TY  - JOUR
AU  - Najar, Jenna
AU  - de Rojas, Itziar
AU  - Dalmasso, Maria Carolina
AU  - Fernandez, Maria Victoria
AU  - de Boer, Sterre C M
AU  - Ramirez, Alfredo
AU  - Priller, Josef
AU  - Laske, Christoph
AU  - Kleineidam, Luca
AU  - Schneider, Anja
AU  - Wagner, Michael
AU  - Heilmann-Heimbach, Stefanie
AU  - Scherer, Martin
AU  - Froelich, Lutz
AU  - Peters, Oliver
AU  - Hellmann-Regen, Julian David Nicolai
AU  - Wiltfang, Jens
AU  - Düzel, Emrah
AU  - Buerger, Katharina
AU  - Perneczky, Robert
AU  - Teipel, Stefan
AU  - Jessen, Frank
AU  - Kornhuber, Johannes
AU  - Lemstra, Afina W
AU  - Pijnenburg, Yolande A L
AU  - van der Lee, Sven J
AU  - Reus, Lianne M
TI  - Polygenic risk for psychiatric disorders and its association with neuropsychiatric symptoms in dementia.
JO  - International review of psychiatry
VL  - 37
IS  - 8
SN  - 0954-0261
CY  - Abingdon
PB  - Taylor & Francis Group
M1  - DZNE-2026-00039
SP  - 816 - 826
PY  - 2025
AB  - Neuropsychiatric symptoms are common in Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD), yet their genetic underpinnings remain unclear. To gain insight into biological processes related to neuropsychiatric symptoms in dementia, we investigated whether polygenic risk scores (PRS) for psychiatric disorders - major depressive disorder (MDD), schizophrenia (SCZ), bipolar disorder (BD), and autism spectrum disorder (ASD) - are associated with neuropsychiatric symptoms in dementia. Data included genetic and neuropsychiatric data of 6240 AD patients, 428 FTD patients and 390 DLB patients from five European cohorts (ADC, GR@ACE, DELCODE, AgeCoDe, and DCN). PRS for MDD, BD, SCZ, and ASD were calculated using LDpred2. Neuropsychiatric symptoms were assessed using total scores from the Neuropsychiatric Inventory (NPI) (NPI-12 and NPI-Q) and Geriatric Depression scale (GDS). Associations between PRS and symptoms were examined using linear regression models, followed by meta-analyses. In FTD, higher SCZ-PRS associated with lower NPI scores in the meta-analysis (β = -0.12, p = .001). No associations were found in AD and DLB. This is the first study to show that genetic liability for SCZ associates with lower NPI in FTD, warranting further investigation.
KW  - Humans
KW  - Multifactorial Inheritance: genetics
KW  - Aged
KW  - Male
KW  - Female
KW  - Alzheimer Disease: genetics
KW  - Lewy Body Disease: genetics
KW  - Frontotemporal Dementia: genetics
KW  - Depressive Disorder, Major: genetics
KW  - Bipolar Disorder: genetics
KW  - Genetic Predisposition to Disease
KW  - Schizophrenia: genetics
KW  - Schizophrenia: physiopathology
KW  - Autism Spectrum Disorder: genetics
KW  - Dementia: genetics
KW  - Middle Aged
KW  - Mental Disorders: genetics
KW  - Aged, 80 and over
KW  - Dementia (Other)
KW  - frontotemporal dementia (Other)
KW  - neuropsychiatric symptoms (Other)
KW  - polygenic risk scores (Other)
KW  - psychiatric disorders (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:41437785
DO  - DOI:10.1080/09540261.2025.2600619
UR  - https://pub.dzne.de/record/283143
ER  -