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. 2024 Feb;20(2):986-994.
doi: 10.1002/alz.13501. Epub 2023 Oct 14.

Depressive symptoms and hippocampal volume in autosomal dominant Alzheimer's disease

Stephanie Langella  1 , Francisco Lopera  2 , Ana Baena  2 , Joshua T Fox-Fuller  1   3 , Diana Munera  1 , Jairo E Martinez  1   3 , Averi Giudicessi  1   3 , Patrizia Vannini  1   4 , Bernard J Hanseeuw  5   6 , Gad A Marshall  1   4 , Yakeel T Quiroz  1   2 , Jennifer R Gatchel  1   7   8   9
Affiliations

Depressive symptoms and hippocampal volume in autosomal dominant Alzheimer's disease

Stephanie Langella et al. Alzheimers Dement. 2024 Feb.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Discussion: 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.

Highlights: 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.

Keywords: autosomal dominant Alzheimer's disease; depression; hippocampus; preclinical; presenilin-1.

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Conflict of interest statement

S.L. has nothing to disclose. F.L. has nothing to disclose. A.B. has nothing to disclose. J.T.F.F. has nothing to disclose. D.M. has nothing to disclose. J.E.M. has nothing to disclose. A.G. has nothing to disclose. P.V. has nothing to disclose. B.H. has nothing to disclose. G.A.M. has served as site principal investigator for AD clinical trials sponsored by Eli Lilly and Company, Eisai Inc., and Genentech. Y.T.Q. serves as a consultant for Biogen. J.R.G. has nothing to disclose. Author disclosures are available in the supporting information.

Figures

FIGURE 1
FIGURE 1
Depressive symptoms and hippocampal volume in PSEN1 carriers and non‐carriers. Distribution of (A) Geriatric Depression Scale scores and (B) normalized hippocampal volume by group. Scatterplot with estimated regression line and standard error bands of (C) Geriatric Depression Scale scores and (D) normalized hippocampal volume by age in carriers (red) and non‐carriers (black). PSEN1, presenilin‐1
FIGURE 2
FIGURE 2
Association between hippocampal volume and depressive symptoms in carriers and non‐carriers. Scatterplots showing Geriatric Depression Scale scores plotted by normalized hippocampal volume in (A) carriers and (B) non‐carriers with regression lines and standard error bands.
See this image and copyright information in PMC

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