Blood Test Predicts Cognitive Decline and Resilience

Low blood levels of beta-amyloid 42 were linked to a significant risk of cognitive decline in elderly patients, marking 'a huge step forward' in research.

Low blood levels of beta-amyloid 42, a protein-like substance, were associated with the risk of significant cognitive decline within nine years in a group of elders, according to data published in the Journal of the American Medical Association.

The study also showed that among the elders with low beta-amyloid 42—which has long been known to collect in the brain of patients with Alzheimer's disease—cognitive decline was less pronounced in those who had higher literacy, or more education, or who lacked the APOE e4 gene known to be associated with a greater risk of dementia.

"We show that a blood test for beta-amyloid 42 might be a good way to predict those at risk for cognitive decline," said lead researcher Kristine Yaffe, MD, chief of geriatric psychiatry at the San Francisco VA Medical Center. “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 described the findings as "potentially of great importance for clinical care of Alzheimer's disease and dementia." Currently, she said, "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."

Yaffe noted that an experimental test for beta-amyloid in cerebral spinal fluid already exists, "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 blood and spinal fluid, she said, indicate high levels in the brain, "which acts as a sink for beta amyloid in Alzheimer's disease."

The research team studied 997 community-dwelling older adults who were enrolled in the Health ABC Study, a prospective observational study sponsored by the National Institute on Aging and coordinated by the San Francisco Coordinating Center at UCSF.

Subjects, whose average age at the start of the study, were first assessed in 1997 to 1998 and followed for nine years. Their cognitive abilities were measured at the beginning and end of the study with a standard neurocognitive test. In 2010, the subjects' blood, which had been drawn at the beginning of the study and then frozen, was tested for beta-amyloid 42 as well as for the ratio of beta-amyloid 42 to beta-amyloid 40, a less toxic form of the substance.

Low beta-amyloid 42 and low ratio of 42 to 40 at the outset of the study were associated with greater cognitive decline over the next nine years, even after the researchers adjusted for age, race and other confounding factors.

The link held up after the 72 participants who developed full-blown dementia over the course of the study were excluded 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.

However, within the group of subjects with low beta-amyloid 42, the association with cognitive decline was less pronounced among 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.

Source: UCSF Medical Center