Prevalence of Biologically vs Clinically Defined Alzheimer Spectrum Entities Using the National Institute on Aging-Alzheimer's Association Research Framework.
Level 3 - non-randomized controlled study
Prospective population-based observational cohort with nested biomarker imaging sub-cohorts
PubMed 31305929 · doi:10.1001/jamaneurol.2019.1971
What was done
Researchers evaluated the prevalence of biologically defined Alzheimer spectrum entities (based on the NIA-AA research framework using amyloid and tau PET) versus clinically defined Alzheimer entities in the population-based Mayo Clinic Study of Aging (MCSA) in Olmsted County, Minnesota. The overall clinical cohort included 5,213 individuals aged 60 to 89 years (4,660 in-person participants and 553 passively ascertained individuals with dementia). Nested sub-cohorts underwent amyloid PET (n = 1,524) or both amyloid and tau PET (n = 576) between 2004 and 2018.
What was found
The prevalence of both biological and clinical entities increased sharply with age. At age 70, the prevalence of biological Alzheimer disease (abnormal amyloid and tau) was 10% (95% CI, 6%-14%) in women and 9% (95% CI, 5%-12%) in men, compared to 1% (95% CI, 1%-1%) and 1% (95% CI, 0%-1%) for clinically defined probable Alzheimer disease. By age 85, biological Alzheimer disease prevalence reached 33% (95% CI, 25%-41%) in women and 31% (95% CI, 24%-38%) in men, compared to clinical probable Alzheimer disease prevalence of 10% (95% CI, 9%-12%) in women and 9% (95% CI, 8%-11%) in men (P < .001 for both comparisons). The only marked sex difference was a higher prevalence of mild cognitive impairment or dementia among men.
Why it matters
This study demonstrates that biological Alzheimer pathology is approximately threefold more prevalent than symptomatic probable Alzheimer disease in older adults, highlighting a large asymptomatic window where disease-modifying therapies could potentially intervene before clinical onset.
Limits
The study is restricted to a single geographic area (Olmsted County, Minnesota), limiting generalizability to more diverse populations. The sample size for dual-biomarker assessment (tau PET, n = 576) was substantially smaller than the parent cohort, introducing potential selection bias for advanced imaging participation.
Cited by
- supports Neuroimaging shows that some elderly individuals have full-blown Alzheimer's disease with zero brain protein deposits, while others have high amyloid plaque and tau tangle burdens with completely normal cognition.