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Dementia in PD May Occur Less Frequently Than Previously Thought
Dementia occurrence in Parkinson disease (PD) may occur less frequently or take more time to develop than previous studies have shown, according to recent results from 2 ongoing prospective studies published in Neurology.
“Development of dementia is a long-term concern of patients with PD, and the combination of a motor and cognitive disorder can be devastating to patients and loved ones. This is increasingly recognized by clinicians, researchers, and those involved in treatment development,” authors noted. “These results provide updated, and more hopeful, estimates of long-term dementia risk in PD, suggesting a longer window to intervene to prevent or delay cognitive decline.”
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Researchers recruited PD participants from the Parkinson's Progression Markers Initiative (PPMI) and a long-standing PD research cohort at the University of Pennsylvania (Penn). PPMI enrolled de novo, untreated PD participants, while Penn included a convenience cohort from a large clinical center. Both studies involved cognitive assessments, with PPMI administering a cognitive battery annually and Penn doing so either annually or biennially. Cognitive diagnoses in PPMI were made by site investigators, whereas Penn used expert consensus. Interval-censored survival curves were used to analyze the time from PD diagnosis to stable dementia diagnosis for each cohort, with Montreal Cognitive Assessment (MoCA) scores and Movement Disorder Society—Unified Parkinson's Disease Rating Scale (MDS-UPDRS) cognition scores serving as secondary endpoints, and dementia probability estimates by disease duration were calculated for each cohort.
In the PPMI cohort, 417 participants with PD (mean age 62 years, 65% male) were followed and had an estimated 9% (site investigator diagnosis), 15% (MoCA), or 12% (MDS-UPDRS Part I cognition) probability of dementia at year 10 disease duration. The Penn cohort followed 389 participants with PD (mean age 69 years, 67% male), and 184 participants (47%) were diagnosed with dementia. The interval-censored curve for the Penn cohort had a median time to dementia of 15 years (95% CI 13–15); the estimated probability of dementia was 27% at 10 years of disease duration, 50% at 15 years, and 74% at 20 years.
Both studies had limitations that could have affected study results. The PPMI had missing data in later years, partly due to COVID-19, as well as a reliance on site investigators for dementia diagnoses without necessarily considering cognitive test results. Additionally, the comparison between PD participants and healthy controls in the PPMI cohort is limited by uncertainty about whether they were drawn from the same population, though they were demographically similar. The Penn cohort had a longer duration between PD diagnosis and enrollment, possibly excluding those with advanced dementia, potentially inflating the estimated time to dementia diagnosis. Both cohorts were predominantly White, highly educated, and specifically recruited for research, which may limit the generalizability of the findings. Authors noted that they also did not investigate the impact of death as a “competing risk,” which may have influenced the estimated rates of dementia.
“Future analyses could examine neurobiological predictors of conversion to dementia in the two cohorts, which may help further explain differences in dementia risk rates between the two cohorts,” authors concluded.
