{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T03:30:07Z","timestamp":1782703807298,"version":"3.54.5"},"reference-count":63,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T00:00:00Z","timestamp":1670803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Introduction<\/jats:title>\n<jats:p>Classically, cognitive impairment (CI) was not considered as a paramount feature of multiple system atrophy(MSA) in both parkinsonian(MSA-P) and cerebellar(MSA-C) motor-subtypes. Yet, growing evidence indicates currently the commonness of such deficits among MSA patients in different populations. Our aim was to evaluate the cognitive profile of MSA Tunisian patients and to analyze the underlying clinical and genetic determinants<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>In a retrospective cross-sectional study, clinically-diagnosed MSA patients were included. All subjects underwent clinical and neuropsychological assessments to characterize their cognitive profile. The associations with their <jats:italic>APOE<\/jats:italic> genotype status were analyzed. Determinant of CI were specified.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>We included 71 MSA patients. Female gender(sex-ratio = 0.65) and MSA-P subtype(73%) were predominant. Mean age of disease onset was 59.1years. CI was found in 85.7% of patients(dementia in 12.7% and Mild cognitive impairment(MCI) in 73% of patients mainly of multiple-domain amnestic type(37.3%)). Mean MMSE score was lower among MSA-P compared to MSA-C(23.52 <jats:italic>vs<\/jats:italic>. 26.47;p = 0.027). Higher postural instability gait disorder(PIGD) and MDS-UPDRS-III scores were noted in demented MSA patients(p = 0.019;p = 0.015 respectively). The main altered cognitive domain was attention(64.8%). Executive functions and mood disorders were more affected in MSA-P(p = 0.029,p = 0.035 respectively). Clinical and neurophysiological study of dysautonomia revealed no differences across cognitive subtypes. <jats:italic>APOE<\/jats:italic> genotyping was performed in 51 MSA patients with available blood samples. Those carrying <jats:italic>APOE\u03b54<\/jats:italic> had 1.32 fold higher risk to develop CI, with lower MMSE score(p = 0.0001). Attention and language were significantly altered by adjusting the p value to <jats:italic>APOE\u025b4<\/jats:italic> carriers(p = 0.046 and p = 0.044 respectively). Executive dysfunction was more pronounced among MSA-P<jats:italic>APOE\u03b54<\/jats:italic> carriers(p = 0.010).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>In this study, the main determinants of CI in Tunisian MSA patients were MSA-P motor-subtype, mainly of PIGD-phenotype, disease duration and <jats:italic>APOE\u03b54<\/jats:italic> carrying status, defining a more altered cognitive phenotype. This effect mainly concerned executive, attention and language functions, all found to be more impaired in <jats:italic>APOE\u03b54<\/jats:italic> carriers with variable degrees across MSA motor-subtypes.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0277798","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T18:27:20Z","timestamp":1670869640000},"page":"e0277798","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Determinants of cognitive impairment in multiple system atrophy: Clinical and genetic 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Ben","family":"Djebara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imen","family":"Kacem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9615-3797","authenticated-orcid":true,"given":"Riadh","family":"Gouider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,12,12]]},"reference":[{"key":"pone.0277798.ref001","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s40035-020-0185-5","article-title":"Insights into the pathogenesis of multiple system atrophy: focus on glial cytoplasmic inclusions","volume":"9","author":"S Kaji","year":"2020","journal-title":"Transl 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