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The angiotensin receptor blocker (ARB) candesartan had cognitive benefits that were likely independent of the drug's blood pressure (BP)-lowering effect, a small randomized trial indicated.

People randomized to candesartan instead of the angiotensin-converting enzyme (ACE) inhibitor lisinopril had better executive function 1 year later as demonstrated by the trail-making test (effect size -12.8, 95% CI -22.5 to -3.1), according to a group led by Ihab Hajjar, MD, MS, of Emory University School of Medicine in Atlanta.

Candesartan recipients also beat peers on lisinopril in the episodic memory component of the Hopkins Verbal Learning Test-Revised, the investigators .

For most of these measures, the apparent ARB benefit was an actual increase from baseline, not merely slower decline.

"Although further larger and longer-term studies are needed, this randomized clinical trial provides additional and incremental support to the positive neurocognitive effects of candesartan that are likely independent and additive to their BP-lowering effects," the authors said, noting that lisinopril and candesartan groups achieved similar BPs at 12 months.

The apparent cognitive benefit of candesartan was not consistent, as recipients had no better scores than the lisinopril group on other instruments including Digit Span, the Boston Naming Test, and the for executive abilities.

Even so, the study's findings show that "ARBs provide neurocognitive protection on executive function even over the short-term" and suggest a role for candesartan in amnestic disorders such as Alzheimer's disease, Hajjar and colleagues said.

Their double-blind trial was performed at a single center and included 176 adults (mean age 66 years, 57.4% of whom were women, 64.2% African American). All had hypertension and executive mild cognitive impairment.

Study participants stopped all prior BP-lowering therapy and were randomized to oral candesartan or lisinopril once daily. To achieve BP less than 140/90 mm Hg, medications were given at escalating doses with the addition of other antihypertensive medications as needed.

Notably, only 141 people completed the trial: 25 had dropped out from the lisinopril arm, and 10 from the candesartan arm.

This large differential in drop-outs was a major limitation that could have caused large imbalances in the findings, cautioned Jackie Bosch, PhD, of McMaster University in Hamilton, Ontario, who was not involved in the study.

She also noted baseline differences such as the candesartan group having fewer participants with a history of family dementia (67.5% vs 79.3%), along with less cardiovascular disease and risk factors, which may contribute to the decreased risk of cognitive decline.

Hajjar's team reported no difference between the two groups in the qualifying task for executive dysfunction during the screening process. Pre-enrollment use of or was similar as well.

Brain magnetic resonance imaging scans performed on 104 participants showed that the candesartan group had no significant increase in white matter lesions at 12 months, whereas those randomized to lisinopril had significant accumulation, indicative of microvascular brain injury. The difference in white matter lesion accumulation was not statistically significant between groups, the authors noted.

"My conclusion is that these data are suggestive of a potential effect, but are not conclusive in terms of a clear benefit of candesartan," Bosch said.

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