Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Introduction: An integrative polygenic risk score (iPRS) capturing the neurodegenerative and vascular contribution to dementia could identify high-risk individuals and improve risk prediction.
Methods: We developed an iPRS for dementia (iPRS-DEM) in Europeans (aged 65+), comprising genetic risk for Alzheimer's disease (AD) and 23 vascular or neurodegenerative traits (excluding apolipoprotein E [APOE]). iPRS-DEM was evaluated across cohorts comprising older community-dwelling people (N = 3702), a multi-ancestry biobank (N = 130,797 Europeans; 105,404 non-Europeans), and dementia-free memory clinic participants (N = 2032).
Results: iPRS-DEM was associated with dementia risk independently of APOE in the elderly (subdistribution hazard ratio [sHR]= 1.15, 95% confidence interval [CI]: 1.03 to 1.28), which generalized to Europeans (EUR-sHR= 1.28, 95% CI: 1.09 to 1.51]), East-Asians (EAS-sHR= 5.29, 95% CI: 1.43 to 34.36), and memory-clinic participants (sHR= 1.25, 95% CI: 1.11 to 1.42). Prediction was comparable to clinical risk factors in older community-dwelling people, with improved performance among memory-clinic patients. Risk stratification was enhanced by defining four genetic risk groups with iPRS-DEM and APOE ε4, reaching five-fold increased risk in APOE ε4+/iPRS-DEM+ memory-clinic participants.
Discussion: Alongside APOE ε4, iPRS-DEM may refine risk stratification for the enrichment of dementia clinical trials and prevention programs.
Highlights: iPRS-DEM reflects neurodegenerative and vascular contribution to dementia. We show iPRS-DEM captures additional dementia genetic risk beyond APOE and AD-PRS. iPRS-DEM, in combination with APOE ε4, shows promise for dementia risk stratification. Our results generalize across both population-based and memory-clinic settings. We show transportability of iPRS-DEM to East Asian ancestry.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881617 | PMC |
| http://dx.doi.org/10.1002/alz.70014 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Preoperatively predicting failure to achieve the minimum clinically important difference and substantial clinical benefit for total knee arthroplasty patients using machine learning.
Knee Surg Relat Res
September 2025
Florida Orthopaedic Institute, Gainesville, FL, 32607, USA.
Background: A clear understanding of minimal clinically important difference (MCID) and substantial clinical benefit (SCB) is essential for effectively implementing patient-reported outcome measurements (PROMs) as a performance measure for total knee arthroplasty (TKA). Since not achieving MCID and SCB may reflect suboptimal surgical benefit, the primary aim of this study was to use machine learning to predict patients who may not achieve the threshold-based outcomes (i.e.
View Article and Find Full Text PDFA simplified clinical frailty scale predicts mortality in emergency department patients with acute dyspnea.
Geroscience
September 2025
Department of Emergency and Internal Medicine, Skåne University Hospital, Malmö, Sweden.
To evaluate a simplified version of the Clinical Frailty Scale (SCFS) among older adults presenting to the emergency department (ED) with acute dyspnea. In this retrospective single-center cohort study, we included patients from the Acute Dyspnea Study (ADYS) cohort. Severity of illness was assessed using the Medical Emergency Triage and Treatment System (METTS).
View Article and Find Full Text PDFPhenotypic age acceleration as a novel predictor of benign prostatic hyperplasia: a prospective cohort study.
Geroscience
September 2025
Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
This study aims to investigate the predictive value of combined phenotypic age and phenotypic age acceleration (PhenoAgeAccel) for benign prostatic hyperplasia (BPH) and develop a machine learning-based risk prediction model to inform precision prevention and clinical management strategies. The study analyzed data from 784 male participants in the US National Health and Nutrition Examination Survey (NHANES, 2001-2008). Phenotypic age was derived from chronological age and nine serum biomarkers.
View Article and Find Full Text PDFItalian guidelines for cervical cancer screening. Multisocietal recommendations on the use of biomarkers in HPV screening with risk-based approach and GRADE methodology.
Br J Cancer
September 2025
Istituto Oncologico Veneto IOV-IRCCS, Padova, Italy.
The European Council recommends adopting risk-based screening when relevant. In triaging HPV-positive women, it can be an effective strategy to reduce overtreatment and referral to colposcopy. HPV genotyping and p16/ki67 expression may allow a better risk stratification than cytology.
View Article and Find Full Text PDFChanges in food choices and dietary patterns during the lifestyle intervention and their association with type 2 diabetes risk in participants with high or low genetic risk for type 2 diabetes.
Eur J Nutr
September 2025
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, PO Box 1627, 70211, Kuopio, Finland.
Purpose: To investigate how a group-based lifestyle intervention affects food choices and if the dietary patterns at the end of the intervention are associated with incidence type 2 diabetes (T2D). We also investigated if the possible associations between diet and T2D risk were modified by the genetic risk for T2D.
Methods: Participants in the T2D-GENE study were men with prediabetes aged 50-75 years, body mass index ≥ 25 kg/m, belonging in either low or high genetic risk score (GRS) tertile for T2D.