Changes in Plasma Beta Amyloid Levels May Predict Late-Life Cognitive Decline
By Caroline Cassels
Medscape Medical News
October 15, 2009 — A high ratio of beta amyloid peptides (Aβ) 40 and 42 in midlife may be a predictor of future cognitive decline in late life, new research suggests.
A large community-based study conducted by researchers at Brigham and Women's Hospital, Boston, Massachusetts, shows that individuals with higher plasma Aβ 40:42 ratios in late midlife and then increases in these ratios 10 years later were significantly associated with greater decline in cognitive function in later life.
"By showing that there are earlier measurable risk markers of future cognitive decline, we have hope in the possibility of someday using blood biomarkers to find people at risk years before cognitive decline becomes apparent," principal investigator Olivia Okereke, MD, said in a statement.
"This is an important step in the effort to prevent and to provide early intervention against dementia," Dr. Okereke added.
The study is published in the October 12 issue of the Archives of Neurology.
Trend Toward Depression
Using 481 health participants from the Nurses' Health Study, investigators measured plasma Aβ40 and Aβ42 levels in late midlife (mean age, 63.6 years) and again 10 years later (mean age, 74.6 years). Approximately 10 years after the initial blood draw, women underwent cognitive testing 3 times at approximately 2-year intervals.
Testing included the Telephone Interview for Cognitive Status to test general cognition, as well as immediate- and delayed-recall trials for the East Boston Memory Test.
General cognition and verbal memory were the study's primary outcomes. The researchers note that verbal memory in particular is a strong predictor of eventual Alzheimer's disease.
Health and lifestyle characteristics of the subjects were similar. At midlife, participants were divided into quartiles according to ratios of Aβ40 to Aβ42. Overall, the investigators report, the characteristics were similar across quartiles. However, they note, there was a trend toward increased prevalence of depression with increasing Aβ40 and Aβ42 ratios.
In addition, women with the lowest Aβ40 to Aβ42 ratios tended to have a lower prevalence of heart disease and current smoking, and there was a suggestion that they also had higher levels of physical activity.
Value Lies in Early Identification
After adjustment for multiple confounders, midlife plasma Aβ40 to Aβ42 ratios, but not Aβ42 plasma levels alone, were associated with significantly worse late-life decline in global cognition.
Similarly, over time, a greater increase in Aβ40 and Aβ42 ratios, but not in Aβ42 levels alone, from midlife to late life predicted a significantly faster rate of cognitive decline.
According to investigators, this is the first large-scale study to examine the ability of midlife plasma Aβ levels and change in plasma Aβ levels over time to predict cognitive decline."Therefore, our findings contribute uniquely to the literature," they write.
According to the authors, the benefits of this research are clear: "Midlife Aβ40 to Aβ42 ratios alone predicted late-life cognitive decline, which suggests that this ratio may prove valuable for early identification of those at high risk of cognitive impairments," they write.
However, they add, these findings need to be confirmed by other large-scale longitudinal studies.
The authors have disclosed no relevant financial relationships.
