Objective: To identify subjects with dopamine transporter (DaT) deficit being at high risk for prodromal PD.

Background: Neurodegeneration and dopaminergic deficit in PD occur before the development of motor features upon which the clinical diagnosis is made. Subjects at risk can be identified by risk factors and prodromal markers, including DaT deficit. Recruitment strategies for prodromal cohorts are urgently needed in the quest of improving early diagnosis and developing preventive or even curative therapies.

Method: As part of the Healthy Brain Ageing (HeBA) Initiative [1], the local population of Kassel, Germany (age 50 to 80) wasinvited to take part in an Online Survey [2] via individualized mailings in a population-based recruitment strategy. Addresses of the residents were received from the local resident registry. Subjects at various risk according to MDS criteria [3] received an University of Pennsylvania Smell Test (UPSIT) via mail. Subjects with ≤ 15th age- and gender-stratified UPSITpercentile [4] were invited to DaT scan imaging. Here we present exploratory analysis data of subjects with and without DaT deficit.

Results: The Kassel study flow and exploratory analysis results for subjects with and without DaT deficit can be found in [figure1] and [table1]. Of the 51 subjects with a DaT scan, 21 (41%) showed an age- and gender-stratified deficit; these subjects were more likely to express dream enactment behavior (p=0.0075). Without statistical significance, these subjects tended to express subjective hyposmia and cognitive decline; their motor and depression scores were higher, while non-motor scores were lower.

Conclusion: A direct recruitment approach and a step-wise strategy (Online survey, UPSIT, in-person DaT scan) might be a feasiblestrategy to identify subjects at risk for prodromal PD in the general population. Only dream enactment behavior was statistically significant. Additional non-significant trends need detailed analysis of sub-scores and individual variables.Further analysis and follow-up are needed to improve the recruitment strategy for (a) prediction of pathological DaT scan imaging, (b) identifying prodromal PD subjects, and (c) conversion to manifest PD. This future analysis should include integration of in-person investigations and a comparison to other centers of the HeBA initiative with different recruitment strategies.

Table 1 exploratory analysis results

Figure 1 HeBA Kassel study flow

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. Schade, C. Vega Moreno, C. Horlings, A. Garrido, T. Marques, P. Mahlknecht, E. Bryan, C. Gomes, C. Pauly, S. Ghosh, K. Rege, R. Rawal, T. Wicke, E. Lang, S. Schnell, V. Satagopam, K. Seppi, M. Marti, E. Tolosa, W. Poewe, R. Krüger, C. Trenkwalder, B. Mollenhauer. Identifying prodromal NMS in a population-based recruitment strategy: Kassel data of Healthy Brain Ageing [abstract]. Mov Disord. 2023; 38 (suppl 1)
[3] 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
[4] 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

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MDS Abstracts - https://www.mdsabstracts.org/abstract/identifying-subjects-with-dopamine-transporter-deficit-in-a-population-based-recruitment-strategy-kassel-data-of-healthy-brain-ageing/