Highlights
- •In this systematic review and meta-analysis, we collected the current evidence to evaluate the association between the ApoE genotype and the cognitive outcomes in patients with MS.
- •13 studies were included in our systematic review, and 5 of them were included in the quantitative synthesize.
- •ApoE4 may have a domain-specific association with cognitive impairment in MS patients; so that ApoE4 patients had more delayed responses to stimuli, but the rate of impaired visuospatial perception is lower in these patients.
- •There is a doubt about the clinical significance of the association between ApoE and cognitive outcomes of MS patients.
Abstract
Background
Multiple sclerosis (MS) is a neuroinflammatory disorder commonly seen in young female
adults. Cognitive impairment is one of the widespread symptoms of MS. In recent years
multiple studies sought the possible risk factors for MS-related cognitive deficit.
Apolipoprotein E (ApoE) genotype is one of the genetic factors which correlated significantly
with cognitive status and it is a well-known risk factor for Alzheimer's Disease.
In this systematic review and meta-analysis, we collected the current evidence to
evaluate the association between the ApoE genotype and the cognitive outcomes in patients
with MS.
Method
Results of searches through Medline via PubMed, Scopus, and ISI web of science, as
well as hand searching, were screened in the title/abstract and full-text stages.
English observational studies in which the association between ApoE and cognitive
outcomes, in patients with MS were included in this systematic review. Animal studies,
conference abstracts, reviews, clinical trials, case reports, letters and withdrawn
studies, were not included. Risk of bias was assessed using the Joanna Briggs Institute
(JBI) critical appraisal tools and the meta-analysis was conducted with Comprehensive
Meta-Analysis (CMA.2) software. The numbers of patients with impairment in both ApoE4+
and ApoE4- groups were utilized for the calculation of the odds ratios (ORs) with
95% confidence intervals (CI) and a 0.05 level of significance for p-value.
Result
Out of 224 results of searching, 13 studies met the eligibility criteria and were
included in our systematic review, and 5 of them were included in the quantitative
synthesis. Eleven studies assessed the cognitive status of patients with MS in two
groups of ApoE4+ and ApoE4- while 2 rests, reported the rate of ApoE4+ patients in
cognitively impaired and non-impaired groups. The phenotype of MS was only Relapsing-remitting
multiple sclerosis (RRMS) in 3 studies and in the other 10 studies, it was a mixture
of RRMS, clinically isolated syndrome (CIS), and progressive MS. Most of the reports
did not find a significant association between ApoE genotype and cognitive outcomes
in patients with MS. Contrary to the expectations, patients in ApoE4- group were more
likely to have impairment in Judgment of Line Orientation (JLO) (OR: 0.405; 95% CI:
0.173 to 0.949, p-value:0.038), while ApoE4+ patients had more rate of impairment
in SRT (OR:1.901; 95%CI: 1.237 to 2.920; p-value:0.003). Appropriate identifying and
dealing with cofounding factors were the most common source of bias in our included
studies.
Conclusion
ApoE may have a domain-specific association with cognitive impairment in MS patients.
ApoE4 patients had more delayed responses to stimuli, but the rate of impaired visuospatial
perception is lower in these patients. Based on the current evidence, there is a doubt
about the clinical significance of this association.
Keywords
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Article info
Publication history
Published online: July 02, 2022
Accepted:
July 1,
2022
Received in revised form:
June 11,
2022
Received:
March 24,
2022
Identification
Copyright
© 2022 Elsevier B.V. All rights reserved.
