Episodic Memory and Hippocampal Volume Predict 5-Year Mild Cognitive Impairment Conversion in Healthy Apolipoprotein ε4 Carriers

Abstract

Objective: The Apolipoprotein (APOE) ε4 allele increases the risk for mild cognitive impairment (MCI) and dementia, but not all carriers develop MCI/dementia. The purpose of this exploratory study was to determine if early and subtle preclinical signs of cognitive dysfunction and medial temporal lobe atrophy are observed in cognitively intact ε4 carriers who subsequently develop MCI. Methods: Twenty-nine healthy, cognitively intact ε4 carriers (ε3/ε4 heterozygotes; ages 65–85) underwent neuropsychological testing and MRI-based measurements of medial temporal volumes over a 5-year follow-up interval; data were converted to z-scores based on a non-carrier group consisting of 17 ε3/ε3 homozygotes. Results: At follow-up, 11 ε4 carriers (38%) converted to a diagnosis of MCI. At study entry, the MCI converters had significantly lower scores on the Mini-Mental State Examination, Rey Auditory Verbal Learning Test (RAVLT) Trials 1–5, and RAVLT Immediate Recall compared to non-converters. MCI converters also had smaller MRI volumes in the left subiculum than non-converters. Follow-up logistic regressions revealed that left subiculum volumes and RAVLT Trials 1–5 scores were significant predictors of MCI conversion. Conclusions: Results from this exploratory study suggest that ε4 carriers who convert to MCI exhibit subtle cognitive and volumetric differences years prior to diagnosis.

Novel characterization of the relationship between verbal list‐learning outcomes and hippocampal subfields in healthy adults

“…Indeed, subfield volumetry has become a more promising method to detect incipient AD than total hippocampal volumetry. Selective atrophy of hippocampal subfields, especially of the cornu ammonis (CA) 1, subiculum, and presubiculum, predicts AD's early‐onset (Abraham et al, 2020; Broadhouse et al, 2019; Carlesimo et al, 2015; Hanseeuw et al, 2011; Hata et al, 2019; Jacobs et al, 2020; La Joie et al, 2013; Lindberg et al, 2017; Ogawa et al, 2019; Parker et al, 2018; Vasta et al, 2016) and conversion from mild cognitive impairment or diagnoses (Apostolova et al, 2010; Chételat et al, 2008; Hata et al, 2019; Khan et al, 2015; Nadal et al, 2020; West, Kawas, Martin, & Troncoso, 2006).…”

Textual Inference Comprehension in Mild Cognitive Impairment: The Influence of Semantic Processing and Verbal Episodic Memory

“…On the other hand, the verbal episodic memory tests (3W3S) were able to differentiate between controls and MCI as well established in the literature (Ding et al, 2019;Wasserman et al, 2019;Abraham et al, 2020;Silva et al, 2020).…”

Validation and Normative Data of the Spanish Version of the Rey Auditory Verbal Learning Test and Associated Long-Term Forgetting Measures in Middle-Aged Adults

“…Thus, this test has been widely used in longitudinal studies to help describe the memory trajectory in cognitively normal and MCI subjects as an indicator of dementia risk. Sum Trials I to V, the RAVLT learning score (V-I), and 25-min delayed recall play an important role in the prediction of progression from MCI to AD dementia ( Crane et al, 2012 ; Wang et al, 2016 ; Li et al, 2017 ; Li et al, 2018 ; Ding et al, 2019 ; Abraham et al, 2020 ). Also, error scores have been associated with different types and stages of cognitive impairment ( Baños et al, 2005 ; Thomas et al, 2018 ; Weitzner et al, 2020 ).…”