Elevated amyloid proves a warning sign of cognitive decline to come

People with elevated amyloid levels in the brain but no signs of cognitive decline are indeed more likely to develop impairment down the road, potentially leading to full-on Alzheimer’s, according to a study published online June 12 in JAMA.

The team behind the finding suggests that dealing with the sticky protein at the preclinical stage could slow the disease if not stop it in its tracks, although they acknowledge that more long-term research is needed to determine the clinical importance of the associations they observed.

Michael C. Donohue, PhD, of the Alzheimer’s Therapeutic Research Institute at USC’s Keck School of Medicine and colleagues used PET scans and cerebrospinal fluid taps to measure amyloid levels in 445 people of normal cognitive function at baseline and over a period of up to 10 years, prospectively testing for cognitive function along the way.

The participants’ average age was 74, and they were grouped into normal amyloid at baseline (n = 242) and elevated at baseline (n = 202).

The team’s key finding: Baseline elevated brain amyloid was significantly associated with worse cognitive measures after a median of 3.1 years.

Donohue and colleagues further report that, at the four-year mark, 32 percent of the elevated-amyloid participants had developed symptoms consistent with early-stage Alzheimer’s.

Just 15 percent of the normal-amyloid participants showed such a falloff.

Adding to the association of amyloid elevation with cognitive decline, the elevated amyloid group was older, less educated and had more participants with at least one copy of the ApoE4 gene, which increases the odds for developing Alzheimer’s.

What’s more, at year 10 the team assessed a subgroup of the cohort and found functional predictors of mental decline in 88 percent of the elevated-amyloid group vs. 29 percent in the normal-level group.

“Although this work did not establish a causal role of elevated amyloid in subsequent decline, these results supported other findings (e.g., genetic data) pointing to the critical role of amyloid in the neurobiology of Alzheimer’s disease,” the authors write in their discussion.

In an accompanying commentary piece, two researchers in the Netherlands state that the availability of Alzheimer’s biomarkers, combined with deep-phenotyped longitudinal cohort studies like the present one by Donohue et al., will help “pave the way for the development of preventive strategies that ultimately may enable persons with Alzheimer’s disease to live without dementia.”

In a feature article posted online by USC’s news office, Paul Aisen, MD, senior author of the study, says the new research represents “a significant step toward the idea that elevated amyloid levels are an early stage of Alzheimer’s, an appropriate stage for anti-amyloid therapy.”