Memory precision of object-location binding is unimpaired in APOE ε4-carriers with spatial navigation deficits

Gellersen, Helena M, Coughlan, Gillian, Hornberger, Michael ORCID: and Simons, Jon S (2021) Memory precision of object-location binding is unimpaired in APOE ε4-carriers with spatial navigation deficits. Brain Communications, 3 (2). ISSN 2632-1297

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Research suggests that tests of memory fidelity, feature binding and spatial navigation are promising for early detection of subtle behavioural changes related to Alzheimer’s disease. In the absence of longitudinal data, one way of testing the early detection potential of cognitive tasks is through the comparison of individuals at different genetic risk for Alzheimer’s dementia. Most studies have done so using samples aged 70 years or older. Here, we tested whether memory fidelity of long-term object-location binding may be a sensitive marker even among cognitively healthy individuals in their mid-60s by comparing participants at low and higher risk based on presence of the ε4-allele of the apolipoprotein gene (n = 26 ε3ε3, n = 20 ε3ε4 carriers). We used a continuous report paradigm in a visual memory task that required participants to recreate the spatial position of objects in a scene. We employed mixture modelling to estimate the two distinct memory processes that underpin the trial-by-trial variation in localization errors: retrieval success which indexes the proportion of trials where participants recalled any information about an object’s position and the precision with which participants retrieved this information. Prior work has shown that these memory paradigms that separate retrieval success from precision are capable of detecting subtle differences in mnemonic fidelity even when retrieval success could not. Nonetheless, Bayesian analyses found good evidence that ε3ε4 carriers did not remember fewer object locations [F(1, 42) = 0.450, P = 0.506, BF01 = 3.02], nor was their precision for the spatial position of objects reduced compared to ε3ε3 carriers [F(1, 42) = 0.12, P = 0.726, BF01 = 3.19]. Because the participants in the sample presented here were a subset of a study on apolipoprotein ε4-carrier status and spatial navigation in the Sea Hero Quest game [Coughlan et al., 2019. PNAS, 116(9)], we obtained these data to contrast genetic effects on the two tasks within the same sample (n = 33). Despite the smaller sample size, wayfinding deficits among ε3ε4 carriers could be replicated [F(1, 33) = 5.60, P = 0.024, BF10 = 3.44]. Object-location memory metrics and spatial navigation scores were not correlated (all r < 0.25, P > 0.1, 0 < BF10 < 3). These findings show spared object-location binding in the presence of a detrimental apolipoprotein ε4 effect on spatial navigation. This suggests that the sensitivity of memory fidelity and binding tasks may not extend to individuals with one ε4-allele in their early to mid-60s. The results provide further support to prior proposals that spatial navigation may be a sensitive marker for the earliest cognitive changes in Alzheimer’s disease, even before episodic memory.

Item Type: Article
Additional Information: Funding Information: This work was supported by an Alzheimer's Research UK grant (ARUK-SHQ2018-001). HMG is funded by a Medical Research Council doctoral training grant (#RG86932) and a Pinsent Darwin Award. GC was funded by a Foundation Grant from the Canadian Institutes of Health Research (#143311), MH by the Biotechnology and Biological Sciences Research Council, National Institute for Health Research, Wellcome Trust and the UK Department for Transport and JSS by a James S. McDonnell Foundation Scholar award #220020333. The funders had no role in the conceptualization, analysis or publication of this data.
Uncontrolled Keywords: apoe,alzheimer's disease,early detection,memory,spatial navigation,psychiatry and mental health,biological psychiatry,cellular and molecular neuroscience,neurology ,/dk/atira/pure/subjectarea/asjc/2700/2738
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health
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Depositing User: LivePure Connector
Date Deposited: 27 May 2021 00:10
Last Modified: 19 Oct 2023 02:58
DOI: 10.1093/braincomms/fcab087


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