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Subjective memory decline and associations with non-demented memory aging: The moderating role of genetic risk, vascular dysfunction and sex

  • Author / Creator
    Drouin, Shannon M
  • INTRODUCTION: Subjective memory decline (SMD), defined as a self-perceived change in memory function without objective impairment, has been identified as a potential early marker of cognitive decline and other Alzheimer’s disease (AD) related outcomes. A standard approach to SMD assessment includes two facets: memory complaints and memory concerns. We previously developed a four-facet model of SMD which encompassed the two standard facets, plus two additional facets: memory compensation and memory self-efficacy. In this study, we assembled a distribution of memory aging trajectories, classified into separate change-related classes, and tested SMD facets, sex and vascular health for class discrimination. We then examined the potential roles of SMD and additional AD risk factors (sex, APOE) in moderating pulse pressure and memory trajectory predictions.

    METHODS: The accelerated longitudinal design featured individualized memory trajectories across a 40-year band (55-95 years) of non-demented aging (n = 580; M age at baseline = 70.2 years; 65% female) from the Victoria Longitudinal Study. We established two research goals, each with two parts, to examine prediction patterns for memory trajectories. For our first research goal, we used latent class growth analyses (LCGA) to identify distinct classes (based on an algorithm of level and slope) of episodic memory trajectories. Then, the four SMD facets, sex, and pulse pressure were tested as predictors of class membership. For our second research goal, we used a conditional latent growth model (CLGM) to test the independent effect of pulse pressure on memory change. In parallel, we utilized LCGA to identify latent classes for all four SMD facets. The SMD facet class membership results (for all four facets) were used as stratification variables in order to test SMD moderation of pulse pressure predictions on memory trajectories. We then examined two-way interactions by further stratifying the analyses by: (1) SMD facet class and sex, and (2) SMD facet class and APOE genetic risk.
    RESULTS: First, the LCGA produced four distinguishable and interpretable classes of memory trajectories. The classes were characterized as: (1) stable memory aging (SMA), (2) typical memory aging (TMA), (3) slowly declining memory aging (SDMA) and (4) rapidly declining memory aging (RDMA). Being male, having more memory concerns and higher pulse pressure was predictive of membership to at least one of the declining classes when using the SMA class as a benchmark. For the second research goal, after first determining that higher pulse pressure predicted lower memory level and steeper decline, our subsequent results revealed that memory complaints and memory concerns class membership significantly moderated these predictions. For females only, we observed significant sex and SMD class moderation for all four facets. For ε4- individuals only, we observed significant APOE and memory complaints class membership moderation as well as APOE and memory self-efficacy class membership moderation.
    DISCUSSION: For the prediction of memory trajectory class membership, memory concerns was the only SMD facet predicting membership to the RDMA (lowest) as compared to the SMA (highest) class. Sex also differentiated the SMA class from more rapidly declining classes (e.g., RDMA). Pulse pressure predicted membership to the SDMA class as compared to the SMA class. For the moderated pulse pressure predictions of individualized memory trajectories, the two standard SMD facets demonstrated significant moderation. When stratified by sex groups, class membership for all four SMD facets demonstrated moderation selectively for females. When stratified by APOE genetic risk, membership to memory complaints and memory self-efficacy classes significantly moderated pulse pressure predictions of memory trajectories for ε4- individuals. These findings elucidate SMD prediction patterns in a number of at-risk groups, thus identifying potential precision targets prior to the onset of pathological and clinical neurodegeneration associated with exacerbated memory decline.

  • Subjects / Keywords
  • Graduation date
    Fall 2019
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/r3-v9zp-1c16
  • License
    Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.