ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026
Risk factors underlying brain structure change rate in cognitive decline: Results from genomewide and phenomewide investigations.
Yin Jin, Apostolia Topaloudi, Petros Drineas, Peristera Paschou
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In one paragraphArticle in Alzheimer's & dementia : the journal of the Alzheimer's Association, 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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5 · Who and what moneyAuthors and funding
4 authors.
Apostolia TopaloudiDepartment of Biological Sciences, Purdue University, West Lafayette, Indiana, USA.
Petros DrineasComputer Science, Purdue University, West Lafayette, Indiana, USA.
Peristera PaschouDepartment of Biological Sciences, Purdue University, West Lafayette, Indiana, USA.ORCID 0000-0002-9783-1024 Funding
Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0MTechnology and Remote Assessment CoreU19AG063911 · NIA · MAYO CLINIC ROCHESTER · PI KEJAL KANTARCI · 2019 to 2026
$120.9MNational Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8MTRIAL OF VALPROATE TO ATTENUATE THE PROGRESSION OF ADU01AG010483 · NIA · UNIVERSITY OF ROCHESTER · PI AISEN, PAUL S. · 1991 to 2012
$116.2MNATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8MEarly Onset AD Consortium - the LEAD Study (LEADS)U01AG057195 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI APOSTOLOVA, LIANA G, CARRILLO, MARIA C · 2018 to 2023
$70.3MSmartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5MTDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2MThe Clinical Significance of Incidental White Matter Lesions on MRI Amongst a Diverse Population with Cognitive Complaints (INDEED)U19NS120384 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Kumar B. Rajan · 2020 to 2026
$61.9MAlzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4MTHERAPEUTIC EFFECTS OF INTRA-NASAL INSULIN DETEMIRP50AG005136 · NIA · UNIVERSITY OF WASHINGTON · PI GRABOWSKI, THOMAS J. · 1985 to 2019
$57.2MVIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LAGIER-TOURENNE, CLOTILDE · 1985 to 2018
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6 · The paper itselfAbstract
introductionThe genetic and clinical factors influencing the rate of brain structure change in cognitive decline remain poorly understood. This study aimed to identify genetic variants and risk factors contributing to these changes and explore potential causal relationships.
methodsWe analyzed data from 2036 individuals across three longitudinal cohorts to assess change rates in 17 brain regions associated with cognitive decline. Genome-wide association studies (GWASs) were followed by phenome-wide association studies (PheWASs), Mendelian randomization (MR), and independent replication.
resultsWe identified loci associated with brain structure change, including known Alzheimer's disease genes (apolipoprotein E, APOC1) and novel signals (BEAN1, SDHC). PheWAS and MR analyses in large biobanks suggested potential causal links between brain atrophy and anemia-related traits as well as type 2 diabetes. DISCUSSION: Our findings highlight genetic contributors and clinical traits associated with brain structure change in cognitive decline. Larger studies with broader cognitive assessments are needed to validate these findings.
Indexed as
BrainCognitive DysfunctionAgedAlzheimer DiseaseAtrophyDiabetes Mellitus, Type 2FemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansLongitudinal StudiesMagnetic Resonance ImagingMaleMendelian Randomization AnalysisPhenotypePolymorphism, Single NucleotideAlzheimer's disease risk factorsanemia and hematological factorsbrain structure changes in cognitive declinegenome‐wide association studiesneuroimaging markerstype 2 diabetes
Identifiers
PMID42010774
PMCPMC13095869
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