No Effect of Intensive BP Lowering on Biomarkers of Dementia

Intensive reducing of blood strain (BP) in older sufferers with hypertension doesn’t seem to scale back the danger for the prevalence of mind biomarkers which were linked to mild cognitive impairment (MCI) or Alzheimer’s disease (AD) and will even enhance the danger, a brand new imaging examine suggests.

Using mind MRI, investigators discovered a small however statistically vital lower in hippocampal quantity in sufferers who underwent intensive remedy to decrease BP compared with sufferers who underwent commonplace remedy to decrease BP. There have been no vital variations in different AD mind biomarkers.

“We investigated imaging biomarkers of AD and vascular illness within the mind utilizing MRI. In temporary, whereas numerous particular person measures appeared extra favorable in a single group or one other, we didn’t see a constant impact or any group distinction that’s prone to be vital within the 4-year time-frame,” examine investigator Ilya Nasrallah, MD, PhD, assistant professor of radiology on the Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, informed Medscape Medical News.

The examine was published online March 8 in JAMA Neurology.

Hallmark Biomarker

The present examine was a secondary evaluation of findings from the SPRINT MIND trial, a big randomized trial that had discovered much less development of white matter lesions in those that had acquired extra intensive BP management, in comparison with those that had acquired commonplace remedy, Nasrallah stated.

White matter lesions are a biomarker for cerebrovascular damage. Other research have had comparable findings, however “different mechanistic markers of cognitive impairment and dementia have but to be explored,” the authors notice.

Although earlier analysis had discovered that treating hypertension might cut back the incidence of AD, it’s “unclear whether or not this may very well be a direct impact on AD-related neurodegeneration or comorbid vascular pathology,” the investigators write. The neurodegeneration of AD leads to mind atrophy specifically mind areas, they notice.

“Biomarkers measuring these modifications could also be extra delicate to early AD-related change than downstream cognitive or medical variables, resembling incident dementia,” they write.

The most generally studied MRI biomarker for AD-related mind change is hippocampal atrophy, a “hallmark of typical gentle cognitive impairment and AD,” though areas aside from the hippocampus could also be implicated as nicely, the authors notice.

In addition to hippocampal atrophy, new analysis has recognized “patterns of AD-like atrophy that always have reported increased sensitivity and specificity than hippocampal atrophy,” the authors notice. The Spatial Pattern of Abnormality for Recognition of Early Alzheimer’s Disease (SPARE-AD) assigns a single international rating that’s primarily based on general similarity of the mind to an AD sample compared with the conventional mind and consists of different areas as nicely.

Moreover, “previous to SPRINT, there was consensus that treating hypertension was useful; nonetheless, there was no consensus on whether or not intensive remedy would add additional profit or would possibly itself trigger hurt,” Nasrallah added.

Short Time Frame

Participants with hypertension, no historical past of diabetes, however elevated cardiovascular threat (n = 673; imply [SD] age, 67.3 [8.2] years; 40.3% girls; 32.4% Black) underwent baseline MRI; 454 contributors accomplished the follow-up MRI roughly 4 years after randomization.

In the full pattern, the imply systolic BP was 138.1 [16.7] mm Hg; the imply diastolic BP was 77.9 [11.5] mm Hg.

At baseline, 6.4% of contributors had constructive SPARE-AD scores, indicating a “sample extra AD-like than regular.” The remaining contributors had adverse SPARE-AD scores. Among older contributors (≥75 years), baseline hippocampal volumes have been decrease and SPARE-AD scores have been worse compared with youthful contributors. Lower hippocampal quantity was related to increased SPARE-AD rating.

Participants within the intensive remedy group skilled bigger declines in imply hippocampal quantity in the course of the follow-up interval, in contrast with these in the usual remedy group.

The between-group distinction in change was -.033 cm³ (−0.062 to −0.003; P = .03).

There have been no vital variations within the remedy group with regard to measures of AD regional atrophy, cerebral blood movement, or imply fractional anisotropy, and there have been no variations in SPARE-AD rating.

Changes in most AD-related biomarkers have been better in older adults compared with sufferers aged <75 years — specifically, hippocampal volumes have been smaller and SPARE-AD scores have been increased.

Nasrallah famous that discovering a clinically vital, constant impact or group distinction is “unlikely” within the 4-year time-frame of the SPRINT-MIND examine.

“Unfortunately, it is arduous to make a examine lengthy sufficient to match the time scale of AD and vascular illness, which progress over many years, however, briefly, we do not see that differential results on both pathology level to a transparent profit for mind well being or for any clear adversarial threat for the intensive remedy,” he stated.

He defined that the SPRINT-MIND trial didn’t present an affiliation between decrease threat for MCI/dementia and extra intensive antihypertensive remedy compared with commonplace antihypertensive remedy.

However, the trial did present profit in lowering charges of deadly and nonfatal main cardiovascular occasions and demise from any trigger, and it was stopped early.

“SPRINT confirmed a transparent discount in cardiovascular morbidity within the intensive group, which is the explanation the trial was stopped early. So it could be that intensive remedy reduces the incidence of MCI/dementia by eradicating systemic illness boundaries that in any other case would possibly intervene with affected person practical talents,” Nasrallah instructed.

“Elusive” Link

Commenting on the examine for Medscape Medical News, Susan Landau, PhD, a analysis scientist on the Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, California, described the hyperlink between cardiovascular risk management and AD as “elusive.”

Landau, who’s the coauthor of an accompanying editorial and was not concerned with the examine, stated, “Reducing cardiovascular occasions seems to be the important thing profit of intensive hypertension management.”

The SPRINT-MIND examine “doesn’t level to an additional extra profit of intensive hypertension management in sustaining cognitive operate or in lowering the danger of Alzheimer’s illness,” stated Landau.

The Systolic Blood Pressure Intervention Trial was funded by the National Institutes of Health (together with the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; the National Institute on Aging; and the National Institute of Neurological Disorders and Stroke. It was additionally supported partially with sources and use of services via the US Department of Veterans Affairs and the Alzheimer’s Association. Additional sources of funding are listed on the unique article. Nasrallah acquired grants from the National Institutes of Health in the course of the conduct of the examine and private charges from Biogen outdoors the present examine. The different authors’ disclosures are listed on the unique article. Landau has acquired grants from the National Institutes of Health and the US Department of Defense. Theresa M. Harrison, PhD, coauthor of the editorial, has disclosed no related monetary relationships.

JAMA Neurology. Published on-line March 8, 2021. Abstract, Editorial

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