PREDICT-PD Algorithm Shows Ability to Identify Early Motor Dysfunction, Parkinsonism

Alastair Noyce, PhD, MSc, BMedSci

Findings from an analysis of 3 separate longitudinal studies showed that individuals stratified as higher risk using the PREDICT-PD algorithm were more likely to develop new onset sub-threshold parkinsonism (SP) over time, with a doubling of SP at follow-up per 1 unit change in the risk score. Overall, the low intensity and cost-efficient approach may be able to estimate the occurrence of motor disturbances in the future.¹

Of 181 participants seen at baseline, 2 died, and 15 declined for personal and medical reasons. After excluding those who lost contact (n = 32), 132 participants were reviewed in person. The analysis featured a sample of participants from the PREDICT-PD pilot cohort, observed across 2012-2018. These patients were over the age of 60, had no known neurological disease, and resided in the UK.

Led by Alastair Noyce, PhD, MSc, BMedSci, professor of neurology and neuroepidemiology at Queen Mary University of London, PREDICT-PD participants underwent online assessments that included an evidence-based questionnaire derived from a systematic review, followed by a validated keyboard tapping test, and completion of a smell test. Using the PREDICT-PD algorithm, patients were stratified as high (HR)- or low-risk (LR) based on rank estimates above or below the 15th centile, respectively. HR individuals also completed the MDS-Unified Parkinson’s Disease Rating Scale (UPDRS)-III, a follow-up assessment in 2018 that included a timed handwriting test, and the Montreal Cognitive Assessment (MoCA).

The priori age-related PD risk was calculated and adjusted depending on the presence and absence of determinants of risk, which included the following factors: sex, coffee use, current/former/never smoker, alcohol consumption, 1st degree relative with PD, constipation, erectile dysfunction, depression/anxiety, pesticides exposure, diabetes, head injury and non-steroidal anti-inflammatory drugs, calcium channel blockers, and beta blocker use.

Considering the low incidence of PD, the study authors used 3 surrogate markers at the follow-up examination as binary outcomes for the prediction model. These included the development of SP, based on the MDS research criteria for prodromal PD, motor decline, demonstrated by changes of at least 5 points on the MDS-UPDRS-III compared between 4 groups, and abnormality of single motor domains from the MDS-UPDRS-III. Analyses on participants from PREDICT-PD were also replicated in 2 separate studies, the Bruneck study and the Parkinson Progression Marker Initiative (PPMI) study.

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The final analysis included 128 participants (HR: n = 33; LR: n = 95), with the HR group older (P <.001) and more likely to be male (P = .001). Both groups had a similar proportion of vascular risk factors, including type 2 diabetes, hypertension, and high cholesterol. In PREDICT-PD, a higher proportion of new cases of incident SP was observed in the HR group, with the odds increasing 1.7-fold greater per 1 unit change in the risk score (OR, 1.70; 95% CI, 0.99-2.94; coefficient, 0.53; intercept, 0.33; P = .053).

Using the same algorithm, the association between risk scores and incident SP were observed in the Bruneck (OR, 2.28; 95% CI, 1.55-3.34; P <.001) and PPMI studies (OR, 1.90; 95% CI, 1.19-3.03; P =.007). When combining all 3 cohorts, meta-analyses showed an OR of 2.01 (95% CI, 1.55-2.61; P <.001).

On motor decline, the HR and LR groups had median MDS-UPDRS-III scores of 5 (IQR, 2-6) and 2 (IQR, 0-4), respectively, at baseline. After 6 years of follow-up, the HR group maintained a higher motor score than the LR group (HR: median, 7 [IQR, 3-9] and LR: median, 3 [IQR, 1-5]; P = .001), Over time, 30.3% (10 of 33) of those in the HR group demonstrated motor decline, considered at least a 5-point change in motor score, compared with 12.6% (12 of 95) of those in the LR group (P = .031). There was nominal evidence to suggest that the HR group had a 3-fold greater odds of experiencing motor decline than the LR group (OR, 3.01; 95% CI, 1.15-7.84; coefficient, 1.10; intercept, –1.28; P = .024).

The algorithm appeared to estimate the occurrence of bradykinesia as well. Between the risk groups, bradykinesia were found in 57.6% of HR-individuals and 28.4% of LR-individuals. Similarly, people classified in the HR were more likely to have new onset action tremor (75.7% vs 46.3%; P = .004). Using a logistic regression model, investigators observed nominal evidence that HR people had more than twice the odds of developing bradykinesia over time (OR, 2.67; 95% CI, 1.07-6.62; coefficient, 0.98; intercept, –1.67; P = .035). The association between incident bradykinesia and HR of PD became stronger after adjusting for age and sex (adjusted OR, 5.88; 95% CI, 1.83-18.92; coefficient, 1.78; intercept, 7.49; P = .011).

REFERENCE
1. Simonet C, Mahlknecht P, Marini K, et al. The emergence and progression of motor dysfunction in individuals at risk of Parkinson’s disease. Mov Disord. 2023;38(9):1636-1644. doi:10.1002/mds.29496