Midbrain hyperechogenicity, hyposmia, mild parkinsonian signs and risk for incident Parkinson's disease over 10 years: A prospective population-based study

Mahlknecht, Philipp; Stockner, Heike; Marini, Kathrin; Gasperi, Arno; Djamshidian, Atbin; Willeit, Peter; Kiechl, Stefan; Willeit, Johann; Rungger, Gregorio; Poewe, Werner; Seppi, Klaus

doi:10.1016/j.parkreldis.2019.12.008

Cited by 25 publications

(22 citation statements)

References 14 publications

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“…Furthermore, we note that the sex-related meta-regression analyses were significantly influenced by the male-only Honolulu Study [24]. In studies that examined effect modification at an individual rather than a group level, effect estimates of olfactory dysfunction were actually higher among men, which further adds to our cautious interpretation of sex-specific differences in risk estimates [12,21].…”

Section: Discussionmentioning

confidence: 85%

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

Daalen

Tosserams

Mahlknecht

et al. 2021

Parkinsonism & Related Disorders

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Background: 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. Methods: 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. Results: 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). Conclusion: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.

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Section: Discussionmentioning

confidence: 85%

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

Daalen

Tosserams

Mahlknecht

et al. 2021

Parkinsonism & Related Disorders

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“…Older people with olfactory dysfunction are at higher risk of developing PD (Ross et al, 2008 ; Berg et al, 2012 ; Chen et al, 2017 ; Fullard et al, 2017 ). Two recent studies have reported that the relative risk of developing incident PD in hyposimc subjects over non-hyposmic subjects up to a 10-year follow-up period was 3–4 (Chen et al, 2017 ; Mahlknecht et al, 2020 ). These findings suggest that there is a long prodromal phase of the illness and that the patients in this phase may be underdiagnosed as merely having “age-related olfactory dysfunction.”…”

Section: Olfactory Dysfunction Associated With Neurodegenerative Disementioning

confidence: 99%

Age-Related Olfactory Dysfunction: Epidemiology, Pathophysiology, and Clinical Management

Kondo

Kikuta

Ueha

et al. 2020

Front. Aging Neurosci.

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Like other sensory systems, olfactory function deteriorates with age. Epidemiological studies have revealed that the incidence of olfactory dysfunction increases at the age of 60 and older and males are more affected than females. Moreover, smoking, heavy alcohol use, sinonasal diseases, and Down's syndrome are associated with an increased incidence of olfactory dysfunction. Although the pathophysiology of olfactory dysfunction in humans remains largely unknown, studies in laboratory animals have demonstrated that both the peripheral and central olfactory nervous systems are affected by aging. Aged olfactory neuroepithelium in the nasal cavity shows the loss of mature olfactory neurons, replacement of olfactory neuroepithelium by respiratory epithelium, and a decrease in basal cell proliferation both in the normal state and after injury. In the central olfactory pathway, a decrease in the turnover of interneurons in the olfactory bulb (OB) and reduced activity in the olfactory cortex under olfactory stimulation is observed. Recently, the association between olfactory impairment and neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), has gained attention. Evidence-based pharmacotherapy to suppress or improve age-related olfactory dysfunction has not yet been established, but preliminary results suggest that olfactory training using odorants may be useful to improve some aspects of age-related olfactory impairment.

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“…The PREDICT‐PD score was developed as an online tool only including items that can be assessed remotely and therefore does not require in‐person examinations. It did not include the established and stronger “intermediate” markers shown to clearly associate to a substantially increased PD risk 2,14 that could theoretically also be remotely assessed. Instead, these markers were used in the original publication as surrogate markers until sufficient incident cases had occurred during the follow‐up of 3 years, but the group very recently reported that the inclusion of these markers into an updated algorithm may boost its performance 19 .…”

Section: Discussionmentioning

confidence: 99%

“…The following established risk markers (“intermediate” surrogate outcomes in the original PREDICT‐PD study) 12 were available: olfactory loss, assessed with the 12‐item sniffin' sticks identification test; probable RBD, assessed throughout the RBD Screening Questionnaire; possible subthreshold parkinsonism using the motor section of the UPDRS (Part III); and substantia nigra (SN) echogenicity on transcranial sonography. The distribution of these risk markers and of the Movement Disorder Society (MDS) research criteria for prodromal PD 13 at the same time point in the Bruneck cohort and their performance in predicting incident cases of PD is published elsewhere 10,14 …”

Section: Methodsmentioning

confidence: 99%

“…The distribution of these risk markers and of the Movement Disorder Society (MDS) research criteria for prodromal PD 13 at the same time point in the Bruneck cohort and their performance in predicting incident cases of PD is published elsewhere. 10,14 A detailed description of the ascertainment of all markers and respective cut-offs is available in the Supplementary Methods.…”

Section: Ascertainment Of Early Nonmotor Features and Pd Risk Markersmentioning

confidence: 99%

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Application of a Simple Parkinson's Disease Risk Score in a LongitudinalPopulation‐BasedCohort

et al. 2020

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Background Identifying individuals at risk of developing Parkinson's disease (PD) is critical to define target populations for future neuroprotective trials. Objective The objective of this study was to apply the PREDICT‐PD algorithm of risk indicators for PD in a prospective community‐based study (the Bruneck study), representative of the general elderly population. Methods PREDICT‐PD risk scores were calculated based on risk factor assessments obtained at baseline (2005, n = 574 participants). Cases of incident PD were identified at 5‐year and 10‐year follow‐ups. Participants with PD or secondary parkinsonism at baseline were excluded (n = 35). We analyzed the association of log‐transformed risk scores with the presence of well‐established markers as surrogates for PD risk at baseline and with incident PD at follow‐up. Results A total of 20 participants with incident PD were identified during follow‐up (11 after 5 years and 9 after 10 years). Baseline PREDICT‐PD risk scores were associated with incident PD with odds ratios of 2.09 (95% confidence interval, 1.35–3.25; P = 0.001) after 5 years and of 1.95 (1.36–2.79; P < 0.001) after 10 years of follow‐up per doubling of risk scores. In addition, higher PREDICT‐PD scores were significantly correlated with established PD risk markers (olfactory dysfunction, signs of rapid eye movement sleep behavior disorder and motor deficits) and significantly associated with higher probability for prodromal PD according to the Movement Disorder Society research criteria at baseline. Conclusions The PREDICT‐PD score was associated with an increased risk for incident PD in our sample and may represent a useful first screening step in future algorithms aiming to identify cases of prodromal PD. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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Midbrain hyperechogenicity, hyposmia, mild parkinsonian signs and risk for incident Parkinson's disease over 10 years: A prospective population-based study

Cited by 25 publications

References 14 publications

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

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

Age-Related Olfactory Dysfunction: Epidemiology, Pathophysiology, and Clinical Management

Application of a Simple Parkinson's Disease Risk Score in a LongitudinalPopulation‐BasedCohort

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