Unrecognized preclinical Alzheimer disease confounds rs-fcMRI studies of normal aging

Objective: To determine whether, and to what degree, preclinical Alzheimer disease (AD) confounds studies of healthy aging where "healthy" is based on cognitive normality alone. Methods: We examined the effects of preclinical AD in cognitively normal older individuals using resting-state functional connectivity MRI. We investigated 2 groups of cognitively normal participants: one group with evidence of preclinical AD as assessed by CSF markers of AD and the other group with normal CSF biomarkers. Results: There were significant interactions between age and biomarker status in the defaultmode, dorsal attention, and salience resting-state networks. In the group with evidence of preclinical AD, there were dramatic changes in functional connectivity with age. In the group without evidence of preclinical AD, those changes were greatly attenuated. In most regions with significant interactions of age and biomarker status, the age-related change in functional connectivity in the normal biomarker group was indistinguishable from zero. Conclusions: These results suggest that preclinical AD accounts for a substantial portion of the reported effects of aging in the extant functional connectivity literature.