Towards subgroup-specific risk estimates: A meta-analysis of longitudinal studies on olfactory dysfunction and risk of Parkinson's disease

Interest has risen in identifying individuals at high risk of incident Parkinson's disease (PD) to facilitate inclusion in neuroprotective treatment trials. Current risk estimates of prodromal markers are based on aggregated data of an entire population, but this approach disregards differences...

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Bibliographic Details
Published in:Parkinsonism & related disorders 2021-03, Vol.84, p.155-163
Main Authors: Janssen Daalen, Jules M., Tosserams, Anouk, Mahlknecht, Philipp, Seppi, Klaus, Bloem, Bastiaan R., Darweesh, Sirwan K.L.
Format: Article
Language:English
Subjects:
Female
Humans
Longitudinal Studies
Male
Olfaction Disorders - epidemiology
Parkinson Disease - epidemiology
Prodromal Symptoms
REM Sleep Behavior Disorder - epidemiology
Risk Assessment
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Summary:Interest has risen in identifying individuals at high risk of incident Parkinson's disease (PD) to facilitate inclusion in neuroprotective treatment trials. Current risk estimates of prodromal markers are based on aggregated data of an entire population, but this approach disregards differences in risk estimates by subgroups of a population. In this proof of concept, we determine subgroup-specific risk estimates of olfactory dysfunction for incident PD. PubMed, EMBASE and Cochrane were searched for prospective studies investigating the association between olfactory dysfunction and incident PD. Random-effects meta-analysis, subgroup analyses and meta-regression were performed to investigate general and subgroup risk estimates. Individuals with odor identification dysfunction seemed to be at greater risk of incident PD compared to controls without olfactory dysfunction (OR = 4.18; 95%CI [2.47–7.07]). Risk estimates were higher in studies that included higher percentages of women (regression slope β = 0.053 increase in log odds ratio per 1% increase 1%, p = 0.0006), increased with mean study age (β = 0.21 per one year increase; p = 0.005) and in REM-sleep behavior disorder cohorts (β = 1.95; p = 0.03). Furthermore, the association between olfactory dysfunction and incident PD was most distinct in studies with shorter follow-up duration (ß = −0.56; p = 0.0047). The presence of olfactory dysfunction conveys a considerably elevated risk of incident PD, likely more in studies with a higher proportion of women, older individuals or short follow-up duration. Individual patient data are warranted to confirm these findings and to yield subgroup-specific risk estimates of other common markers to refine prodromal PD criteria. •Olfactory dysfunction is associated with a significantly increased risk of Parkinson's disease (PD).•Risk estimates were higher for studies with higher % women, increased mean study age and REM-sleep behavior disorder cohorts.•PD risk decreased with longer latency after olfactory dysfunction onset.•Personalized risk estimates are needed for accurate PD diagnosis.
ISSN:1353-8020
1873-5126
DOI:10.1016/j.parkreldis.2021.01.005