New Alzheimer’s Insights

(Ivanhoe Newswire) — Two studies released in this week’s JAMA, provide new insights into Alzheimer’s disease (AD).

The first insight occurred when researchers used molecular imaging to identify a biomarker commonly linked to Alzheimer’s. This biomarker, called beta-amyloid, is discovered during autopsies of AD patients but may now be observed in living patients.

Doctors would be better able to diagnose and eventually treat AD by observing the noninvasive biomarkers that assist in the patient’s pathology. Between 10 and 20 percent of AD patients do not have AD pathology at the time of autopsy, and 33 percent of patients with mild symptoms go undiagnosed.

To observe these biomarkers, the researchers experimented with different types of positron emission tomographic (PET) imaging tests. The most promising looked to be florbetapir F 18 PET, which uses a chemical that binds to beta-amyloid to help identify it. At this point, however, the direct relationship between florbetapir-PET image and beta-amyloid has not been defined.

Avid Radiopharmaceuticals’ Christopher M. Clark, M.D., and his associates, tested the efficacy of florbetapir F 18 PET in predicting beta-amyloid presence in the brain during autopsy. They collected PET images of 35 near-death patients in various health care centers and corresponding images of a control set of 74 younger, presumably beta-amyloid-free individuals aged 18 to 50. “Florbetapir-PET images and postmortem results rated as positive or negative for beta-amyloid agreed in 96 percent of the 29 individuals in the primary analysis cohort,” the researchers wrote.

In the younger group, the florbetapir-PET image was found to be amyloid negative.

The researchers believe that impaired functionality may partially result from the patient’s ability or inability to tolerate accumulated amyloid in their brain. Genetics, lifestyle habits, environmental risks and neuropathological comorbidities may determine this.

The second study also involved beta-amyloid, as older adults containing lower levels of protein fragments of the biomarkers beta amyloid 42/40 were found to be more likely to suffer from cognitive decline over a nine-year period. Less education and literacy also contributed to this trend, putting such individuals at a higher risk of developing dementia.

University of California, San Francisco’s Kristine Yaffe, M.D., who also works with the San Francisco Veterans Affairs Medical Center, collaborated with a team of colleagues to look at the relationship between plasma beta-amyloid 42/40 accumulation and cognitive decline in older adults who did not suffer from dementia. They also tried to discern whether or not “cognitive reserve,” or levels of education and literacy, contributed to prevention.

Dr. Yaffe and her associates observed beta-amyloid 42/40 levels in 997 elderly adults who were registered in the Health ABC study, a prospective observational study that initially began in 1997-1998 and included a 2006-2007 follow-up. They found a strong connection between low beta-amyloid 42/40 levels and cognitive decline over nine years. Plasma beta-amyloid 42 was also strongly associated.

As for cognitive reserve, individuals who had a “low reserve,” measured by an education level below a high school graduate and a literacy level equivalent to sixth grade or below, were significantly associated with beta-amyloid 42/40 level, which was not the case in those with “high reserve.”

“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 levels that are relatively easy to obtain and minimally invasive could be useful. In addition, our finding of an interaction of cognitive reserve with the association of plasma beta-amyloid level and cognitive decline could have public health importance because it may suggest pathways for modifying beta-amyloid effects on cognition,” the authors of the study wrote.

Source: JAMA, January 2011