Reader Response: Frequency of Biologically Defined Alzheimer Disease in Relation to Age, Sex, APOE ε4, and Cognitive Impairment

We read the article by Therriault et al.,1 which highlights a frequency of biologically defined Alzheimer disease (AD) of 85.2% in patients with clinically defined AD and 7.88% in cognitively unimpaired individuals. The biological definition of AD leads to an increase in AD frequency as compared to a clinical definition2 because the biological definition of AD allows for the detection of disease in both symptomatic and asymptomatic individuals.2,3 A major issue is now to confirm that cognitive symptoms in patients with biologically defined AD with Alzheimer clinical syndrome are exclusively due to Alzheimer pathology and not associated with systemic factors, other brain diseases (e.g., vascular lesions, Lewy bodies, and TDP-43), or psychological comorbidities affecting attention. Indeed, if Alzheimer clinical syndrome is not restricted to Alzheimer pathology,4,5 and Alzheimer pathology is not rare in cognitively unimpaired individuals,1,2 there are probably patients with Alzheimer clinical syndrome and Alzheimer pathology in which this syndrome is not explained by this pathology. In these cases, AD is at a preclinical stage, and the clinical syndrome is secondary to other conditions. A better individual diagnosis would be an essential step forward in the field of individualized care for neurocognitive disorders.