Prediction of cognition in Parkinson's disease with a clinical–genetic score: a longitudinal analysis of nine cohorts

Abstract

Summary Background Cognitive decline is a debilitating manifestation of disease progression in Parkinson’s disease. We aimed to develop a clinical-genetic score to predict global cognitive impairment in patients with the disease. Methods A prediction algorithm for global cognitive impairment (defined as Mini Mental State Exam (MMSE) ≤25) was built using data from 1,350 patients with 5,165 longitudinal visits over 12.8 (median, 2.8) years. Age at onset, MMSE, education, motor exam score, gender, depression and GBA mutations, machine selected through stepwise Cox’ hazards analysis and Akaike’s information criterion, were used to compute the multivariable predictor. Independent validation was achieved in another 1,132 patients with 19,127 visits over 8.6 (median, 6.5) years. Findings The cognitive risk score accurately predicted cognitive impairment within ten years of disease onset with an area under the curve (AUC) of >0.85 in both the discovery (95% CI, 0.821–0.902) and validation populations (95% CI, 0.779 – 0.913). 72.6% of patients scoring in the highest quartile were cognitively impaired by ten years vs. 3.7% in the lowest quartile (hazard ratio, 18.4, 95% CI, 9.4 – 36.1). Dementia or disabling cognitive impairment was predicted with an AUC of 0.877 (95% CI 0.788–0.943) and high negative predictive value (0.920, 95% 0.877–0.954) at the predefined cutoff (0.196). Performance was stable in 10,000 randomly resampled subsets. Interpretation Our predictive algorithm provides a potential test for future cognitive health or impairment in patients with Parkinson’s. It could improve trials of cognitive interventions and inform on prognosis.

Visual tests predict dementia risk in Parkinson disease

“…Inclusion criteria were early-stage PD (Queen Square Brain Bank criteria), within 10 years of diagnosis, aged 49-82 years. Exclusion criteria were confounding neurologic or psychiatric disorders, a diagnosis of dementia or Mini-Mental State Examination (MMSE) less than 25, 13 and ophthalmic disease sufficient to impair visual acuity. Two patients were excluded because of dementia, and 3 were excluded because of ophthalmic disease (glaucoma).…”

“…We defined dementia risk using a recently described, prospectively validated algorithm. 13 This combines clinical information on sex, age at disease onset, years of education, UPDRS-III (motor examination), and MMSE to generate a risk score (e-Methods for details, links.lww. com/CPJ/A137).…”

“…Age and sex did not differ between PD and controls: mean age PD 64.3 ± 8 years, mean age controls 64.8 ± 9 years (t(49) = 0.3, p = 0.74). Fifty-six people with PD were assigned low risk, based on a median split of the risk score, 13 and 56 were high risk. The average disease duration was 4.1 ± 2.5 years and did not differ between high-and lowrisk patients.…”

“…New algorithms have emerged that combine measures such as age and motor severity with sensitivity to predict cognitive change in PD. [13][14][15] Although these algorithms are useful, they do not allow tracking of disease progression or relate directly to changes in the parkinsonian brain.…”

Comparative sensitivity of the MoCA and Mattis Dementia Rating Scale‐2 in Parkinson's disease

“…Although the MoCA and DRS‐2 are not intended to replace comprehensive neuropsychological testing, there are circumstances in which neuropsychological evaluation is unavailable or impractical. Because of their brevity and ease of administration, the MoCA and DRS‐2 are often used in clinics with limited financial resources or time restrictions and in studies that include thousands of participants, such as consortium biomarker and genetic studies . Consequently, guidelines for interpreting the MoCA and DRS‐2 subsections for domain‐specific impairments would be of great benefit …”