Clinical Manifestations

Performance on neuropsychological measures can be used to predict conversion to Alzheimer's disease. However, few studies have examined the relationship between neuropsychological test performance and the presence of biomarkers (Gainotti et al., 2014). Neuropsychological approaches that are sensitive enough to detect subtle cognitive changes specific to Alzheimer's disease pathology before functional declines are observed will be essential for early identification and effective intervention. van Harten et al. (2021) found that cerebrospinal fluid (CSF) total tau (t-tau) to beta-amyloid peptide (Aβ_1-42) and hyperphosphorylated tau181 (p-tau181) to Aβ_1-42 ratios are robust indicators of Alzheimer's disease. The present study hypothesized that a change in neuropsychological test performance would predict a change in t-tau/Aβ_1-42 and p-tau181/Aβ_1-42 ratios.

Participants included 137 healthy older adults (52% female) who underwent baseline neuropsychological testing and lumbar puncture. Participants completed the Rey Auditory Verbal Learning Test (RAVLT), and CSF t-tau, p-tau181, and Aβ_1-42 were collected via lumbar puncture as part of a more extensive evaluation. Follow-up testing was completed two years later with 92 participants. A bivariate latent change score model was used to analyze the longitudinal relationships between baseline and latent two-year change for delayed recall on the RAVLT with the CSF t-tau/Aβ_1-42 and p-tau181/Aβ_1-42 ratios.

Baseline delayed recall scores were negatively associated with a two-year change in the CSF t-tau/Aβ_1-42 ratio (γ1 = -0.01, z = 0.0068, p = 0.036). Baseline CSF p-tau181/Aβ_1-42 ratio was negatively associated with a two-year change in delayed recall scores (γ2 = -4.14, z = -2.01, p = 0.046). These results suggest that delayed recall on a verbal learning task can predict a change in the CSF t-tau/Aβ_1-42 ratio and that CSF p-tau181/Aβ_1-42 ratios can predict change in delayed recall among cognitively healthy older adults.

These findings support the hypothesis that neuropsychological test performance, specifically delayed recall, is sensitive to a two-year change in some Alzheimer's disease biomarkers while other biomarkers predict change in neuropsychological test performance. Therefore, delayed recall tasks may be practical screening tests for early intervention studies to identify persons at high risk for AD while other biomarkers can predict decline in memory.