SAN DIEGO — People who were diagnosed as having “objectively-defined subtle cognitive difficulties” appeared to accumulate amyloid more quickly than those deemed cognitively normal, according to a new study. That information could potentially improve early detection of Alzheimer’s disease.

An article in Neurology pointed out that classification of Obj-SCD, which has been previously shown to predict progression to mild cognitive impairment and dementia, is determined using noninvasive but sensitive neuropsychological measures, including measures of how efficiently someone learns and retains new information or makes certain types of errors.1

VA San Diego Healthcare System and University of San Diego School of Medicine explained that their new findings suggested that Obj-SCD can be detected during the preclinical state of AD when amyloid plaques are accumulating in the brain. At that stage, neurodegeneration is just starting, but symptoms of impairment on total scores on thinking and memory tests have not yet been recorded.

“The scientific community has long thought that amyloid drives the neurodegeneration and cognitive impairment associated with Alzheimer’s disease,” said senior author Mark W. Bondi, PhD, of the VA San Diego Healthcare System. “These findings, in addition to other work in our lab, suggest that this is likely not the case for everyone and that sensitive neuropsychological measurement strategies capture subtle cognitive changes much earlier in the disease process than previously thought possible.”

Bondi, who also is a professor of psychiatry at UC San Diego School of Medicine, explained that the research “has important implications for research on treatment targets for AD, as it suggests that cognitive changes may be occurring before significant levels of amyloid have accumulated. It seems like we may need to focus on treatment targets of pathologies other than amyloid, such as tau, that are more highly associated with the thinking and memory difficulties that impact people’s lives.”

For the study, participants were enrolled in the Alzheimer’s Disease Neuroimaging Initiative, an ongoing effort launched in 2003 to test whether regular, repeated brain imaging, combined with other biological markers and clinical assessments, can measure the progression of MCI and early AD. Involved in the study were 747 participants—305 had been adjudged to be cognitively normal, 153 with Obj-SCD and 289 MCI.

After the participants underwent neuropsychological testing and both PET and MRI scans, researchers determined that amyloid accumulation was speedier in those classified with Obj-SCD than in the cognitively normal group. The authors explained that those classified as Obj-SCD also experienced selective thinning of the entorhinal cortex, a region of the brain affected very early in Alzheimer’s disease and associated with memory, navigation and perception of time.

While participants with MCI had more amyloid in their brain at study initiation, they did not have faster accumulation of amyloid compared to those with normal cognition, although they did have more widespread temporal lobe atrophy, including the hippocampus.

Background information in the article described how the amyloid hypothesis or amyloid cascade model posits that accumulating amyloid protein plaques in the brain kill neurons and gradually impair specific cognitive functions, such as memory, resulting in AD dementia. That supposition is being questioned by many scientists, however, because drugs which have targeted and successfully cleared amyloid from the brain did not seem to affect the rate of cognitive decline.

“While the emergence of biomarkers of Alzheimer’s disease has revolutionized research and our understanding of how the disease progresses, many of these biomarkers continue to be highly expensive, inaccessible for clinical use or not available to those with certain medical conditions,” said first author Kelsey R. Thomas, PhD, research health scientist at the VA San Diego Healthcare System and assistant professor of psychiatry at UC San Diego School of Medicine. “A method of identifying individuals at risk for progression to AD using neuropsychological measures has the potential to improve early detection in those who may otherwise not be eligible for more expensive or invasive screening.”

  1. Thomas KR, Bangen KJ, Weigand AJ, Edmonds EC, et. Al. for the Alzheimer’s Disease Neuroimaging Initiative. Objective subtle cognitive difficulties predict future amyloid accumulation and neurodegeneration. NeurologyDec.2019, 10.1212/WNL.0000000000008838; DOI: 10.1212/WNL.0000000000008838