Cognition in Patients With Memory Difficulties and Dementia Relative to APOE e4 Status.

Knut Hestad,Knut Engedal,Bjørn Heine Strand,Peter Horndalsveen

doi:10.3389/fpsyg.2021.686036

Abstract

The aim of this study was to investigate whether cognitive performance was equally influenced by Apolipoprotein E (APOE, with its three alleles, e2, e3, and e4) in patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer’s disease (AD). In addition, we examined a group of patients with a combination of Vascular dementia (VaD) and AD (VaD/AD). We asked if the APOE e4 allele influenced cognition in these patient groups in the same way. Our study comprised data from 1,991 patients (55% women), with a mean age of 70.9 years (SD 10.8) and 12.1 years of education (SD 3.8). Of them, 1,111 (56%) had at least one APOE e4 allele; 871 (44%) had one and 240 (12%) had two e4 alleles. Three neurocognitive tests were used to measure cognition: the Mini Mental State Examination (MMSE), the 10-word test of the Consortium to Establish a Registry for Alzheimer’s Disease Word List (CERAD-WL) (immediate and delayed recall), and the Trail Making Test Part A (TMTA). The APOE genotypes were regressed against cognitive function using linear regression, adjusting for diagnosis, age, sex, and education. The interaction diagnosis∗APOE was investigated. The allele type had the largest effect on cognitive performance assessed by the CERAD-WL delayed recall test, less for the other tests. Those without the e4 type scored 0.7 units better than those with e4 allele(s) (p < 0.001). Furthermore, there was a significant inverse dose-response pattern between number of e4 alleles and cognitive performance; those with one allele scored 0.4 units better than those with two alleles (p = 0.006), and those without e4 scored 0.7 units better than those with one e4 (p < 0.001). This pattern did not differ between the four diagnostic groups studied.

Highlights

The human Apolipoprotein E (APOE) gene has three common allelic variants—e2, e3, and e4— which are encoded on chromosome 19 (Mahley et al, 2009)
As the e4 allele is reported to have a negative effect on episodic memory in both normal aging and Alzheimer’s disease (AD), we examined whether the APOE e4 allele affected cognition, especially episodic memory, in persons with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia due to AD
The occurrence of e4 differed by diagnosis and was most prevalent among AD patients (51% monozygotic and 20% homozygote) and least prevalent among SCD (38% monozygotic, 3% homozygote) and MCI patients (39% monozygotic and 12% homozygote)

Summary

Introduction

The human Apolipoprotein E (APOE) gene has three common allelic variants—e2, e3, and e4— which are encoded on chromosome 19 (Mahley et al, 2009). According to a review of several studies, it is well known that persons with the e4 allele have an increased risk of developing Alzheimer’s disease (AD) compared with persons without the e4 allele (Saunders et al, 1993). This finding could be secondary to a dosage effect, as persons with homozygote combinations of APOE e4 (e4/e4) have the highest risk for development and early onset of dementia due to AD (Verghese et al, 2011). Even though there seems to be a dose-dependent risk regarding the development and course of the second most common dementia type, Vascular dementia (VaD), with a higher risk related to homozygote e4 alleles, more studies are needed to understand how VaD and Apo E status are related to each other (Verghese et al, 2011)

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