47 Amyloid/Tau Ratio and Early Predictors of Alzheimer's Disease

Objective: Early cognitive signs of Alzheimer's disease are often subtle and go unnoticed until they become more prominent and debilitating. Thus, symptoms begin long before an actual Alzheimer's diagnosis is given. However, it is known that cognitively healthy older individuals with lower amyloid/tau ratios (PAT) are more likely to develop Alzheimer's disease than those with higher amyloid/tau ratios (NAT). Therefore, we explored whether this ratio can be used in conjunction with neuropsychological tests to isolate cognitive predictors of Alzheimer's disease amongst cognitively healthy older adults. We were interested in potential group differences on the California Verbal Learning Test, Second Edition (CVLT-II) Long Delay Free Recall scores and Cued Recall scores. We hypothesized that: (a) individuals in the PAT group would have weaker CVLT-II Long Delay Free Recall scores than individuals in the NAT group; and (b) individuals in the PAT group would recall fewer words on the CVLT-II Long Delay Cued Recall trial than individuals in the NAT group. Participants and Methods: There were 115 older individuals recruited via Huntington Medical Research Institutes and the University of Southern California who had their cerebral spinal fluid extracted to measure amyloid/tau ratios. They completed the California Verbal Learning Test-II as part of a larger neuropsychological battery and were determined to be cognitively healthy. The mean age of these participants was 74.5 years (SD = 8.3), and there were 36 who met the threshold for the amyloid/tau ratio associated with Alzheimer's disease (PAT) while the other 79 did not (NAT). A hierarchical linear regression tested the hypotheses, with two blocks used for the analyses. Block 1 for both analyses contained variables to control for the potential effects of various factors in performance on the Long Delay tasks. Block 2 consisted of the amyloid groups (NAT vs. PAT). Results: After controlling for age, sex, education, body mass index, Montreal Cognitive Assessment scores, and depression, we found no significant difference between CVLT-II Long Delay Free Recall scores or Long Delay Cued Recall scores for the two groups. Conclusions: While no significant difference was found on the long delay trials of the CVLT-II, it is important to note that it is unclear at what stage Alzheimer's related decline begins or can be detected using cognitive testing. Longitudinal studies would help to better understand if this lack of association holds true over time. Other aspects of the CVLT-II, such as intrusions and repetitions, would also help to better understand the different ways that symptoms of Alzheimer's disease can manifest early on.

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