TY - JOUR
T1 - Apathy as a Within-Person Mediator of Depressive Symptoms and Cognition in Parkinson's Disease
T2 - Longitudinal Mediation Analyses
AU - Szymkowicz, Sarah M.
AU - Jones, Jacob D.
AU - Timblin, Holly
AU - Ryczek, Cameron A.
AU - Taylor, Warren D.
AU - May, Pamela E.
N1 - Funding Information:
This work was supported by National Institutes of Health (NIH) Grants SC3NS124906 (to JDJ) and U24MH100925 (to PEM). No disclosures to report.
Funding Information:
Data used in the preparation of this article were obtained from the Parkinson's Progression Markers Initiative (PPMI) database ( www.ppmi-info.org/data ). For up-to-date information on the study, visit www.ppmi-info.org . PPMI – a public-private partnership – is funded by the Michael J. Fox Foundation for Parkinson's Research and funding partners, including 4D Pharma PLC, AbbVie, AcureX Therapeutics, Allergan, Amathus Therapeutics, Aligning Science Across Parkinson's (ASAP), Avid Radiopharmaceuticals, Bial BioTech, Biogen Idec, BioLegend, Bristol-Meyers Squibb, Calico, Celgene, Dacapo Brain Science, Denali Therapeutics, Edmond J. Safra Philanthropic Foundation, Eli Lilly, GE Healthcare, Genentech, GlaxoSmithKline, Golub Capital, Handl Therapeutics, Insitro, Janssen Neuroscience, Lundbeck, Merck, Meso Scale Discovery, Neurocrine Biosciences, Pfizer Inc., Piramal Imaging, Prevail Therapeutics, Roche group, Sanofi-Genzyme, Servier, Takeda, TEVA, UCB, Verily, and Voyager Therapeutics.
Publisher Copyright:
© 2021 American Association for Geriatric Psychiatry
PY - 2022/6
Y1 - 2022/6
N2 - Objective: Greater depressive symptoms are associated with worse cognitive functions in Parkinson's disease (PD); however, it is unclear what underlying factors drive this association. Apathy commonly develops in PD and may be a pathway through which depressive symptoms negatively influence cognition. Prior research examining depressive symptoms, apathy, and cognition in PD is limited by being predominantly cross-sectional. This study examined the role of apathy as a within- and between-person mediator for the longitudinal relationships between depression severity and cognitive functioning in patients with early PD. Methods: Participants included 487 individuals newly diagnosed with PD followed annually for up to 5 years by the Parkinson's Progression Marker Initiative. At each visit, participants completed depressive symptom measures, apathy ratings, and cognitive tests. Multi-level structural equation models examined both the within- and between-person effects of depressive symptoms on cognition through apathy, controlling for demographics and motor severity. Results: At the within-person level, apathy mediated the association between depressive symptoms and select cognitive functions (global cognition, attention/working memory, visuospatial functions, and immediate verbal memory; indirect effects, bootstrap p's <0.05). Significant between-person direct effects were found for depressive symptoms predicting apathy (boostrap p <0.001) and lower scores on most cognitive tests (bootstrap p's <0.05). However, the indirect effects did not reach significance, suggesting between-person mediation did not occur. Conclusion: Findings suggest worsening of depressive symptoms over time in patients with PD may be a risk factor for increased apathy and subsequent decline in specific cognitive functions.
AB - Objective: Greater depressive symptoms are associated with worse cognitive functions in Parkinson's disease (PD); however, it is unclear what underlying factors drive this association. Apathy commonly develops in PD and may be a pathway through which depressive symptoms negatively influence cognition. Prior research examining depressive symptoms, apathy, and cognition in PD is limited by being predominantly cross-sectional. This study examined the role of apathy as a within- and between-person mediator for the longitudinal relationships between depression severity and cognitive functioning in patients with early PD. Methods: Participants included 487 individuals newly diagnosed with PD followed annually for up to 5 years by the Parkinson's Progression Marker Initiative. At each visit, participants completed depressive symptom measures, apathy ratings, and cognitive tests. Multi-level structural equation models examined both the within- and between-person effects of depressive symptoms on cognition through apathy, controlling for demographics and motor severity. Results: At the within-person level, apathy mediated the association between depressive symptoms and select cognitive functions (global cognition, attention/working memory, visuospatial functions, and immediate verbal memory; indirect effects, bootstrap p's <0.05). Significant between-person direct effects were found for depressive symptoms predicting apathy (boostrap p <0.001) and lower scores on most cognitive tests (bootstrap p's <0.05). However, the indirect effects did not reach significance, suggesting between-person mediation did not occur. Conclusion: Findings suggest worsening of depressive symptoms over time in patients with PD may be a risk factor for increased apathy and subsequent decline in specific cognitive functions.
KW - Apathy
KW - Parkinson's disease
KW - cognitive functioning
KW - depression
KW - mediation
KW - structural equation modeling
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U2 - 10.1016/j.jagp.2021.11.007
DO - 10.1016/j.jagp.2021.11.007
M3 - Article
C2 - 34922823
AN - SCOPUS:85121246059
SN - 1064-7481
VL - 30
SP - 664
EP - 674
JO - American Journal of Geriatric Psychiatry
JF - American Journal of Geriatric Psychiatry
IS - 6
ER -