Undetected Neurodegenerative Disease Biases Estimates of Cognitive Change in Older Adults
Karra Harrington, Andrew J. Aschenbrenner, Paul Maruff, Colin L. Masters, Anne M. Fagan, Tammie L.S. Benzinger, Brian A. Gordon, Carlos Cruchaga, John C. Morris, Jason Hassenstab
Abstract
Neurodegenerative disease is highly prevalent among older adults and, if undetected, may obscure estimates of cognitive change among aging samples. Our aim in this study was to determine the nature and magnitude of cognitive change in the absence of common neuropathologic markers of neurodegenerative disease. Cognitively normal older adults (ages 65–89 years, N = 199) were classified as normal or abnormal using neuroimaging and cerebrospinal-fluid biomarkers of β-amyloid, tau, and neurodegeneration. When cognitive change was modeled without accounting for biomarker status, significant decline was evident for semantic memory, processing speed, and working memory. However, after adjusting for biomarker status, we found that the rate of change was attenuated and that the biomarker-normal group demonstrated no decline for any cognitive domain. These results indicate that estimates of cognitive change in otherwise healthy older adults will be biased toward decline when the presence of early neurodegenerative disease is not accounted for.