[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 34.238.248.103. Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Original Investigation
July 15, 2019

Prevalence of Biologically vs Clinically Defined Alzheimer Spectrum Entities Using the National Institute on Aging–Alzheimer’s Association Research Framework

Author Affiliations
  • 1Department of Radiology, Mayo Clinic, Rochester, Minnesota
  • 2Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota
  • 3Department of Neurology, Mayo Clinic, Rochester, Minnesota
  • 4Department of Nuclear Medicine, Mayo Clinic, Rochester, Minnesota
  • 5Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota
JAMA Neurol. 2019;76(10):1174-1183. doi:10.1001/jamaneurol.2019.1971
Key Points

Question  How does the prevalence of 3 imaging biomarker–based definitions of the Alzheimer disease spectrum from the National Institute on Aging–Alzheimer’s Association research framework compare with clinically defined diagnostic entities commonly linked with Alzheimer disease?

Findings  Among a sample of 5213 individuals from Olmsted County, Minnesota, in this population-based cohort study, biologically defined Alzheimer disease is more prevalent than clinically diagnosed probable Alzheimer disease at any age and is 3 times more prevalent at age 85 years among both women and men.

Meaning  Most patients with biologically defined Alzheimer disease are not symptomatic, which creates potential confusion around the definition of Alzheimer disease.

Abstract

Importance  A National Institute on Aging–Alzheimer’s Association (NIA-AA) workgroup recently published a research framework in which Alzheimer disease is defined by neuropathologic or biomarker evidence of β-amyloid plaques and tau tangles and not by clinical symptoms.

Objectives  To estimate the sex- and age-specific prevalence of 3 imaging biomarker–based definitions of the Alzheimer disease spectrum from the NIA-AA research framework and to compare these entities with clinically defined diagnostic entities commonly linked with Alzheimer disease.

Design, Setting, and Participants  The Mayo Clinic Study of Aging (MCSA) is a population-based cohort study of cognitive aging in Olmsted County, Minnesota. The MCSA in-person participants (n = 4660) and passively ascertained (ie, through the medical record rather than in-person) individuals with dementia (n = 553) aged 60 to 89 years were included. Subsets underwent amyloid positron emission tomography (PET) (n = 1524) or both amyloid and tau PET (n = 576). Therefore, this study included 3 nested cohorts examined between November 29, 2004, and June 5, 2018. Data were analyzed between February 19, 2018, and March 26, 2019.

Main Outcomes and Measures  The sex- and age-specific prevalence of the following 3 biologically defined diagnostic entities was estimated: Alzheimer continuum (abnormal amyloid regardless of tau status), Alzheimer pathologic change (abnormal amyloid but normal tau), and Alzheimer disease (abnormal amyloid and tau). These were compared with the prevalence of 3 clinically defined diagnostic groups (mild cognitive impairment or dementia, dementia, and clinically defined probable Alzheimer disease).

Results  The median (interquartile range) age was 77 (72-83) years in the clinical cohort (n = 5213 participants), 77 (70-83) years in the amyloid PET cohort (n = 1524 participants), and 77 (69-83) years in the tau PET cohort (n = 576 participants). There were roughly equal numbers of women and men. The prevalence of all diagnostic entities (biological and clinical) increased rapidly with age, with the exception of Alzheimer pathologic change. The prevalence of biological Alzheimer disease was greater than clinically defined probable Alzheimer disease for women and men. Among women, these values were 10% (95% CI, 6%-14%) vs 1% (95% CI, 1%-1%) at age 70 years and 33% (95% CI, 25%-41%) vs 10% (95% CI, 9%-12%) at age 85 years (P < .001). Among men, these values were 9% (95% CI, 5%-12%) vs 1% (95% CI, 0%-1%) at age 70 years and 31% (95% CI, 24%-38%) vs 9% (95% CI, 8%-11%) at age 85 years (P < .001). The only notable difference by sex was a greater prevalence of the mild cognitive impairment or dementia clinical category among men than women.

Conclusions and Relevance  Results of this study suggest that biologically defined Alzheimer disease is more prevalent than clinically defined probable Alzheimer disease at any age and is 3 times more prevalent at age 85 years among both women and men. This difference is mostly driven by asymptomatic individuals with biological Alzheimer disease. These findings illustrate the magnitude of the consequences on public health that potentially exist by intervening with disease-specific treatments to prevent symptom onset.

×