Long-Term Dementia Risk in Parkinson Disease
By onParticipants from the Parkinson's Progression Markers Initiative (PPMI), a multisite international study, and a long-standing PD research cohort at the University of Pennsylvania (Penn), a single site study at a tertiary movement disorders center, were recruited. PPMI enrolled de novo, untreated PD participants and Penn a convenience cohort from a large clinical center. For PPMI, a cognitive battery is administered annually, and a site investigator makes a cognitive diagnosis. At Penn, a comprehensive cognitive battery is administered either annually or biennially, and a cognitive diagnosis is made by expert consensus. Interval-censored survival curves were fit for time from PD diagnosis to stable dementia diagnosis for each cohort, using cognitive diagnosis of dementia as the primary end point and Montreal Cognitive Assessment (MoCA) score <21 and Movement Disorder Society—Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I cognition score ≥3 as secondary end points for PPMI. In addition, estimated dementia probability by PD disease duration was tabulated for each study and end point. For the PPMI cohort, 417 participants with PD (mean age 61.6 years, 65% male) were followed, with an estimated probability of dementia at year 10 disease duration of 9% (site investigator diagnosis), 15% (MoCA), or 12% (MDS-UPDRS Part I cognition). For the Penn cohort, 389 participants with PD (mean age 69.3 years, 67% male) were followed, with 184 participants (47% of cohort) eventually 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.
Dementia with Lewy bodies and Parkinson disease dementia – the same or different and is it important?
By onReview compares late Parkinson's disease with dementia with Lewy bodies, discussing a biological assay for Lewy pathology. Suggests one assay may not capture complex brain pathologies, favoring diverse sequential mechanisms at various disease stages.
Convergent molecular pathways to inherited Parkinson’s disease
By onCommon genetic factors for Parkinson's are pathogenic *LRRK2* and *GBA1* variants. LRRK2 affects Rab GTPases, lysosome function, and cilia formation. Inhibiting LRRK2 in mutant mice shows promise in restoring cilia and neuroprotection.