p-tau/Aβ42 Ratio Associates with Cognitive Decline in Alzheimer’s disease, Mild Cognitive Impairment, and Cognitively Unimpaired Older Adults

INTRODUCTIONThe most well-studied biomarkers in AD are CSF amyloid beta-42 (Aβ42), tau, p-tau, and the ratio p-tau/Aβ42. The ratiometric measure of p-tau/Aβ42 shows the best diagnostic accuracy, and correlates reliably with metrics of cognition in unimpaired participants. However, no study has examined the impact of the CSF p-tau/Aβ42 ratio in predicting cognitive decline in both healthy and AD individuals in one sample. The goal of this study was to examine whether CSF-based p-tau/Aβ42 predicts changes in global cognitive functioning, episodic memory, and executive functioning over a two-year period in cognitively impaired older adults (CU), and in individuals with Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD).METHODSThis study involves secondary analysis of data from 1215 older adults available in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Neuropsychological variables, collected at baseline, 6-month, 12-month, and 24-month follow-ups, included the Preclinical Alzheimer’s Cognitive Composite (PACC) to assess global cognitive functioning, ADNI-MEM to assess episodic memory functioning, and ADNI-EF to assess executive functioning. Linear mixed models were constructed to examine the effect of CSF p-tau/Aβ42, diagnostic group, and change over time (baseline, 6-month, 12-month, and 24-month) on cognitive scores.RESULTSCSF p-tau/Aβ42 ratios predicted worsening cognitive impairment, both on global cognition and episodic memory in individuals with MCI and AD, but not in CU older adults and predicted decline in executive functioning for all three diagnostic groups.DISCUSSIONOur study, including CU, MCI, and AD individuals, provides evidence for differential cognitive consequences of accumulated AD pathology based on diagnostic groups.