Amyloid Positivity Increases Risk for Cognitive Impairment in Dementia-Free Patients

Amyloid plaques damaging neurons.
Amyloid plaques damaging neurons.
The findings from the study are limited in generalizability to the dementia-free patient population.

Amyloid-positive patients without dementia have a >2-fold increased risk for amnestic mild cognitive impairment (aMCI) compared with amyloid-negative dementia-free patients, according to a study published in JAMA Neurology.

In addition, amyloid-positive patients with mild cognitive impairment (MCI) and no cognitive impairment at baseline are at greater risk for progression to Alzheimer’s disease (AD) compared with their amyloid-negative counterparts.

A total of 3894 dementia-free patients were randomly selected to undergo clinical and cognitive evaluation at baseline and every 15 months from 2008 to 2018.

Of these patients, a total of 1671 underwent carbon 11-Pittsburgh compound B positron emission tomography imaging (mean [SD] age, 71.3 [9.8]). Prevalent MCI was found in 10.7% (n=179) of participants. The primary study outcome was the prevalence of amyloid positivity and the risk for progression from normal cognition to incident aMCI and from MCI or aMCI to incident AD.

In patients age 50 to 59 and 80 to 89 at baseline, the prevalence of amyloid positivity in the absence of MCI increased from 2.7% (95% CI, 0.5%-4.9%) to 41.3% (95% CI, 33.4%-49.2%) during follow-up, respectively. In addition, the prevalence of amyloid-positive MCI in patients age 50 to 59 and 80 to 89 increased from 0% to 16.4% (95% CI, 10.3%-22.5%), respectively.

An analysis adjusted for age, sex, and education revealed a 2.3-fold increased risk for incident aMCI in amyloid-positive vs amyloid-negative participants (hazard ratio [HR] 2.26; 95% CI, 1.52-3.35; P <.001).

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There was also a significantly greater risk for AD in amyloid-positive vs amyloid-negative patients who were either free from cognitive impairment or had aMCI (HR 2.56; 95% CI, 1.35-4.88]; P =.004]). The risk was higher in women (HR 5.27; 95% CI, 1.52-18.32]; P =.01) compared with men (HR 1.69; 95% CI, 0.77-3.68]; P =.19).

The study findings are limited in generalizability to the dementia-free patient population.

Overall, the investigators suggest their findings “may provide reliable and valid information from a population-based study for estimating the outcome of a successful anti-amyloid therapeutic agent on a general North American population.”


Roberts RO, Aakre JA, Kremers WK, et al. Prevalence and outcomes of amyloid positivity among persons without dementia in a longitudinal, population-based setting [published online April 30, 2018]. JAMA Neurol. doi:10.1001/jamaneurol.2018.0629