Didn't your doctor use this on you years ago?
generic drug candesartan (brand name: ATACAND®) Blood Pressure Drug Helps Alzheimer's June 2018
Can Managing Blood Pressure Slow Alzheimer's Disease?
SPRINT MIND imaging findings muddy the picture
Aggressively lowering blood pressure in hypertensive older adults did not consistently affect Alzheimer's imaging biomarkers, a substudy of SPRINT MIND participants showed.
MRI markers of Alzheimer's disease -- regional atrophy, cerebral blood flow, and mean fractional anisotropy -- were similar over 4 years whether patients had standard or aggressive blood pressure treatment, reported Ilya Nasrallah, MD, PhD, of University of Pennsylvania, and co-authors.
However, intensive blood pressure treatment was associated with a small but statistically significant larger decrease in hippocampal volume (mean difference -0.033 cm3, 95% CI -0.062 to -0.003, P=0.03), they wrote in JAMA Neurology.
"As vascular disease and Alzheimer's disease are the most common causes of cognitive decline in people of the age of those in the SPRINT study, we wanted to see whether brain biomarkers that are sensitive to these diseases could give a hint at whether either process was affected positively or adversely by the intervention," Nasrallah said.
"In short, we did not find a consistent difference between the two groups in measures of Alzheimer's disease or vascular disease, and all differences were of small magnitude," he told MedPage Today.
A 4-year study is relatively short in terms of the time courses of both diseases, Nasrallah pointed out. "There were small differences in biomarkers of brain health between the SPRINT treatment arms, but none likely clinically meaningful in the time frame of the study," he said.
SPRINT MIND was a substudy of the NIH-funded Systolic Blood Pressure Intervention Trial (SPRINT), which aimed to determine whether aggressively lowering blood pressure could protect the heart, kidneys, and brain over 5 years. The success of the heart disease portion -- which raised questions about trial design and how results should be applied -- led to the study's early termination.
In 2019, SPRINT MIND findings showed that treating hypertensive older adults to a systolic blood pressure goal of <120 mm Hg, compared with treating them to a goal of <140 mm Hg, reduced the risk of probable dementia by 17%, a statistically non-significant difference (HR 0.83, 95% CI 0.67-1.04). Intensive blood pressure control showed statistically significant benefits in secondary outcomes, including a 19% lower rate in mild cognitive impairment (HR 0.81, 95% CI 0.69-0.95).
The imaging substudy involved 454 SPRINT MIND participants who had a follow-up MRI at a median of 3.98 years after randomization. The researchers used MRI measurements that were sensitive but not specific to Alzheimer's neurodegeneration and white matter tract changes; amyloid and tau biomarkers were not available.
Participants were dementia-free at baseline; they had systolic blood pressure levels between 130 and 180 mm Hg at the screening visit and increased cardiovascular risk. Median baseline age was 67, 40% were women, and 32% were Black. Final follow-up was in July 2016.
Cognitive testing in the substudy showed that longitudinal declines across all cognitive domains were small. Intensive treatment was associated with larger declines in executive function (mean change per year -0.019, 95% CI -0.034 to -0.005, vs 0.005, 95% CI -0.011 to 0.02, P=0.02), but other cognitive domains showed no significant between-group differences.
The MRI substudy sample included only 5% of the participants of the main study, and the reduced mild cognitive impairment incidence with intensive hypertension control reported in the main study was not replicated in the smaller group, noted Susan Landau, PhD, and Theresa Harrison, PhD, both of the University of California Berkeley, in an accompanying editorial.
"Insufficient statistical power is a likely explanation, along with reported differences in the MRI subsample (younger, more likely to be female, less likely to be Hispanic, lower systolic blood pressure, higher cognitive function) compared with the larger SPRINT MIND sample," they wrote.
But these differences may have reduced the likelihood of detecting brain changes in the MRI sample, Landau and Harrison pointed out. While the researchers "examined well-validated MRI biomarkers that perform well in differentiating Alzheimer's disease from healthy controls," it's not clear how much Alzheimer's-related neurodegeneration would be expected in this relatively young and unimpaired group, they observed.
Other findings in this imaging substudy, like hippocampal atrophy, also raise questions about the statistical power and representativeness of the subsample, they added: "The fact that these associations were examined in different subsamples with varying representativeness of the main trial cohort adds to the complexity of interpretation."
In addition, there was no ascertainment of amyloid or tau status or clinical categorization of dementia subtype, further limiting the findings, Nasrallah and co-authors said. Because early Alzheimer's-related neurodegeneration develops slowly, the 4-year follow-up period may have been too short, they added.
Disclosures
SPRINT was funded by the NIH and supported in part by the U.S. Department of Veterans Affairs. This analysis also had funding from the Alzheimer's Association.
Researchers reported relationships with Biogen, Alzheimer's Association, UpToDate, Merck, Eli Lilly, Functional Neuromodulation DSMB, Neuronix Consultation, and Galileo CDS.
The editorialists have received grants from the NIH and the U.S. Department of Defense.
Primary Source
JAMA Neurology
Secondary Source
JAMA Neurology
Source Reference: Landau S, Harrison T "A link between cardiovascular risk management and Alzheimer disease is still elusive" JAMA Neurol 2021; DOI: 10.1001/jamaneurol.2021.0083.
Brian McMillen
March 9, 2021
Often
the aggressive treatment to get values to low values, diastolic <120
mm Hg, does more damage than a more modest goal. That has been the
case with type 2 diabetics, an A1c level below 8 is good, but treatment
to achieve “normal” below 6 results in new pathologies.
I think of greater interest is the repeated findings that those perils
and Spartans that cross into the brain greatly reduce the incidence of
AD. Thus, lisinopril, but not enalapril, crosses into the brain and is
associated with lowered rates of AD. Ditto for losartan. There is a
group of neurons in the hypothalamus that project to the hippocampus,
part of the Papez circuit, that use angiotensin as one of their
neurotransmitter/modulator substances. That leads one to suggest that
if hypertension develops during a patient’s 40’s or 50’s, then one of
these drugs should be used as a preferred treatment. When a patient is
finally diagnosed with AD, more than a billion neurons are gone and
there is no putting them back.
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