20-year depressive symptoms, dementia, and structural neuropathology in older women

Andrew J Petkus¹, Xinhui Wang¹, Diana Younan², Lauren E Salminen³, Susan M Resnick⁴, Stephen R Rapp^{5

6}, Mark A Espeland^{7

8}, Margaret Gatz⁹, Keith F Widaman¹⁰, Ramon Casanova⁷, Helena Chui¹, Ryan T Barnard⁷, Sarah A Gaussoin⁷, Joseph S Goveas¹¹, Kathleen M Hayden⁶, Victor W Henderson¹², Bonnie C Sachs⁵, Santiago Saldana⁷, Aladdin H Shadyab¹³, Sally A Shumaker⁵, Jiu-Chiuan Chen^{1

2}

Affiliations

¹ Department of Neurology, University of Southern California, Los Angeles, California, USA.
² Department of Population and Public Health Sciences, University of Southern California, Los Angeles, California, USA.
³ Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Marina del Rey, California, USA.
⁴ Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, Maryland, USA.
⁵ Department of Neurology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
⁶ Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
⁷ Department of Biostatistics and Data Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
⁸ Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
⁹ Center for Economic and Social Research, University of Southern California, Los Angeles, California, USA.
¹⁰ Graduate School of Education, University of California, Riverside, Riverside, California, USA.
¹¹ Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
¹² Departments of Epidemiology and Population Health and of Neurology and Neurological Sciences, Stanford University, Palo Alto, California, USA.
¹³ Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, La Jolla, California, USA.

PMID: 38591250
PMCID: PMC11095467
DOI: 10.1002/alz.13781

20-year depressive symptoms, dementia, and structural neuropathology in older women

Andrew J Petkus et al. Alzheimers Dement. 2024 May.

. 2024 May;20(5):3472-3484.

doi: 10.1002/alz.13781. Epub 2024 Apr 9.

Authors

Affiliations

¹ Department of Neurology, University of Southern California, Los Angeles, California, USA.
² Department of Population and Public Health Sciences, University of Southern California, Los Angeles, California, USA.
³ Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Marina del Rey, California, USA.
⁴ Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, Maryland, USA.
⁵ Department of Neurology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
⁶ Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
⁷ Department of Biostatistics and Data Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
⁸ Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
⁹ Center for Economic and Social Research, University of Southern California, Los Angeles, California, USA.
¹⁰ Graduate School of Education, University of California, Riverside, Riverside, California, USA.
¹¹ Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
¹² Departments of Epidemiology and Population Health and of Neurology and Neurological Sciences, Stanford University, Palo Alto, California, USA.
¹³ Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, La Jolla, California, USA.

PMID: 38591250
PMCID: PMC11095467
DOI: 10.1002/alz.13781

Abstract

Introduction: The course of depressive symptoms and dementia risk is unclear, as are potential structural neuropathological common causes.

Methods: Utilizing joint latent class mixture models, we identified longitudinal trajectories of annually assessed depressive symptoms and dementia risk over 21 years in 957 older women (baseline age 72.7 years old) from the Women's Health Initiative Memory Study. In a subsample of 569 women who underwent structural magnetic resonance imaging, we examined whether estimates of cerebrovascular disease and Alzheimer's disease (AD)-related neurodegeneration were associated with identified trajectories.

Results: Five trajectories of depressive symptoms and dementia risk were identified. Compared to women with minimal symptoms, women who reported mild and stable and emerging depressive symptoms were at the highest risk of developing dementia and had more cerebrovascular disease and AD-related neurodegeneration.

Discussion: There are heterogeneous profiles of depressive symptoms and dementia risk. Common neuropathological factors may contribute to both depression and dementia. Highlights The progression of depressive symptoms and concurrent dementia risk is heterogeneous. Emerging depressive symptoms may be a prodromal symptom of dementia. Cerebrovascular disease and AD are potentially shared neuropathological factors.

Keywords: Alzheimer's disease neurodegeneration; cerebrovascular disease; dementia; depression; joint modeling; women.

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Conflict of interest statement

The authors have no conflicts of interest to disclose. Author disclosures are available in the supporting information.

Figures

**FIGURE 1**
Flowchart of study participation (Panel A) and timeline of study assessments (Panel B).

**FIGURE 2**
Graph of estimated mean score of 15‐item Geriatric Depression Scale over time for each joint latent class (Panel A) and cumulative incidence of dementia (Panel B) for each latent class of depressive symptoms. The dashed line in Panel A represents the recommended cutoff suggestive of clinically elevated depressive symptoms.

See this image and copyright information in PMC

References

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20-year depressive symptoms, dementia, and structural neuropathology in older women

Affiliations

20-year depressive symptoms, dementia, and structural neuropathology in older women

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical