Journal Article

DZNE-2026-00039

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Polygenic risk for psychiatric disorders and its association with neuropsychiatric symptoms in dementia.

Najar, J. ; de Rojas, I. ; Dalmasso, M. C.DZNE* ; Fernandez, M. V. ; de Boer, S. C. M. ; Ramirez, A.DZNE* ; Priller, J.DZNE* ; Laske, C.DZNE* ; Kleineidam, L.DZNE* ; Schneider, A.DZNE* ; Wagner, M.DZNE* ; Heilmann-Heimbach, S. ; Scherer, M. ; Froelich, L. ; Peters, O.DZNE* ; Hellmann-Regen, J. D. N.Extern* ; Wiltfang, J.DZNE* ; Düzel, E.DZNE* ; Buerger, K.DZNE* ; Perneczky, R.DZNE* ; Teipel, S.DZNE* ; Jessen, F.DZNE* ; Kornhuber, J. ; Lemstra, A. W. ; Pijnenburg, Y. A. L. ; van der Lee, S. J. ; Reus, L. M.

2025
Taylor & Francis Group Abingdon

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Please use a persistent id in citations: doi:10.1080/09540261.2025.2600619

Abstract: 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.

Keyword(s): Humans (MeSH) ; Multifactorial Inheritance: genetics (MeSH) ; Aged (MeSH) ; Male (MeSH) ; Female (MeSH) ; Alzheimer Disease: genetics (MeSH) ; Lewy Body Disease: genetics (MeSH) ; Frontotemporal Dementia: genetics (MeSH) ; Depressive Disorder, Major: genetics (MeSH) ; Bipolar Disorder: genetics (MeSH) ; Genetic Predisposition to Disease (MeSH) ; Schizophrenia: genetics (MeSH) ; Schizophrenia: physiopathology (MeSH) ; Autism Spectrum Disorder: genetics (MeSH) ; Dementia: genetics (MeSH) ; Middle Aged (MeSH) ; Mental Disorders: genetics (MeSH) ; Aged, 80 and over (MeSH) ; Dementia ; frontotemporal dementia ; neuropsychiatric symptoms ; polygenic risk scores ; psychiatric disorders

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Contributing Institute(s):

1. Patient Studies (Bonn) (Patient Studies (Bonn))
2. Translational Neuropsychiatry (AG Priller)
3. Parkinson Genetics (AG Gasser)
4. Neuropsychology (AG Wagner)
5. Translational Dementia Research (Bonn) (AG Schneider)
6. Molecular biomarkers for predictive diagnostics of neurodegenerative diseases (AG Wiltfang)
7. Clinical Alzheimer’s Disease Research (AG Jessen)
8. Biomarker-Assisted Early Detection of Dementias (AG Peters)
9. Clinical Neurophysiology and Memory (AG Düzel)
10. Clinical Research (Munich) (Clinical Research (Munich))
11. Vascular Cognitive Impairment & Post-Stroke Dementia (AG Dichgans)
12. Clinical Dementia Research (Rostock /Greifswald) (AG Teipel)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

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Database coverage:
; BIOSIS Previews ; BIOSIS Reviews Reports And Meetings ; Clarivate Analytics Master Journal List ; Current Contents - Social and Behavioral Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Social Sciences Citation Index

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