Subjective cognitive decline as an early marker of cognitive impairment in Parkinson’s disease

Abstract

Cognitive impairment is one of the non-motor symptoms with the greatest impact on patients and caregiver quality of life. Given its onset and significant relevance during the prodromal phase of Parkinson’s disease (PD), and its potential role as an at-risk state for cognitive impairment, this study investigated the role of subjective cognitive decline in PD (PD-SCD) as an early prognostic marker of subsequent cognitive impairment to enhance timely detection and prediction. Additionally, it evaluated how mood-related symptoms (depression, anxiety and apathy) influence this relationship. Data from 577 people with Parkinson’s disease (PwPD) and 308 control participants from the Parkinson’s Precision Medicine Initiative (PPMI) cohort, together with 142 PwPD from the Luxembourg Parkinson’s Study cohort, were analyzed over four visits. PD-SCD, with a baseline prevalence of 21.66% in PPMI and 18.31% in the Luxembourg Parkinson’s Study, was associated with an at-risk state for cognitive decline over time. Higher levels of mood-related symptoms (apathy, depression, and anxiety) were observed in the PD-SCD group compared with the people with Parkinson’s disease presenting normal cognition group (PD-NC) depending on the cohort. In addition, apathy and depression were cross-sectionally associated with higher levels of subjective cognitive complaints (SCC), underscoring their role as a key feature of the PD-SCD clinical profile, without masking the association between PD-SCD and cognitive impairment. Overall, PD-SCD emerged as a relevant at-risk state of cognitive impairment in PD and as a potential dynamic tracker of cognitive impairment trajectories, highlighting its clinical relevance within the continuum of cognitive impairment in PD.