Thalamic volume mediates associations between cardiorespiratory fitness (VO2max) and cognition in Parkinson's disease

Andrew J Petkus; Behnaz Jarrahi; Daniel P Holschneider; Megan E Gomez; J Vincent Filoteo; Dawn M Schiehser; Beth E Fisher; John D Van Horn; Michael W Jakowec; Sarah C McEwen; Giselle Petzinger

doi:10.1016/j.parkreldis.2021.03.019

Thalamic volume mediates associations between cardiorespiratory fitness (VO₂max) and cognition in Parkinson's disease

Parkinsonism Relat Disord. 2021 May:86:19-26. doi: 10.1016/j.parkreldis.2021.03.019. Epub 2021 Mar 29.

Authors

Affiliations

¹ Department of Neurology, University of Southern California, 1520 San Pablo St., HCC-2, Suite 3000, Los Angeles, CA, 90033, USA. Electronic address: Petkus@usc.edu.
² Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Palo Alto, CA, 94305, USA.
³ Department of Neurology, University of Southern California, 1520 San Pablo St., HCC-2, Suite 3000, Los Angeles, CA, 90033, USA; Department of Psychiatry and the Behavioral Sciences, University of Southern California, 1333 San Pablo St., Los Angeles, CA, 90033, USA.
⁴ Department of Psychology, Tibor Rubin Veterans Administration Medical Center, Long Beach, CA, 90822, USA.
⁵ Psychology and Research Services, Veterans Administration San Diego Health Care System, San Diego, CA, 92161, USA; Departments of Psychiatry and Neurosciences, University of California San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA.
⁶ Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, CA, 90033, USA.
⁷ Department of Psychology and School of Data Science, University of Virginia, Charlottesville, VA, 22904, USA.
⁸ Department of Neurology, University of Southern California, 1520 San Pablo St., HCC-2, Suite 3000, Los Angeles, CA, 90033, USA.
⁹ Department of Translational Neurosciences and Neurotherapeutics, Saint John's Cancer Institute, Santa Monica, CA, 90404, USA.

Abstract

Introduction: Cognitive deficits occur in Parkinson's disease (PD). Cardiorespiratory fitness (CRF) is associated with better cognitive performance in aging especially in executive function (EF) and memory. The association between CRF and cognitive performance is understudied in people with PD. Brain structures underlying associations also remains unknown. This cross-sectional study examined the associations between CRF and cognitive performance in PD. We also examined associations between CRF and brain structures impacted in PD. Mediation analysis were conducted to examine whether brain structures impacted in PD mediate putative associations between CRF and cognitive performance.

Methods: Individuals with PD (N = 33) underwent magnetic resonance imaging (MRI), CRF evaluation (estimated VO₂max), and neuropsychological assessment. Composite cognitive scores of episodic memory, EF, attention, language, and visuospatial functioning were generated. Structural equation models were constructed to examine whether MRI volume estimates (thalamus and pallidum) mediated associations between CRF and cognitive performance (adjusting for age, education, PD disease duration, sex, MDS-UPDRS motor score, and total intracranial volume).

Results: Higher CRF was associated with better episodic memory (Standardized β = 0.391; p = 0.008), EF (Standardized β = 0.324; p = 0.025), and visuospatial performance (Standardized β = 0.570; p = 0.005). Higher CRF was associated with larger thalamic (Standardized β = 0.722; p = 0.004) and pallidum (Standardized β = 0.635; p = 0.004) volumes. Thalamic volume mediated the association between higher CRF and better EF (Indirect effect = 0.309) and episodic memory (Indirect effect = 0.209) performance (p < 0.05). The pallidum did not significantly mediate associations between CRF and cognitive outcomes.

Conclusion: The thalamus plays an important role in the association between CRF and both EF and episodic memory in PD.

Keywords: Cardiorespiratory fitness; Cognition; Exercise; Imaging; MRI; Structural magnetic resonance imaging; Thalamus.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Aged
Cardiorespiratory Fitness / physiology*
Cognition / physiology
Cognitive Dysfunction / etiology
Cognitive Dysfunction / physiopathology*
Cross-Sectional Studies
Female
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Parkinson Disease / complications
Parkinson Disease / physiopathology*
Thalamus / physiopathology*

Abstract

Publication types

MeSH terms

Grants and funding