Elderly people who have low blood levels of beta-amyloid 42 (the protein believed to play a role in Alzheimer's disease) were more prone to significant mental decline within nine years, according to a new study.
The study, headed by Dr. Kristine Yaffe, chief of geriatric psychiatry at the San Francisco VA Medical Center, included 997 older adults (average age of 74) from Memphis, Tenn., and Pittsburgh who were enrolled in the Health ABC Study, sponsored by the National Institute on Aging and coordinated by the San Francisco Coordinating Center at UCSF. [Related: Alzheimer's Disease: Bad News and Good News]
Interestingly, among the participants found to have low beta-amyloid 42, cognitive decline was less prominent in those with higher literacy levels, more education, or who lacked a specific gene, called APOE e4, which is linked to a greater risk of dementia. The researchers call this group of factors "cognitive reserve."
"We show that a blood test for beta-amyloid 42 might be a good way to predict those at risk for cognitive decline," said Yaffe. "Also, for the first time, we show that cognitive reserve — a general level of resiliency in the brain — might modify that risk in the elderly."
Yaffe said that currently, "there is no reliable method of predicting ahead of time who will experience cognitive decline and go on to develop dementia. A blood test would be a huge step forward."
She added that there is currently an experimental test that looks for beta-amyloid in cerebral spinal fluid, "but a blood test would be far easier, less invasive, and less expensive than the lumbar puncture required to obtain spinal fluid."
Low levels of beta-amyloid 42 in the blood and spinal fluid, she said, point to high levels in the brain, "which acts as a sink for beta- amyloid in Alzheimer's disease."
However, she adds that "we might actually be able to modify the risk of dementia before it becomes manifest."
"If you find out that you have low beta-amyloid 42, but you haven't yet experienced any obvious cognitive decline, you might try and increase your cognitive reserve by staying mentally active — reading, taking classes — and thereby mitigate or at least delay the damage."
The study began when the participants were first assessed in 1997-98, and then they were followed for nine years. Their cognitive skills were analyzed at the beginning and end of the study with a standard neurocognitive test. Blood was also drawn in the beginning of the study and then frozen; in 2010 their blood was tested for beta-amyloid 42 and also for the ratio of beta-amyloid 42 to beta-amyloid 40, a more harmless form of the substance.
It was discovered that lower levels of beta-amyloid 42 and also a low ratio of 42 to 40 at the beginning of the study was linked to greater cognitive decline throughout the nine years, even when age, race and other factors were adjusted. The association held true even after the 72 participants who developed total dementia during the study were removed from the analysis.
"This way, we knew the numbers would not be weighted by the subjects with dementia, and we would simply be looking at gradual cognitive decline," explained Yaffe.
Furthermore, among the participants with low beta-amyloid 42, the association with mental decline was less pronounced for those with at least a high school education, a literacy level higher than sixth grade, or no APOE e4 gene.
"This is in line with evidence from other research that if you have high education, high literacy, or other compensatory factors, your brain is more resilient to certain insults, whether they be vascular or Alzheimer's," Yaffe said.
"Can you increase cognitive reserve?" Yaffe asked. "We think so. It's been shown that the brain can keep changing and growing and learning well into advanced old age. And we think you can do that with mental activities."
The research is published in the Journal of the American Medical Association.
