Elevated Amyloid Levels Point to Increased Risk of Cognitive Decline

PiB status alone was predictive of cognitive decline associated with MCI.

Normal individuals with elevated levels of ß-amyloid may be more likely to develop clinical signs of mild cognitive impairment and/or dementia than those whose levels are normal, according to data from a study published in JAMA Neurology.1

Researchers from the Mayo Clinic in Rochester, MN, looked at data collected from January, 2006 to January, 2014 in a total of 564 participants aged 70 to 89 (median age = 78) from the Mayo Clinic Study of Aging, a longitudinal, population-based study conducted in Olmstead County, MN. They found that elevated levels of ß-amyloid at baseline were associated with increased rates of cognitive decline and neurodegeneration later on, as well as a number of cognitive and imaging biomarkers for Alzheimer’s disease (AD).

All participants were deemed cognitively normal upon entry. Baseline evaluations included magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG-PET), and Pittsburgh Compound B PET scanning (PiB-PET), with clinical evaluations performed every 15 months. After a median follow up of 2.5 years, 84 of the study participants were shown to progress to clinical mild cognitive impairment (MCI) and 4 to dementia.

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Nearly one-third (31.7%; n=179) of the patients in the study had elevated amyloid levels at baseline (PiB+ = standardized uptake value >1.5 on PiB-PET), which corresponded to poorer cognition in all measured domains and a faster rate of cognitive decline (with the exception of language). The same association was seen with PiB+ patients and markers of neurodegeneration, including hippocampal atrophy (30mm3 per year), ventricular expansion (565 mm3 per year), and increased amyloid accumulation rates (1.6% per year) when compared with individuals who showed normal amyloid levels (PiB-).

The investigators also examined potential links between PiB status and the presence of the apolipoprotein E4 (APOE4) allele shown to be associated with the development of MCI in previous studies.2 Results indicated essentially similar rates of progression on MCI biomarkers in PiB+ individuals regardless of whether they carried the APOE4 allele or not. 

After adjusting for PiB status, APOE4 status was not an independent factor in cognitive decline, although it did appear to increase cognitive changes over time, as PiB+/APOE4 carriers were more likely to progress to MCI. This potentially confounding result was attributed to differences among the participants at baseline. The investigators determined that PiB status alone (and not APOE4 status alone) could be considered predictive of MCI decline, and further, that the effects of APOE4 occur as a result of PiB positivity.


  1. Petersen RC, Wiste HJ, Weigand SD, et al. Association of Elevated Amyloid Levels With Cognition and Biomarkers in Cognitively Normal People From the Community. JAMA Neurol. 2015; doi:10.1001/jamaneurol.2015.3098.
  2. Boyle PA, Buchman AS, Wilson RS, et al. The APOE ∊4 allele is associated with incident mild cognitive impairment among community-dwelling older persons. Neuroepidemiology. 2010; 341: 43–49.