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

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 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 C-UCB-J PET data were available in 54 participants. 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 f showed moderate effect sizes for subcortical (range, 0.30-0.35), cortical (0.28-0.35) and cerebellar VOIs (0.31).

Conclusion: MMS in healthy aging are associated with lower synaptic density throughout the brain. © 2023 International Parkinson and Movement Disorder Society.