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Is APOE ?4 associated with cognitive performance in early MS?

ABSTRACT: OBJECTIVE:To assess the impact of APOE polymorphisms on cognitive performance in patients newly diagnosed with clinically isolated syndrome (CIS) or relapsing-remitting MS (RRMS). METHODS:This multicenter cohort study included 552 untreated patients recently diagnosed with CIS or RRMS according to the 2005 revised McDonald criteria. The single nucleotide polymorphisms rs429358 (?4) and rs7412 (?2) of the APOE haplotype were assessed by allelic discrimination assays. Cognitive performance was evaluated using the 3-second paced auditory serial addition test and the Multiple Sclerosis Inventory Cognition (MUSIC). Sum scores were calculated to approximate the overall cognitive performance and memory-centered cognitive functions. The impact of the APOE carrier status on cognitive performance was assessed using multiple linear regression models, also including demographic, clinical, MRI, and lifestyle factors. RESULTS:APOE ?4 homozygosity was associated with lower overall cognitive performance, whereas no relevant association was observed for APOE ?4 heterozygosity or APOE ?2 carrier status. Furthermore, higher disability levels, MRI lesion load, and depressive symptoms were associated with lower cognitive performance. Patients consuming alcohol had higher test scores than patients not consuming alcohol. Female sex, lower disability, and alcohol consumption were associated with better performance in the memory-centered subtests of MUSIC, whereas no relevant association was observed for APOE carrier status. CONCLUSION:Along with parameters of a higher disease burden, APOE ?4 homozygosity was identified as a potential predictor of cognitive performance in this large cohort of patients with CIS and early RRMS.

SUBMITTER: Engel S

PROVIDER: S-EPMC7217661 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Is <i>APOE</i> ε4 associated with cognitive performance in early MS?

Engel Sinah S Graetz Christiane C Salmen Anke A Muthuraman Muthuraman M Toenges Gerrit G Ambrosius Björn B Bayas Antonios A Berthele Achim A Heesen Christoph C Klotz Luisa L Kümpfel Tania T Linker Ralf A RA Meuth Sven G SG Paul Friedemann F Stangel Martin M Tackenberg Björn B Then Bergh Florian F Tumani Hayrettin H Weber Frank F Wildemann Brigitte B Zettl Uwe K UK Antony Gisela G Bittner Stefan S Groppa Sergiu S Hemmer Bernhard B Wiendl Heinz H Gold Ralf R Zipp Frauke F Lill Christina M CM Luessi Felix F

Neurology(R) neuroimmunology & neuroinflammation 20200501 4

<h4>Objective</h4>To assess the impact of <i>APOE</i> polymorphisms on cognitive performance in patients newly diagnosed with clinically isolated syndrome (CIS) or relapsing-remitting MS (RRMS).<h4>Methods</h4>This multicenter cohort study included 552 untreated patients recently diagnosed with CIS or RRMS according to the 2005 revised McDonald criteria. The single nucleotide polymorphisms rs429358 (ε4) and rs7412 (ε2) of the <i>APOE</i> haplotype were assessed by allelic discrimination assays<i ...[more]

PMID: 32358224

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Project description:BackgroundSubjective cognitive decline (SCD) is characterized by self-reported cognitive deficits without measurable cognitive impairment. It has been suggested that individuals with SCD exhibited brain structural alterations in widespread cortical thinning or gray matter loss in the medial temporal and frontotemporal regions. Apolipoprotein E (APOE) ε4 allele is thought to be a genetic marker associated with risk of SCD. Neuropsychiatric symptoms may provide insight in detecting higher-risk elders for early Alzheimer's disease as well. Therefore, we aim to explore the characteristics of brain morphology in SCD and to determine whether it is influenced by APOE ε4 as well as neuropsychiatric symptoms in SCD.MethodsA total of 138 cognitively normal older individuals from the SILCODE cohort underwent a clinical interview, neuropsychological assessments, a blood test, and MRI. A two-sample t-test was used to examine the cortex volume and bilateral cortical surface area alterations between SCD (n = 65) and controls (n = 73). A general linear model analysis was used to test for both main and interaction effects of clinical phenotype (SCD vs. controls) and APOE on global and regional cortex volume and bilateral cortical surface area and thickness. A multiple linear regression analysis was conducted to determine the effects of the APOE genotype on the relationships between morphometric features and neuropsychiatric symptoms in SCD.ResultsCompared with controls, individuals with SCD showed decreased total cortical volumes and cortical surface area. SCD APOE ε4 carriers showed additive reduction in the right cortical surface area. The evaluation scores of anxiety symptoms were negatively associated with the right cortical surface area in SCD APOE 4 non-carriers.ConclusionsIndividuals with SCD had an altered cortical surface area, and APOE genotype and anxiety symptoms are modified factors on the cortical surface area decrease in SCD.Trial registrationClinicalTrials.gov (Identifier: NCT03370744 ). Registered 15 March 2017.

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Is APOE ?4 associated with cognitive performance in early MS?

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Is <i>APOE</i> ε4 associated with cognitive performance in early MS?

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