Longitudinal change in serial position scores in older adults with entorhinal and hippocampal neuropathologies

Abstract

Objective: Serial position scores on verbal memory tests are sensitive to early Alzheimer’s disease (AD)-related neuropathological changes that occur in the entorhinal cortex and hippocampus. The current study examines longitudinal change in serial position scores as markers of subtle cognitive decline in older adults who may be in preclinical or at-risk states for AD. Methods: This study uses longitudinal data from the Religious Orders Study and the Rush Memory and Aging Project. Participants (n = 141) were included if they did not have dementia at enrollment, completed follow-up assessments, and died and were classified as Braak stage I or II. Memory tests were used to calculate serial position (primacy, recency), total recall, and episodic memory composite scores. A neuropathological evaluation quantified AD, vascular, and Lewy body pathologies. Mixed effects models were used to examine change in memory scores. Neuropathologies and covariates (age, sex, education, APOE e4) were examined as moderators. Results: Primacy scores declined (β = −.032, p < .001), whereas recency scores increased (β = .021, p = .012). No change was observed in standard memory measures. Greater neurofibrillary tangle density and atherosclerosis explained 10.4% of the variance in primacy decline. Neuropathologies were not associated with recency change. Conclusions: In older adults with hippocampal neuropathologies, primacy score decline may be a sensitive marker of early AD-related changes. Tangle density and atherosclerosis had additive effects on decline. Recency improvement may reflect a compensatory mechanism. Monitoring for changes in serial position scores may be a useful in vivo method of tracking incipient AD.

Delayed primacy recall performance predicts post mortem Alzheimer's disease pathology from unimpaired ante mortem cognitive baseline

“…Later, after a delay of several minutes, participants are asked to recall as many words from the initial list as possible in any order, providing a total delayed recall score. Following Gicas et al 23,24 we defined immediate primacy as the ability to recall the first three words presented in the first three trials (i.e., A1-A3, B1-B3, and C1-C3), immediately after presentation of that list, and then divided that sum by the total number of possible items (i.e., nine). For comparison, we also computed an alternative measure of immediate primacy which included only the first three words presented in the first trial (i.e., A1-A3; one list immediate primacy).…”

“…Gicas et al, 23 for example, have shown that higher immediate primacy performance is associated with less risk of AD neuropathology, including hippocampal sclerosis; and increased pathology predicted greater longitudinal decline in primacy performance. 24 Gicas et al 23,24 the words in any order (immediate recall). Subsequently, they are also asked to free recall the words after a delay (delayed recall).…”

“…In particular, a reduction of the primacy effect has been reported frequently in immediate recall tests in conjunction with AD risk and pathology (e.g., 21,22 ). Gicas et al., 23 for example, have shown that higher immediate primacy performance is associated with less risk of AD neuropathology, including hippocampal sclerosis; and increased pathology predicted greater longitudinal decline in primacy performance 24 …”

“…Gicas et al 23,24 . measured serial position performance using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) memory test.…”

“…Gicas et al., 23 for example, have shown that higher immediate primacy performance is associated with less risk of AD neuropathology, including hippocampal sclerosis; and increased pathology predicted greater longitudinal decline in primacy performance. 24 …”