Lower gray matter integrity found at the microstructural level may be an important prognostic marker for the development of mild parkinsonian signs (MPS), likely reflecting earlier changes in the brain structure, according to study results published in Parkinsonism and Related Disorders. This association between neuroimaging markers of gray matter changes and MPS progression was only seen in patients who were MPS-negative at the start of the study.

Participants enrolled in the Health, Aging, and Body Composition (Health ABC) ancillary study were screened. A total of 819 patient who did not use walking assisted devices, could complete a 6-minute walking test, and were eligible to undergo brain magnetic resonance imaging (MRI) were recruited between 2006 and 2008. Of these, 315 met eligibility for a 3T MRI, and 205 had complete Unified Parkinson Disease Rating Scale (UPDRS) data both at baseline and follow-up, were not taking any medications that could induce or inhibit parkinsonism, and did not have a diagnosis of Parkinson Disease (PD) or other neurologic disease.

The UPDRS Part III was used to identify bradykinesia, rigidity, tremor, and gait disturbance; the total score was used to quantify the severity of parkinsonian signs. MPS was considered present if: 2 or more items had a score of 1; 1 item had a score of ≥2, or rest tremor had a score of 1. MPS progression was measured as the change in UPDRS-III score between 2 time points using scores from baseline and a follow-up visit at least 2 years after the baseline visit. Participants’ demographic information were included as well as cardiovascular disease and risk factors, body mass index, muscle strength, and results of a mini-mental status exam. Gray matter, white matter, and cerebrospinal fluid were examined by a neurologist from MRI and diffusion tensor imaging (DTI) findings.

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The investigators reported that MPS were present in 62 of 205 participants (30%) at the start of the study. The mean age of participants was 82.7 years. The mean UPDRS-III score at baseline for was 1.5±2.8. Mean follow-up time was 3.8±0.8 years, and the average rate of UPDRS-III change was 0.6±1.0 points per year for a mean total of 2.29 points. The change was significantly higher in the MPS negative group compared with the MPS positive group.

“The association between neuroimaging markers of gray matter integrity and MPS progression was present only for those participants who were free of MPS at baseline,” the researchers said. “A significant portion of UPDRS-III scores in the MPS+ group actually improved at follow-up, likely contributing to the lack of observed association in this group.” The author contributed this to possible neuroplasticity that may reverse MPS and the difficulty in identifying small changes (from baseline to follow-up) in patients who were MPS positive.

Older age, male sex, and patients with diabetes were associated with a faster rate of UPDRS-III change in those without MPS but not those with MPS. Among those without MPS, the only imaging marker associated with faster UPDRS-III progression was higher gray matter mean diffusivity. No imaging factors were associated with UPDRS-III change among MPS positive patients.

“Future studies with larger sample sizes are needed to further explore the associations we found,” the study authors concluded. “As gray matter loss appears to be linked to MPS development, any future management linked to gray matter preservation may have a role in prevention of MPS and its associated morbidity.”


Miller-Patterson C, Han J, Yaffe K, et al. Clinical and neuroimaging correlates of progression of mild parkinsonian signs in community-dwelling older adults. Parkinsonism Relat Disord. 2020;75:85-90.