APOEε4 Carriers Exhibit Objective Cognitive Deficits: A Cross-Sectional Study in a Single Center Trial

Abstract

Objective: To explore the association between the apolipoprotein E (APOE) genotype and objectively assessed cognitive function. Methods: In this cross-sectional study, 537 participants underwent a neuropsychological assessment for cognitive function and blood testing for APOE genotype. Based on cognitive test results, participants were stratified into two cohorts: Cognitively Unimpaired participants (CU) and Cognitively Impaired participants (CI). The CI group was further divided into Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD). Furthermore, we conducted age stratification, categorizing participants into three age groups: age 1: <65 years, age 2: 65–75 years, and age 3: >75 years. We assessed the disparities in cognitive function associated with ε4 carrier status across different age brackets. Plasma amyloid-β levels were measured in a cohort of 294 participants to investigate potential interactions involving ε4 carrier status, diagnosis, sex, or plasma markers. Results: The APOE genotypic distribution among the 537 participants was characterized as follows: ε2/ε2 (5 participants), ε2/ε3 (67), ε2/ε4 (13), ε3/ε3 (330), ε3/ε4 (113), and ε4/ε4 (9). Allele frequencies were: ε3 at 78.21%, ε4 at 13.41%, and ε2 at 8.38%. Notably, the ε4 carrier frequency was markedly elevated in the AD group at 81.8% when compared to MCI at 32.8% and CU at 21.3% (p < 0.05). Within the Cognitively Unimpaired (CU) cohort, the sole discernible contrast between ε4+ and ε4− emerged in STT-B (p < 0.05). Within the CI group, ε4 carriers showed statistically poorer scores as compared to non-ε4 carriers in several cognitive tests (p < 0.05). Age stratification result revealed that, among ε4 carriers, cognitive function scores within the age 3 group were significantly inferior to those of age 1 and age 2 groups (p < 0.05). Plasma amyloid-β detection was applied to the 294 participants. We tested plasma amyloid-β (Aβ42) and plasma amyloid-β (Aβ40) levels and calculated the Aβ42/Aβ40 ratio. We found that among female ε4 carriers, both Aβ42 and the Aβ42/Aβ40 ratio were notably lower than their male counterparts (p < 0.05). Conclusions: The ε3/ε3 was the most prevalent among participants, succeeded by ε3/ε4 and ε2/ε3. The least prevalent were ε2/ε4, ε4/ε4, and ε2/ε2 genotypes. The ε3 was predominant, followed by the ε4 and ε2. Individuals with the ε4 allele exhibited significant cognitive impairment, with an especially high prevalence in AD group at 81.8%. The study unveils a pronounced correlation between the ε4 allele and cognitive deficits, implying its potential role in the advancement and severity of cognitive disorders, notably Alzheimer’s disease. Cognitive function declines with age in individuals carrying the ε4, and women are more affected by ε4.