By Wayne Forrest, AuntMinnie.com staff writer

April 11, 2017 -- Florbetapir-PET scans show that midlife adults with two or more vascular risk factors are significantly more likely to have greater levels of amyloid deposits in their brains later in life than peers with no such risk factors, according to a study published April 11 in the Journal of the American Medical Association.

Interestingly, the researchers found no significant association between Alzheimer's and vascular risk factors during a person's later years, which places greater urgency on determining the potential causes of the disease earlier in a person's life.

"It is already well-understood that future attempts to prevent Alzheimer's disease, as well as other types of dementia, need to focus on the preclinical stage before symptoms of dementia develop," wrote lead author Dr. Rebecca Gottesman, PhD, an associate professor of neurology and epidemiology at Johns Hopkins University, in an email to AuntMinnie.com. "By emphasizing the particular importance of vascular risk factors in middle age, with a decreasing and then absent association as vascular risk factors in later life are considered, our data suggest that the vulnerable period for brain health may be decades before any cognitive problems develop."

Dementia's development

Previous studies have offered evidence that vascular risk factors such as hypertension, diabetes, obesity, smoking, and hypercholesterolemia during an adult's midlife could lead to dementia later in life. However, questions remain as to what degree these risk factors might contribute to brain amyloid deposition, which also has been linked to dementia and Alzheimer's progression.

Dr. Rebecca Gottesman, PhD
Dr. Rebecca Gottesman, PhD, from Johns Hopkins.

The current paper pulls from the Atherosclerosis Risk in Communities (ARIC) study, in which vascular risk factor data were collected from approximately 16,000 participants for more than 25 years, beginning in 1987-1989. At that time, the subjects had a mean age of 52 years. People from four communities participated in five in-person evaluations and annual (now semiannual) follow-up phone calls to record vascular risk factors and track any cardiovascular events.

For the current study, the researchers selected 322 ARIC participants who had zero to four vascular risk factors when the study commenced in the mid-1980s (baseline) and showed no signs of dementia. Florbetapir-PET scans were performed from 2011 to 2013, when the subjects' mean age had advanced to 76 years. Florbetapir is marketed under the trade name Amyvid in the U.S. and Europe by Eli Lilly and its subsidiary Avid Radiopharmaceuticals. Image analysis was completed for the ARIC PET subjects in 2015 (JAMA, April 11, 2017, Vol. 317:14, pp. 1443-1450).

Gottesman and colleagues defined an elevated level of florbetapir as a standardized uptake value ratio (SUVR) of more than 1.2.

"This means that when [florbetapir] is injected in an IV and then the person undergoes a PET scan, we can quantify where there is amyloid and in what quantity," Gottesman explained. "Our participants were all free of dementia when we enrolled them and completed their PET scans, but many still had amyloid in their brains by florbetapir PET."

Risk vs. reality

At baseline, 65 participants had no vascular risk factors, while 123 had one risk factor and 134 had two or more risk factors. By 2011-2013, the number of subjects with no vascular risk factors decreased to 35, while those with one risk factor fell to 82. However, the number of people with two or more risk factors increased to 205.

Upon follow-up, the researchers found that 61% of participants with two or more vascular risk factors in midlife had elevated amyloid deposits in the brain. By comparison, 31% of midlife adults with no risk factors had increased amyloid accumulation.

With each additional midlife vascular risk factor, the odds of having amyloid deposits increased. Compared with subjects who had no risk factors, the odds ratio for elevated SUVR for someone with one vascular risk factor was 1.88, while those with two or more vascular risk factors had an odds ratio of 2.88.

The researchers also concluded that having vascular risk factors later in life was not associated with increased amyloid, regardless of a participant's apolipoprotein E (APOE) genotype.

Breaking new ground

"This study adds new information by showing an association not only between vascular risk factors and clinical symptoms of dementia or Alzheimer's, but the specific pathology of Alzheimer's," Gottesman said. "This means that vascular risk factors may play a direct role in the development of Alzheimer's."

Gottesman and colleagues plan to continue their research by following subjects in the ARIC PET group and those in the overall ARIC study to pursue the vascular role in cognition, cognitive decline, dementia, and brain amyloid deposition.

"We are following the cognitive status of people who had a PET scan, so we will be able to see the relative roles that vascular risk factors, brain MRI vascular changes, and brain amyloid all play in the potential for progression to dementia," she added. "In addition, we will be repeating florbetapir-PET scans to understand whether these same risk factors are associated with more progression of amyloid and if this progression also parallels progression to cognitive impairment and dementia."


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