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HT, genetics interact to increase amyloid deposition.


Patients with uncontrolled hypertension showed greater deposition of beta-amyloid on florbetapir PET imaging of the brain than did those without HT or those whose HT was controlled with medication in a cross-sectional study of healthy, cognitively normal, middle-aged and older adults with at least one apolipoprotein E epsilon-4 allele.

This finding indicates that uncontrolled HT may increase the risk for Alzheimer's disease beyond that conferred by having one or more copies of the high-risk apolipoprotein E epsilon-4 (apo E-epsilon-4) allele in adults who are cognitively normal. It also raises the question of whether such patients may be able to attenuate their Alzheimer's risk through proper control of blood pressure, Karen M. Rodrigue, Ph.D., of the Center for Vital Longevity, University of Texas School of Behavioral and Brain Sciences, Dallas, and her associates reported in the journal. "'We may be able to prevent, or at least slow, pathological aging in some individuals through lifestyle modification or pharmacologic intervention," they wrote.

Dr. Rodrigue and her colleagues examined both the individual and the combined impact of apo E-epsilon-4 carriage and HT on beta-amyloid deposition in a subgroup of 118 subjects aged 47-89 years who were participating in a brain-imaging study. This subgroup involved well-educated middle-age and older adults who performed normally on a battery of cognitive tests, showed no abnormalities on neurological and psychiatric testing, and were free of vascular disease on clinical examination.

The subjects" blood pressure was measured on seven separate occasions during the study, and apo E status was determined from DNA analysis of venous blood samples. All the study subjects also underwent MRI and PET scanning of the brain.

A total of 18.6% of the study subjects had one apo E-epsilon-4 and another 4.2% had two apo E-epsilon-4 alleles.

Fifty-four of the study subjects had physician-diagnosed HT for which they took medication (mean age, 74 years), including beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, potassium-sparing diuretics, alpha-blockers, or a combination of these drugs. Another 15 subjects reported no diagnosis of HT (mean age, 73 years) but consistently showed blood pressure elevations exceeding stage 1 criteria for the disorder. The 49 normotensive individuals ranged in age from 47 to 88 years.

Study subjects who carried at least one apo E-epsilon-4 allele and had uncontrolled HT showed the greatest levels of beta-amyloid deposition on brain scans, compared with subjects who had only one of those risk factors and subjects who had neither of those risk factors, the investigators said (JAMA Neurol. 2013 March 18 [doi: 10.1001/jamaneurol.2013.1342]).

Study subjects whose HT was controlled by medication showed "'significantly less amyloid burden than the unmedicated group" and only a slightly higher amyloid burden than did the subjects who had no HT.

"Our study demonstrates that hypertension, a prevalent vascular risk factor in aging populations, interacts with apo E-epsilon-4 genotype to increase amyloid deposition in cognitively healthy middle-age and older adults," Dr. Rodrigue and her associates noted. It also highlights the complex interactions that vascular and genetic risk factors exert on the aging brain, and suggests that the two types of risk factors may act synergistically in inducing cognitive decline.

Their findings "should not be over-interpreted" because the study design was cross-sectional rather than prospective, and the study population was exceptionally healthy rather than representative of the general population. "Future studies with larger sample sizes that examine additional factors, such as duration of hypertension treatment, are needed to support these findings," they said.

This study was funded by the National Institutes of Health, the Alzheimer's Association, and the National Institute on Aging. Dr. Rodrigue reported no financial conflicts of interest.
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Author:Moon, Mary Ann
Publication:Family Practice News
Article Type:Clinical report
Geographic Code:1USA
Date:Apr 1, 2013
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