Apolipoprotein-E (Apoe) ε4 and cognitive decline over the adult life course

Abstract

We tested the association between APOE-ε4 and processing speed and memory between ages 43 and 69 in a population-based birth cohort. Analyses of processing speed (using a timed letter search task) and episodic memory (a 15-item word learning test) were conducted at ages 43, 53, 60–64 and 69 years using linear and multivariable regression, adjusting for gender and childhood cognition. Linear mixed models, with random intercepts and slopes, were conducted to test the association between APOE and the rate of decline in these cognitive scores from age 43 to 69. Model fit was assessed with the Bayesian Information Criterion. A cross-sectional association between APOE-ε4 and memory scores was detected at age 69 for both heterozygotes and homozygotes (β = −0.68 and β = −1.38, respectively, p = 0.03) with stronger associations in homozygotes; no associations were observed before this age. Homozygous carriers of APOE-ε4 had a faster rate of decline in memory between ages 43 and 69, when compared to non-carriers, after adjusting for gender and childhood cognition (β = −0.05, p = 0.04). There were no cross-sectional or longitudinal associations between APOE-ε4 and processing speed. We conclude that APOE-ε4 is associated with a subtly faster rate of memory decline from midlife to early old age; this may be due to effects of APOE-ε4 becoming manifest around the latter stage of life. Continuing follow-up will determine what proportion of this increase will become clinically significant.

Assessing the effectiveness of subjective cognitive decline plus criteria in predicting the progression to Alzheimer’s disease: an 11‐year follow‐up study

“…The effect of ApoE ε4 allele on the risk of progression from SCD to objective cognitive decline (MCI or AD) has already been demonstrated in previous studies . This is not surprising as ApoE ε4 is recognized to be the major genetic risk factor for AD . Our findings contribute to quantitatively define the effect of ApoE ε4 on the risk of progression from SCD to AD.…”

Genetic risk factors for cancer-related cognitive impairment: a systematic review

“…It should be noted that the studies investigating e4 as a risk factor for CRCI all dichotomized groups into non-carriers vs. carriers of at least one e4 allele. While the dichotomization is probably due to the low frequency of e4 homozygotes in the included studies, for example in the study by Vardy et al [27] only two of 243 patients and three of 70 healthy controls were e4 homozygotes, studies with healthy elderly have reported a gene dose-response relationship showing that e4 homozygotes have faster age-related cognitive decline compared with e4 heterozygotes [39]. It would thus be of interest to investigate whether a similar gene dose-response relationship exists in cancer patients.…”

Systemic inflammation and modifiable risk factors for cognitive impairment in older persons: Findings from a British birth cohort

“…Our findings are unique in the following respects: First, participants were in their seventh decade, younger than other cohorts and perhaps at a critical period for when dementia pathophysiology is being initiated . In addition, the ACE‐III is a more detailed cognitive measure compared with briefer tests used in other studies, such as the Mini‐Mental State Examination.…”