Prevalence of preclinical Alzheimer disease: Comparison of current classification systems

Abstract

Objective: To determine the prevalence of preclinical Alzheimer disease (AD) according to current classification systems by examining CSF from a representative general population sample of 70-year-olds from Gothenburg, Sweden.

Method: The sample was derived from the population-based H70 Gothenburg Birth Cohort Studies in Gothenburg, Sweden. The participants (n = 322, age 70 years) underwent comprehensive neuropsychiatric, cognitive, and somatic examinations. CSF levels of β-amyloid (Aβ)₄₂, Aβ₄₀, total tau, and phosphorylated tau were measured. Preclinical AD was classified according to criteria of the A/T/N system, Dubois 2016, National Institute on Aging-Alzheimer's Association (NIA-AA) criteria, and International Working Group-2 (IWG-2) criteria. Individuals with Clinical Dementia Rating score >0 were excluded, leaving 259 cognitively unimpaired individuals.

Results: The prevalence of amyloid pathology was 22.8%, of total tau pathology was 33.2%, and of phosphorylated tau pathology was 6.9%. With the A/T/N system, the prevalence of A+/T-/N- was 13.1%, A+/T-/N+ was 7.3%, A+/T+/N+ was 2.3%, A-/T-/N+ was 18.9%, and A-/T+/N+ was 4.6%. When the Dubois criteria were applied, the prevalence of asymptomatic at risk for AD was 36.7% and of preclinical AD was 9.7%. With the NIA-AA criteria, the prevalence of stage 1 was 13.1% and stage 2 was 9.7%. With the IWG-2 criteria, the prevalence of asymptomatic at risk for AD was 9.7%. The APOE ε4 allele was associated with several of the categories. Men more often had total tau pathology, A+/T-/N+, preclinical AD according to Dubois 2016, asymptomatic at risk for AD according to the IWG-2 criteria, and NIA-AA stage 2.

Conclusion: The prevalence of pathologic AD markers was very common (46%) in a representative population sample of 70-year-olds. The clinical implications of these findings need to be scrutinized further in longitudinal studies.

Figure. Venn diagram

Venn diagram of the ATN distribution of amyloid and tau pathology according to the A/T/N classification scheme in a representative population-based sample of 70-year-olds with a Clinical Dementia Rating score of 0. A+ refers to Aβ pathology (CSF Aβ₄₂ levels ≤530 pg/mL), T+ to pathologic p-tau (CSF p-tau ≥ 80 pg/mL), and N+ to neurodegeneration biomarker (CSF total tau ≥350 pg/mL) in 259 cognitively normal elderly all 70 years of age. Aβ = β-amyloid; p-tau = phosphorylated tau.