Genetic Risk for Alzheimer's Disease Alters Perceived Executive Dysfunction in Cognitively Healthy Middle-Aged and Older Adults

Abstract

Background: Subjective cognitive complaints (SCC) may be an early indicator of future cognitive decline. However, findings comparing SCC and objective cognitive performance have varied, particularly in the memory domain. Even less well established is the relationship between subjective and objective complaints in non-amnestic domains, such as in executive functioning, despite evidence indicating very early changes in these domains. Moreover, particularly early changes in both amnestic and non-amnestic domains are apparent in those carrying the Apolipoprotein-E ɛ4 allele, a primary genetic risk for Alzheimer's disease (AD).

Objective: This study investigated the role of the ɛ4 allele in the consistency between subjective and objective executive functioning in 54 healthy, cognitively intact, middle-aged and older adults.

Methods: Participants (M_age = 64.07, SD = 9.27, range = 48-84; ɛ4+ = 18) completed the Frontal Systems Behavior Scale (FrSBe) Executive Dysfunction Scale (EXECDYS) to measure subjective executive functioning (SEF) and multiple executive functioning tasks, which were condensed into a single factor.

Results: After accounting for age, depression, and anxiety, objective executive functioning performance significantly predicted SEF. Importantly, ɛ4 moderated this effect. Specifically, those carrying the ɛ4 allele had significantly less accurate self-awareness of their executive functioning compared to ɛ4 non-carriers.

Conclusions: Utilizing an approach that integrates self-evaluation of executive functioning with objective neurocognitive assessment may help identify the earliest signs of impending cognitive decline, particularly in those with genetic risk for AD. Such an approach could sensitively determine those most prone to future cognitive decline prior to symptom onset, when interventions could be most effective.

Keywords: APOE ɛ4; Aging; Alzheimer’s disease; executive function; subjective cognitive complaints.

Fig. 1

Theoretical model depicting APOE ɛ4 (W) moderating the relationship between objective executive functioning (X, predictor) and subjective executive functioning (Y, outcome).

Fig. 2

Moderation analysis [simple-slopes analysis via PROCESS; 92] showing the interaction of objectively measured executive functioning (EF_Factor) and APOE ɛ4 group, predicting subjective executive functioning (EXECDYS). Age, depression, and anxiety were covaried. APOE ɛ4 carriers (ɛ4+) were less accurate in identifying executive concerns than ɛ4 non-carriers (ɛ4-). Specifically, in ɛ4-, perceived executive dysfunction was greater in those with poorer objective executive functioning, while in ɛ4+, the opposite pattern was evident; perceived executive dysfunction was lower in those with poorer objective executive functioning.