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Wednesday, November 28, 2018

Early Predictors of Mortality in Parkinsonism and Parkinson’s Disease


What predicts survival and the risk for mortality in Parkinson's disease and parkinsonism? Cognitive status may play a role as does age and disease-specific features, suggests a Swedish prospective, community-based study published online on October 31 in Neurology.

Consistent with earlier studies, the current analysis found that the life expectancy is reduced in Parkinson's disease (PD) patients compared to those in the general population, independent of comorbidities. But it also found that PD patients with mild disease and normal cognitive function at onset had a life expectancy similar to the general population.

Those with mild cognitive impairment (MCI) at baseline were 2.4 times more likely to die during follow-up, compared with PD patients who had normal cognition at baseline (p<0.001).

Assuming the mean age of 71.2 years at baseline, the expected survival in PD patients was 11.6 years without MCI and 8.2 years with MCI, the researchers, led by David Backstrom, MD, of Umea University in Sweden, reported.

Other independent predictors of reduced survival in PD included older onset age, hyposmia, greater postural instability, reduced dopamine transporter uptake in the caudate, and cerebrospinal fluid (CSF) leukocytosis.

The researchers said their findings "underscore the importance of an early PD-MCI diagnosis, as defined by the Movement Disorders Society."

To identify predictors of mortality in PD, the researchers studied 182 patients diagnosed with new-onset, idiopathic parkinsonism in a geographic area of 142,000 inhabitants in Northern Sweden from January 2004 to April 2009. Of the 182 patients, 143 had PD, 18 had progressive supranuclear palsy (PSP), 13 had multiple system atrophy (MSA), and four patients were unclassified. The researchers followed patients prospectively for up to 13.5 years.

The team tested patients for PD symptoms and cognitive function at the baseline and at least once a year.

Using the mortality rates in the general Swedish population, the researchers calculated the standardized mortality ratio and expected survival of participants relative to the entire population.

During the study period, 109 patients died; 53.8 percent of deaths occurred in the PD group; 92.3 percent in the MSA group; and 88.9 percent in the PSP group. The four patients with unclassifiable parkinsonism likely represented cases of late-onset PD, but the researchers excluded them from further analyses since they did not fulfill specific diagnostic criteria. The overall mean age at death was 82 years.

The researchers found the standardized mortality ratio for the whole parkinsonism cohort was 1.84 (95% CI 1.50-2.22, p<0.001) times higher than the comparable age and sex distribution standardized mortality of the Swedish population during the years 2004 to 2017.

However, within the parkinsonism group, mortality varied highly.

Those with atypical parkinsonism, such as MSA or PSP, had a far worse prognosis than patients with PD. Standardized mortality ratios were 3.32 for patients with atypical parkinsonism and 1.58 for patients with PD.

Low-grade inflammatory reaction in the CSF of 13.1 percent of PD patients was strongly associated with a reduced survival, with a 6.3 times increased hazard of death (p<0.001), which suggests an immunologic reaction.

"The shorter lifespans in patients with a CSF leukocytosis indicate a rationale for further investigating immunomodulation to reduce PD mortality," the researchers noted.

Overall, they concluded "the survival in parkinsonism is highly dependent on the type and characteristics of the parkinsonism disorder."

Study limitations included possible uncontrolled confounding factors and the fact that the confirmed diagnosis by autopsy was obtained in only five of the 109 deaths.

The Swedish Research Council, Erling Persson Foundation, Umea University, Vasterbotten County Council, King Gustaf V and Queen Victoria Freemason Foundation, Swedish Parkinson Foundation, Kempe Foundation, Swedish Parkinson's Disease Association, Torsten Soderberg Foundation, Swedish Brain Foundation, European Research Council, and Knut and Alice Wallenberg Foundation supported the study.

The researchers reported relationships with GSK, Lundbeck, Boehringer Ingelheim, Abbott, AbbVie, Solvay, Orion Pharma, UCB, Nordic InfuCare, Medtronic, IPSEN, Roche Diagnostics, Eli Lilly, Teva, Brain Biomarker Solutions Alzheon, Bio-Arctic, Biogen, Fujirebio Europe, IBL International, Merck, Novartis, and Pfizer.


Backstrom D, Granasen G, Eriksson Domellof M, et al. Early predictors of mortality in parkinsonism and Parkinson disease: A population-based study. Neurology 2018; Epub 2018 Oct 31.