The apolipoprotein E (APOE) gene is the strongest known genetic risk factor for late-onset Alzheimer's disease (AD), particularly the ε4 allele. Evidence suggests that women carrying at least one APOE ε4 allele have a higher risk of developing AD compared to men. However, data addressing genetic risk and sex-specific effects in Middle Eastern and North African populations remain limited.
To address this gap, we evaluated APOE allele frequencies, their association with AD risk, and their contribution to sex-specific variability in a cohort of 63 clinically diagnosed AD patients and 201 cognitively healthy controls recruited across Egypt.
The APOE ε3 allele was the most prevalent in both AD cases (83.3%) and controls (83.6%). The ε4 allele was more frequent among AD patients (12.7%) than controls (8.0%) (adjusted odds ratio [OR] = 1.09, 95% confidence interval [CI]: 0.46 to 2.49, p = 0.85), while the ε2 allele was less frequent in AD patients (4.0%) compared to controls (8.5%) (adjusted OR = 0.82, 95% CI: 0.24 to 2.36, p = 0.73). However, neither association reached statistical significance after Benjamini–Hochberg false discovery rate correction. Sex-stratified analyses revealed no significant sex-specific effects of APOE alleles.
This pilot study provides the first characterization of APOE genotype and allele frequencies in Egyptians with clinically confirmed AD. No statistically significant association was observed between APOE status and AD risk in either males or females. Larger, geographically representative studies are needed to further elucidate the role of APOE in AD susceptibility within the Egyptian population and to explore potential alternative genetic or environmental contributors.
Background:
Quality of life (QoL) in multiple sclerosis (MS) is multifactorial, reflecting the combined effects of physical disability, cognitive impairment, and depressive symptoms. While physical disability is a key determinant, the independent contributions of cognition and depression to QoL remain incompletely defined. This study aimed to assess the frequency of cognitive impairment and depressive symptoms in MS and examine their independent impact on QoL beyond physical disability.
Methods:
This cross-sectional study included 242 patients with clinically definite MS who were evaluated using standardized clinical and neuropsychological measures. Physical disability was assessed by the Expanded Disability Status Scale (EDSS), motor function by the Nine-Hole Peg Test (9-HPT) and 25-Foot Walk Test (25-FWT), cognition by the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test (CVLT), and Brief Visuospatial Memory Test-Revised (BVMT-R), depression by the Hamilton Depression Rating Scale (HAM-D), and QoL by the MS Impact Scale (MSIS-29). Hierarchical multiple regression was performed to identify independent predictors of total QoL. In this study, cognitive impairment was defined as performance ≥1.5 standard deviations below normative means on at least one cognitive test, and depressive symptoms as HAM-D ≥ 8.
Results:
Cognitive impairment was present in 47.9% and depressive symptoms in 61.3% of the cohort. EDSS showed the strongest correlation with MSIS-29 total score (r = 0.698, p < 0.001), followed by HAM-D (r = 0.438, p < 0.001) and BVMT-R (r = −0.340, p < 0.001). In regression analysis, physical disability (β = 0.65, p < 0.001), depression (β = 0.23, p < 0.001), and processing speed (β = −0.12, p = 0.009) were independent predictors of QoL, explaining 64% of its variance.
Conclusion:
Although physical disability remains the dominant determinant of QoL in MS, depressive symptoms and cognitive slowing contribute independent and clinically meaningful effects. Routine screening and early intervention for mood and cognitive disturbances are essential to improve overall well-being in patients with MS.