Mild Motor Signs in Healthy Aging Are Associated with Lower Synaptic Density in the Brain

Margot G A Van Cauwenberge; Aline Delva; Thomas Vande Casteele; Maarten Laroy; Ahmed Radwan; Kristof Vansteelandt; Jan Van den Stock; Filip Bouckaert; Koen Van Laere; Louise Emsell; Wim Vandenberghe; Mathieu Vandenbulcke

doi:10.1002/mds.29570

Mild Motor Signs in Healthy Aging Are Associated with Lower Synaptic Density in the Brain

Mov Disord. 2023 Oct;38(10):1786-1794. doi: 10.1002/mds.29570. Epub 2023 Aug 13.

Authors

Margot G A Van Cauwenberge^{1

2}, Aline Delva^{2

3}, Thomas Vande Casteele^{1

4}, Maarten Laroy¹, Ahmed Radwan^{5

6}, Kristof Vansteelandt¹, Jan Van den Stock^{1

4}, Filip Bouckaert^{1

4}, Koen Van Laere^{7

8}, Louise Emsell^{1

4

5}, Wim Vandenberghe^{2

3}, Mathieu Vandenbulcke^{1

4}

Affiliations

¹ Department of Neurosciences, Neuropsychiatry, Leuven Brain Institute, KU Leuven, Leuven, Belgium.
² Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
³ Department of Neurosciences, Laboratory for Parkinson Research, Leuven Brain Institute, KU Leuven, Leuven, Belgium.
⁴ Geriatric Psychiatry, University Psychiatric Center KU Leuven, Leuven, Belgium.
⁵ Department of Imaging and Pathology, Translational MRI, KU Leuven, Leuven, Belgium.
⁶ Department of Radiology, University Hospitals Leuven, Leuven, Belgium.
⁷ Division of Nuclear Medicine, University Hospitals Leuven, Leuven, Belgium.
⁸ Department of Imaging and Pathology, Nuclear Medicine and Molecular Imaging, KU Leuven, Leuven, Belgium.

PMID: 37574924
DOI: 10.1002/mds.29570

Abstract

Objective: To investigate whether mild motor signs (MMS) in old age correlate with synaptic density in the brain.

Background: Normal aging is associated with a decline in movement quality and quantity, commonly termed "mild parkinsonian signs" or more recently MMS. Whether MMS stem from global brain aging or pathology within motor circuits remains unresolved. The synaptic vesicle glycoprotein 2A positron emission tomography (PET) ligand ¹¹ C-UCB-J allows the investigation of brain-motor associations at the synaptic level in vivo.

Method: Fifty-eight healthy older adults (≥50 years) were included from two monocentric control cohorts. Brain magnetic resonance imaging and ¹¹ C-UCB-J PET data were available in 54 participants. ¹¹ C-UCB-J PET binding was quantified by standardized uptake value ratio (SUVR) values in grey matter (GM) volumes of interest (VOIs): caudate, putamen, globus pallidus, substantia nigra, thalamus, cerebellum, and the frontal, parietal, temporal, and occipital cortex. Multiple linear regression analyses were performed with Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score measuring MMS as the dependent variable and mean SUVR values in each VOI as the independent variable with age, Fazekas score (white matter lesion [WML] load), VOI and cohort as covariates.

Results: Participants (68 ± 7.5 years; 52% female) had an average MDS-UPDRS part III score of 3.3 ± 2.8. The MDS-UPDRS part III score was inversely associated with synaptic density, independently of WML load or GM volume, in the caudate, substantia nigra, thalamus, cerebellum, and parietal, occipital, temporal cortex. Cohen's f² showed moderate effect sizes for subcortical (range, 0.30-0.35), cortical (0.28-0.35) and cerebellar VOIs (0.31).

Keywords: MRI; PET; aging; mild parkinsonian signs; synaptic density.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aging / metabolism
Brain / pathology
Female
Gray Matter / diagnostic imaging
Healthy Aging*
Humans
Male
Movement Disorders* / pathology
Positron-Emission Tomography / methods