biostudies-literatureLangella SNIA NIH HHSFonds De La Recherche Scientifique - FNRSDepartamento Administrativo de Ciencia, Tecnología e InnovaciónNINDS NIH HHSNational Institute on Aging986-994https://www.ebi.ac.uk/biostudies/studies/S-EPMC10916972biostudies-literatureUnknown20(2)<h4>Introduction</h4>Depressive symptoms are among early behavioral changes in Alzheimer's disease (AD); however, the relationship between neurodegeneration and depressive symptoms remains inconclusive. To better understand this relationship in preclinical AD, we examined hippocampal volume and depressive symptoms in cognitively unimpaired carriers of the presenilin-1 (PSEN1) E280A mutation for autosomal dominant AD.<h4>Methods</h4>A total of 27 PSEN1 mutation carriers and 26 non-carrier family members were included. Linear regression was used to test the relationship between hippocampal volume and 15-item Geriatric Depression Scale.<h4>Results</h4>Carriers and non-carriers did not differ in depressive symptoms or hippocampal volume. Within carriers, lower hippocampal volume was associated with greater depressive symptoms, which remained significant after adjusting for age and cognition. This relationship was not significant in non-carriers.<h4>Discussion</h4>Hippocampal neurodegeneration may underlie depressive symptoms in preclinical autosomal dominant AD. These findings provide support for the utility of targeting depressive symptoms in AD prevention.<h4>Highlights</h4>We compared unimpaired autosomal dominant Alzheimer's disease (AD) mutation carriers and non-carriers. Carriers and non-carriers did not differ in severity of depressive symptoms. In carriers, hippocampal volume was inversely associated with depressive symptoms. Depressive symptoms may be a useful target in AD prevention.Alzheimer's & dementia : the journal of the Alzheimer's AssociationDepressive symptoms and hippocampal volume in autosomal dominant Alzheimer's disease.PMC10916972R01AG078191R01 AG054671R01 AG071074R42 AG069629RM1 NS132996111565741185R01 AG053184RF1 AG077627RF1AG077627F31AG062158R21 AG064413F31 AG062158R01 AG067021#CCL40010417#40010035K23 AG058805R01 AG078191R21 AG070877Langella SMartinez JEHanseeuw BJMarshall GAVannini PGatchel JRGiudicessi AFox-Fuller JTQuiroz YTLopera FBaena AMunera DfalseDepressive symptoms and hippocampal volume in autosomal dominant Alzheimer's disease.<h4>Introduction</h4>Depressive symptoms are among early behavioral changes in Alzheimer's disease (AD); however, the relationship between neurodegeneration and depressive symptoms remains inconclusive. To better understand this relationship in preclinical AD, we examined hippocampal volume and depressive symptoms in cognitively unimpaired carriers of the presenilin-1 (PSEN1) E280A mutation for autosomal dominant AD.<h4>Methods</h4>A total of 27 PSEN1 mutation carriers and 26 non-carrier family members were included. Linear regression was used to test the relationship between hippocampal volume and 15-item Geriatric Depression Scale.<h4>Results</h4>Carriers and non-carriers did not differ in depressive symptoms or hippocampal volume. Within carriers, lower hippocampal volume was associated with greater depressive symptoms, which remained significant after adjusting for age and cognition. This relationship was not significant in non-carriers.<h4>Discussion</h4>Hippocampal neurodegeneration may underlie depressive symptoms in preclinical autosomal dominant AD. These findings provide support for the utility of targeting depressive symptoms in AD prevention.<h4>Highlights</h4>We compared unimpaired autosomal dominant Alzheimer's disease (AD) mutation carriers and non-carriers. Carriers and non-carriers did not differ in severity of depressive symptoms. In carriers, hippocampal volume was inversely associated with depressive symptoms. Depressive symptoms may be a useful target in AD prevention.2024-01-01T00:00:00Z2024 Feb2026-03-12T23:18:23.49Z2025-08-12T03:04:34.082ZS-EPMC109169723783752410.1002/alz.13501