The neuropsychology of preclinical alzheimer's disease: Differential sensitivity of component processes of memory performance on biomarker evidence of amyloidosis

BACKGROUND & OBJECTIVE:Memory decline in older adults can occur for multiple reasons. Determining if these changes are an early indicator of a neurodegenerative process, such as Alzheimer's disease (AD), is vital for early identification and early intervention. Recent work indicates that deficits in cued recall (i.e. recognition or facilitated recall), may be particularly specific to AD-related memory decline at the stage of Mild Cognitive Impairment. Our goal was to test this hypothesis in the preclinical period, where clinically normal (CN) older adults exhibit biomarker evidence of amyloid-beta deposition (Ab) and subtle memory changes detectable on challenging associative memory tests. DESIGN/METHODS:A total of 127 CN older adults (Ab+ n=37, Abn= 90) from the Harvard Aging Brain Study completed the Memory Capacity Test (MCT) at baseline and at 4 year follow-up. Baseline inclusion criteria included CDR=0 and performance above education adjusted cut-offs for Logical Memory delayed recall and MMSE. Performance on delayed free recall and delayed cued recall of 32 wordcategory pairs of the MCT was examined cross-sectionally and over time controlling for age, sex, and education. RESULTS:At baseline, Ab+ subjects performed worse on free recall compared with Ab-subjects (p=0.012) but performed equivalently on cued recall (p=0.233). All subjects exhibit nonsignificant decrements in free recall over 4 year follow-up, but only individuals who were Ab+ at baseline exhibited declines in cued recall (p=0.032). CONCLUSIONS:Subtle, yet measurable performance differences on a challenging associative memory test are associated with amyloid status in CN adults. Longitudinal decline in cued, rather than free recall alone appears to be specific to underlying AD pathology, even in the preclinical stage of disease. Challenging associative memory tests with cueing paradigms may be particularly useful for early identification of memory deficits and for detecting response to intervention in clinical trials in the preclinical population.