Lowering Blood Pressure May Reduce Dementia in the Elderly

By John Gever
LONDON, 9 july 2008-- For patients ages 80 or older, hypertension treatment may afford a small reduction in dementia risk, researchers found.
When findings from a placebo-controlled trial that was stopped early were included in a meta-analysis with three similar trials, the combined results showed a 13% reduction in dementia rates with lowered blood pressure, Ruth Peters, Ph.D., of Imperial College London, and colleagues reported online in The Lancet Neurology.
The findings came from a sub-study (HYVET-COG) of the placebo-controlled double-blind Hypertension in the Very Elderly Trial (HYVET), which assessed the cardiovascular benefits of treating hypertension in participants ages 80 or older. The sub-study included assessment of cognitive function.
Patients in HYVET were recruited from hospital-based and general-practitioner-based centers in western and eastern Europe, China, Tunisia, southeast Asia, and Australia.
Patients with hypertension (sitting systolic pressure 160-200 mm Hg; sitting diastolic pressure less than 110 mm Hg) who were 80 or older were enrolled in the HYVET-COG sub-trial. Mean age was 83.5 and about 60% were women.
Participants were randomly assigned to receive drug therapy -- either 1.5 mg slow-release indapamide (Lozol) or 2-4 mg of perindopril (Aceon) -- or placebo.
The target systolic blood pressure was 150 mm Hg; the target diastolic blood pressure was 80 mm Hg.
Participants had no clinical diagnosis of dementia at baseline. Cognitive function was assessed at baseline and annually with the mini-mental state examination (MMSE).

Possible cases of incident dementia (a fall in the MMSE score to <24 points or a drop of three points in one year) were assessed by standard diagnostic criteria and expert review.
The main trial was stopped early in 2007 at the second year analysis after treatment showed a reduction in stroke, heart failure, and total mortality, thus affecting follow-up in the cognitive study.
In the sub-trial of 3,336 HYVET participants with at least one follow-up assessment (mean 2.2 years), 1,687 participants were randomly assigned to the treatment group and 1,649 to the placebo group.
Only five reports of adverse effects were attributed to the medication: three in the placebo group and two in the treatment group.
The mean decrease in systolic blood pressure between the treatment and placebo groups at two years was systolic -15 mm Hg, P<0.0001, and diastolic -5.9 mm Hg, P<0.0001.
There were 263 cases of incident dementia (cognitive decline, vascular dementia, and Alzheimer's disease).
The rates of incident dementia were 38 per 1,000 patient-years in the placebo group and 33 per 1,000 patient-years in the treatment group.
Thus, there was no significant difference between the treated and the placebo patients (HR 0.86, 95% CI 0.67 to 1.09).
However, in a combined meta-analysis with three other placebo-controlled trials of hypertension treatment, the combined risk ratio for cognitive decline favored treatment by 13% (HR 0.87, 0.76 to 1.00, P=0.045).
These trials included the Perindopril Protection against Recurrent Stroke (PROGRESS) trial, the Systolic Hypertension in Elderly Patients (SHEP) trial, and the Systolic Hypertension in Europe (Syst-Eur) trial.
Because the HYVET trial was stopped earlier than planned after the second interim analysis showed benefits that made it unethical to continue, the mean follow-up for dementia was only 2.2 years (7,400 patient years). Any effect of blood pressure lowering on dementia might take more time to be seen, and 2.2 years might not have been sufficient, the researchers said.
Also, the choice of treatment may have affected the results. Investigators in the Syst-Eur trial, achieved the greatest reduction in dementia with a calcium channel blocker in contrast to the more modest results with other drug types, they said.
The authors noted that the inconclusive findings of the HYVET-COG study may have been a result of short-follow-up, the early termination of the trial, or the modest effect of treatment.
However, they concluded, the meta-analysis with three similar trials showed that the reduction in the risk of dementia associated with lowering blood pressure "might be clinically significant."
In an accompanying comment, Ingmar Skoog, M.D., Ph.D., of Goteburg University in Sweden, pointed out that the results of the HYVET trial, along with findings from other studies, did not increase the risk of dementia or cognitive decline.
This, he noted, contrasts with a belief held by many doctors that treatment of hypertension in the very elderly might have a negative effect on brain function via a reduction in cerebral blood flow.
As for the clinical implications of this study, Dr. Skoog wrote that detecting and treating hypertension in the elderly is important for preventing stroke and total mortality. Therefore, he said, regardless of whether treatment prevents dementia, it is important because it may prevent cardiovascular disease.
Because most people with hypertension or dementia are not detected by the healthcare system, Dr. Skoog wrote, "the importance of diagnosing cognitive impairment in elderly patients with hypertension needs to be emphasized because low cognitive function might have implications for patient compliance."
The study was sponsored by Imperial College London. Salary support was received by Imperial College from academic grants from the British Heart Foundation and the Institute de Recherches Internationales Servier.
Consultancy fees for one co-author were received by Imperial College in 2005 as an academic grant from Servier. Investigator fees to cover the cost of the trial and investigations, such as CT scans, were paid to two researchers by Imperial College. None of the other authors received any financial remuneration.
Dr. Skoog, the Comment author, reported receiving consultancy fees from AstraZeneca and being on the speakers' bureau for Shire, AstraZeneca, Janssen-Cilag, Pfizer, Novartis, Eisai, and Hoechst Marion Roussel.

Primary source: The Lancet NeurologySource reference:Peters R, et al "Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG): a double-blind, placebo controlled trial" The Lancet Neurology 2008; DOI: 10.1016/S1474-4422(08)70143-1. Additional source: The Lancet NeurologySource reference: Skoog, I "Antihypertensive treatment and dementia prevention" The Lancet Neurology 2008; DOI: 10. 1016/S1474-4422(08)70142-x