#522

Blood pressure and the brain: the conundrum of hypertension and dementia 2025

Many studies have begun to examine the cumulative burden of hypertension in late life through examination of younger to middle-aged adults. In the Coronary Artery Risk Development in Young Adults (CARDIA) study, every 5 mmHg increment in time-weighted average (TWA) of SBP in young adults is associated with approximately 1-year greater brain age. Likewise, participants with TWA BP over the recommended guidelines (SBP <120 mmHg, DBP <80 mmHg) had on average 3-year greater brain age compared to age peers with healthy BP.24 Additionally, individuals with moderate to increasing BP trajectories were more likely to have higher abnormal WM volume and/or lower grey matter CBF.25
In more recent years, the findings from the SPRINT-MIND trial have received considerable attention showing that intensive BP control (<120 mmHg) did not significantly reduce the risk of probable dementia as compared to standard BP control (<140 mmHg) in individuals with hypertension, but did find that intensive BP treatment reduced the risk of mild cognitive impairment (MCI) and the combined rate of MCI or probable dementia.
More comprehensive evidence came from a recent meta-analysis of 14 clinical trials (96 158 participants), including SPRINT-MIND,45 which found that BP lowering with anti-hypertensive medication compared to control was associated with a lower risk of dementia or cognitive impairment, although with a very small absolute risk reduction (0.39%).
Beyond the broad potential effects of anti-hypertensive medications, it is important to further explore whether certain class-specific anti-hypertensive drugs show a more beneficial effect in reducing dementia risk and if different effects of different drugs might explain the inconsistent trial results (SPRINT-MIND, for instance, allowed all anti-hypertensive drugs). […] A recent meta-analysis also concluded that angiotensin II receptor blockers, along with calcium channel blockers, could significantly reduce dementia risk.51 A drug’s ability to cross (vs. not cross) the blood–brain barrier (BBB) is also likely to impact its role in reducing cognitive decline: BBB-penetrant renin–angiotensin drugs appear to reduce cognitive decline in older adults with normal cognition more than do drugs that are not BBB penetrant.
Hypertension makes the BBB leaky
One of the outstanding questions in the field is whether hypertension-induced BBB leakage is involved in the initiation of dementia or is a consequence of the complex neurovascular pathology.150 The answer remains unclear, but many studies have used young hypertensive animals to study this mechanism. Findings have shown a higher BBB leakage in cardiovascular regulatory regions in young hypertensive rats compared to normotensive controls.

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#523

Nebivolol gives me crazy nightmares if i take it after 6:00pm so I’m thinking about taking it in the morning then carvedilol afternoon to see how it works out :thinking:

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#524

Beta blockers can mess up with melatonin and trigger RBD ( https://academic.oup.com/sleep/article/45/Supplement_1/A346/6592654 ). Why are you using a beta blocker? They’re not the first line treatment for blood pressure and they come with many issues (glycemic dysregulation being another one).

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#525

I went to my yearly checkup yesterday and blood pressure was 108/68 !! The nurse checked several times and also several times during my stress test. Afterward the doc wanted to know if I was on something to increase my NO. I said just celery and he shook his head. Also I was still conversational after 15 minutes of BRUCE protocol and my heart rate was 140. It took me till I got home to think what the difference might be. I’m pretty sure it was the chelation, which has been shown to lower blood pressure.

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#526

Are you taking minoxidil? Other medicine?

#527

I’ve never taken anything for BP. All my drugs are for getting rid of glucose. Acarbose rarely with carbs because I rarely have many carbs. Empag just to use them up because this drug wears me out. I’m going back on Dapag as soon as I order again. And Colchicine.

Pioglitazone and Bempedoic acid are both bad for all cause mortality. And Pio does seem to interfere with Rapa in ways I don’t understand. So though I have them I don’t take them for now.

#528

ADHD is a chronic neurodevelopmental disorder that significantly affects life outcomes, and current treatments often have adverse side effects, high abuse potential, and a 25% non-response rate, highlighting the need for new therapeutics. This study investigates amlodipine, an L-type calcium channel blocker, as a potential foundation for developing a novel ADHD treatment by integrating findings from animal models and human genetic data. Amlodipine reduced hyperactivity in SHR rats and decreased both hyperactivity and impulsivity in adgrl3.1−/− zebrafish. It also crosses the blood-brain barrier, reducing telencephalic activation. Crucially, Mendelian Randomization analysis linked ADHD to genetic variations in L-type calcium channel subunits (α1-C; CACNA1C, β1; CACNB1, α2δ3; CACNA2D3) targeted by amlodipine, while polygenic risk score analysis showed symptom mitigation in individuals with high ADHD genetic liability. With its well-tolerated profile and efficacy across species, supported by genetic evidence, amlodipine shows potential to be refined and developed into a novel treatment for ADHD.

Validation of L-type calcium channel blocker amlodipine as a novel ADHD treatment through cross-species analysis, drug-target Mendelian randomization, and clinical evidence from medical records 2025

Is there any other traditional longevity drugs (e.g BP lowering) with effects on e.g cognition for ADHD, depression, or schizophrenia (all are genetically correlated)?

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#529

The devil is in the details when it comes to BA and all cause mortality as well as cardiovascular mortality depending on the group treated. It is better for primary than secondary prevention. Elevated gout and renal problems. Polypharmacy indicated, seems to me.

For pioglitazone, it’s pretty clear that ACM is lower in treated diabetics, but of course off label use (such as folks here might use) is less studied. I certainly wouldn’t take it with rapamycin, but otherwise would consider short term treatment (a few months) for specific goals. And while caution advised while on rapamycin, polypharmacy seems helpful in combination with SGLT2i like empagliflozin. YMMV.

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#530

Statistical illiteracy is also bad for all cause mortality.

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#531

I have a rule that if I laugh at a post I have to like it, no matter why. Laughter increases both healthspan and lifespan, this is important.

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#532

Interesting regarding amlodipine. I’m taking it and didn’t notice any benefits other than BP lowering.

Other interesting ones:

  • Telmisartan
  • Lithium orotate
  • Selegiline
  • SGLT2i
  • Rapa + ketamine

See: 抑郁症和心理健康：你用什么？

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#533

@DrFraser and others - My SBP tends to vacillate between 115 (resting) and 138 (after moderate exercise - like walking quickly (rushing)) while my DBP and heart rates are static at 80-81. Do you think it makes sense to add amlodipine 5 mg to reduce both resting and non-resting SBP?

I just did a test at the doctor’s office where I was rushing to get there and 5 minutes after arriving my SBP was 138. I waited in the office for about 15-30 minutes while resting and my SBP dropped to 115 on a re-test. Do you think the Dr.'s BP machine is defective due to the large variance? Thank you in advance.

This is why that 23 mm HG variance worries me…

Is a Fluctuating Blood Pressure Serious?

Normal variations may differ by person. However, large variations may indicate a health condition. One study looked at patients taking blood pressure medicine. They found variations of more than 14 mm Hg in systolic pressure were associated with a 25% increased risk of heart failure.11

#534

I don’t have a link handy to studies, but here’s an article on orthostatic hypertension. IMO the answer here is more widespread use of 24 hour blood pressure monitors to see trends throughout the day. I’m not aware of any studies that have linked 24 hour blood pressure readings to risk, however.

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#535

There’s a growing body of evidence showing that blood pressure variability (intra day or between days) is as important if not more than BP readings at a certain point in time.

For instance from the 2024 Lancet report on dementia prevention: Dementia Prevention - 2024 report of the Lancet standing Commission - #5 by adssx

These meta-analyses did not cover blood pressure variability, but a cohort study (n=2234; aged ≥65 years) measured blood pressure variability with assessments over 3, 6, 9, and 12 years and reported that each unit increase in systolic variability was associated with increased risk of dementia, with HRs ranging from 1·02 (95% CI 1·01–1·04) to 1·10 (1·05–1·16).

See also:

It seems that long-acting CCBs (e.g. amlodipine), ARBs (e.g. telmisartan), and diuretics (e.g. indapamide SR) are best to control BPV. (While beta-blockers make it worse!)

Does this mean that you should add amlodipine @DeStrider? I don’t know. What’s your current telmisartan dose?

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#536

I’m currently taking 40 mg of telmisartan daily.

#537

I created a topic on BPV: Blood pressure variability (BPV)

@DeStrider: I would increase telmisartan to 80 mg, it won’t change much the BP but it might improve the BPV and insulin resistance a bit. If you think that’s still not enough then you can add amlodipine 2.5 mg and see.

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#538

If tolerated (and agreed to by your doctor) increasing telmisartan to 80 mg for those who have enough BP to do so is often advised as the Gamma-PPAR action doesn’t have much effect at 40 mg, but does at 80 mg.

Now in regard to BP measuring - 24 hour Ambulatory Measuring is the Gold Standard. Getting a large amount of data, including overnight is important to predict risk.

Here is a brief review and sources from Vera-Health.ai

24-hour ambulatory blood pressure monitoring (ABPM) is a valuable tool in the diagnosis and management of hypertension. It provides a comprehensive assessment of blood pressure (BP) over a full day, capturing variations that might not be detected during a single office visit. This method is particularly useful for identifying white-coat hypertension and masked hypertension, conditions where BP readings differ significantly between clinical settings and daily life16,14.

ABPM is superior to office BP measurements in predicting cardiovascular outcomes and organ damage, such as left ventricular hypertrophy [2]. It provides insights into nocturnal BP patterns, which are crucial for assessing cardiovascular risk. For instance, a non-dipping BP pattern, where BP does not decrease at night, is associated with higher cardiovascular risk 6.

The use of ABPM can improve diagnostic accuracy and risk stratification, leading to better management of hypertension. It is particularly beneficial in primary care settings, where it can reduce healthcare costs by preventing unnecessary treatment in cases of white-coat hypertension 16.

In summary, 24-hour ABPM is a critical tool for accurate BP assessment, offering significant advantages over traditional office measurements. It enhances the detection of hypertension subtypes and provides valuable prognostic information, ultimately contributing to more effective hypertension management.

References

  1. To compare 24 hour blood pressure values of a conventional 24 hours ambulatory blood pressure device versus a wristband using an artificial intelligence algorithm based on photophletysmography
    European Heart Journal
    Ronner et al.
    Initial evidence is demonstrated supporting the accuracy of the evaluated wrist-worn PPG-based device in measuring 24-hour as well as day- and nighttime BP, which can provide an accurate and more patient friendly alternative to ABPM.

  2. Lessons to be learned from 24-hour ambulatory blood pressure monitoring.
    Kidney international. Supplement Mancia et al.1996
    Evidence of the clinical relevance of 24-hour ambulatory blood pressure monitoring data are scanty, but the results of a recent prospective study have clearly shown the superiority of average 24 hour, daytime and nighttime blood pressure values over clinical readings in predicting the regression of left ventricular hypertrophy in treated hypertensive patients.

  3. Home Blood Pressure Measurements Will Not Replace 24-Hour Ambulatory Blood Pressure Monitoring HYPERTENSION Verdecchia et al.
    The present review holds the position that 24-hour ABP should not be replaced by home BP because of its unequivocal superiority under several diagnostic and prognostic aspects.

  4. Ambulatory Arterial Stiffness Index Derived From 24-Hour Ambulatory Blood Pressure Monitoring
    HYPERTENSION Li et al. 2006
    AASI is a new index of arterial stiffness that can be easily measured under ambulatory conditions and is probably normal values of AASI are probably <0.50 and 0.70 in young and older subjects, respectively.

  5. Efficacy of Once-Daily Urapidil Treatment in Mild or Moderate Essential Hypertension Assessed by Ambulatory 24-Hour Blood Pressure Monitoring Drugs Trimarcö et al.
    During long term therapy, the tolerability but not the efficacy of urapidil appears to be directly related to its peak serum concentrations, which is in contrast to previous studies which have shown that tolerability and efficacy are related to each other.

  6. Usefulness of Blood Pressure Variability Indices Derived From 24‐Hour Ambulatory Blood Pressure Monitoring in Detecting Autonomic Failure
    Journal of the American Heart Association : Cardiovascular and Cerebrovascular Disease
    Lodhi et al.
    20 citations
    2019
    Daytime SD of SBP is a better screening tool than nondipping status in detecting autonomic dysfunction and was significantly higher in patients with ATF than in controls in both discovery and validation cohorts.

Open Access
Influential Journal
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7. Clinical and Epidemiological Implications of 24‐Hour Ambulatory Blood Pressure Monitoring for the Diagnosis of Hypertension in Kenyan Adults: A Population‐Based Study
Journal of the American Heart Association : Cardiovascular and Cerebrovascular Disease
Etyang et al.
19 citations
2016
Screening BP measurement significantly overestimated hypertension prevalence while failing to identify ≈50% of true hypertension diagnosed by ABPM, suggesting significant clinical and epidemiological benefits of ABPM use for diagnosing hypertension in Kenyan adults.

Open Access
Influential Journal
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8. Sleep‐Disordered Breathing and 24‐Hour Ambulatory Blood Pressure Monitoring in Renal Transplant Patients: Longitudinal Study
Journal of the American Heart Association : Cardiovascular and Cerebrovascular Disease
Mallamaci et al.
7 citations
2020
In renal transplant patients, worsening SDB associates with a parallel increase in average 24‐hour, daytime, and nighttime systolic BP, compatible with the hypothesis that the link between SDB and hypertension is causal in nature.

Open Access
Influential Journal
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9. Accuracy of 24-hour ambulatory blood pressure monitoring by a novel cuffless device in clinical practice
Heart
Krisai et al.
28 citations
2018
In clinical practice over 24 hours, there was a significant difference between the TestBP and RefBP with higher systolic and diastolic BP measured with the cuffless PTT device.

Influential Journal
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10. 24-hour blood pressure control by once-daily administration of irbesartan assessed by ambulatory blood pressure monitoring. Irbesartan Multicenter Investigators’ Group.
Journal of Hypertension
Fogari et al.
49 citations
1997
All irbesartan regimens significantly reduced mean 24 h ADBP and ambulatory systolic blood pressure, and were well tolerated.

Influential Journal
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11. Evaluation of the antihypertensive effect of once-a-day trandolapril by 24-hour ambulatory blood pressure monitoring. The Italian Trandolapril Study Group.
American Journal of Cardiology
Mancia et al.
31 citations
1992
The aim of this study was to evaluate the effects of trandolapril on 24-hour blood pressure in patients with mild-to-moderate essential hypertension, and the differences between the lower treatment, versus the higher pre- and post-treatment, values were all statistically significant.

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12. Hemodynamic profiles of arterial hypertension with ambulatory blood pressure monitoring
Hypertension Research
Aristizábal-Ocampo et al.
5 citations
2023
The hemodynamic profiles of different hypertension (HT) subtypes derived from a new method for total arterial compliance (Ct) estimation in a large group of individuals undergoing 24 h ABPM are described.

Open Access
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13. Comparison of Optimal Diagnostic Thresholds of Hypertension With Home Blood Pressure Monitoring and 24-Hour Ambulatory Blood Pressure Monitoring
American Journal of Hypertension
Park et al.
19 citations
2017
Lowering the diagnostic thresholds of HBP measurement from 135/85 mm Hg to 130/80 mm HG to improve diagnostic accuracy for hypertension is suggested.

Open Access
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14. Prevalence of Masked Hypertension: a Population-Based Survey in a Large City by Using 24-Hour Ambulatory Blood Pressure Monitoring
Korean Circulation Journal
Rhee et al.
12 citations
2016
The estimated prevalence of hypertension by 24-hour ABPM was higher than that by CBPM, revealing high prevalence of masked hypertension, which supports the adoption of ABPM in the national population survey and clinical practice to improve public health and reduce health care costs.

Open Access
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15. Current status of ambulatory blood pressure monitoring in Asian countries: A report from the HOPE Asia Network
The Journal of Clinical Hypertension
Shin et al.
31 citations
2019
It was found that ABPM use was very limited in primary care settings and almost exclusively available in referral settings, and HBPM could be a reasonable alternative.

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16. Diagnostic value and cost-benefit analysis of 24 hours ambulatory blood pressure monitoring in primary care in Portugal
BMC Cardiovascular Disorders
Pessanha et al.
16 citations
2013
In PC, the widespread use of ABPM in newly diagnosed HTs increases diagnostic accuracy of hypertension, improves cardiovascular risk stratification, reduces health expenses showing a highly favourable benefit-cost ratio vs a strategy without ABPM.

Open Access
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17. Comparison of Ambulatory Tonometric and Oscillometric Blood Pressure Monitoring in Hypertensive Patients
Integrated Blood Pressure Control
Hornstrup et al.
6 citations
2020
The BPro device for tonometric monitoring of BP and classification of hypertension and non-dipping in patients diagnosed with hypertension leads to misclassification of patients, and is not suitable for clinical practice in hypertensive patients from a Renal Outpatient Clinic.

Open Access
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18. Accuracy and User Acceptability of 24-hour Ambulatory Blood Pressure Monitoring by a Prototype Cuffless Multi-Sensor Device Compared to a Conventional Oscillometric Device
Blood Pressure
Heimark et al.
3 citations
2023
It is demonstrated that a general PAT-based BP model had unsatisfactory agreement with ambulatory BP during 24ABPM, especially during nighttime, and pulse arrival time alone can be used to estimate blood pressure accurately during 24-hour ambulatory blood pressure monitoring.

Open Access
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19. Ambulatory blood pressure monitoring in treated patients with hypertension in the COVID-19 pandemic - The study of European society of hypertension (ESH ABPM COVID-19 study).
Blood Pressure
Wojciechowska et al.
7 citations
2023
The impact of a COVID-19 pandemic on blood pressure control and the quality of medical care is identified in order to develop the strategy to control cardiovascular risk factors during unpredictable global events.

Open Access
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20. Comparison of automated office blood pressure measurement with 24-hour ambulatory blood pressure measurement
Blood Pressure
Peeters et al.
6 citations
2022
It is concluded that 30–60 min AOBP measurements cannot replace a 24-h ABPM and it is proposed to perform 24-H ABPM at least on a yearly basis to confirm A OBP measurements.

Open Access

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#539

One approach you might consider is to reduce BP as much as possible without side effects. In particular, light headedness. This is of course not without risk, as you don’t want to have an unexpected fall should your situation change.

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#540

I’ll be increasing Telmisartan to 80 mg starting this summer. I’ll also start taking Tadalafil. Hopefully, both will reduce my BP to the optimal range with less BPV.

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#541

Following up on this paper: Intensive Blood-Pressure Control in Patients with Type 2 Diabetes 2024

Findings with respect to fatal or nonfatal myocardial infarction, treatment or hospitalization for heart failure, and death from cardiovascular causes were similar in the treatment groups. Death from any cause occurred in 169 patients (0.69 events per 100 person-years) in the intensive-treatment group and in 179 patients (0.73 events per 100 person-years) in the standard-treatment group (hazard ratio, 0.95; 95% CI, 0.77 to 1.17) (Table 2 and Table S7).
Unlike the SPRINT trial, we did not observe a between-group difference with regard to death from any cause, for which the incidence rate was lower in our trial than in the SPRINT trial; however, the incidence rate in our trial was similar to that in other trials that tested systolic blood-pressure treatment targets in the Chinese population.
Treatments used:

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Good evidence in favor of 120 mmHg! I think the results would be even better if everyone was on ACEi or ARB (instead of giving everyone a CCB).