Frequency of biologically-defined AD in relation to age, sex, APOEε4 and cognitive impairment

Abstract

Objective:To assess the frequency of biologically-defined Alzheimer’s disease (AD) in relation to age, sex, APOEε4, and clinical diagnosis in a prospective cohort study evaluated with amyloid-PET and tau-PET.Methods:We assessed cognitively unimpaired (CU) elderly (n=166), amnestic MCI (n=77) and probable AD dementia (n=62) subjects who underwent evaluation by dementia specialists and neuropsychologists in addition to amyloid-PET with [18F]AZD4694 and tau-PET with [18F]MK6240. Individuals were grouped according to their AD biomarker profile. Positive predictive value for biologically-defined AD was assessed in relation to clinical diagnosis. Frequency of AD biomarker profiles were assessed using logistic regressions with odds ratios and 95% CIs.Results:The clinical diagnosis of probable AD dementia demonstrated good agreement with biologically-defined AD (positive predictive value: 85.2%). 7.88% of CU elderly subjects were positive for both amyloid-PET and tau-PET. Frequency of biologically-defined AD increased with age (OR: 1.14; p<0.0001) and frequency of APOEε4 allele carriers (Single ε4: OR: 3.82; p<0.0001; Double ε4: OR: 17.55, p<0.0001).Discussion:While we observed strong, but not complete, agreement between clinically-defined “probable AD” dementia and biomarker positivity for both amyloid-β and tau, we also observed that biologically-defined AD was not rare in CU elderly. Abnormal tau-PET was almost exclusively observed in individuals with abnormal amyloid-PET. Our results highlight that even in tertiary care memory clinics, detailed evaluation by dementia specialists systematically underestimates the frequency of biologically-defined AD and related entities.Classification of evidence:This study provides Class I evidence that biologically-defined AD (abnormal amyloid PET and tau PET) was observed in 85.2% of people with clinically defined AD and 7.88% of cognitively unimpaired elderly.