A study in the Journal of the American Medical Association Neurology suggests that controlling or preventing risk factors, such as hypertension, earlier in life may limit or delay the brain changes associated with Alzheimer's disease and other age-related neurological deterioration.
Dr. Karen Rodrigue, assistant professor in the UT Dallas Center for Vital Longevity (CVL), was lead author of a study that looked at whether people with both hypertension and a common gene had more buildup of a brain plaque called amyloid protein, which is associated with Alzheimer's disease. Scientists believe amyloid is the first symptom of Alzheimer's disease and shows up a decade or more before symptoms of memory impairment and other cognitive difficulties begin. The gene, known as APOE 4, is carried by 20 percent of the population.
Until recently, amyloid plaque could be seen only at autopsy, but new brain scanning techniques allow scientists to see plaque in living brains of healthy adults. Findings from both autopsy and amyloid brain scans show that at least 20 percent of typical older adults carry elevated levels of amyloid, a substance made up mostly of protein that is deposited in organs and tissues.
"I became interested in whether hypertension was related to increased risk of amyloid plaques in the brains of otherwise healthy people," Rodrigue said. "Identifying the most significant risk factors for amyloid deposition in seemingly healthy adults will be critical in advancing medical efforts aimed at prevention and early detection."
Based on evidence that hypertension was associated with Alzheimer's disease, Rodrigue suspected that the combination of hypertension and the presence of the APOE-e4 gene might lead to particularly high levels of amyloid plaque in healthy adults.
Rodrigue's research was part of the Dallas Lifespan Brain Study, a comprehensive study of the aging brain in a large group of adults of all ages funded by the National Institute on Aging. Rodrigue's group recruited 147 participants (ages 30-89) to undergo cognitive testing, magnetic resonance imaging (MRI) and PET imaging using Amyvid. Amyvid is a compound that when injected travels to the brain and binds with amyloid proteins, allowing the scientists to visualize the amount of amyloid plaque. Blood pressure also was measured at each visit.
Rodrigue classified participants in the study as hypertensive if they reported a current physician diagnosis of hypertension or if their blood pressure exceeded the established criteria for diagnosis. The participants were further divided into groups based on whether they were taking anti-hypertensive medications or if they were unmedicated and showed blood pressure elevations consistent with a diagnosis of hypertension. Finally, study subjects were classified in the genetic risk group if they were in the 20 percent of adults who had one or two copies of an APOE ε4 allele, a genetic variation linked to dementia.
The most striking result of the study was that nonmedicated hypertensive adults who also carried a genetic risk factor for Alzheimer's disease showed much higher amyloid levels than all other groups. Adults with medication-controlled hypertension, even those with genetic risk, had levels of amyloid plaque equivalent to participants without hypertension or genetic risk.
The study suggests that controlling hypertension may significantly decrease the risk of developing amyloid deposits, even in those with genetic risk. Rodrigue noted that long-term studies are needed to be certain that the use of hypertensive medications decreased amyloid deposits. Nevertheless, this early finding provides a window into the potential benefits of controlling hypertension that goes beyond lowering the risk of strokes and other cardiovascular complications.
Scientists cannot fully explain the neural mechanisms underlying the effect of hypertension and APOE ε4 on amyloid accumulation. But earlier research in animal models has shown that chronic hypertension may enable easier penetration of the blood-brain barrier, resulting in more amyloid deposition.
The recent study is significant because it focuses on a group of healthy and cognitively normal middle-aged and older adults, which enables the examination of risk factors and amyloid burden before the development of preclinical dementia. The team plans for long-term, longitudinal follow-up with participants to determine the proportion of the subjects who eventually develop the disease.
The study's co-authors included Dr. Denise Park, director of the Dallas Lifespan Brain Study and co-director of the Center for Vital Longevity, Dr. Kristen Kennedy and doctoral student Jennifer Rieck, all from The University of Texas at Dallas. The team also included Dr. Michael Devous and Dr. Ramon Diaz-Arrastia from UT Southwestern Medical Center and the Uniformed Services University of the Health Sciences. In addition to the National Institute on Aging support, the Alzheimer's Association provided funds for the study and Avid Radiopharmaceutical provided doses of Amyvid used in scanning.
- Karen M. Rodrigue et al. Risk Factors for β-Amyloid Deposition in Healthy Aging
Vascular and Genetic Effects Factors for β-Amyloid Deposition in Healthy Aging. JAMA Neurology, 2013; 1 DOI: 10.1001/jamaneurol.2013.1342
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