Autobiographical Memory Fluency Reductions in Cognitively Unimpaired Middle-Aged and Older Adults at Increased Risk for Alzheimer’s Disease Dementia

Abstract

Objective: Recent research has revealed that cognitively unimpaired older adults who are at higher risk for developing Alzheimer’s disease (AD) dementia often exhibit subtle cognitive alterations in their neuropsychological profiles. Emerging evidence suggests that autobiographical memory, which is memory for personal events and knowledge, may be sensitive to early AD-related cognitive alterations. In the present study, we investigated whether the rapid generation of autobiographical memory category exemplars, a retrieval process that taxes the neural network that is vulnerable to early AD, is compromised in cognitively unimpaired middle-aged and older carriers of the e4 allele of the apolipoprotein E gene (APOE4), which increases risk for AD dementia. Methods: In addition to standard neuropsychological tests, we administered a fluency task that requires generating exemplars for two types of autobiographical memory, namely episodic memories and personal semantics, to a group of cognitively unimpaired middle-aged and older adults (n = 45) enriched with APOE4 carriers (n = 20). Results: While no APOE4 deficits were found on standard neuropsychological tests, episodic and personal semantic exemplar generation was reduced in the APOE4 group. Discussion: Autobiographical memory aberrations associated with a higher risk for AD are evident in fluency and affect both episodic memory and personal semantics.

Brain connectivity patterns associated with individual differences in the access to experience-near personal semantics: a resting-state fMRI study

“…These findings support the specificity of the EAM condition to test episodic components of autobiographical memory, as well as the suitability of the enPS condition as a measure of context-dependent, experience-near personal semantics. The notion that the AFT effectively taps enPS also is in line with the results of a recent study, in which performance in both the EAM and enPS condition of the AFT was found to be reduced in cognitively unimpaired older adults at risk to develop Alzheimer’s disease (Grilli et al, 2021 ). Importantly, the AFT requires participants to access autobiographical memories from different life periods (see below); thus, this feature further allows to ensure that the retrieved EAMs and enPS are temporally contextualized and to consistently sample across individuals’ memories, providing a way to finely assess individual differences in the access to autobiographical memories.…”

“…The present study has different limitations. As mentioned, because the AFT does not require to elaborate on retrieved items, this test mainly assesses individual variations in the strategic retrieval of autobiographical memories (Grilli et al, 2021 ). Thus, present results are not directly informative of connectivity patterns associated with complete access and elaboration of such memories.…”

“…Because this was the very first study to assess brain correlates of individual differences in the access to experience-near personal semantics versus episodic autobiographical memories, we choose to use the AFT, which has been previously shown to be a reliable and effective measure of autographical memory (Dritschel et al, 1992 ; Addis & Tippett, 2004 ; Tomadesso et al, 2015 ; Grilli et al, 2021 ; Conti et al, 2023 ). Future studies should extend the present investigation to different types of personal semantic information to establish more reliably a correspondence between individual differences in these domains and intrinsic connectivity patterns.…”

Past and future episodic detail retrieval is reduced among clinically normal older adults at higher genetic risk for late-onset Alzheimer’s disease.

“…Relatedly, prior studies have shown that Alzheimer’s disease risk-related neural alterations in the hippocampus and its cortical connections are linked to cognitive mechanisms that may be needed to retrieve episodic details of past events, including spatial context memory, verbal memory recall, and cognitive control (Rajah et al, 2017; Shafer et al, 2021; Westlye et al, 2012). Older adult APOE4 carriers have deficits in other hippocampally dependent memory mechanisms that may also have a role in episodic detail generation, such as autobiographical category fluency and memory consolidation (Grilli et al, 2021; Tort-Merino et al, 2020; Zimmermann & Butler, 2018). Therefore, while the present study raises doubt about the role of relational processing, other cognitive mechanisms dependent on the hippocampus and its cortical connections may account for APOE4-associated reductions in episodic detail generation.…”

Consistency of earliest memories is related to direct retrieval.

“…Second, direct and generative retrieval may form a continuum of ease of retrieval. Earlier researchers (e.g., Benjamin & Bjork, 2014; Dritschel et al, 1992; Grilli et al, 2021) used the concepts of memory/retrieval fluency to denote the subjective experience of the ease of retrieval. The self-report measure of retrieval used here corresponds to the same concept.…”