How hypertension increases the risk of dementia

Originally published in MedPage Today

by John Gever, MedPage Today Senior Editor

Another study has found that hypertension may contribute to increased risk of dementia, this time with evidence of actual brain abnormalities.

Data from an offshoot of the Women’s Health Initiative found that participants’ baseline blood pressure was strongly correlated with volume of lesions in their brains’ white matter, according to Lewis Kuller, MD, DrPH, of the University of Pittsburgh, and colleagues.

Along with earlier studies linking blood pressure to clinical dementia, the evidence “supports tight control of blood pressure levels, especially beginning at younger and middle age as a possible and perhaps only way to prevent dementia,” Kuller and colleagues concluded online in the Journal of Clinical Hypertension.

One study reported in 2006 found that successful hypertension control reduced the risk of dementia, while another reported the following year indicated that uncontrolled high blood pressure increased the risk.

Kuller and colleagues analyzed data collected from 1,424 participants in the Women’s Health Initiative who agreed to undergo MRI scans performed an average of eight years after starting the trial. Blood pressure was measured at baseline and annually throughout the trial.

About half the women had been assigned to placebo in the trial, which primarily was designed to test two hormone replacement regimens. Some 436 received a combination of conjugated equine estrogen and medroxyprogesterone acetate, while the remainder received the equine estrogen alone.

Kuller and colleagues found significant relationships between baseline systolic blood pressure and abnormal white matter lesion volumes as measured with MRI.

Among participants not taking blood pressure medications, the lesion volume averaged 4.07 cm3 for those with baseline pressure of less than 100 mm Hg, compared with 5.20 cm3among those with systolic pressure of 140 mm Hg or higher (P=0.0044 for trend).

A similar but weaker relationship was seen for lesion volumes according to systolic pressure at the last available measurement (P=0.03) among subjects who were not on antihypertensive therapy.

Baseline systolic pressure was also significantly correlated with lesion volumes in women taking blood pressure drugs, Kuller and colleagues reported.

Women with baseline pressure below 100 mm Hg had lesion volumes averaging 5.56 cm3 whereas those with pressures of 140 mm Hg or higher at baseline had average lesion volume of 6.09 mm Hg (P=0.002 for trend).

There was a nonsignificant trend toward higher lesion volumes with increasing systolic pressure at the last measurement.

After adjusting for age, race, treatment assignment, total cranial volume, clinical site, and time from study termination to MRI scan, the researchers found that women with normal blood pressure (<140/90 mm Hg) had lower lesion volumes, not only in their white matter but also in the basal ganglia, than participants with high blood pressure.

The finding held both for baseline blood pressure measurements and for pressure at the last available evaluation (P<0.0001 for all comparisons).

High baseline blood pressure, though not later measurements, was also significantly correlated with the number of brain regions containing abnormal white matter lesions (P=0.035).

Regions in which high blood pressure seemed to promote abnormal lesions most strongly included frontal, parietal, and temporal lobes in both hemispheres. The frontal lobes in particular have been associated with vascular dementia and abnormal performance on cognition tests.

Occipital lobes and the corpus callosum did not appear significantly affected, the MRI data indicated.

“The association of blood pressure levels with white matter abnormalities years before the MRI is consistent with a long incubation period for the development of the white matter abnormalities,” Kuller and colleagues wrote.

They said their findings are also consistent with earlier observations that midlife blood pressure is more strongly related to dementia later on than is blood pressure measured at older ages.

Kuller and colleagues cautioned that it remained uncertain whether blood pressure treatment can prevent development of white matter abnormalities. Nor is it clear what the most appropriate blood pressure targets should be, or what type of treatment may be best.

“We have only suggestive evidence that the progression of white matter lesions can be slowed by blood pressure-lowering therapy,” they wrote, calling for more clinical trials to clear up these issues.

Nevertheless, they concluded, “a prudent clinical approach at present would encourage maintaining as low a blood pressure as possible, especially beginning in young and middle ages, in order to possibly prevent dementia as well as stroke. There are no other potentially effective preventive therapies.”

Study limitations included a lack of MRI data on brain infarcts, no corroborating clinical data on cognitive performance, and, of course, the trial’s restriction to women.

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