Study heterogeneity hinders mortality predictions in Parkinson’s disease

By Laura Cowen, medwireNews Reporter

Poor study quality and heterogeneity in study methods and patients make it difficult to determine the impact Parkinson’s disease (PD) has on mortality, UK researchers report.

In their systematic review and meta-analysis of 88 studies of mortality in PD, Angus Macleod (University of Aberdeen) and colleagues found that standardised mortality ratios ranged from 0.9 to 3.8. However, they note that major heterogeneity (up to 95%) among the studies meant that calculating an overall mortality ratio was “inappropriate.”

Among the nine studies that used inception cohorts (n=1801 patients followed up for a median of 9 years), in which patients were recruited at, or soon after diagnosis, the overall mortality ratio was 1.52, but heterogeneity was still high, at 73.5%. Excluding one study, which was responsible for the majority of the heterogeneity, resulted in an overall mortality ratio of 1.41 with heterogeneity of 3.8%.

Inception cohorts, measurements at longer follow-up duration, older study recruitment year and post-levodopa (L-dopa) studies were all associated with lower mortality ratios but were not robust to sensitivity analyses.

“The L-dopa era variable in particular was not robust, because [the] only 2 pre–L-dopa studies had heterogeneous mortality ratios”, Macleod and co-authors remark. Contrary to previous reports, the team therefore does not think that “there is good evidence that L-dopa has led to a reduction in mortality in PD.”

Among the nine studies that reported mortality ratios at multiple time points, there was a trend for increased ratios with longer study duration. In addition, survival (reported at multiple time points in 45 studies) decreased by approximately 5% per year of follow-up.

The duration from disease onset to death, reported in 10 studies, ranged from 7.6 to 14.9 years, again with major heterogeneity (97.4%). However, some of this variation was explained by year of study and age at diagnosis, the authors note.

Furthermore, older age at onset, along with the presence of dementia, were the two variables most consistently reported as independent predictors of mortality.

Writing in Movement Disorders, Macleod et al recommend that future studies of mortality in PD should, at a minimum, recruit community-based inception cohorts with expert-confirmed diagnoses, have no exclusion criteria, have prospective and long-term follow-up and use the point of diagnosis as a baseline.

They add that several such studies are already underway.

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