Blood pressure treatment, regardless of medication
class, was tied to lower dementia and Alzheimer's disease risk in
hypertensive people, a meta-analysis showed.
Among people with high blood pressure -- defined as systolic
pressure of ≥140 mm Hg, or diastolic pressure ≥90 mm Hg -- those who
used any of five major classes of antihypertensive drugs, singly or in
combination, had 12% less risk for dementia and 16% less risk for
Alzheimer's disease than those not using blood pressure medication,
reported Lenore Launer, PhD, of the National Institute on Aging at the
NIH in Baltimore, and colleagues.
There were no differences between one drug class versus all others on the risk of dementia, they reported in
Lancet Neurology.
And in people with normal blood pressure (systolic pressure <140 mm
Hg and diastolic pressure <90 mm Hg), there was no association
between antihypertensive medication use and incident dementia or
Alzheimer's.
"Dementia is a major health concern and prevention and treatment
strategies remain elusive. Lowering high blood pressure, a known
strategy to prevent cardiovascular disease, has been considered as
candidate intervention to reduce the risk for dementia," Launer said.
"It has also been suggested by experimental and observational studies
that specific classes of anti-hypertensive medications may have a direct
effect on reducing dementia-related brain pathology."
Earlier research showed that angiotensin-converting enzyme
(ACE) inhibitors and angiotensin receptor blockers (
ARBs) may have protective effects against dementia and Alzheimer's disease. The
SPRINT MIND
trial found that aggressively lowering blood pressure in hypertensive
older adults reduced mild cognitive impairment by 19%, but did not
significantly reduce dementia risk.
This
meta-analysis "extends findings of the recent SPRINT MIND trial that
showed lowering blood pressure levels reduced the risk for a combined
dementia and mild cognitive impairment outcome," Launer told
MedPage Today.
"We were able to study the effects of specific medications in a group
of people who did not have elevated blood pressure levels, which has
not been investigated in previous clinical trials," she noted. "Also,
not possible in a trial, we had long-term follow-up data on the
participants, which given the time it takes to develop clinical
dementia, is essential to understanding prevention of the condition."
The meta-analysis included people with multiple co-morbidities and
"their characteristics better reflect the typical person seen in general
medical practices," she added.
In their analysis, Launer and colleagues looked at six large,
longitudinal community-based studies of 31,090 dementia-free adults (age
>55) that had baseline data collected from 1987 to 2008. Mean
participant ages ranged from 59 to 77 and median follow ups ranged from 7
to 22 years.
The
researchers stratified participants into two groups: 15,553 people with
high (systolic ≥140 mm Hg, or diastolic ≥90 mm Hg), and 15,537 people
with normal blood pressure (systolic <140 mm Hg and diastolic <90
mm Hg). Both groups included people on antihypertensive drugs and people
who were not.
The researchers performed a meta-analysis by drug class using
individual participant data, looking at five major classes: ACE
inhibitors, ARBs, beta blockers, calcium channel blockers, and
diuretics. Other drug classes, such as vasodilators or aldosterone
blockers, were not included. Participants were classified as users if
they took medication with or without other antihypertensive drugs.
Throughout the studies, there were 3,728 incident cases of dementia,
including 1,741 incident Alzheimer's disease diagnoses. In fully
adjusted models of the high blood pressure group, people using any
antihypertensive drug had a reduced risk for developing dementia (HR
0.88, 95% CI 0.79-0.98,
P=0.019) and Alzheimer's disease (HR 0.84, 0.73-0.97,
P=0.021), compared with people not using drugs.
In
the high blood pressure group, there were no significant differences
between one drug class versus others on dementia risk, but beta blockers
and diuretics showed a potentially protective effect compared with no
drug use. Also in this group,
APOE ε4 carriers using any antihypertensive medication showed a decreased risk of incident dementia (HR 0.77, 95% CI 0.64-0.93).
In the normal blood pressure group, incident dementia and Alzheimer's
risks were similar in people regardless of whether people were using
antihypertensive drugs. No evidence suggested any single drug class
differed in its association with the outcomes.
Although this meta-analysis could not account for duration of drug
treatment, its findings are supported by a parallel meta-analysis not
yet published, noted Craig Anderson, MD, PhD, and Ruth Peters, PhD, both
of the University of New South Wales in Sydney, Australia, in an
accompanying editorial.
In the parallel study, which required a minimum drug class exposure
of 12 months, "a similar neutral effect for specific drug classes was
found for both dementia and cognitive decline, consistent in subgroup
analyses in which individuals with only a few years of follow-up were
excluded to minimize reverse causality," they wrote. "A similar signal
for a protective effect of diuretic-based blood pressure lowering was
also seen in some of the analyses."
This
research had other limitations, the investigators noted. Some subgroups
contained few cases, such as the ARBs users in the high blood pressure
group. The analysis could not evaluate the effect of change in blood
pressure and dementia risk. Misclassification may have occurred "in the
grey area between mild cognitive impairment and mild dementia," the
authors pointed out, as well as residual confounding.
Last Updated November 11, 2019
Disclaimer
The study funded by the Alzheimer's Drug Discovery Foundation and the National Institute on Aging Intramural Research Program.
Launer and co-authors disclosed no relevant relationships with industry.
Peters
and Anderson disclosed relevant relationships with the National Health
and Medical Research Council of Australia, Takeda China, Boehringer
Ingelheim, and Amgen.
Primary Source
Lancet Neurology
Secondary Source
Lancet Neurology
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