Major Finding: High initial levels of plasma Abeta-40 and Abeta-42, and stable or decreasing Abeta-42 at follow-up, were associated with faster global cognitive decline regardless of dementia status.
Data Source: Plasma samples and neuropsychological tests from 880 participants in a prospective, population-based study of aging and dementia in northern Manhattan.
Disclosures: The study was funded by grants from the National Institutes of Health. The investigators had no relevant disclosures to report.
When plasma levels of beta-amyloid rise above normal and then decrease or stabilize in healthy elderly patients, it signals the onset of a rapid decline in several cognitive domains, a study has shown.
In most patients, that decline takes the form of Alzheimer's disease. In the minority who don't develop full-blown dementia, there is a marked cognitive decline that primarily affects memory rather than language or visuospatial domains, said Stephanie A. Cosentino, Ph.D., of the Taub Institute for Research in Alzheimer's Disease and the Aging Brain, New York, and her associates.
Studies have shown a correlation between elevated plasma beta-amyloid (Abeta) levels and the development of mild amnestic cognitive impairment or frank Alzheimer's disease (AD) within a few years. But other studies have found that decreasing, rather than elevated levels, correlate with these cognitive declines.
Dr. Cosentino's study suggests that the timing of the plasma sampling and of the subjects' disease stage may account for these discrepant results.
The investigators used data from a population-based study of aging to examine the link between plasma levels of the soluble oligomers Abeta-40 and −42 and cognitive changes. A total of 880 nondemented study subjects provided one blood sample at baseline in 1999 and a second sample 4.5 years later. They underwent a battery of neuropsychological tests at 18-month intervals.
During follow-up, 481 remained cognitively healthy, 329 developed cognitive or functional impairment but no dementia, and 70 developed AD. The cohort involved nearly equal percentages of Hispanics (37%), whites (31%), and African Americans (31%).
“Overall, high initial levels of plasma Abeta-40 and Abeta-42, and stable or decreasing Abeta-42 at follow-up, were associated with faster global cognitive decline regardless of dementia status,” Dr. Cosentino and her associates wrote (Arch. Neurol. 2010 Aug. 9 [doi:10.1001/archneurol.2010.189]).
Subjects whose initial Abeta-40 and Abeta-42 levels were in the top three quartiles had significantly faster cognitive decline than did those in the lowest quartile. Those with either decreasing or stable Abeta-42 levels at the second measurement had significantly faster cognitive decline than other subjects.
An elevated level of Abeta-42 at baseline predicted cognitive decline in memory, language, and visuospatial domains, with subjects in the highest quartile of beta-amyloid level consistently declining significantly faster than subjects in the lowest quartile. However, in the subgroup of subjects who remained cognitively unimpaired, those with high baseline levels of Abeta-42 showed declines only in the memory domain.
The researchers suggested that these subjects may be in the early stages of AD but have not yet shown sufficient decline in nonmemory domains to meet the criteria for dementia. Alternatively, they may remain free of dementia due to biological factors such as the ability to clear high levels of beta-amyloid or psychosocial factors such as the presence of cognitive reserve.
“Another interpretation of the association between plasma Abeta-42 and memory is that amyloid changes are an important factor in cognitive aging, independent of underlying AD. Stated differently, the observable change in both plasma Abeta and memory in this group could be a fundamentally different process than that involved in AD or might fall short of a critical threshold beyond which the full pathological presentation and clinical dementia syndrome of AD would unfold,” they wrote.
Future studies must “determine more definitively the specificity of Abeta profiles for predicting dementia vs their significance for cognitive aging more generally,” they added.
The study was funded by the National Institutes of Health. The researchers had no conflicts to report.