The key to possible prevention of cognitive impairment in patients with Alzheimer disease (AD) lies in preclinical detection using serologic, radiographic, and other novel biomarkers. In the prospective observational cohort study of cognitively unimpaired adults, adults with mild cognitive impairment, and adults with probable AD dementia by Therriault and colleagues, they report that 1 in 12 cognitively unimpaired adults had biologic evidence of Alzheimer pathology using amyloid PET and tau PET imaging. In this study, 7.88% of cognitively unimpaired adults had abnormalities in both imaging modalities, which would be consistent with biologically defined AD. Dr. Garnier-Crussard and Krolak-Salmon acknowledge that Alzheimer pathology is not unusual among unimpaired adults and further suggest that additional factors (e.g., comorbid conditions and exposures) may be contributing to the clinical features of the disease. Ongoing studies exploring preclinical biomarkers may one day elucidate which mechanism (or mechanisms) are responsible for later cognitive impairment in at-risk individuals. Furthermore, such a panel of biomarkers may become useful in the personalization of disease-modifying therapy for such patients.