Older adults without dementia who had a low ratio of beta-amyloid 42:40 in plasma showed faster cognitive decline in a 9-year study than did those with a higher ratio of the two beta-amyloid peptides, according to a report in JAMA.
This cognitive decline was more marked in subjects who had less cognitive reserve, as estimated by their lower educational attainment and lower literacy.
“These results are important, as the prevalence of cognitive impairment is increasing exponentially and prevention will be crucial. To identify those at risk of dementia, biomarkers like plasma beta-amyloid level that are relatively easy to obtain and minimally invasive could be useful,” wrote Dr. Kristine Yaffe of the University of California, San Francisco, and her associates.
The investigators assessed the relationship between beta-amyloid levels and cognitive decline using a cohort of 3,075 community-dwelling residents of Memphis and Pittsburgh who had been enrolled in an aging study in 1997-1998 when they were 70-79 years old. They studied 997 of the individuals who had undergone repeated cognitive assessments during follow-up through 2007.
The mean age at baseline was 74 years. Approximately 555 of the study subjects were women, and 54% were African American.
A low beta-amyloid 42:40 ratio at baseline was significantly associated with greater cognitive decline on the Modified Mini-Mental State Examination, which has a maximum score of 100. Mean scores on the Modified Mini-Mental State Examination after 9 years of follow-up declined 6.59 points among people in the lowest tertile of plasma beta-amyloid 42:40 ratio, 6.16 points among those in the middle tertile, and 3.60 points among those in the highest tertile.
The investigators also detected a significant, but less robust, association between tertiles of plasma beta-amyloid 42 levels and cognitive decline.
Both associations remained significant when the data were adjusted to account for subject age, race, education level, smoking status, diabetes status, and apolipoprotein E e4 status, according to Dr. Yaffe and her colleagues (JAMA 2011;305:261-6).
Moreover, the association between plasma beta-amyloid 42:40 ratio and cognitive decline was strongest among people with a low cognitive reserve (as measured by less than a high school diploma or 6th grade literacy) and weakest among people with higher cognitive reserve.
People who carried the apolipoprotein E e4 allele also showed a stronger association between plasma beta-amyloid 42:40 ratio and cognitive decline.
“Our results suggest that the plasma beta-amyloid 42:40 ratio appears to be a biomarker of cognitive decline,” the researchers noted.
The modifying effect of cognitive reserve on the association between cognitive decline and plasma beta-amyloid 42:40 ratio “suggests possible pathways, such as cognitive activity or ongoing education, for mitigating or preventing beta-amyloid effects on cognition,” they added.
The investigators did not measure cerebrospinal fluid levels of beta-amyloid 42 and 40 and so could not correlate them with plasma levels of the peptides, Dr. Yaffe and her associates said.
This study was supported by the National Institute on Aging. No relevant financial disclosures were reported.