The association between β-amyloid plasma levels and cognition is strongest in persons with less education, lower literacy, and the apolipoprotein ε4 allele.
Lower levels of plasma β-amyloid 42/40 in older adults without dementia are associated with cognitive decline and an increased risk of developing Alzheimer’s disease within nine years, according to the results of a study published in the January 19, 2011, issue of JAMA.
Kristine Yaffe, MD, of the University of California, San Francisco and the San Francisco Veterans Affairs Medical Center, and colleagues conducted a prospective, observational study of 997 adults without dementia to investigate the link between levels of plasma β-amyloid 42/40 and 42 and declining cognitive function.
The authors included black and white older adults who were already enrolled in the ongoing Health, Aging, and Body Composition Study. Individuals were eligible if they were free of life-threatening cancers and were able to perform certain daily activities without difficulty. Age at enrollment ranged from 70 to 79, with a mean age of 74.0. The majority of participants (55.2%) were female, and 54% were black. Seventy-two participants with incident dementia were excluded from the study.
Participants’ cognitive function was measured with use of the Modified Mini-Mental State Examination (MMSE), administered at baseline visit and repeated throughout the nine-year follow-up. β-Amyloid 40 and β-amyloid 42 levels were measured from stored plasma obtained from each participant at the first follow-up visit, and participants were grouped into lowest, middle, and highest tertiles.
After analyzing MMSE results for nine years, the researchers found that participants with low β-amyloid 42/40 levels were associated with greater cognitive decline, compared with those with higher levels. Persons in the lowest β-amyloid tertile scored an average of 6.59 points lower on the MMSE, the middle tertile declined 6.16 points, and lowest tertile declined 3.60 points.
β-Amyloid, Cognitive Reserve, and Education
Dr. Yaffe’s group adjusted the results for variables including age, race, diabetes, and measures of cognitive reserve (determined by literacy and years of education). The association between plasma β-amyloid 42/40 levels and cognitive decline was significant, and it was strongest in participants with a lower reserve. The average decline in the lowest tertile was -8.94 points (compared with -4.45 for the highest tertile); for those with a high reserve, decline was -4.60 points for the lowest tertile and -2.88 points for the highest tertile.
The investigators noted an association between plasma β-amyloid 42 and cognitive decline, but they did not detect an association between β-amyloid 40 and cognitive decline.
“Our finding of an interaction of cognitive reserve with the association of plasma β-amyloid level and cognitive decline could have public health importance because it may suggest pathways for modifying β-amyloid effects on cognition,” the authors wrote.
In an accompanying editorial, Monique M.B. Breteler, MD, PhD, who is affiliated with the University Medical Center Rotterdam in the Netherlands, noted that cognitive reserve’s modification of this association provides “further evidence that for [Alzheimer’s disease], the presence of pathology is not the whole story. The most important message from this and similar studies is that differences in proteins and peptides can be found in peripheral fluids years before clinical onset of dementia.… To identify those at risk of dementia, risk factor profiles and biomarkers must be obtained relatively easily and with minimal invasiveness.”
—Ariel Jones
Imaging Detects Biomarker Associated With Alzheimer’s Disease
Florbetapir F 18 PET imaging may provide an accurate assessment of β-amyloid burden during life, according to the results of a study published in the January 19, 2011, issue of JAMA.
Christopher M. Clark, MD, of Avid Radiopharmaceuticals in Philadelphia, and colleagues conducted a prospective observational study to determine if florbetapir-PET imaging performed antemortem was related to β-amyloid burden in the brain postmortem.
To ensure a valid correlation and minimize time between PET imaging and autopsy, the investigators included 35 older individuals (six to establish protocol and 29 to validate) who were clinically assessed as likely to die within six months of enrollment. Other inclusion criteria included absence of any known destructive lesion in the brain. The mean interval from imaging to death was 99 days (range, 1 to 377 days).
Dr. Clark and colleagues noted significant correlations between the two measures of amyloid on florbetapir-PET (SUVr vs semiquantitative visual score) and the two measures of amyloid aggregation at autopsy (immunochemistry vs silver stain).
Low β-amyloid aggregation levels were recorded in 14 participants in the autopsy cohort, and all had negative florbetapir-PET scans. In addition, 15 participants in the autopsy cohort met pathologic criteria for Alzheimer’s disease, 14 of whom had florbetapir-PET scans that were interpreted as visually positive, further strengthening the correlation.