Journal of Alzheimer's disease reports最新文献

{"title":"Glial-adjusted residual transcriptomics with leave-one-out transcriptome-wide association study influence analysis prioritizes GALNT6 and other high-impact genes in Alzheimer's disease.","authors":"Ngo Cheung","doi":"10.1177/25424823261478053","DOIUrl":"10.1177/25424823261478053","url":null,"abstract":"<p><strong>Background: </strong>Bulk transcriptomic studies of Alzheimer's disease are difficult to interpret because the diseased brain is not only transcriptionally altered, but structurally remodeled. Neuronal and synaptic loss, reactive gliosis, and vascular or extracellular-matrix changes can all shift measured expression.</p><p><strong>Objective: </strong>To reanalyze GSE5281 with glial marker-derived adjustment and integrate residual gene sets with Alzheimer's disease S-PrediXcan/transcriptome-wide association study (TWAS) results to prioritize genes relevant to disease pathogenesis and target discovery.</p><p><strong>Methods: </strong>We used age, composite glial score, and surrogate-variable adjustment to define residual upregulated and downregulated genes, then evaluated these sets in brain-tissue TWAS outputs using Stouffer meta-Z statistics, permutation/bootstrap set-level testing, and gene-level leave-one-out influence analysis.</p><p><strong>Results: </strong>The residual sets did not show significant set-level enrichment. AD_RESIDUAL_DOWN showed Stouffer Z = 0.862, permutation p = 0.6982, and bootstrap 95% CI = -3.18 to 5.38. AD_RESIDUAL_UP showed Stouffer Z = -1.564, permutation p = 0.5002, and bootstrap 95% CI = -5.43 to 2.26. However, gene-level analysis identified 41 influential gene-disease entries. GALNT6 was the strongest signal in the residual upregulated set and the strongest overall gene-level signal. C1QTNF4 and NTSR2 were the largest influence signals in the residual downregulated set, while EPHX2 ranked among the influential genes.</p><p><strong>Conclusions: </strong>These findings support glial-adjusted residual transcriptomics with leave-one-out TWAS influence analysis as a computational prioritization strategy for Alzheimer's disease, rather than as evidence of broad pathway-level genetic enrichment.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"10 ","pages":"25424823261478053"},"PeriodicalIF":2.8,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186753","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":"Blood lipids as accessible biomarkers for early dementia risk screening: Bridging diagnostic gaps in resource-limited settings.","authors":"Foster Appiah, David Larbi Simpong, George Nkrumah Osei, John Dogah, Esther Marfo, Maxwell Hubert Antwi, David Mawutor Donkor, Kwaku Sarfo Manu, Ansumana Bockarie","doi":"10.1177/25424823261475263","DOIUrl":"10.1177/25424823261475263","url":null,"abstract":"<p><strong>Background: </strong>Dementia prevalence is rising globally, with the greatest increase occurring in low- and middle-income countries where access to advanced diagnostic tools remains limited. Circulating lipid parameters have been increasingly investigated as accessible biomarkers for dementia risk and cognitive decline.</p><p><strong>Objective: </strong>To systematically review and synthesize existing evidence on the relationship between circulating lipid parameters and dementia risk, Alzheimer's disease, and cognitive decline, with particular consideration of their potential utility in resource-limited settings.</p><p><strong>Methods: </strong>A systematic literature review was conducted in accordance with PRISMA guidelines. Studies published between 2000 and May 2025 evaluating associations between lipid profiles and cognitive outcomes, dementia, or neurodegenerative disease were included and narratively synthesized.</p><p><strong>Results: </strong>Evidence across studies suggests that lipid dysregulation is associated with dementia-related outcomes, although findings remain heterogeneous. Elevated total cholesterol, low-density lipoprotein cholesterol, and triglycerides were frequently associated with increased risk of dementia, Alzheimer's disease, or cognitive decline, whereas high-density lipoprotein cholesterol generally showed protective associations. Several studies also identified prognostic value in composite lipid ratios and lipid variability measures. However, the strength and direction of associations varied according to age, sex, timing of lipid assessment, and study population.</p><p><strong>Conclusions: </strong>Circulating lipid parameters alone are insufficient as definitive diagnostic biomarkers. However, when interpreted in a population-specific and life-course context, they may contribute to early risk stratification and complement neuropsychological screening, particularly in resource-limited settings where access to advanced neuroimaging and cerebrospinal fluid testing is restricted.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"10 ","pages":"25424823261475263"},"PeriodicalIF":2.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186772","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":"Does depression in Alzheimer's disease show evidence of differential gene expression in neurons or microglia compared to Alzheimer's disease without depression?","authors":"Lindsey I Sinclair, Mizuki Morisaki, Peter P Henley, Emma L Dempster, Clive G Ballard, Jordan T Lin, Robert MacLachlan, Seth Love","doi":"10.1177/25424823261472076","DOIUrl":"10.1177/25424823261472076","url":null,"abstract":"<p><strong>Background: </strong>Depression in Alzheimer's disease (AD) is common, distressing, difficult to treat and inadequately understood.</p><p><strong>Objective: </strong>We compared gene expression in neurons and microglia from AD patients +/- depression, stratified according to depression polygenic risk score (PRS-D) and looked for differential pathway regulation.</p><p><strong>Methods: </strong>We identified AD patients with (<i>n</i> = 95) or without depression (<i>n</i> = 25) whose brains had been donated to a UK brain bank. Exclusion criteria included other disorders known to affect cognition, previous major psychiatric disorder and a neuropathological diagnosis of a non-AD dementia. Depression was defined as a clinical depression diagnosis or Geriatric Depression Scale/Center for Epidemiologic Studies Depression Scale >7. PRS-D was calculated using LDpred2. In the AD + depression group, only the top (<i>n</i> = 29) and bottom tertile (<i>n</i> = 30) of PRS-D were analyzed by microarray. Tissue from superior frontal gyrus (SFG) and anterior insula (AIns) was sorted into neuronal and microglial fractions, and gene expression measured using a ClariomS Pico microarray.</p><p><strong>Results: </strong>After quality control, microarray data were available for AIns microglia (<i>n</i> = 51), AIns neurons (<i>n</i> = 59), SFG microglia (<i>n</i> = 60) and SFG neurons (<i>n</i> = 63). No individual genes had a <i>p</i> < 0.05, adjusted for false discovery rate. Gene set enrichment analysis identified significantly upregulated and downregulated pathways in both brain regions and cell types. More pathways were differentially expressed in microglia than in neurons. Many of these pathways related to infection or inflammation but also included olfactory transduction and Parkinson's disease.</p><p><strong>Conclusions: </strong>In conclusion we have identified pathways that may contribute to the development of depression in AD. A majority were identified predominantly in microglia.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"10 ","pages":"25424823261472076"},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198191","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":"Retinal tau imaging and histopathology as emerging Alzheimer's disease biomarkers: A systematic review.","authors":"Mohamed S Abdelkader, Hadeer N Atalah, Ayat Mamdouh, Rim Ghazal, May Bakr, Mohamed Salama","doi":"10.1177/25424823251391710","DOIUrl":"https://doi.org/10.1177/25424823251391710","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) deposition and tau protein aggregation. The retina, as an extension of the central nervous system, has emerged as a promising site for detecting biomarkers of AD.</p><p><strong>Objective: </strong>This systematic review synthesizes the current evidence on retinal tau protein as a diagnostic tool for AD and related tauopathies.</p><p><strong>Methods: </strong>This systematic review adhered to PRISMA guidelines, analyzing studies on retinal tau biomarkers, structural changes, and diagnostic imaging techniques. The included studies encompassed molecular investigations, experimental models, and clinical imaging approaches.</p><p><strong>Results: </strong>Retinal phosphorylated tau (p-tau) and related isoforms were consistently identified as correlating with systemic AD pathology, including Braak staging. Experimental and clinical studies revealed early retinal changes, such as ganglion cell degeneration and blood-retina barrier breakdown, that preceded cognitive decline. Diagnostic advancements, including curcumin fluorescence imaging, ferritin nanocages, and hyperspectral imaging, demonstrated enhanced precision and feasibility for detecting retinal tau and Aβ in vivo and postmortem. These findings suggest that retinal tau serves as a robust biomarker for AD.</p><p><strong>Conclusions: </strong>Retinal tau pathology represents a powerful diagnostic tool, providing non-invasive access to early AD pathology. By integrating molecular insights with advanced imaging modalities, retinal biomarkers could enable earlier diagnosis, therapeutic monitoring, and personalized treatment strategies. Future research should focus on longitudinal validation of retinal biomarkers across diverse populations.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"10 ","pages":"25424823251391710"},"PeriodicalIF":2.8,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198458","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":"Normative data of the coding test in Korean middle-aged and elderly population.","authors":"Yura Choi, Hyejin Ahn, Woo-Jin Cha, Seunghyuk Ha, Yoon Seok Oh, Gijung Jung, Min Soo Byun, Dahyun Yi, Dong Young Lee","doi":"10.1177/25424823261470043","DOIUrl":"10.1177/25424823261470043","url":null,"abstract":"<p><strong>Background: </strong>The Coding (CD) subtest is widely recognized as a sensitive and reliable measure of age-related cognitive decline, particularly in processing speed, which is known to be vulnerable in the early stages of Alzheimer's disease. However, normative data for middle-aged and older Korean adults, who exhibit wide variability in educational backgrounds, remain limited. Establishing norms that reflect this demographic diversity is essential for accurate cognitive assessment and interpretation.</p><p><strong>Objective: </strong>This study aimed to examine the effects of age, education, and gender on CD performance in cognitively unimpaired Korean adults aged 50 years and older, and to establish normative data for the Korean aging population.</p><p><strong>Methods: </strong>A total of 534 cognitively unimpaired adults aged 50 to 92 years participated. The CD subtest was administered following standardized procedures. Analysis of variance and hierarchical multiple linear regression analyses were performed to examine the demographic effects on CD performance.</p><p><strong>Results: </strong>Younger age and higher education were associated with better CD performance, with a significant age-by-education interaction, while gender did not show a significant effect. Accordingly, normative data were established for three age groups (50-59, 60-74, and ≥75 years) and three education levels (0-8, 9-12, and ≥13 years).</p><p><strong>Conclusions: </strong>The normative data presented in this study provide a valuable reference for clinicians and researchers to more accurately evaluate processing speed abilities in middle-aged and older Korean adults.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"10 ","pages":"25424823261470043"},"PeriodicalIF":2.8,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198474","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":"The single cell origin of sporadic Alzheimer's disease: A developmental biallelic somatic mutation model.","authors":"Simon A Morris","doi":"10.1177/25424823261472068","DOIUrl":"https://doi.org/10.1177/25424823261472068","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disorder beginning decades prior to diagnosis and characterized by aggregates of amyloid-β (Aβ)₄₂ and of hyperphosphorylated tau (ptau) proteins. The etiology of sporadic AD (sAD) is unclear and there are problems in our understanding of dominantly inherited familial AD (fAD). In carriers the dominant mutation is expressed throughout the brain in every neuron <i>in utero</i>; why then is the appearance of Aβ₄₂ plaques focal? To explain this, a single cell origin model for sAD is proposed based on Knudson's biallelic mutation model for neoplasia. Familial neoplasia (fN) syndromes have an autosomal dominant pattern of inheritance. However, if the fN mutations are dominant at the cellular level then every cell expressing the mutation would become a tumor and that is not the case. Tumors originate from single cells and somatic loss of heterozygosity (LOH) in a fN carrier cell is necessary for tumorigenesis and defines fN mutations as recessive. Analogously somatic LOH is necessary in a fAD carrier neuron for it to produce Aβ₄₂ monomers in sufficient concentration (Aβ₄₂ neuron) to potentiate Aβ₄₂ nucleation and to generate prion-like Aβ₄₂ oligomers. In sAD the biallelic mutations in the founder Aβ₄₂ neuron are somatic. Endogenous neuronal somatic mutations peak in incidence during development. The number of founder Aβ₄₂ neurons, the variant of the fAD mutation, and the location and neural connectivity of the Aβ₄₂ neuron to the locus coeruleus will impact the age of onset and clinical heterogeneity. Knudson's biallelic somatic mutation model in development is applicable to all prion-like neurodegenerative disorders.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"10 ","pages":"25424823261472068"},"PeriodicalIF":2.8,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149197695","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":"Herpes simplex virus, <i>APOE</i> ε4, and olfactory function in older adults: A cohort study.","authors":"Eva-Stina Hemmingsson, Jan Olsson, Maria Josefsson, Fredrik Elgh, Maria Larsson, Bodil Weidung, Hugo Lövheim","doi":"10.1177/25424823261470737","DOIUrl":"10.1177/25424823261470737","url":null,"abstract":"<p><strong>Background: </strong>Olfactory dysfunction (OD) is associated with neurodegenerative disorders, including Alzheimer's disease (AD). Herpes simplex virus type 1 (HSV1) may increase AD risk, but longitudinal changes in olfaction related to HSV1 carriage and apolipoprotein ε4 (<i>APOE</i> ε4) status remain unclear.</p><p><strong>Objective: </strong>To investigate if OD is associated with carriage of HSV1, and whether <i>APOE</i> ε4 status modulates this possible association.</p><p><strong>Methods: </strong>From a large population-based cohort study in northern Sweden (Betula study), 1288 individuals with a baseline odor identification assessment were included, with follow-up assessment (n = 950) after five or ten years. Odor sensitivity (odor threshold test) was tested at a single time point for 651 individuals. HSV1 carriership and apolipoprotein E genotype were established for all participants.</p><p><strong>Results: </strong>Weighted linear mixed-model analyses showed that carriage of HSV1, regardless of <i>APOE</i> ε4 status, was not associated with decline in odor identification. At baseline, male gender and higher age were associated with impaired odor identification, while better semantic memory was associated with better odor identification ability. Higher age, low education level and better semantic memory were associated with poorer odor identification performance over time. Furthermore, multiple linear regression showed that male gender, higher age and low education level were significantly associated with impaired odor sensitivity.</p><p><strong>Conclusions: </strong>HSV1 did not associate with OD in this population-based cohort study with 5-10 years of follow-up, where olfaction was measured and analyzed using two different objective measurements. The association between OD and neurodegenerative diseases needs further investigation.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"10 ","pages":"25424823261470737"},"PeriodicalIF":2.8,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186730","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":"Identifying facility-level and infrastructure-level bottlenecks in Japan's lecanemab rollout through an online survey of dementia specialists.","authors":"Saki Nakashima, Kenichiro Sato, Yoshiki Niimi, Ryoko Ihara, Atsushi Iwata, Kiyotaka Nemoto, Tetsuaki Arai, Shinji Higashi, Ataru Igarashi, Kensaku Kasuga, Haruhiko Akiyama, Shuichi Awata, Manabu Ikeda, Tatsushi Toda, Takeshi Iwatsubo","doi":"10.1177/25424823261470054","DOIUrl":"10.1177/25424823261470054","url":null,"abstract":"<p><strong>Background: </strong>The approval of lecanemab has created new operational demands for Alzheimer's disease care. Japan's nationwide rollout under universal health insurance offers an opportunity to identify real-world bottlenecks in treatment delivery.</p><p><strong>Objective: </strong>To identify facility-level and infrastructure-level factors associated with wait time to initial lecanemab infusion and treated patient volume among dementia specialists in Japan.</p><p><strong>Methods: </strong>We performed a secondary analysis of an anonymous online survey of 296 dementia specialists certified to prescribe lecanemab in Japan approximately one year after approval. We examined associations between physician/facility characteristics, diagnostic and infusion resources, perceived implementation barriers, and two delivery metrics: wait time from first consultation to first infusion and number of treated patients per respondent. Bayesian accelerated failure-time and zero-truncated Poisson mixed-effects models were used.</p><p><strong>Results: </strong>Approximately 80% of respondents reported average wait times of 3 months or less, whereas the median treated caseload was modest at 5 patients per physician. Perceived mismatch between treatment capacity and demand was associated with longer wait time (time ratio 1.323, 95% credible interval 1.045-1.682). Cerebrospinal fluid (CSF)-dominant amyloid-testing strategies tended to be associated with smaller caseloads, while in-house CSF testing and <i>APOE</i> testing were associated with larger caseloads. High-volume centers reported constrained outpatient infusion space. Lack of reimbursement for infusion-related tasks and <i>APOE</i> testing were perceived as major system-level barriers.</p><p><strong>Conclusions: </strong>Japan's rollout may be constrained by some bottlenecks in diagnostics, infusion infrastructure, and uncompensated tasks. Appropriate policy interventions might help secure equitable access to the treatment.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"10 ","pages":"25424823261470054"},"PeriodicalIF":2.8,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149185989","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":"Lecanemab real-world treatment outcomes from cohort study in early Alzheimer's disease.","authors":"Alyanna Ferrer, Justin Moon","doi":"10.1177/25424823261470042","DOIUrl":"https://doi.org/10.1177/25424823261470042","url":null,"abstract":"<p><p>Lecanemab has demonstrated amyloid reduction and slowed clinical decline in early Alzheimer's disease trials. Herein, we report retrospective case series results on lecanemab treatment in our clinic. Overall, 61 individuals were included. For the 33 patients with Kokmen Mental Status Exam baseline and post-baseline scores, 67% had either improved or stable scores. Nine incident amyloid-related imaging abnormalities were observed with all but one patient continuing treatment. Six patients were safely transitioned from aducanumab to lecanemab treatment upon market withdrawal of aducanumab. In a real-world clinical practice setting, the lecanemab effectiveness and safety profile were similar to that observed in clinical studies.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"10 ","pages":"25424823261470042"},"PeriodicalIF":2.8,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198391","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":"Central nervous system-active medication polypharmacy and risk for nursing home admission among adults with early-onset dementia: A retrospective cohort study.","authors":"Nistha Shrestha, ChienWei Chiang, Yu-Jung Jenny Wei","doi":"10.1177/25424823261472831","DOIUrl":"10.1177/25424823261472831","url":null,"abstract":"<p><strong>Background: </strong>While central nervous system (CNS)-active medication polypharmacy is prevalent among adults with early-onset dementia (EOD), its impact on nursing home (NH) admission is unclear.</p><p><strong>Objective: </strong>To examine whether CNS-active medication polypharmacy is associated with risk for NH admission among patients with EOD.</p><p><strong>Methods: </strong>A retrospective cohort study using 2012-2021 MarketScan Databases was conducted with adults aged 30 to 64 years diagnosed with Alzheimer's disease and related dementias (ADRD). CNS-active medication polypharmacy was assessed during a fixed 6-month period after an indexed ADRD diagnosis and defined as concurrent use of ≥3 CNS-active medications on the American Geriatrics Society Beers Criteria list that overlapped for ≥30 consecutive days. Cox hazards models were used to estimate the hazard ratio (HR) of NH admission between patients with versus without CNS-active medication polypharmacy, with adjustment for baseline covariates via inverse probability of treatment weighting.</p><p><strong>Results: </strong>Of the 18,029 patients with EOD identified, those with CNS-active medication polypharmacy (versus those without) had an increased risk of NH admission (HR, 1.34 [95% CI, 1.16-1.56]). The risk was pronounced in patients aged >50 years, male patients, patients with a diagnosis of Alzheimer's disease or senile dementia, and patients having baseline use of anti-dementia medications.</p><p><strong>Conclusions: </strong>In this commercially insured population of adults with EOD, receipt of CNS-active medication polypharmacy was associated with risk for NH admission. The finding, however, should be interpreted with caution, as it may reflect differences in the underlying disease severity and clinical indications treated by the studied CNS-active medications.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"10 ","pages":"25424823261472831"},"PeriodicalIF":2.8,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198225","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}