Alzheimer disease and associated disorders最新文献

{"title":"Discordance Between Cognitive Impairment Status and Claims-Based ADRD Diagnosis: Temporal Patterns and Racial Differences in the REGARDS Cohort, 2006 to 2021.","authors":"Min Hee Kim, Lisandro D Colantonio, M Maria Glymour, Rita Hamad, Julia Adler-Milstein, Kiarri N Kershaw, John Boscardin, Zhixin Wang, Ayse Sert Oti, Virginia J Howard","doi":"10.1097/WAD.0000000000000743","DOIUrl":"10.1097/WAD.0000000000000743","url":null,"abstract":"<p><strong>Introduction: </strong>Understanding the concordance between incident cognitive impairment status and the diagnosis of Alzheimer disease and related dementias (ADRD) is clinically important, as a diagnosis serves as the gateway for treatment, care planning, and supportive services.</p><p><strong>Methods: </strong>Using the REGARDS cohort (2006 to 2021) linked to Medicare claims, we examined the discordance between incident cognitive impairment and claims-based ADRD diagnoses. Directly standardized diagnosis rates were estimated by year, overall, and race, and stratified by cognitive impairment status. Logistic regression models were used to examine sociodemographic correlates of diagnosis.</p><p><strong>Results: </strong>The sample included 45,191 observations (23% Black) of 8368 participants. Among those with incident cognitive impairment, 30.8% received a claim-based diagnosis, and while 8.9% of those without incident cognitive impairment received a claim-based diagnosis. ADRD diagnosis rates remained stable, whereas rates among observations with incident cognitive impairment rose through the early 2010s, then plateaued and declined. The black race and education below the college level were associated with lower odds of diagnosis in this group; female sex was associated with higher odds. Among observations without cognitive impairment, older age and female sex were associated with higher odds; Midwest or West/Northeast residence and less than high school education were associated with lower odds.</p><p><strong>Discussion: </strong>Differences observed in the study may potentially represent underlying disparities in access to care and dementia diagnosis in clinical practice.</p>","PeriodicalId":520551,"journal":{"name":"Alzheimer disease and associated disorders","volume":" ","pages":"183-191"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using a Survey to Monitor Participant Experience in a Population-Based Study of Older Adults.","authors":"Isabella Wood, Erin Jacobsen, Tiffany Hughes, Mary Ganguli","doi":"10.1097/WAD.0000000000000746","DOIUrl":"10.1097/WAD.0000000000000746","url":null,"abstract":"<p><p>Consumer surveys are increasingly used in business and clinical practice, but less so in human subjects research. Within a longitudinal, population-based study of older adults, we administered a survey to monitor participants' experiences and address potential challenges. We invited participants to provide feedback on their study experience following their annual interviews, using a survey with Likert-scale questions and open-ended comments. In the first round of surveys between 2022 and 2024, 82% responded who were more likely to be White, cognitively normal, and endorse fewer than 5 depression symptoms compared with their counterparts who did not respond. In the open-ended comments, 63.2% mentioned positive overall experience, 44.3% mentioned positive interactions with staff, 19.4% mentioned the study's COVID-19 guidelines, and 17.4% shared their motivation for study participation. The survey amplified participants' voices and identified aspects of the study important to them. Understanding participants' experiences and expectations may help with retention.</p>","PeriodicalId":520551,"journal":{"name":"Alzheimer disease and associated disorders","volume":" ","pages":"249-252"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CHMP2B p.Ala30Ser Variant in Biomarker-Confirmed Early-Onset Alzheimer Disease: A Potential Endolysosomal Disease Modifier.","authors":"Ozlem Totuk","doi":"10.1097/WAD.0000000000000737","DOIUrl":"10.1097/WAD.0000000000000737","url":null,"abstract":"<p><p>Endolysosomal dysfunction has been increasingly implicated in the pathogenesis of neurodegenerative diseases. The charged multivesicular body protein 2B (CHMP2B) gene encodes a component of the endosomal sorting complexes required for transport (ESCRT-III), which regulates endosomal trafficking, multivesicular body formation, and autophagosome-lysosome fusion. Mutations in CHMP2B are classically associated with autosomal dominant frontotemporal dementia. Here, we report a 59-year-old woman with biomarker-confirmed Alzheimer disease (AD) (A+T+N+) carrying a heterozygous CHMP2B c.90C>T (p.Ala30Ser) variant identified by targeted exome sequencing after negative testing for APP, APOE, PSEN1, and PSEN2. The patient presented with progressive episodic memory impairment and spatial disorientation over 3 years. Brain MRI showed prominent posterior cortical atrophy, and cerebrospinal fluid biomarkers demonstrated decreased Aβ42 and elevated phosphorylated and total tau levels consistent with AD pathology. Dysfunction of CHMP2B-mediated endolysosomal pathways may impair intracellular protein degradation and influence tau clearance mechanisms. This observation suggests that rare variants in endolysosomal pathway genes may contribute to AD pathophysiology.</p>","PeriodicalId":520551,"journal":{"name":"Alzheimer disease and associated disorders","volume":" ","pages":"243-245"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148166668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Speech-in-Noise Hearing Impairment and Incident Dementia: A UK Biobank Cohort Study Across Polygenic, APOE ε4, and Familial Risk Strata.","authors":"Cong Peng, Guoqing Gong, Zhetian Chen, Jingwei Wu, Dan Liu, Bin Chen","doi":"10.1097/WAD.0000000000000747","DOIUrl":"10.1097/WAD.0000000000000747","url":null,"abstract":"<p><strong>Objective: </strong>Hearing impairment is considered an important modifiable risk factor for dementia, but whether its association with incident dementia is consistent across inherited susceptibility profiles remains unclear.</p><p><strong>Methods: </strong>This prospective cohort study included 80,287 UK Biobank participants aged 40 to 69 years at baseline with valid Digit Triplet Test measurements, genetic data, linked follow-up data, and complete prespecified covariates. Hearing function was quantified using the better-ear speech reception threshold (SRT). Incident dementia was ascertained from linked hospital admission and death registry records. Cox proportional hazards models were used to estimate associations between baseline hearing status and incident dementia. The fully adjusted model included demographic, socioeconomic, lifestyle, cardiometabolic, visual, psychosocial, hearing-aid-use, and genetic ancestry covariates. Effect modification by inherited susceptibility, including dementia polygenic risk score (PRS), APOE ε4 carrier status, and parental history of dementia, was assessed using stratified analyses and multiplicative interaction tests.</p><p><strong>Results: </strong>During ∼988,462 person-years of follow-up, 1086 incident dementia cases were identified. Compared with normal hearing, mild and severe hearing impairment were associated with higher dementia risk in the fully adjusted model, with HRs of 1.33 (95% CI: 1.13-1.56) and 1.53 (95% CI: 1.15-2.02), respectively. Restricted cubic spline analyses supported a nonlinear dose-response association between higher SRT and dementia risk. The hearing impairment-dementia association was observed across PRS, APOE ε4 carrier status, and parental family-history strata, with no statistically significant multiplicative interaction by APOE ε4 status or parental family history and only suggestive evidence by PRS category.</p><p><strong>Conclusions: </strong>Speech-in-noise hearing impairment was associated with a higher risk of incident dementia in the UK Biobank, and this association was broadly observed across inherited-risk strata. These findings support hearing impairment as a potentially modifiable marker relevant to dementia-risk assessment across polygenic, APOE ε4, and familial risk backgrounds.</p>","PeriodicalId":520551,"journal":{"name":"Alzheimer disease and associated disorders","volume":" ","pages":"192-201"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148883287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-Design and Development of Digital Health Solution for Informal Alzheimer's Caregivers.","authors":"Maria Maia Almeida, Carla Sílvia Fernandes, Marta Campos Ferreira","doi":"10.1097/WAD.0000000000000740","DOIUrl":"10.1097/WAD.0000000000000740","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer disease (AD) imposes significant cognitive, emotional, and practical challenges on individuals and their caregivers. Informal caregivers, often family members, assume a central role in managing complex care routines, frequently with limited support. Digital tools offer promising avenues for addressing these challenges, yet existing solutions often lack integration, personalization, or user-centered design.</p><p><strong>Methods: </strong>This study presents the design, development, and validation of AlzCare, a digital health solution developed using a user-centered design (UCD) methodology. The needs assessment involved 52 survey respondents and 6 in-depth interviews with caregivers and healthcare professionals. Based on this, a prototype was developed integrating modules for health monitoring, cognitive stimulation, task management, and caregiver support. Usability and functionality were evaluated through testing with 25 participants using task-based interaction, semistructured interviews, and the System Usability Scale (SUS).</p><p><strong>Results: </strong>The solution received highly positive feedback regarding usability, relevance, and emotional resonance. The SUS yielded a mean score of 90.9, indicating \"Best Imaginable\" usability. Users valued features such as daily health tracking, the \"Who Am I?\" reminiscence tool, and the caregiver support section. Suggestions included automating data entry and integrating wearables.</p><p><strong>Discussion: </strong>AlzCare demonstrates how digital technologies developed through participatory approaches can support informal dementia caregiving across practical and emotional dimensions. Future work will focus on broader clinical integration, automation, and longitudinal validation in real-world settings. The findings reinforce the value of accessible, holistic digital tools in advancing dementia care within telemedicine ecosystems.</p>","PeriodicalId":520551,"journal":{"name":"Alzheimer disease and associated disorders","volume":" ","pages":"217-223"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148835626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"More Publications Needed on Cognitively Impaired-Not MCI: Call for Papers.","authors":"Jose A Luchsinger","doi":"10.1097/WAD.0000000000000736","DOIUrl":"10.1097/WAD.0000000000000736","url":null,"abstract":"","PeriodicalId":520551,"journal":{"name":"Alzheimer disease and associated disorders","volume":" ","pages":"67-68"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148201981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut Microbiome Differences Between Early Alzheimer Disease and Idiopathic Normal Pressure Hydrocephalus.","authors":"Emilia Brandt, Anne Koivisto, Pedro Pereira, Ella Mustanoja, Petri Auvinen, Toni Saari, Minna Rusanen, Ville Leinonen, Filip Scheperjans, Virve Kärkkäinen","doi":"10.1097/WAD.0000000000000726","DOIUrl":"10.1097/WAD.0000000000000726","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer disease (AD) and idiopathic normal pressure hydrocephalus (iNPH) are neurodegenerative diseases causing memory decline. Previous studies have demonstrated an altered gut microbiome (GM) in both conditions. In this study, we compared the GM composition between the groups to find out how if the GM composition differed between the cognitively healthy individuals (CO) and AD groups, as well as between the AD and iNPH groups.</p><p><strong>Methods: </strong>Thirty-seven CO participants, 21 mild AD patients and 10 participants with shunted iNPH gave fecal samples, which were subjected to 16S amplicon sequencing. Then, genus-level differences were analyzed. Information about comorbidities and diet was collected, and cognitive function was evaluated.</p><p><strong>Results: </strong>Compared with the CO group, Anaerovorax and an unknown genus of the Comamonadaceae family increased, whereas Enterobacter, Absicoccus, Buttiauxella, Raoultella , and Lacticaseibacillus decreased in the AD group. Compared with the iNPH group, Paramuribaculum , an unknown genus of the Desulfovibrionaceae family, Ruficoccus and Mitsuokella increased, whereas Anaeromassilibacillus and Desulfovibrio decreased in the AD group.</p><p><strong>Conclusions: </strong>We demonstrated differences in the GM composition between the AD and CO groups, as well as between the AD and iNPH groups. To our knowledge, this is the first report to compare the 2 neurodegenerative diseases and demonstrate GM differences.</p>","PeriodicalId":520551,"journal":{"name":"Alzheimer disease and associated disorders","volume":" ","pages":"101-106"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13281972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148045017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validity of the Montreal Cognitive Assessment-Basic (MoCA-B) in a Dutch Memory Clinic.","authors":"Roy P C Kessels, Floor S van Bergen, Calijn M A Vogel, Marloes Smarius, Iris S Pouwels, Paul D Dautzenberg","doi":"10.1097/WAD.0000000000000729","DOIUrl":"10.1097/WAD.0000000000000729","url":null,"abstract":"<p><p>People with low educational levels or low literacy skills tend to obtain lower scores on cognitive screens, even in the absence of cognitive impairments, possibly resulting in false positive diagnoses. The Montreal Cognitive Assessment-Basic (MoCA-B) has been developed to overcome this, but studies so far are limited to low-income countries. This study examined the MoCA-B [total score and Memory Index Score (MIS)] in a European memory clinic context. Fifty-five controls, 37 patients with mild cognitive impairment and 47 dementia patients were included. Results showed that a MoCA-B total cutoff score <25 is valid for distinguishing controls from MCI or dementia patients. The MoCA-B MIS showed an acceptable diagnostic accuracy for controls versus MCI (<12) and controls versus dementia (<11). No valid cutoff score could be established for MCI versus dementia patients. Our findings show that the MoCA-B can also be validly applied in a European memory clinic setting.</p>","PeriodicalId":520551,"journal":{"name":"Alzheimer disease and associated disorders","volume":" ","pages":"166-170"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13281967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148044958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Olfaction, Cognition, and Early Signs of Neurodegenerative Disease in a Community-Based Sample of Older Adults.","authors":"Erin Jacobsen, Yingjin Zhang, Mary Ganguli, Chung-Chou H Chang, M Ilyas Kamboh, Thomas K Karikari, Sarah B Berman, Beth E Snitz","doi":"10.1097/WAD.0000000000000730","DOIUrl":"10.1097/WAD.0000000000000730","url":null,"abstract":"<p><strong>Introduction: </strong>We investigated associations of impaired odor identification with signs of early Alzheimer disease (AD) and Lewy Body disease (LBD).</p><p><strong>Methods: </strong>In 787 community-sampled adults aged ≥65 without dementia or Parkinson disease, we evaluated cross-sectional associations of olfaction (Brief Smell Identification Test, BSIT) with 5 cognitive domain scores, gait, tone, tremor, REM sleep behavior disorder (RBD) symptoms, and plasma biomarkers of neurodegeneration.</p><p><strong>Results: </strong>In adjusted regression models, worse BSIT scores were associated with lower cognitive scores in all domains, slowed gait, resting tremor, and RBD-like symptoms. The association between BSIT and memory was stronger in APOE4 carriers. In cognitively unimpaired participants (Clinical Dementia Rating=0), most associations remained significant. BSIT scores were associated with plasma p-tau217 and NfL in exploratory analyses.</p><p><strong>Conclusion: </strong>Odor identification is associated with cognition in an undifferentiated pattern and with Parkinsonian signs in older adults, even among those with normal cognition. The stronger association in APOE4 carriers potentially suggests an emerging AD-like pathway, consistent with exploratory plasma biomarker analyses. In sum, evidence points to olfactory dysfunction as relevant for both AD and LBD-associated future risk.</p>","PeriodicalId":520551,"journal":{"name":"Alzheimer disease and associated disorders","volume":" ","pages":"85-92"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13700015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148039095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive and Neuroanatomical Effects of Fatty Acid Amide Hydrolase Polymorphism rs324420 in Aging and Alzheimer Disease.","authors":"Daniel K Mori-Fegan, Yuen Yan Wong, Shiropa Noor, Che-Yuan Wu, Siwon Ryoo, Catharine Mielnik, Ruth A Ross, Walter Swardfager","doi":"10.1097/WAD.0000000000000723","DOIUrl":"10.1097/WAD.0000000000000723","url":null,"abstract":"<p><strong>Introduction: </strong>Therapeutic options for Alzheimer disease (AD) are limited. Modulating the endocannabinoid system through fatty acid amide hydrolase (FAAH) is a promising target. We investigated how the FAAH functional polymorphism rs324420 influences cognition and brain structure across the AD continuum, particularly in interaction with amyloid (Aβ) pathology.</p><p><strong>Methods: </strong>One thousand, five hundred seven Alzheimer Disease Neuroimaging Initiative participants were analyzed [631 cognitively normal (CN); 876 AD/Mild Cognitive Impairment (ADMCI)]. Cross-sectional and 48-month longitudinal models assessed interactions between rs324420 minor-allele carrier status and Aβ-positivity [(18F)-Florbetapir PET SUVR>1.11] on cognitive tests and regional brain volumes as judged by MRI.</p><p><strong>Results: </strong>Cross-sectionally, CN and Aβ-positive CN carriers demonstrated better executive function than noncarriers. Aβ-positive ADMCI carriers showed greater baseline episodic memory, while Aβ-negative carriers had larger inferior temporal and nucleus accumbens volumes compared with noncarriers. Longitudinally, Aβ-positive CN carriers showed slower whole-brain atrophy. Whole-ADMCI carriers exhibited significantly slower declines in global cognition and language. Aβ-positive ADMCI carriers showed preserved anterior cingulate, fusiform gyrus, and nucleus accumbens volumes. Aβ-negative ADMCI carriers had greater atrophy in the inferior temporal and nucleus accumbens regions.</p><p><strong>Discussion: </strong>Neuroprotective effects of rs324420 (lowered FAAH activity) appear contingent on cerebral Aβ-positivity, specifically preserving brain volume and slowing cognitive decline longitudinally. Findings support biomarker-informed precision approaches for endocannabinoid-targeted interventions in AD and aging.</p>","PeriodicalId":520551,"journal":{"name":"Alzheimer disease and associated disorders","volume":" ","pages":"115-123"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147937046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}