Prevalence and Outcomes of Amyloid Positivity Among Persons Without Dementia in a Longitudinal, Population-Based Setting

Abstract

Importance: Brain amyloid deposition is a marker of Alzheimer disease (AD) pathology. The population-based prevalence and outcomes of amyloid positivity in a population without dementia are important for understanding the trajectory of amyloid positivity to clinically significant outcomes and for designing AD prevention trials.

Objective: To determine prevalence and outcomes of amyloid positivity in a population without dementia.

Design, setting, and participants: In the prospective, population-based Mayo Clinic Study of Aging in Olmsted County, Minnesota, participants without dementia were randomly selected from the county population and were clinically and cognitively evaluated at baseline and every 15 months from August 1, 2008, to September 18, 2018. They were also invited to undergo carbon11-Pittburgh compound B positron emission tomography (PET) imaging.

Exposures: Amyloid positivity (defined as a standardized uptake value ratio >1.42 on PET).

Main outcomes and measures: Prevalence of amyloid positivity in the Olmsted County population without dementia and risk of progression from no cognitive impairment (ie, normal cognition for age) to incident amnestic MCI (aMCI) and from MCI or aMCI to incident AD dementia.

Results: Of 3894 participants, 1671 underwent PET imaging and were included in the study; 2198 did not undergo imaging, and 25 were excluded for other reasons. The mean (SD) age of participants was 71.3 (9.8) years; 892 (53.4%) were men, and 179 (10.7%) had prevalent MCI. The prevalence of amyloid positivity without cognitive impairment in the population without dementia increased from 2.7% (95% CI, 0.5% to 4.9%) in persons aged 50 to 59 years to 41.3% (95% CI, 33.4% to 49.2%) in those aged 80 to 89 years at baseline. Prevalence of amyloid-positive MCI in the population without dementia increased from 0% in persons aged 50 to 59 years to 16.4% (95% CI, 10.3% to 22.5%) in those aged 80 to 89 years. The incident aMCI risk increased more than 2-fold in participants without cognitive impairment who were amyloid positive vs those who were amyloid negative (hazard ratio [HR], 2.26; 95% CI, 1.52 to 3.35; P < .001). The risk of AD dementia was 1.86 (95% CI, 0.89 to 3.88; P = .10) for amyloid-positive participants with MCI vs amyloid-negative participants with MCI, 1.63 (95% CI, 0.78 to 3.41; P = .20) for participants with aMCI who were amyloid positive vs amyloid negative, and 2.56 (95% CI, 1.35 to 4.88; P = .004) for amyloid-positive participants who were either without cognitive impairment or had aMCI vs those who were amyloid negative. Global cognitive and memory domain z scores declined significantly in amyloid-positive individuals during follow-up. The mean (SD) follow-up time from baseline was 3.7 (1.9) years to incident aMCI and 3.8 (2.0) years to incident AD dementia.

Conclusions and relevance: Population-based prevalence of amyloid-positive status and progression rates of amyloid positivity provide valid information for designing AD prevention trials and assessing the public health outcomes of AD prevention and interventions.

Figure 1.. Progression During the Follow-up Period

A, Progression from unimpaired status to amnestic mild cognitive impairment (aMCI) in amyloid-positive vs amyloid-negative participants. B, Progression from mild cognitive impairment (MCI) to Alzheimer disease (AD) dementia in amyloid-positive vs amyloid-negative participants. C, Progression from aMCI to AD dementia in amyloid-positive vs amyloid-negative participants. D, Progression from no cognitive impairment or aMCI to AD dementia in amyloid-positive vs amyloid-negative participants. Models were adjusted for age, sex, and education using time from baseline as the time scale. At 3 years, the percentage free of aMCI was 88.0% of amyloid-positive participants who were initially cognitively unimpaired vs 96.2% of amyloid-negative participants who were initially cognitively unimpaired; the percentage free of AD dementia was 73.9% of amyloid-positive people who initially had MCI vs 90.8% of amyloid-negative people with the same condition; the corresponding rates for aMCI were 68.3% vs 90.8%, respectively, after censoring.

Figure 2.. Changes in Global Cognitive Domain and Memory Domain z Scores

A and B, Slopes for global cognitive domain z scores and memory domain z scores for participants who were amyloid positive and cognitively unimpaired; amyloid negative and cognitively unimpaired; amyloid positive with MCI; and amyloid negative with MCI. All slopes were centered on age, sex, and education. Slopes for all groups declined significantly except the global z score for participants who were amyloid negative and cognitively unimpaired and the memory z score for amyloid negative participants with MCI; the memory z score for amyloid-negative participants without cognitive impairment increased significantly.