Selective familiarity deficits in otherwise cognitively intact aging individuals with genetic risk for Alzheimer's disease

Abstract

IntroductionFamiliarity has been associated with integrity of the rhinal cortex. Thus, impairment in familiarity is expected in very early stages of Alzheimer's disease (AD). The apolipoprotein E (APOE) ε4 allele is a major risk factor for AD. Here, we investigated the effect of the APOE ε4 status on familiarity in cognitively normal aging individuals.MethodsEighty-one individuals aged between 55 and 80 years, 21 carriers and 60 noncarriers, were used in these analyses. A cognitive evaluation was performed on all participants to document the absence of objective cognitive deficits. The effect of APOE ε4 status on familiarity was tested using independent sample t test and an analysis of covariance controlling for age, gender, and education.ResultsThe groups did not differ in term of age, education, and male/female ratio. APOE ε4 carriers showed a significant reduction in familiarity. No other cognitive deficit was observed in the group of ε4 carriers, relative to noncarriers.DiscussionAPOE ε4 is associated with a reduction in familiarity in the absence of other cognitive deficits. These results suggest that performance in familiarity could represent an early cognitive marker for individuals at risk of AD.

Familiarity deficits in cognitively normal aging individuals with APOE ε4: A follow‐up investigation of medial temporal lobe structural correlates

“…In a previous article, we highlighted a significant and selective impairment in the familiarity performance of APOE ε4 carriers [5]. Here, we provide evidence that the familiarity deficit in APOE ε4 carriers is related to the structural integrity of the perirhinal cortex and, although to a lesser extent, the entorhinal cortex.…”

“…Thus, familiarity impairments could represent one of the earliest cognitive manifestations of this disease. In accordance with this hypothesis, we recently outlined a selective impairment in familiarity in cognitively normal aging individuals carrying the apolipoprotein E ε4 allele ( APOE ε4), a significant risk for the development of AD [5]. In this follow-up investigation, and within the same population, we now aimed to explore the medial temporal lobe structural correlates of this selective impairment.…”

“…Accordingly, aging individuals carrying one or more ε4 alleles are at considerably greater risk of developing AD over time. In an effort to characterize early cognitive manifestations of AD, we previously outlined selective deficits in familiarity-based recognition in otherwise asymptomatic carriers of the APOE ε4 allele (Schoemaker et al, 2016). In this followup report, we aimed to explore the neural correlates of this selective cognitive impairment.…”

Impaired familiarity in individuals at risk for Alzheimer's disease: Commentary on Schoemaker et al. (2016)

“…The results showed that APOE ε4 carriers and noncarriers did not differ on the recollection score, but APOE ε4 carriers had a significantly poorer familiarity score. Schoemaker et al (2016) [5] concluded that individuals at increased risk of developing AD have impaired familiarity. With the caveat that one does not know how many participants will eventually develop AD, as carefully considered by the authors in their discussion, these findings may represent a first step toward supporting the idea of familiarity impairment as an early and specific marker of Alzheimer's disease.…”

“…Finally, the poorer familiarity score in APOE ε4 carriers may actually reflect fewer instances of failed recollection. Indeed, when considering the proportion of recognized targets (i.e., hits) that were accompanied by incorrect source attribution (from the means in Table 3 [5]), it appears that failure to retrieve the source occurred for about 53% of the hits in APOE ε4 carriers versus around 61% in noncarriers. So, if this difference is significant, the poorer familiarity sore in APOE ε4 carriers may actually mean that, when correctly recognizing the faces, they retrieved the source more often.…”