APOE-ε4 is not associated with cognitive impairment in relapsing - Remitting multiple sclerosis

Department of Neurology, University of Florence, Florence, Italy.
Multiple Sclerosis (Impact Factor: 4.82). 11/2009; 15(12):1489-94. DOI: 10.1177/1352458509348512
Source: PubMed


The objective of this article was to assess the association between apolipoprotein E (APOE)-epsilon4 and cognitive impairment (CI) in relapsing-remitting multiple sclerosis (RRMS). The APOE genotype was assessed in 85 RRMS cases (58 females, mean age 43 +/- 8.4 years, mean disease duration 15.8 +/- 9.6 years, mean Expanded Disability Status Scale (EDSS) 1.7 +/- 1.0). Cognitive functioning was evaluated in the whole sample using Rao's Brief Repeatable Battery (BRB). Performance on each test was assessed by applying the normative values for the Italian population. In a subgroup of 50 patients, a brain magnetic resonance (MR) study was performed including measurement of T2 lesion volumes (T2LV), neocortical volume (NCV) and normalized brain volume (NBV). The relationship between APOE genotype, CI and MR variables was assessed through univariate and multivariate logistic regression models. CI, most commonly involving complex attention and verbal memory tasks, was found in 28 cases (33%). We identified a total of 19 epsilon4carriers (22.4%), who did not differ from non-carriers regarding clinical and demographic characteristics. The presence of the epsilon4 genotype was associated with neither CI (p = 0.28) nor impairment on each neuropsychological test (p > 0.32; corrected for age, gender, disease duration, EDSS, depression and fatigue). The APOE genotype and CI were also not related in the subgroup of younger patients (age < 45 years; p > 0.9). Moreover, CI was related to higher T2LV (p = 0.008) and lower NCV (p = 0.006). In conclusion, in our sample CI was associated with higher subcortical damage and cortical atrophy but not with APOE-epsilon4 genotype. The role of APOE-epsilon4 as a possible biomarker in multiple sclerosis is still questionable.

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    • "Significant results were reported in all seven studies [20, 25, 29, 33, 34, 39, 54] evaluating patients with a mix of MS subtypes. In RRMS patients, only two [24, 33] of seven [13, 18, 24, 30, 33, 47, 48] studies reported significant correlations. A longitudinal study conducted in RRMS patients found a strong correlation between the change in brain volume and change in PASAT score over one year (r = 0.64) and an even stronger correlation between the change in brain volume and change in SDMT score over the same period (r = 0.75) [33]. "
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    ABSTRACT: Objectives. To examine relationships between conventional MRI measures and the paced auditory serial addition test (PASAT) and symbol digit modalities test (SDMT). Methods. A systematic literature review was conducted. Included studies had ≥30 multiple sclerosis (MS) patients, administered the SDMT or PASAT, and measured T2LV or brain atrophy. Meta-analysis of MRI/information processing speed (IPS) correlations, analysis of MRI/IPS significance tests to account for reporting bias, and binomial testing to detect trends when comparing correlation strengths of SDMT versus PASAT and T2LV versus atrophy were conducted. Results. The 39 studies identified frequently reported only significant correlations, suggesting reporting bias. Direct meta-analysis was only feasible for correlations between SDMT and T2LV (r = -0.45, P < 0.001) and atrophy in patients with mixed-MS subtypes (r = -0.54, P < 0.001). Familywise Holm-Bonferroni testing found that selective reporting was not the source of at least half of significant results reported. Binomial tests (P = 0.006) favored SDMT over PASAT in strength of MRI correlations. Conclusions. A moderate-to-strong correlation exists between impaired IPS and MRI in mixed MS populations. Correlations with MRI were stronger for SDMT than for PASAT. Neither heterogeneity among populations nor reporting bias appeared to be responsible for these findings.
    Full-text · Article · Mar 2014
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    • "It has been recently suggested that Apo-E polymorphism may interact with cigarette smoking in promoting MS progression [156]. Although some authors have shown an association between Apo-E ε4 and cognitive impairment in MS patients [157], the others could not confirm this finding [158]. "
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    ABSTRACT: Following emerging evidence that neurodegenerative processes in multiple sclerosis (MS) are present from its early stages, an intensive scientific interest has been directed to biomarkers of neuro-axonal damage in body fluids of MS patients. Recent research has introduced new candidate biomarkers but also elucidated pathogenetic and clinical relevance of the well-known ones. This paper reviews the existing data on blood and cerebrospinal fluid biomarkers of neuroaxonal damage in MS and highlights their relation to clinical parameters, as well as their potential predictive value to estimate future disease course, disability, and treatment response. Strategies for future research in this field are suggested.
    Full-text · Article · May 2011

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