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

BACKGROUNDEpisodic 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 Alzheimers disease risk factor APOE4 and early Alzheimers pathology constrain the neural resources required to cope with increasing task demands. METHODSIn this preregistered behavioral study named EMCOMP (Episodic Memory & COMPensation), we conducted a semantic episodic memory retrieval task using a sentence-based task demand manipulation 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 Alzheimers pathology. Third, we assessed correlations between EMCOMP recognition and recall and established cognitive tests. RESULTSYoung 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 recognition-task demand 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 Alzheimers pathology. EMCOMP performance was positively correlated with established cognitive tests. CONCLUSIONOur study demonstrates age- and APOE4-related differences in episodic memory retrieval under increasing task demands - differences that may not be detectable in paradigms with only one or two levels of task demand. By manipulating semantic 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 Alzheimers pathology. Future research should extend this work to more diverse samples and combine behavioral assessment with fMRI to examine underlying brain activation patterns and functional connectivity.