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Accelerated long‐term forgetting over six months in cognitively normal APOE ɛ4 carriers
Author(s) -
TortMerino Adrià,
Laine Matti,
Fortea Juan,
MartinezLage Pablo,
SanchezValle Raquel,
Rami Lorena,
RodríguezFornells Antoni
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.041928
Subject(s) - forgetting , neuropsychology , audiology , psychology , abstinence , apolipoprotein e , developmental psychology , medicine , cognition , pediatrics , disease , cognitive psychology , neuroscience , psychiatry
Background Accelerated long‐term forgetting (ALF) refers to an abnormally rapid loss of information over days or weeks despite normal acquisition and encoding. The potential usefulness of ALF in the early detection of subtle cognitive difficulties in asymptomatic stages of familial (Weston et al., 2018) and sporadic (Zimmermann & Butler, 2018) Alzheimer’s disease (AD) has attracted particular attention. However, research on the relationships between ALF and AD biomarkers is still lacking, and forgetting curves have not been followed up over an extended period of time. We aimed to fill these gaps by administering a particularly demanding memory task, correlating task results with AD biomarkers, and registering forgetting curves over a 6‐month follow‐up. Method Twenty‐two cognitively healthy subjects were included: 11 APOE ɛ4 carriers (heterozygous for ɛ3 and ɛ4) were age‐, sex‐, and education‐matched with 11 APOE ɛ4 non‐carriers (homozygous for ɛ3). All subjects underwent APOE genotyping, standard neuropsychological assessment, a lumbar puncture for determining CSF Aß 42 , tau and ptau levels, and the demanding Ancient Farming Equipment Test (AFE‐T). The AFE‐T calls for learning 24 novel object/name pairs through two learning sessions of seven runs performed on two consecutive days (range 0‐24 points per run). Free and cued long‐term recall was examined at one week, three months and six months after the initial learning. Result Demographics and CSF levels are shown in Table 1. The AFE‐T showed no group differences in the learning scores, but a significant group difference ( F (1,19) = 4.99; p < 0.05) emerged in the cued recall at 3 months. The APOE ɛ4 carriers showed ALF in their cued forgetting rate at 3 months ( F (1,19) = 5.60; p < 0.05) and the forgetting rate between the 1‐week and 3‐month recall ( F (1,19) = 8.70; p < 0.01) (Figure 1B). Correlation analyses showed a significant association between the cued forgetting rate at 3 months and the ratio CSF Aβ 42 /ptau (Figure 2A; r = .614; p < 0.01). Also, a significant correlation was found between the cued forgetting rate at 3 months and subjective cognitive ratings (Figure 2B; r = .636; p < 0.01). Conclusion Accelerated long‐term forgetting is detectable in at‐risk individuals and is linked with CSF AD biomarkers. We strongly recommend the use of demanding memory tests coupled with long‐term forgetting measures for identifying and tracking the earliest cognitive manifestations in presymptomatic Alzheimer’s disease.