Episodic memory retrieval with increasing task demand: associations with age, APOE4 genotype, and Alzheimer’s disease pathology

Abstract Episodic memory declines early with aging, reflecting reduced neural resources and diminished memory specificity. However, few studies have created a cognitive challenge with multiple levels of task demand to investigate this early subtle decline. Furthermore, it is unclear whether the genetic Alzheimer’s disease risk factor APOE4 and early Alzheimer’s pathology constrain the neural resources required to cope with increasing task demands. In this preregistered behavioral study named EMCOMP (Episodic Memory & COMPensation), we conducted a sentence-based episodic memory retrieval task where we manipulated retrieval difficulty by varying the required degree of memory specificity, thereby increasing task demands on episodic retrieval with five demand levels at recognition (novel foils, “old” target sentences, and three lure levels) and two demand levels at free and cued recall (gist and details). We collected data from 100 cognitively unimpaired adults (37 young (mean age 24 years), 63 older (mean age 72 years)) with additional neuropsychological testing and blood-based measures available for the older group. First, we investigated differences in EMCOMP episodic memory retrieval accuracy and confidence between young and older adults in linear mixed-effects models. Second, we investigated differences associated with the APOE4 genotype and plasma-derived Alzheimer’s pathology. Third, we assessed correlations between EMCOMP recognition and recall and established cognitive tests. Young adults showed higher recognition accuracy and confidence as well as a higher recall score and a lower recall error rate compared to older adults. As target-lure similarity increased there was a steeper decline in recognition accuracy and a steeper increase in high-confidence errors in older compared to younger adults and in older APOE4 carriers compared to older non-carriers. However, we found no associations with Alzheimer’s pathology. EMCOMP performance was positively correlated with established cognitive tests. Our study demonstrates age- and APOE4-related differences in episodic memory retrieval under increasing retrieval difficulty - differences that may not be detectable in paradigms with only one or two levels of variation. By manipulating sentence-based retrieval specificity, we provide a novel approach to detect subtle cognitive deficits and potential functional compensation in cognitively unimpaired older adults with risk factors or early Alzheimer’s pathology. Future research should extend this work to more diverse samples and combine behavioral assessment with functional MRI to examine underlying brain activation patterns and functional connectivity.