Cognitive-Driven Activities of Daily Living Impairment as a Predictor for Dementia in Parkinson Disease: A Longitudinal Cohort Study

Abstract

Objectives: One-third of Parkinson's disease (PD) patients with mild cognitive impairment (PD-MCI) convert to dementia within a few years. Markers with a high prognostic value for dementia conversion are needed. Loss of everyday function primarily caused by cognitive dysfunction is the core criterion for the diagnosis of PD dementia, with an onset of more complex instrumental activities of daily living (IADL) dysfunction in the prodromal stage. This study evaluated the phenotype associated with cognitive IADL impairment and its predictive value for defining a high-risk group for PD dementia.

Methods: An observational longitudinal study using cognitive and clinical scores in addition to genetic and CSF biomarkers was conducted. The Functional Activities Questionnaire (FAQ) quotient (cut-off ≥1), indicating more cognitive than motor-driven IADL impairment, defined cognitive IADL impairment status at baseline. Hazard ratios (HR) were used to compare the impact of baseline classifications on dementia conversion.

Results: Of 268 patients with PD assessed at baseline, 108 (40.3%) had PD-MCI. After a period of 3.78±0.84 years, 164 (61.2%) patients were re-assessed. At follow-up, 93 (56.7%) patients had no cognitive impairment, 54 (32.9%) fulfilled PD-MCI criteria, and 17 (10.4%) had developed dementia. The HR of baseline cognitive IADL impairment (n=37) for dementia conversion was descriptively higher than for PD-MCI, but highest in patients with both markers (HR=12.01, 95%-CI 4.47-32.22, p<0.001). In the follow-up sample, nearly half of patients (n=10, 47.6%) with baseline classification of cognitive IADL impairment and PD-MCI converted to dementia. Baseline status of cognitive IADL impairment was associated with higher non-motor burden, worse cognitive performance, and more severe IADL progression over the study period.

Conclusion: The importance of differentiating between cognitive and motor aspects on ADL function in PD and monitoring cognitive ADL impairment in the prodromal stage of dementia is paramount. Patients with PD-MCI and cognitive IADL impairment may be a valuable target group for clinical trials aiming to slow down development of dementia.

Trial registration information: ClinicalTrials.gov NCT03687203.

Classification of evidence: This study provides Class II evidence that impairment of cognitive activities of daily living is associated with progression from mild cognitive impairment to dementia among patients with Parkinson's disease.

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Figures

Figure 1. Flowchart of Patient Recruitment Including Cognitive Diagnosis at Follow-up

Abbreviations: FU = follow-up; PD = Parkinson disease; PD-CN = Parkinson's Disease Cognitively Normal; PDD = Parkinson Disease Dementia; PD-MCI = Parkinson Disease with Mild Cognitive Impairment.

Figure 2. Alluvial Plots Detailing Progression of Cognitive Impairment Over Time in Uncensored Data

(A) Patients with motor IADL impairment (FAQQ ≤ 1). (B) Patients with cognitive IADL impairment (FAQQ > 1). Abbreviations: IADL = instrumental activities of daily living; PD-CN = Parkinson Disease Cognitively Normal; PDD = Parkinson Disease Dementia; PD-MCI = Parkinson Disease with Mild Cognitive Impairment.

Figure 3. Survival Curves in Censored Data Showing Predictive Values for PDD Using Different Baseline Stratifications

Survival curves were adjusted for covariates and based on multivariate Cox regression models of censored data. (1) Predictive values for PDD in patients stratified by baseline IADL status. (2) Predictive values for PDD in patients stratified by baseline cognitive status. (3) Predictive values for PDD in patients with a combination of cognitive IADL impairment and PD-MCI vs patients with all other statuses. Abbreviations: FAQQ>1 = cognitive IADL impairment; FAQQ≤1 = motor IADL impairment; HR = hazard ratio; IADL = instrumental activities of daily living; PDD = Parkinson Disease Dementia; PD-MCI = Parkinson Disease with Mild Cognitive Impairment.

Figure 4. Change in the Functional Activities Questionnaire Total Score Between Uncensored Baseline and Follow-up Data

(A) Patients with PD-CN split according to baseline IADL status. (B) Patients with PD-MCI split according to baseline IADL status. Black lines: FAQQ>1 = cognitive IADL impairment, Gray lines FAQQ≤1 = motor IADL impairment. *Patients classified as both PD-MCI and FAQQ>1 at baseline showed a significant increase between baseline and follow-up visit in the FAQ total scores than patients with baseline status of PD-CN, FAQQ≤1, or both (3-way interaction, visit*cognitive IADL status*cognitive status, p = 0.001). IADL = instrumental activities of daily living; PD-CN = Parkinson Disease Cognitively Normal; PD-MCI = Parkinson Disease with Mild Cognitive Impairment.