Objective:

The aim of the present report was to evaluate the cognitive profile of symptomatic Parkinson’s disease (PD) patients in a p.A30G SNCA genetic cohort.

Background: The novel p.A30G pathogenic mutation in the alpha-synuclein (SNCA) gene has been recently described in members of unrelated families of PD patients in Greece [1].

Method:

We assessed 9 carriers of the p.A30G SNCA mutation. Epidemiological data including PD age at onset were retrieved. Patients underwent cognitive testing using the Montreal Cognitive Assessment test (MoCA) [2 had undergone testing with the Mini Mental State Examination Test (MMSE) which was then converted to MoCA according to published data [2,3]]. Subscores derived from MoCA testing (memory, visuospatial, attention/concentration and phonemic verbal fluency) were also taken into account.

Results: p.A30G SNCA PD patients (5 Male/ 4 Female) had a mean age at disease onset of 54.8±12.8 y.o (range 36-80) with a disease duration of 7.3±4 years (range 2-13 years). The average MoCA score was 15.8±8.4 /30 (range 2-29). Only 1 out of 9 patients scored within Normal Cognition according to the MoCA cut-off of 26/30. Regarding the pattern of cognitive decline domains, delayed recall without cues, phonemic verbal fluency and visuospatial functions were prominently affected. Cerebrospinal fluid biomarkers were only available for one of the most cognitively impaired patients (49 y.o. male with 6 years of disease duration) and were indicative of concomitant amyloid pathology [amyloid-beta 361 pg/ml (610-974), Total-tau 135 pg/ml (47-225), p-tau 36 pg/ml (36-66)].

Conclusion: The degree of cognitive deterioration in this relatively small cohort of PD patients with the novel p.A30G SNCA mutation ranged from intact cognition to frank dementia, with the majority being significantly affected. It appears that the cognitive profile of this group aligns well with previously published data on the p.A53T SNCA PD carriers [4], which represent the archetypal pure synucleinopathy.

This research was funded by the National Precision Medicine Network for Neurodegenerative Diseases (EDIAN).

References: [1] Liu H, Koros C, Strohäker T, Schulte C, Bozi M, Varvaresos S, Ibáñez de Opakua A, Simitsi AM, Bougea A, Voumvourakis K, Maniati M, Papageorgiou SG, Hauser AK, Becker S, Zweckstetter M, Stefanis L, Gasser T. A Novel SNCA A30G Mutation Causes Familial Parkinson’s Disease. Mov Disord. 2021 Jul;36(7):1624-1633.
[2] Scheffels JF, Fröhlich L, Kalbe E, Kessler J. Concordance of Mini-Mental State Examination, Montreal Cognitive Assessment and Parkinson Neuropsychometric Dementia Assessment in the classification of cognitive performance in Parkinson’s disease. J Neurol Sci. 2020 May 15;412:116735. doi: 10.1016/j.jns.2020.116735.
[3] van Steenoven I, Aarsland D, Hurtig H, Chen-Plotkin A, Duda JE, Rick J, Chahine LM, Dahodwala N, Trojanowski JQ, Roalf DR, Moberg PJ, Weintraub D. Conversion between mini-mental state examination, montreal cognitive assessment, and dementia rating scale-2 scores in Parkinson’s disease. Mov Disord. 2014 Dec;29(14):1809-15.
[4] Koros C, Stamelou M, Simitsi A, Beratis I, Papadimitriou D, Papagiannakis N, Fragkiadaki S, Kontaxopoulou D, Papageorgiou SG, Stefanis L. Selective cognitive impairment and hyposmia in p.A53T SNCA PD vs typical PD. Neurology. 2018 Mar 6;90(10):e864-e869.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cognitive-assessment-of-parkinsons-disease-carriers-of-the-novel-p-a30g-mutation-in-the-snca-gene/