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There is an urgent need to improve dementia ascertainment robustness in real-world studies assessing drug effects on dementia risk. We developed algorithms to dementia identification algorithms using Medicare claims (inpatient/outpatient/prescription) from 3,318 Visit 5 (2011-2013) and 1,828 Visit 6 (2016-2017) participants of the Atherosclerosis Risk in Communities (ARIC) Study, validated against ARIC's rigorous syndromic dementia classification. Algorithm performance was compared to existing algorithms (Jain, Bynum, Lee). We further evaluated algorithms effectiveness in a 20% random Medicare sample aged ≥70 who initiating liraglutide or dipeptidyl peptidase 4 inhibitors (DPP4i) to assess 3-year adjusted risk difference (aRD) for dementia. Our incident dementia algorithm required two dementia diagnostic codes within 1-year, or one dementia code plus a new dementia prescription within 90-days. It achieved a positive predictive value (PPV) of 69.2%, specificity of 99.0%, and sensitivity of 34.6% (population prevalence: 8.8%), comparable to extant algorithms (PPV 58.7~68.6%; sensitivity 25.5~40.4%). Prevalent dementia algorithm (without requiring incident diagnoses/prescriptions) demonstrated similar performance. In the Medicare sample, dementia risk ranged from 3.0%-12.5%, aRD comparing liraglutide to DPP4i varied -1.2% to -3.6%, with our algorithm closely matching the Bynum algorithm. Algorithm selection significantly impacts treatment effect estimates, highlighting its importance in in pharmacoepidemiologic research.
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http://dx.doi.org/10.1093/aje/kwaf166 | DOI Listing |
JAMA Neurol
September 2025
Translational Neuropathology Research Laboratory, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
Importance: Exposure to fine particulate matter air pollution (PM2.5) may increase risk for dementia. It is unknown whether this association is mediated by dementia-related neuropathologic change found at autopsy.
View Article and Find Full Text PDFJAMA Neurol
September 2025
Center for Neurodegenerative Diseases and the Aging Brain, University of Bari 'Aldo Moro,' "Pia Fondazione Cardinale G. Panico," Tricase, Lecce, Italy.
Importance: Comprehensive incidence and prevalence rates of frontotemporal dementia are currently not available.
Objective: To estimate the incidence and prevalence of frontotemporal dementia and its clinical variants in the overall population and age subgroups.
Data Sources And Study Selection: We systematically searched PubMed, EMBASE, and Scopus between January 1, 1990, and October 22, 2024, for population-based studies estimating the incidence and/or prevalence of FTD.
Eur J Neurol
September 2025
Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Background: Frontotemporal dementia (FTD) encompasses diverse clinical phenotypes, primarily characterized by behavioral and/or language dysfunction. A newly characterized variant, semantic behavioral variant FTD (sbvFTD), exhibits predominant right temporal atrophy with features bridging behavioral variant FTD (bvFTD) and semantic variant primary progressive aphasia (svPPA). This study investigates the longitudinal structural MRI correlates of these FTD variants, focusing on cortical and subcortical structural damage to aid differential diagnosis and prognosis.
View Article and Find Full Text PDFBrief Funct Genomics
January 2025
School of Mathematics and Statistics, Henan University of Science and Technology, No. 263 Kaiyuan Avenue, Luolong District, Luoyang, Henan 471000, China.
Background: Comorbidities and genetic correlations between gastrointestinal tract diseases and psychiatric disorders have been widely reported, but the underlying intrinsic link between Alzheimer's disease (AD) and inflammatory bowel disease (IBD) is not adequately understood.
Methods: To identify pathogenic cell types of AD and IBD and explore their shared genetic architecture, we developed Pathogenic Cell types and shared Genetic Loci (PCGL) framework, which studied AD and IBD and its two subtypes of ulcerative colitis (UC) and Crohn's disease (CD).
Results: We found that monocytes and CD8 T cells were the enriched pathogenic cell types of AD and IBDs, respectively.
J Cereb Blood Flow Metab
September 2025
iInstitut de Mécanique des Fluides de Toulouse (IMFT), Université de Toulouse, CNRS, INPT, Université Toulouse III - Paul Sabatier (UPS), Toulouse, France.
Cerebral Amyloid Angiopathy, a common age-related small vessel disease leading to hemorrhagic stroke, shares many characteristics with Alzheimer's disease: toxic amyloid deposits, microvascular alterations and enlarged perivascular spaces (EPVS). Together, PVS enlargement, reduced amyloid-β clearance and further accumulation form a vicious cycle underlying disease progression. Yet, the neuropathological correlates of EPVS, including the associated angioarchitecture, are poorly understood.
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