Abnormal cerebrospinal fluid levels of amyloid and tau are associated with cognitive decline over time in cognitively normal older adults: A monozygotic twin study

INTRODUCTION: The contribution of genetic and environmental factors to the relation between cerebrospinal fluid (CSF) biomarkers and cognitive decline in preclinical Alzheimer's disease remains unclear. We studied this in initially cognitively normal monozygotic twins. METHODS: We included 122 cognitively normal monozygotic twins (51 pairs) with a follow‐up of 4.3 ± 0.4 years. We first tested associations of baseline CSF Aβ1‐42/1‐40 ratio, total tau (t‐tau), and 181‐phosphorylated‐tau (p‐tau) status with subsequent cognitive decline using linear mixed models, and then performed twin specific analyses. RESULTS: Baseline abnormal amyloid‐β and tau CSF markers predicted steeper decline on memory (p ≤ .003) and language (p ≤ 0.04). Amyloid‐β and p‐tau markers in one twin predicted decline in memory in the co‐twin and tau markers in one twin predicted decline in language in the co‐twin (r range ‐0.26,0.39; p’s ≤ .02). DISCUSSION: These results suggest that memory and language decline are early features of AD that are in part determined by the same genetic factors that influence amyloid‐β and tau regulation.