Abstract
BACKGROUND AND OBJECTIVES: One-third of Parkinson disease (PD) patients with PD-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 quotient (cut-off ≥1), indicating more cognitive than motor-driven IADL impairment, defined cognitive IADL impairment status at baseline. Hazard ratios (HRs) 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 reassessed. 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 the 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 nonmotor burden, worse cognitive performance, and more severe IADL progression over the study period. DISCUSSION: 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 the 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 MCI to dementia among patients with Parkinson disease.