The Sydney multicenter study of Parkinson's disease: The inevitability of dementia at 20 years

TLDR

Parkinson’s disease patients commonly experience drug‑induced dyskinesia and end‑of‑dose failure, yet the main challenges lie in non‑levodopa‑responsive symptoms and understanding the cellular mechanisms underlying advanced disease beyond dopamine loss. In a 20‑year follow‑up of 136 newly diagnosed Parkinson’s disease patients, 74% died, the standardized mortality ratio rose to 3.1 after 15 years, 83% of survivors had dementia linked to age and mixed pathology, only one remained independent, 48% lived in nursing homes, and common complications included daytime sleepiness (70%), falls (87%), freezing (81%), fractures (35%), postural hypotension (48%), urinary incontinence (71%), dysarthria (81%), choking (48%), and hallucinations (74%).

Abstract

After 20 years follow-up of newly diagnosed patients with Parkinson's disease (PD), 100 of 136 (74%) have died. The mortality rate fell in the first 3 years of treatment, then rose compared to the general population, the standardized mortality ratio from 15 to 20 years reaching 3.1. Drug induced dyskinesia and end of dose failure were experienced by most patients, but the main current problems relate to the non-levodopa responsive features of the disease. Dementia is present in 83% of 20-year survivors. Dementia correlates with increasing age and probably reflects an interplay of multiple pathologies. Seventeen people with dementia had postmortems. Eight had diffuse Lewy bodies as the only cause of dementia, while others had mixed neuropathology. Only one person lives independently and 48% are in nursing homes. Excessive daytime sleepiness is noted in 70%, falls have occurred in 87%, freezing in 81%, fractures in 35%, symptomatic postural hypotension in 48%, urinary incontinence in 71%, moderate dysarthria in 81%, choking in 48%, and hallucinations in 74%. The challenge is to understand the cellular mechanisms underlying the diverse features of advanced PD that go far beyond a lack of dopamine.