Objective: To optimize screening for subjects with dopamine transporter (DaT) imaging deficit being at high risk for prodromal Parkinson’s disease (PD).

Background: Efficient screening methods are urgently needed for prodromal PD cohorts and for future trials with (disease-modifying) preventive or even curative therapies.

Method: The Healthy Brain Ageing (HeBA) initiative [1] invited the local population (age 50 to 80) of Kassel, Germany; Innsbruck, Austria; Barcelona, Spain and Luxembourg, Luxembourg to take part in an online survey (questionnaires see [table1]). Subjects at various risks for PD according to MDS criteria [2] received an additional University of Pennsylvania Smell Test (UPSIT) via mail for a remote smell assessment. Hyposmic subjects based on the UPSIT (defined as ≤15th age- and sex-derived percentile [3]) were invited to DaT single-photon emission computed tomography imaging via the Parkinson’s Progression Marker Initiative (PPMI).

Results: 158 subjects underwent DaT imaging. Characteristics are presented in [table1]. 24 (15%), 54 (34%) and 105 (66%) subjects showed DaT binding <65%, <80% and <100% expected for age and sex [4], respectively [figure1]. Below the 9th UPSIT percentile [3], the number needed to scan (NNS) to identify subjects with <65% and <80% was approx. 6 and 3, respectively. Subjects below 65% of expected DaT binding were more likely to having expressed dream enactment behavior (p=0.03) in the online survey.

Conclusion: The step-wise strategy using an online survey, a remote UPSIT, followed by an in-person DaT scan proved feasible to identify subjects with DaT deficit being at risk for prodromal PD in the general population. In-depth analysis of sub-scores and individual variables of the online survey as well as comparisons to other recruitment initiatives (e.g. PPMI Online) is needed to improve the recruitment strategy and consequently reduce the NNS.

Exploratory analysis of subjects with DaT

Relationship between smell assessment & DaT

References: [1] C. Horlings, A. Garrido, C. Vega Moreno, S. Schade, T. Marques, P. Mahlknecht, C. Gomes, S. Ghosh, K. Rege, R. Rawal, C. Pauly, D. Mcintyre, K. Marini, K. Seppi, M. Marti, C. Trenkwalder, E. Tolosa, W. Poewe, V. Satagopam, R. Krüger, B. Mollenhauer. The Healthy Brain Ageing (HeBA) Parkinson’s disease risk survey: Study design and methods [abstract]. Mov Disord. 2023; 38 (suppl 1)
[2] S. Heinzel, D. Berg, T. Gasser, H. Chen, C. Yao, R. B Postuma, MDS Task Force on the Definition of Parkinson’s Disease. Update of the MDS research criteria for prodromal Parkinson’s disease. Mov Disord 2019; 34(10):1464-1470
[3] M. C Brumm, K. A Pierz, D. Lafontant, C. Caspell-Garcia, C. S Coffey, A. Siderowf, K. Marek. Updated Percentiles for the University of Pennsylvania Smell Identification Test in Adults 50 Years of Age and Older. Neurology 2023; 100(16):e1691-e1701
[4] L. M Chahine, M. C Brumm, C. Caspell-Garcia, W. Oertel, B. Mollenhauer, A. Amara, A. Fernandez-Arcos, E. Tolosa, C. Simonet, B. Högl, A. Videnovic, S. J Hutten, C. Tanner, D. Weintraub, E. Burghardt, C. Coffey, H. R Cho, K. Kieburtz, K. L Poston, K. Merchant, D. Galasko, T. Foroud, A. Siderowf, K. Marek, T. Simuni, A. Iranzo. Dopamine transporter imaging predicts clinically-defined α-synucleinopathy in REM sleep behavior disorder. Ann Clin Transl Neurol. 2021 Jan;8(1):201-212

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MDS Abstracts - https://www.mdsabstracts.org/abstract/identifying-subjects-at-high-risk-for-prodromal-parkinsons-disease-using-dopamine-transporter-imaging-deficit-in-a-step-wise-recruitment-strategy-data-of-healthy-brain-ageing-heba/