Early predictors of mortality in parkinsonism and Parkinson disease: A population-based study

Abstract

Objective: To examine mortality and associated risk factors, including possible effects of mild cognitive impairment, imaging, and CSF abnormalities, in a community-based population with incident parkinsonism and Parkinson disease.

Methods: One hundred eighty-two patients with new-onset, idiopathic parkinsonism were diagnosed from January 2004 through April 2009, in a catchment area of 142,000 inhabitants in Sweden. Patients were comprehensively investigated according to a multimodal research protocol and followed prospectively for up to 13.5 years. A total of 109 patients died. Mortality rates in the general Swedish population were used to calculate standardized mortality ratio and expected survival, and Cox proportional hazard models were used to investigate independent predictors of mortality.

Results: The standardized mortality ratio for all patients was 1.84 (95% confidence interval 1.50-2.22, p < 0.001). Patients with atypical parkinsonism (multiple system atrophy or progressive supranuclear palsy) had the highest mortality. In early Parkinson disease, a mild cognitive impairment diagnosis, freezing of gait, hyposmia, reduced dopamine transporter activity in the caudate, and elevated leukocytes in the CSF were significantly associated with shorter survival.

Conclusion: Although patients presenting with idiopathic parkinsonism have reduced survival, the survival is highly dependent on the type and characteristics of the parkinsonian disorder. Patients with Parkinson disease presenting with normal cognitive function seem to have a largely normal life expectancy. The finding of a subtle CSF leukocytosis in patients with Parkinson disease with short survival may have clinical implications.

Figure 1. Flowchart of patients included in the study

Diagnosis was established according to clinical diagnosis at the latest follow-up and confirmed by autopsy in 5 patients. MSA = multiple system atrophy; PSP = progressive supranuclear palsy.

Figure 2. Survival in incident, idiopathic parkinsonism

(A) Lexis diagram showing follow-up of patients throughout the study. The “atypical parkinsonism” group comprises patients with new-onset MSA and PSP. (B) Kaplan-Meier plot of survival in relation to diagnosis (for number at risk, see supplemental table e-1, links.lww.com/WNL/A762). MSA = multiple system atrophy; PSP = progressive supranuclear palsy.

Figure 3. Survival in Parkinson disease in relation to phenotype

Kaplan-Meier plots of survival in patients with Parkinson disease (n = 143) in relation to clinical and neurobiological phenotype at baseline (except panel B, which is related to phenotype at 3 years). Severe hyposmia is defined by a B-SIT score <4. All variables (A–F) were significantly related to survival at the p < 0.001 level (log rank) except the tremor or PIGD/intermediate variable (C), which was significant at the p = 0.004 level (for number at risk, see supplemental table e-2, links.lww.com/WNL/A762). B-SIT = Brief Smell Identification Test; PIGD = postural imbalance and gait disorder.