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. 2021 Jan 5;12(1):e12132.
doi: 10.1002/dad2.12132. eCollection 2020.

Diminished Learning Over Repeated Exposures (LORE) in preclinical Alzheimer's disease

Aubryn Samaroo  1 , Rebecca E Amariglio  1   2   3 , Samantha Burnham  4 , Paige Sparks  2 , Michael Properzi  1 , Aaron P Schultz  1   3 , Rachel Buckley  1   3   5 , Keith A Johnson  2   3   6 , Reisa A Sperling  1   2   3 , Dorene M Rentz  1   2   3 , Kathryn V Papp  1   2   3
Affiliations

Diminished Learning Over Repeated Exposures (LORE) in preclinical Alzheimer's disease

Aubryn Samaroo et al. Alzheimers Dement (Amst). .

Abstract

Introduction: We determine whether diminished Learning Over Repeated Exposures (LORE) identifies subtle memory decrements in cognitively unimpaired (CU) older adults with Alzheimer's disease (AD) biomarker burden.

Methods: Ninety-four CU participants (mean age = 77.6 ± 5.02) completed a challenging associative memory test, at home, monthly, for up to 1 year (mean = 9.97 months) on a study-issued iPad. Learning curves for face-name memory were computed for two versions completed monthly: same face-name pairs (A-A-A) and alternate face-name pairs (B-C-D). Positron emission tomography (PET) imaging characterized global amyloid (Pittsburgh Compound-B (PiB); amyloid beta (Aβ)+/-) and regional tau burden (flortaucipir).

Results: Diminished LORE for same (but not alternate) face-name pairs was associated with greater amyloid and tau burden. Aβ+/- group differences for same face-name pairs emerged by the fourth exposure and was of medium-to-large magnitude (Cohen's d = 0.66; 95% confidence interval [CI] = 0.25-1.08).

Discussion: Subtle decrements in learning related to AD pathological burden in CU are detectable over short time-intervals (ie, months). Implications for prevention trial design are discussed.

Keywords: amyloid PET; computerized testing; digital biomarkers; learning curves; practice effects; preclinical Alzheimer's disease; tau PET.

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Conflict of interest statement

A. Samaroo, R. Amariglio, S. Burnham, P. Sparks, M. Properzi, A. Schultz, and R. Buckley have no disclosures to report. D. Rentz has served as a consultant for Eli Lilly, Biogen Idec, and Lundbeck Pharmaceuticals, and serves as a member of the Scientific Advisory Board for Neurotrack. R.A. Sperling has received research funding from the NIH, Alzheimer's Association, and Eli Lilly for this research. She has served as a consultant for AC Immune, Biogen, Eisai, Janssen, Neurocentria, and Roche. K. Johnson has served as a consultant to Biogen, Janssen, and Novartis. K. Papp has served as a consultant for Biogen Idec and Digital Cognition Technologies.

Figures

FIGURE 1
FIGURE 1
Learning Over Repeated Exposures (LORE) (Same Version) for Face Name Memory versus general practice effects (Alternate Version) over months. NOTE. The y‐axis represents the mean and standard deviation of the number of correct responses on face‐name memory out of 12. Same = Same Version (A‐A‐A) is a measure of LORE and Altern = Alternate Version (B‐C‐D) is a measure of general practice effects. The time between visit 0 and 1 is 1 week; all other testing is monthly
FIGURE 2
FIGURE 2
Mixed model for repeated measures (MMRM) analysis shows diminished Learning Over Repeated Exposures (LORE) for Aβ+ versus Aβ− groups for face‐name memory accuracy (A; same version) but no difference between groups for general practice effects (B; alternate version). NOTE: The y‐axis represents change in the number of items answered correctly (/12) for face name memory. Diminished LORE for Aβ+ group versus the Aβ− group was observed on monthly same‐version memory testing at time 4 (mean difference in words recalled = −0.75, P = 0.033). There was no difference in general practice effects between Aβ+ versus Aβ− groups for alternate face‐name memory versions. Analyses, by definition, control for baseline performance. Analyses are controlled for age
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