In Reply The Letter to the Editor by Montero-Odasso and colleagues addresses noncognitive manifestations of Alzheimer disease (AD). Their letter discusses a recent article from the Mayo Clinic.1 Using positron emission tomography biomarkers of amyloidosis (A) and tauopathy (T), the Mayo study1 examined the age- and sex-specific prevalence of 3 biologically defined entities: amyloidosis (A+) regardless of tau status, A+T−, and A+T+. We compared the age and sex specific prevalence of these 3 biomarker-defined entities with 3 clinical syndromes commonly associated with AD: clinically defined probable AD using the McKhann et al2 criteria, mild cognitive impairment, and dementia. We found that the prevalence of biological AD (defined by the A+T+ biomarker profile) is more prevalent than the classic syndrome of clinically defined probable AD2 at all ages and roughly 3 times more prevalent at age 85 years in men and women. We attributed this to the fact that brain pathology precedes symptoms by years3; thus, many individuals who have the disease do not have cognitive impairment.
Jack CR. Alzheimer Disease, Biomarkers, and Clinical Symptoms—Quo Vadis?—Reply. JAMA Neurol. 2020;77(3):394. doi:10.1001/jamaneurol.2019.4962
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