Cognitive Impairments in Activities of Daily Living Predict Conversion to Parkinson Disease Dementia

Sara Becker, PhD

An observational longitudinal study published in Neurology suggested that cognitive, not motor-driven, impairments in instrumental activities of daily living (IADL) potentially predicts conversion of patients with Parkinson disease (PD) to PD dementia (PDD). Investigators concluded that patients with both PD and mild cognitive impairment (PD-MCI) and cognitive IADL impairment could be a valuable target group for clinical trials assessing pharmacological and nonpharmacologic approaches to delay or prevent PDD.

In the analysis, a cut-off score of at least 1 on the Functional Activities Questionnaire (FAQ_Q), indicating more cognitive than motor-driven impairment, was used to differentiate patients with more cognitive (FAQ_Q>1) than motor (FAQ_Q≤1) IADL impairment. In an attempt to identify high-risk patients for PDD, a total of 268 individuals with PD were assessed, 40.3% (n = 108) of which had PD-MCI.

Lead investigator Sara Becker, PhD, department of psychology, University of Calgary, and colleagues aimed to identify the phenotype associated with cognitive IADL impairment and its predictive value for defining a high-risk group for PDD. In addition to the 10-item FAQ, patients underwent comprehensive neuropsychological testing as well as had genetic and cerebrospinal fluid biomarkers derived from baseline samples. According to the Hoehn and Yahr score, most of the patients were in mild to moderate disease stages.

After a period of 3.78 (±0.84) years, 61.2% (n = 164) of the sample were reassessed. Most patients lost to follow-up were either not interested in re-examination or deceased. Of the remaining patients, 10.4% (n =17) converted to PDD, with more of these two-third (70.6%) fulfilling level II diagnostic criteria for PDD-2. Almost one-third (32.9%) of patients were classified as PD-MCI at the follow-up, with diagnosis in 18.9% (n = 31) of patients stable across both visits. Between the groups, investigators observed significant differences in age, education, motor severity, nonmotor symptoms, depression severity, FAQ subscores, and neuropsychological test scores.

In the follow-up uncensored cohort, 29.7% (n = 11) of patients with baseline status of cognitive IADL impairment (FAQ_Q>1) converted to PDD during the study period compared with only 4.7% (n = 6) of those in the FAQQ≤1) group. When including dropouts, cox proportional hazard models for the censored cohort for predicting conversion to PDD were descriptively higher for patients with baseline cognitive IADL impairment (hazard ratio [HR], 6.57; 95% CI, 2.38-18.17; AIC, 152.0 than for diagnosis of PD-MCI (HR, 5.34; 95% CI, 1.70-16.73; AIC, 161.70, C-Index = 0.80), but highest in patients with both PD-MCI and FAQ_Q>1 (HR, 12.01; 95% CI, 4.47-32.23; AIC, 142.98, C-Index = 0.89).

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"The prognostic ability of this defined IADL marker was found to substantially add to the prognostic value of PD-MCI diagnosis, where the combination of cognitive and IADL status best predicted future development of PDD," Becker et al wrote.

Using generalized mixed linear regression models, investigators documented that the 3-way interaction of time of visit, baseline cognitive status of PD-cognitively normal or PD-MCI, and baseline cognitive IADL status of FAQ_Q≤1 vs FAQ_Q>1 was significant (P <.05) for calculating change in FAQ total, motor, and cognition scores over time. This indicated that only patients with both PD-MCI and FAQ_Q>1 showed increase in these FAQ scores between visits. Notably, patients with lower education status were more associated with higher scores in the FAQ cognition score at baseline and follow-up visit (P = .048).

"Especially in early stages of cognitive impairment, systematic assessment of everyday function might be neglected by physicians in the clinical daily routine," the study investigators concluded. "We propose a two-step screening approach: First, the application of a standardized IADL scale to screen for patients with cognitive IADL impairment, and second, the evaluation of the impact of these problems in a patient-centered interview for diagnostic purposes."

REFERENCE
1. Becker S, Bode M, Brockmann K, et al. Cognitive-driven activities of daily living impairment as a predictor for dementia in Parkinson disease. Neurology. 2022;99(23). doi:10.1212/WNL.0000000000000201201