multicenter study.","authors":"Xiao-Chang Liu, Juan Zhou, Gui-Rong Cheng, Meng-Liu Yang, Fei-Fei Hu, Dan Liu, Xin-Yan Xie, Yong Ji, Yang Lv, Jian-Ping Niu, Pan Cai, Bao-Zhi Gang, Yong You, Xin-Ling Meng, Zhao-Xia Wu, Xiang-You Li, Wei Tan, Yan Zeng","doi":"10.1177/13872877251353119","DOIUrl":"https://doi.org/10.1177/13872877251353119","url":null,"abstract":"<p><p>BackgroundLimited evidence exists on insomnia symptoms' association with mild cognitive impairment (MCI) and dementia in older Chinese adults across rural and urban areas.ObjectiveTo examine associations between insomnia symptoms, sleep duration, and cognitive impairment.MethodsThis cross-sectional study utilized data from China's Multicenter Dementia Survey (2019-2020), examining the association between insomnia symptoms, sleep duration, and cognitive impairment, using logistic and linear regression models. The cognitive score was obtained using the Mini-Mental State Examination (MMSE).ResultsWe included 10,725 participants (5964 females) aged between 65 and 100 years. Insomnia was significantly associated with an increased risk of MCI (odd ratio [OR], 1.16; 95% confidence interval [CI], 1.05 to 1.29) and lower MMSE scores (β, -0.13; 95% CI, -0.15 to -0.10). Difficulties initiating sleep (DIS; OR, 1.16; 95% CI, 1.03 to 1.31) and sleepiness during the day (SDD; OR, 1.32; 95% CI, 1.02 to 1.70) increased MCI risk, and the latter (OR, 1.79; 95% CI, 1.26 to 2.56) also increased risk of dementia. Insomnia's negative association with MMSE scores was stronger in rural (β, -0.17; 95% CI, -0.20 to -0.14) than urban residents (β, -0.05; 95% CI, -0.08 to -0.02). Sleep duration and MMSE scores showed an inverted U-shaped relationship (peak at 7-8 h/night).ConclusionsInsomnia symptoms, particularly DIS and SDD, are associated with higher MCI risk and poorer cognition in older adults, with amplified effects in rural China.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251353119"},"PeriodicalIF":3.4,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600504","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":"Depression modifies age-associated [¹¹C]PiB-PET amyloid burden in a cohort enriched with risk for Alzheimer's disease.","authors":"Kyle J Edmunds, Alexis R Nelson, Talia L Brach, Matthew Glittenberg, Bradley T Christian, Tobey J Betthauser, Sterling C Johnson, Sanjay Asthana, Ozioma C Okonkwo","doi":"10.1177/13872877251353098","DOIUrl":"https://doi.org/10.1177/13872877251353098","url":null,"abstract":"<p><p>BackgroundDepression-especially late-life onset-is associated with age-related cognitive decline and may be a key risk factor for amyloid-β (Aβ) deposition in preclinical Alzheimer's disease (AD).ObjectiveThis study assesses whether depressive symptoms modify the relationship between age and Aβ burden in a cohort at-risk for AD.MethodsN = 238 cognitively unimpaired participants from the Wisconsin Alzheimer's Disease Research Center participated in Pittsburgh Compound-B positron emission tomography (¹¹C-PiB-PET), where distribution volume ratio scores were used to quantify Aβ burden in nine regions of interest (ROIs) susceptible to early Aβ burden. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS). Cross-sectional linear regression models examined interactions between age and GDS scores, adjusting for sex, apolipoprotein ε4 (<i>APOE</i> ε4) carriage, and age difference between PET imaging and GDS assessment. GDS-stratified analyses were performed to test within-group associations between age and ¹¹C-PiB-PET Aβ aggregation in each ROI, and item-level analyses identified specific depressive symptoms that modified these relationships.ResultsParticipants had a mean age of 68.0 years (SD ± 8.4), 39.7% were <i>APOE</i> ε4 carriers, 64% were female, and 85.3% were White. GDS scores were largely normal (M = 1.29, SD = 1.61). Age × GDS interactions were significant across all ROIs, and stratified models revealed progressively stronger associations as GDS scores increased. Finally, item-level analyses identified the second and tenth GDS items as significant modifiers across six ROIs and the global composite.ConclusionsIn a cohort enriched with risk for AD, emerging depressive symptoms amplified the association between age and Aβ burden.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251353098"},"PeriodicalIF":3.4,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600505","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":"New opioid use and mortality in older people with dementia.","authors":"Christina Jensen-Dahm, Janet Janbek, Thomas Munk Laursen, Christiane Gasse, Gunhild Waldemar","doi":"10.1177/13872877251352469","DOIUrl":"https://doi.org/10.1177/13872877251352469","url":null,"abstract":"<p><p>BackgroundOpioid use is frequent among older people with dementia. Opioid use has been associated with excess mortality in the general population, but whether this also applies to older people with dementia is unknown.ObjectiveInvestigate if new opioid use compared with no use was associated with excess mortality in older people with dementia.MethodsMatched cohort study using Danish nationwide registries including all residents (age 65+) diagnosed with dementia (including Alzheimer's disease) between 2008-2018. Exposure was defined as first opioid prescription after dementia diagnosis (1 year washout before). Persons exposed to opioids were matched with up to two unexposed persons on age and sex. Outcome was all-cause mortality within 180 days after exposure. Cox proportional hazards models compared rates of death and adjusted for potential confounders.ResultsForty-two percent (31,619/75,471) of older people with dementia initiated a prescription for an opioid after dementia diagnosis. 31,619 exposed persons were matched to 63,235 unexposed. Among the exposed, 8540 (27%) died within 180 days after initiating their first opioid prescription compared with 3803 (6.01%) of the unexposed, yielding a 5-fold excess mortality risk (adjusted Hazard ratio: 5.06 (95% CI, 4.86-5.29)). Transdermal fentanyl use was associated with an 8-fold excess mortality risk (8.26 (7.18-9.51)).ConclusionsOpioid use was associated with excess mortality, which may be due to the opioid, the indication or both. This observation calls for further research into the links between opioid use and excess mortality in elderly with dementia as it could have important implications for patient safety.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251352469"},"PeriodicalIF":3.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575452","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 need to adapt after Alzheimer's disease diagnosis: Coping strategies used to maintain identity and quality of life.","authors":"Simone Gamm, Deborah Ummel, Nancy Vasil, Sébastien Grenier","doi":"10.1177/13872877251351596","DOIUrl":"https://doi.org/10.1177/13872877251351596","url":null,"abstract":"<p><p>BackgroundReceiving a diagnosis of a major neurocognitive disorder due to Alzheimer's disease (AD) brings with it the need to adjust to a new life situation. People with AD seek to (1) maintain emotionally positive goals in their current lives, and (2) use positive experiences from the past to create continuity in their lives, with the aim of maintaining their quality of life and gaining a sense of hope.ObjectiveThis research aims to explore the coping strategies and processes used following diagnosis.MethodAn exploratory qualitative design was implemented to study the different coping strategies used by ten people with AD<i>,</i> via semi-structured interviews. The transcribed data was subject to an interpretative phenomenological analysis.ResultsAll participants experienced unpleasant emotions following their diagnosis. Their coping process following two different trajectories: (1) adaptive coping strategies to gain resilience and hope to maintain meaning in their current lives; (2) less adaptive coping strategies essentially resulting in the denial of the diagnosis and withdrawal from social life.ConclusionsThis research makes it possible to identify possible intervention paths adapted to an individual's needs to help them move towards adaptive coping strategies.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251351596"},"PeriodicalIF":3.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575453","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":"Inherited prion disease caused by a novel frameshift mutation of <i>PRNP</i> resulting in protein truncation at codon 157.","authors":"Leah Holm-Mercer, Tze How Mok, Danielle Sequeira, Thomas Coysh, Peter Rudge, Hawraman Ramadan, Lee Darwent, Tracy Campbell, Thomas Murphy, Colin Smith, Diane Ritchie, Sebastian Brandner, Zane Jaunmuktane, John Collinge, Simon Mead","doi":"10.1177/13872877251351182","DOIUrl":"10.1177/13872877251351182","url":null,"abstract":"<p><p>BackgroundPrP systemic amyloidosis is increasingly recognized as a novel inherited prion disease (IPD) syndrome caused by <i>PRNP</i> C-terminal truncating mutations. As well as systemic manifestations they cause gradually progressive cognitive impairment with neurofibrillary tangle pathology which can be mistaken for Alzheimer's disease (AD).ObjectiveWe describe the clinical, biomarker and neuropathological features of a novel frameshift mutation of <i>PRNP</i> resulting in protein truncation at codon 157.MethodsThe clinical phenotype and biomarker findings, including plasma biomarkers measured using Single Molecule Array (SiMOA) technology are reported for affected living individuals, with neuropathological examination available for the index case.ResultsThe Y157X <i>PRNP</i> mutation has resulted in a phenotype of gradually progressive cognitive decline, peripheral sensory and autonomic polyneuropathy, and gastrointestinal symptoms, with one case presenting with recurrent episodes of nausea, vomiting and electrolyte derangement requiring intensive care unit admission. Plasma biomarkers revealed an AD-like pattern with raised neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and phospho-tau 181 (P-tau 181) in affected individuals. On neuropathological examination there was PrP-cerebral amyloid angiopathy (CAA) and neurofibrillary tau pathology.ConclusionsWe present the clinical, biomarker and pathological findings on investigation of this family and provide further evidence for the association of truncation mutations with PrP systemic amyloidosis.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251351182"},"PeriodicalIF":3.4,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12284330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560195","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":"Sleep disturbances and language function impairment in the elderly: Evidence of limbic and prefrontal tracts involvement.","authors":"Yiling Qiu, Xiaole Duan, Zhanxing Zhang, Liping Zhao, Qiong Yuan, Meijuan Wang, Shifu Xiao, Lin Sun","doi":"10.1177/13872877251352074","DOIUrl":"https://doi.org/10.1177/13872877251352074","url":null,"abstract":"<p><p>BackgroundAlthough poor sleep is widely assumed to impair cognitive function, the impact of sleep disturbances (SD) on language function and the underlying mechanisms of this relationship remains unclear.ObjectiveThis study aimed to investigate the association between SD and language function in non-demented elderly individuals, identify potential neuroimaging correlates, and analyze risk factors for SD.MethodsWe analyzed 784 non-demented elderly subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI), categorized into SD (n = 256) and normal sleep groups (n = 528) based on self-reported sleep status. Cognitive differences were assessed, and the findings were validated using the China Longitudinal Aging Study (CLAS) and the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Diffusion tensor imaging (DTI) metrics were correlated with language function, and SD risk factors were examined.ResultsIn the ADNI cohort, elderly individuals with SD exhibited worse language function compared to those with normal sleep, and this finding was validated in the CLAS and CLHLS cohorts. Meanwhile, the decline in longitudinal language function among elderly individuals with SD occurred at a faster rate. Differences in DTI metrics between the two groups were primarily observed in the limbic and prefrontal regions. Finally, the risk factors for elderly with SD mainly included years of education, physical and emotional conditions, lifestyles, living environment, and parental survival status.ConclusionsSD correlates with language impairment in non-demented elderly, possibly due to limbic/prefrontal tract damage. Risk factors encompass demographic, health, lifestyle, and socio-environmental aspects. Effectively managing these factors and treating SD may improve language function.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251352074"},"PeriodicalIF":3.4,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560197","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":"Is US residence a risk factor for Alzheimer's disease?","authors":"Poul F Høilund-Carlsen, Abass Alavi, Tommaso Costa, Rachael L Neve, George Perry, Mona-Elisabeth Revheim, Jorge R Barrio","doi":"10.1177/13872877251356682","DOIUrl":"https://doi.org/10.1177/13872877251356682","url":null,"abstract":"<p><p>Reducing risk factors is a useful way to counteract diseases. The prevalence of Alzheimer's disease (AD) in the US is often quoted as 6.9 million out of 333 million people, or 2.1%. It is around 0.7% in the UK, 0.9% in Denmark, and worldwide the estimate is 0.5%. Alongside risk factor reduction, the Centers for Medicare and Medicaid Services could strengthen the US fight against AD by reconsidering its October 2023 decision to liberalize reimbursement of amyloid PET scans, or better yet, advise replacing these non-specific scans with FDG-PET, which shows what AD is really about: impaired regional brain function.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251356682"},"PeriodicalIF":3.4,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560196","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":"Neighborhood deprivation and mortality among people with Alzheimer's disease and related dementia.","authors":"Joshua L Paley, Grant D Scheiffele, Yujia Li, C Elizabeth Shaaban, Yonghui Wu, Stephen Anton, Steven DeKosky, Jiang Bian, Jingchuan Guo","doi":"10.1177/13872877251352120","DOIUrl":"https://doi.org/10.1177/13872877251352120","url":null,"abstract":"<p><p>BackgroundThere are limited studies quantifying the extent to which neighborhood deprivation affects mortality in individuals living with Alzheimer's disease (AD) and AD-related dementias (AD/ADRD).ObjectiveTo quantify to what extent neighborhood deprivation affects adverse outcomes in individuals living with AD/ADRD.MethodsWe identified individuals with AD/ADRD using a 15% random sample of national Medicare fee-for-service beneficiaries. Area deprivation index (ADI) was spatially linked to the Medicare AD/ADRD cohort using zip codes. Multivariate logistic regression was applied to examine the association between ADI and all-cause mortality among beneficiaries with AD/ADRD.ResultsAfter adjusting for patients characteristics, compared to the lowest ADI quartile (Q1), higher ADI quartiles were associated with higher odds of all-cause mortality in individuals with AD/ADRD (Q2 = OR 1.08 [95% CI: 1.06, 1.10], Q3 = OR 1.09 [95% CI: 1.07, 1.11], and Q4 OR 1.05 [95% CI: 1.03, 1.07]).ConclusionsNeighborhood deprivation is an independent risk factor for mortality in persons with AD/ADRD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251352120"},"PeriodicalIF":3.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553638","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":"Plasma leptin, resistin, tumor necrosis factor-alpha, and interleukin-6 with risk of dementia: A prospective population study.","authors":"Peiqi Zhang, Nianwei Wu, Qingping Xue, Jingyi Li, Qingqing Ouyang, Xinyue Yu, Yunhaonan Yang, Yidan Dong, Fan Li, Tianlei Wang, Shuo Li, Xiong-Fei Pan","doi":"10.1177/13872877251352480","DOIUrl":"https://doi.org/10.1177/13872877251352480","url":null,"abstract":"<p><p>BackgroundAdipokines secreted from adipose tissue may contribute to dementia pathogenesis.<b>Objective:</b> Our study investigated the associations between plasma levels of leptin, resistin, TNF-α, and IL-6 and the risk of all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD).MethodsPlasma protein levels were measured using the Olink Proximity Extension Assay, and dementia was ascertained from hospital admissions and death registries in the UK Biobank. Multivariable Cox proportional hazards models with stepwise covariate adjustments were used to assess associations. Subgroup analyses were conducted to examine whether the associations differed by sociodemographic characteristics, lifestyle factors, and major diseases.ResultsAmong 32,002 participants, 793 developed all-cause dementia, including 260 with AD and 96 with VaD. Plasma levels of resistin and IL-6 were positively associated with risks of all-cause dementia, with hazard ratios (95% confidence intervals) of 1.10 (1.03, 1.18) and 1.10 (1.04, 1.17), respectively. Leptin (0.98; 0.86, 1.12) and TNF-α levels (1.06; 0.98, 1.13) were not significantly associated with all-cause dementia. Resistin (1.28; 1.08, 1.53) and TNF-α levels (1.21; 1.04, 1.40) were associated with VaD risk. There was a lack of evidence for the associations between four adipokines and AD. Subgroup analyses showed stronger associations between resistin and all-cause dementia in those with high body mass index, diabetes, or stroke.ConclusionsPlasma levels of resistin and IL-6 were positively associated with risks of all-cause dementia, with resistin and TNF-α strongly linked to VaD. These findings support a potential role of adipokines in dementia pathogenesis, particularly for VaD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251352480"},"PeriodicalIF":3.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540303","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":"Accuracy of blood-based neurofilament light to different genetic frontotemporal dementia from primary psychiatric disorders.","authors":"Ella Liu, Sherri Lee Jones, Victoria Light, Charlotte Teunissen, Arabella Bouzigues, Lucy L Russell, Phoebe H Foster, Eve Ferry-Bolder, John C van Swieten, Lize C Jiskoot, Harro Seelaar, Raquel Sanchez-Valle, Robert Laforce, Caroline Graff, Daniela Galimberti, Rik Vandenberghe, Alexandre de Mendonça, Pietro Tiraboschi, Isabel Santana, Alexander Gerhard, Johannes Levin, Sandro Sorbi, Markus Otto, Chris R Butler, Isabelle Le Ber, Elizabeth Finger, Maria Carmela Tartaglia, Mario Masellis, James B Rowe, Matthis Synofzik, Fermin Moreno, Barbara Borroni, Henrik Zetterberg, Jonathan D Rohrer, Simon Ducharme","doi":"10.1177/13872877251352103","DOIUrl":"https://doi.org/10.1177/13872877251352103","url":null,"abstract":"<p><p>BackgroundGenetic frontotemporal dementia (FTD) along with Alzheimer's disease (AD), is one of the most prevalent early-onset dementias. The differential diagnosis of FTD from primary psychiatric disorder (PPD) has been challenging due to significant symptom overlap, particular as FTD often presents with prolonged psychiatric prodromes.ObjectiveThis study aims to evaluate whether blood-based neurofilament light chain (NfL) can differentiate genetic FTD from PPD, and to determine a global clinical cutoff to differentiate genetic FTD carriers from PPD with high specificity and sensitivity.MethodsData (ages 40-81) were obtained from FTD mutation carriers (GENFI; <i>n</i> = 474; <i>n</i> = 120 <i>C9orf72, n</i> <i>=</i> 114 <i>GRN, n</i> = 50 <i>MAPT</i>, <i>n</i> = 190 controls), and PPD (Biobanque Signature; <i>n</i> = 848). Blood-based NfL was measured with SIMOA HD-X (BbS) and SIMOA HD-1 (GENFI).ResultsBlood-based NfL was higher in all symptomatic mutations compared to PPD. Mildly symptomatic (0 < FTLD CDR-SOB-NM < 4) <i>C9orf72</i> and <i>GRN</i> carriers also had higher NfL. ROC curve revealed an optimal blood-based NfL cutoff of 22.1 pg/mL (<i>J</i> = 0.647) to distinguish symptomatic genetic FTD from PPD (78.5% sensitivity, 86.2% specificity, AUC = 0.908). For mildly symptomatic subjects, a cutoff of 16.2 pg/mL (<i>J</i> = 0.601) differentiated groups with 86.7% sensitivity and 73.5% specificity (AUC = 0.870).ConclusionsNfL holds potential as a blood-based biomarker for symptomatic genetic FTD carriers, with moderate accuracy to distinguish PPD from mild forms including <i>C9orf72</i>.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251352103"},"PeriodicalIF":3.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553636","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}