Evidence map›Paper›PMID 42594416›Full record

ArticleThe journal of prevention of Alzheimer's disease2026

Predictive value of the Alzheimer polygenic risk score on cognitive decline in patients with mild cognitive impairment and Alzheimer's disease dementia.

Berta Calm, Adrián Hinojosa-Calleja, Fernando García-Gutiérrez, Josep Blazquez-Folch, Montserrat Alegret, Maria Victoria Fernández, Itziar De Rojas, Pablo García-González, Clàudia Olivé, Alejandro Valenzuela-Seba and 18 more

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Article in The journal of prevention of Alzheimer's disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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4 · The record

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5 · Who and what money

Authors and funding

28 authors.

Berta CalmAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain.
Adrián Hinojosa-CallejaAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain.
Fernando García-GutiérrezAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain.
Josep Blazquez-FolchAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain.
Montserrat AlegretAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain.
Maria Victoria FernándezAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain.
Itziar De RojasAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain.
Pablo García-GonzálezAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain; PhD Program in Biotechnology, Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. De Joan XXIII, 27-31, 08028 Barcelona, Spain.
Clàudia OlivéAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain; PhD Program in Biotechnology, Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. De Joan XXIII, 27-31, 08028 Barcelona, Spain.
Alejandro Valenzuela-SebaAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain.
Paula Bayón-BujánAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain.
Amanda CanoAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain.
Raquel PuertaAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain; PhD Program in Biotechnology, Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. De Joan XXIII, 27-31, 08028 Barcelona, Spain.
Maria Capdevila-BayoAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain; Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Science, University of Barcelona, Av. de Joan XXIII, 27-31, 08028 Barcelona, Spain.
Álvaro Muñoz-MoralesAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain.
Andrea MiguelAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain.
Ariadna SolivarAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain.
Laura MontrrealAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain.
Pilar Sanz-CartagenaAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain.
Maitee Rosende-RocaAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain.
Yahveth Cantero-FortizAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain.
Miren Jone GurruchagaAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain.
Lluís TárragaAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain.
Mercè BoadaAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain.
Marta MarquiéAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain.
Agustín RuizAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, 8300 Floyd Curl Drive, San Antonio TX 78229, USA; Department of Microbiology, Immunology and Molecular Genetics. Long School of Medicine. University of Texas Health Science Center, 8300 Floyd Curl Drive, San Antonio TX 78229, USA.
Sergi ValeroAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Gran Via de Carles III, 85 bis, 08028 Barcelona, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain. Electronic address: svalero@fundacioace.org.
Alzheimer’s Disease Neuroimaging Initiative

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
NIA NIH HHS U01 AG024904
6 · The paper itself

Abstract

backgroundPolygenic risk scores for Alzheimer's disease (AD-PRS) are widely used to estimate genetic susceptibility to AD, but their relationship with the rate of cognitive decline (CD) after clinical onset remains insufficiently characterized.

objectivesTo examine the association between AD-PRS and longitudinal CD across the AD spectrum and to evaluate the predictive contribution of individual AD-PRS variants.

designLarge longitudinal observational study in a single-center cohort, with an external cohort to assess generalizability.

settingMemory clinic cohort from Ace Alzheimer Center Barcelona (Ace) with external cohort using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI).

participantsThe study included 7,233 patients from Ace and 863 from ADNI, with a mean follow-up of 5.4 years in Ace and 3.6 years in ADNI. A biomarker sub-cohort included 1075 participants from Ace and 569 from ADNI. MEASUREMENTS: CD was quantified as the annual change in Mini-Mental State Examination (MMSE) scores estimated using linear mixed-effects models. Associations between AD-PRS and longitudinal MMSE trajectories were tested adjusting for clinical and sociodemographic (CSD) variables and APOE genotype. Machine learning models and SHapley Additive exPlanations (SHAP) were used to evaluate the predictive relevance of individual variants.

resultsHigher AD-PRS was associated with faster CD in the full clinical cohort and in biomarker subset, independently of APOE genotype. AD-PRS was not associated with baseline MMSE. APOE ε4 was associated with lower baseline MMSE and faster CD only in the full clinical sample. Genetic predictors provided limited improvement beyond CSD variables, and model performance showed limited reproducibility across cohorts.

conclusionsAD-PRS is associated with longitudinal CD across the AD spectrum. Although polygenic burden contributes to variability in cognitive trajectories, its added predictive value beyond routinely available clinical variables remains modest.

Indexed as

Alzheimer’s diseaseCognitive declineMachine learningPolygenic risk scoresSingle Nucleotide Polymorphisms

Identifiers

PMID42594416
PMCPMC13499134

What Socratic holds

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LicenceCC BY-NC-ND
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.