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 (A{beta}42), tau, p-tau, and the ratio p-tau/A{beta}42. The ratiometric measure of p-tau/A{beta}42 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/A{beta}42 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/A{beta}42 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 Alzheimers disease (AD). METHODSThis study involves secondary analysis of data from 1215 older adults available in the Alzheimers Disease Neuroimaging Initiative (ADNI). Neuropsychological variables, collected at baseline, 6-month, 12-month, and 24-month follow-ups, included the Preclinical Alzheimers 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/A{beta}42, diagnostic group, and change over time (baseline, 6-month, 12-month, and 24-month) on cognitive scores. RESULTSCSF p-tau/A{beta}42 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.