2021.06.23 07:48
Jean K. Ho et al.
See all authors in the original article.
Originally published, 21 Jun 2021
https://doi.org/10.1161/HYPERTENSIONAHA.121.17049
Hypertension.
Abstract
Hypertension is an established risk factor for cognitive decline and dementia in older adults, highlighting the potential importance of antihypertensive treatments in prevention efforts. Work surrounding antihypertensive treatments has suggested possible salutary effects on cognition and neuropathology. Several studies have specifically highlighted renin-angiotensin system drugs, including AT1-receptor blockers and angiotensin-converting-enzyme inhibitors, as potentially benefiting cognition in later life. A small number of studies have further suggested renin-angiotensin system drugs that cross the blood-brain barrier may be linked to lower dementia risk compared to their nonpenetrant counterparts. The present meta-analysis sought to evaluate the potential cognitive benefits of blood-brain barrier crossing renin-angiotensin system drugs relative to their nonpenetrant counterparts. We harmonized longitudinal participant data from 14 cohorts from 6 countries (Australia, Canada, Germany, Ireland, Japan, United States), for a total of 12 849 individuals at baseline, and assessed for blood-brain barrier crossing potential within antihypertensive medications used by cognitively normal participants. We analyzed 7 cognitive domains (attention, executive function, language, verbal memory learning, recall, mental status, and processing speed) using ANCOVA (adjusted for age, sex, and education) and meta-analyses. Older adults taking blood-brain barrier-crossing renin-angiotensin drugs exhibited better memory recall over up to 3 years of follow-up, relative to those taking nonpenetrant medications, despite their relatively higher vascular risk burden. Conversely, those taking nonblood-brain barrier-penetrant medications showed better attention over the same follow-up period, although their lower vascular risk burden may partially explain this result. Findings suggest links between blood-brain barrier crossing renin-angiotensin drugs and less memory decline.
2021.06.23 07:52
2021.06.23 07:55
Examples of ACE inhibitors include:
2021.06.23 09:27
It sounds very encouraging, Dr. HJ!
Wonder it would be beneficial to change/modify to add one of ACE inhibitors to the antihypertensive medication? BTW, I take losartan, one of the ARB medications.
BB
2021.06.23 09:50
Dear Professor,
You have to choose either ace inhibitor or ARB.
You do not take both. No physician will do that partly for fear of
side effects resulting from over suppression on the renin-angiotensin axis.
It used to be that ARBS were reserved for patients who develop
side effects from ACE inhibitors such as cough, but no longer.
Speaking of taking both ace inhibitors and ARBS, out of my faint memory,
early on there was such a study taking both, it turned out mortality of those
patients were higher compared with either ace inhibitor or ARB alone
on long term study so that treating patients with both agents is said to be
contraindicated.
2021.06.23 10:51
Wow, learned something new, thaaaaanks!
Wonder you guys could dig out more story on a new drug for Alzheimer's patients recently approved
by FDA with such controversy!
Share update information with us if you would.
BB Lee
2021.06.23 11:15
MIND & MOOD
June 08, 2021
On June 7, 2021, the FDA granted accelerated approval to the first drug in 18 years for Alzheimer’s disease. This is welcome news to the 6.2 million Americans and more than 30 million people worldwide with the disease. But does the drug slow down the Alzheimer’s disease process and allow people living with it to keep their memory and other cognitive abilities longer? And is it safe?
Aducanumab (brand name Aduhelm) is a monoclonal antibody engineered in a laboratory to stick to the amyloid molecule that forms plaques in the brains of people with Alzheimer’s. Most researchers believe that the plaques form first and damage brain cells, causing tau tangles to form inside them, killing the cells. Once aducanumab has stuck to the plaque, your body’s immune system will come in and remove the plaque, thinking it’s a foreign invader. The hope and expectation are that, once the plaques are removed, the brain cells will stop dying, and thinking, memory, function, and behavior will stop deteriorating.
Based upon the clinical trials in which it was studied, the drug can be potentially considered for use in individuals with early-stage Alzheimer’s disease. This means individuals who have Alzheimer’s in its mild cognitive impairment or mild dementia stage. Individuals in this early stage of Alzheimer’s may be able to function normally, or they may require a little bit of help with complicated activities like paying bills, grocery shopping, preparing meals, or balancing their checkbook. Individuals who need help with dressing, bathing, or other basic activities would be beyond the early stage and the drug would not be indicated for them.
2021.06.23 11:27
https://www.washingtonpost.com/health/2021/06/22/aducanumab-aduhelm-alzheimers-drug-controversy-/
2021.06.23 19:46
Thanks, Dr. HJ, to add some more information on this new drug with such controversy.
Indeed, I read the article at WAPO before, you kindly added as above but I couldn't figure out how much the removal of amyloid deposition would restore the condition of already damaged cells, and further, I have no idea on the pathogenesis of amyloid deposition, how and why, and the relationship with the cognition ability. So, I wish to learn more about the brain physiology involved in senile dementia as an aging(?) sign I am sure you all share the same interests!
Lately, I by myself started to have such visible deterioration of the memory, especially the names, to make me feel wonder - usually, the memory comes back soon! - why!
Wish to hear more about this imminent problem to old folks like us!
Anxiously,
BB Lee
2021.06.23 20:13
A Neuroscientist Explains Exactly How Awesome Exercise Is for Your Brain
https://www.inc.com/jessica-stillman/exercise-brain-health-mental-well-being-neuroscience.html
Aside from the discussion of Alzheimer's the only thing that is proven to be of help for the decline
of elderly's brain is, as the above neuroscientist says, believed to be exercise, exercise, and exercise
so that our brain doesn't atrophy by making new neurons.
The trouble for the elderly like us is that our total energy level is very much down so that
we get tired easily. If we overdo it, we often get punished one way or another.
So the challenge for every one of us is to listen to our body and mind well and
create an exercise regimen that fits us such as walking multiple times a day.
As a cardiologist, I find it very challenging so I can understand the difficulties other
contemporaries go through.
Perhaps you may get a dog like many of my neighbors
which will make you walk several times a day and keep you busy.
One elderly lady with a good size dog told me she walks 3 times a day with her dog.
My wife and I have a pedometer on our belt all the time and dutifully make sure
we walk a minimum of 7500 steps often with a dumbbell for a power walk in my case.
One latest population study on the subject says that the myth, 10,000 steps a day
is not required. 7500 steps a day gives us the maximum benefit of exercise, it says.
2021.06.24 06:35
Thanks for the good news. I have been on Losartan for a long time.
But can meta analysis give us accurate information?
2021.06.24 07:05
To answer Dr. Ohn's question in the below
Strengths and limitations of meta-analysis: larger studies
may be more reliable
M D Flather 1, M E Farkouh, J M Pogue, S Yusuf
Affiliations expand
Meta-analysis of randomized controlled trials combines information from independent studies that address a similar question to provide more reliable estimates of treatment effects. At the present time, the methodology and usefulness of meta-analysis is under scrutiny. In the first part of this paper, we summarize the limitations of meta-analysis and make suggestions for improvements. In the second part, we illustrate strengths and limitations using examples of meta-analyses and subsequent large trials that address the same question. We develop the hypothesis that the size of the meta-analysis may be a useful measure of reliability. Small meta-analyses (i.e., those with less than 200 outcome events) may only be useful for summarizing the available information and generating hypotheses for future research. The results of small meta-analyses should be regarded with caution, even if the p value shows extreme statistical significance. Larger meta-analyses (i.e., those with several hundred events) are likely to be more reliable and may be clinically useful. Well-conducted meta-analyses of large trials using individual patient data may provide the best estimates of treatment effects in the cohort overall and in clinically important subgroups.
“These findings represent the most powerful evidence to-date linking brain-penetrant ACE-inhibitors and angiotensin receptor blockers to better memory. It suggests that people who are being treated for hypertension may be protected from cognitive decline if they medications that cross the blood-brain barrier,” said study co-investigator Jean K. Ho, PhD, a postdoctoral fellow at the University of California, Irvine, in the aforementioned statement.
Examples of ARBs include: