番茄社区

Parkinson's disease patients who had normal cognitive function at the start of a prospective, community-based study had a largely normal life expectancy, researchers reported.

But Parkinson's disease patients who had early freezing of gait, severe hyposmia, cognitive impairment, or subtle inflammation in their cerebrospinal fluid (CSF) had a significantly shorter life span, reported David Backstrom, MD, of Umea University in Sweden, and colleagues in .

"The prognosis of Parkinson's disease and parkinsonism is best studied by long-term follow-up of community-based incident cohorts," Backstrom told 番茄社区. Mortality among Parkinson's disease patients can be highly variable, and "this study provides a better characterization of the neurobiological factors that are associated with short survival in Parkinson's disease."

Life expectancy in Parkinson's disease has changed considerably in the past 50 years, noted Lawrence Golbe, MD, of Rutgers Robert Wood Johnson Medical School in New Brunswick, New Jersey, and Cristian Leyton, PhD, of Massachusetts General Hospital in Boston, in an .

In 1967, Parkinson's patients were expected to live about 9.4 years from onset, "in the era before levodopa and before most of the 'atypical parkinsonisms' other than post-encephalitic parkinsonism were distinguishable from Parkinson's disease," Golbe and Leyton wrote. By 1993 -- after levodopa, but before deep brain stimulation -- life expectancy had improved to 13.1 years from onset. By 2016, it was up to 14.6 (±7.7) years. Still, "Parkinson's disease complexity and heterogeneity make it difficult to stratify prognostic risk," they observed.

To identify predictors of mortality, Backstrom and co-authors studied 182 patients who were diagnosed from 2004 to 2009 with new-onset, idiopathic parkinsonism in a geographic area of Sweden with 142,000 inhabitants. Of those 182 patients, 143 had Parkinson's disease, 18 had progressive supranuclear palsy (PSP), and 13 had multiple system atrophy (MSA). Parkinson's patients had a mean age of 71.2 years at baseline.

The team followed patients prospectively for up to 13.5 years; in that period, 109 patients died. Among Parkinson's patients, 54% of patients died during the study, compared with 89% of PSP patients and 92% of MSA patients. While PSP and MSA patients were a few years older than Parkinson's patients at baseline, their higher death rates were more likely due to the nature of their diseases, the researchers said.

In their analysis, Backstrom and co-authors used the standardized mortality ratio, the chance of dying in a calendar year relative to that of the entire population. Across all idiopathic parkinsonism patients, the standardized mortality ratio was 1.84 (95% CI 1.50-2.22, P <0.001), with PSP and MSA patients having the highest mortality.

Mortality in Parkinson's disease patients with normal cognition at baseline was not significantly different from the general Swedish population, but Parkinson's patients with mild cognitive impairment at baseline had a 2.4 times higher age-adjusted hazard of death during follow-up, compared with patients who had normal cognition at baseline (P< 0.001). Assuming the mean age of 71.2 years at baseline, the expected survival for Parkinson's patients was 11.6 years with normal cognition and 8.2 years with mild cognitive impairment.

After excluding factors strongly correlated to each other and including only strictly significant factors at the P <0.005 level in a multivariable model, older onset age, hyposmia, mild cognitive impairment on the Mini-Mental State Examination, greater postural instability, reduced dopamine transporter uptake in the caudate, and CSF leukocytosis emerged as independent predictors of reduced survival in Parkinson's disease. Low-grade inflammatory reaction in the CSF of 13.1% of Parkinson's patients was strongly tied to a reduced survival, with a 6.3 times increased hazard of death (P<0.001).

While these findings require validation, they are "good news for people with Parkinson's disease, their families, and clinicians," Golbe and Leyton noted. First, the results suggest that Parkinson's patients with mild disease and normal cognition at onset have a mortality rate equivalent to the general population. Second, the researchers stratified risks by incorporating information derived from lab work, genomic data, and neuroimaging to produce a fine-grain estimation of individual risks.

The study also provided new factors to consider in future interventions: "The finding of an inflammatory reaction in the CSF suggests direct secondary prophylaxis via anti-inflammatory treatment; and the finding of cognitive status as a predictor similarly suggests rehabilitative measures, not just as palliation, but potentially as prophylaxis," the team wrote.

Possible uncontrolled confounding factors, the researchers said, are a study limitation, as is the fact that autopsy confirmation of diagnosis was available for only five of the 109 deaths. Backstrom and co-authors added that their results, especially the CSF findings, need to be confirmed by future studies.