Preventing Dementia and Blood Pressure Control

 

A paper came out last week (1) that showed blood pressure control was an effective way to prevent dementia.  One of the most effective ways to prevent stroke is to control blood pressure.  Elevated blood pressure also causes blood vessel damage that can lead to dementia – even in the absence of a clearcut stroke. In one of my clinics, we assessed people with various forms of dementia and it was striking how many people had these kinds of changes on their CT or MRI scans and were unaware of them. In some cases, there was a history of uncontrolled blood pressure like eclampsia during pregnancy that probably resulted in brain changes seen decades later that was not investigated at the time.  Substance use problems, undiagnosed forms of transient hypertension, and substance use problems with intoxication and withdrawal associated hypertension are other possibilities.

The study in question was an interventional study across 163 villages in China and a total of 33,995 research subjects. Inclusion criteria into the study was ≥40 years of age with a mean untreated SBP ≥140 mm Hg and/or a DBP ≥90 mm Hg (or ≥130 mm Hg and/or ≥80 mm Hg among those with clinical CVD, diabetes or chronic kidney disease) or a mean treated SBP ≥130 mm Hg and/or a DBP ≥80 mm Hg, based on six measurements taken on two different days. Additional details are available in the paper on online supplementary information.  Patients were treated across the study by physician supervised non-physician community healthcare providers (NPCHPs).  Research subjects were randomized into treatment as usual (TAU) or non-protocol-based treatment for hypertension and protocol-based care. In the protocol-based care patients received first line antihypertensives like angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), and diuretic or diuretic-like medications. The treatment group also got free blood pressure medication, lifestyle coaching, and home blood pressure monitors but the TAU group did not.

The primary outcome measures for this intervention study were the presence of dementia and cognitive impairment no dementia (CIND).  Both diagnoses were made by expert panels of neurologists using standardized criteria.  Screening tests were administered at clinic visits to assess cognition, instrumental activities of daily living, and symptoms of dementia in a standard way. 

On the main outcome measures the blood pressure intervention group had a 15% lower risk of dementia and a 16% lower risk of CIND compared with the TAU group.  Those numbers are consistent with an additional meta-analysis done by the authors of similar trials and a previous meta-analysis of blood pressure interventions to prevent dementia.

Strokes are the usual obvious consequences of blood pressure problems and they come in two forms – hemorrhagic and ischemic. Hemorrhagic strokes generally occur through a ruptured blood vessel in the substance of the brain or the subarachnoid space.  Because blood is under very high pressure in the brain that jet can cause additional damage.  In many cases clots form and they can be associated with edema and pressure in the brain. Symptoms can vary from an intense headache to signs of cerebral edema or coma and death.  Ischemic strokes consist of blood vessel occlusion or reduced blood flow to the point that there is inadequate blood supply to neurons. This can occur as the result of ruptured plaques, emboli, or mechanical disruption of the blood vessel.  The emboli can be the result of plaque formation in blood vessels as well as blood clots due to other diseases like atrial fibrillation.  Atrial fibrillation can also be caused by hypertension.

During my teaching seminars on dementia and vascular subtypes – I generally taught about vascular subtypes as cortical or parenchymal infarctions due to major blood vessels (yellow areas on the above diagram), lacunar infarctions due to damage to long perforating arteries to the striatum (pink area), and small vessel ischemic disease or Binswanger’s Disease (BD) due to deep arterioles supplying the subcortical white matter (blue area).  Although BD was described in 1895 it has been a controversial diagnosis that has not been clarified by modern brain imaging and the presence of white matter changes ofet referred to as “white matter ischemic changes” by radiologists.  The diagnosis is also complicated by the fact that many patients has features of both Alzheimer's Disease (AD) and BD and in some cases AD, BD, and small infarctions at autopsy.  If there is any confusion about the diagnosis, a history of hypertension, previous treatment for hypertension, a review of all previous brain imaging, and the clinical pattern of changes in cognition and functional capacity should all be described.   

I am restricting my comments in this post to how hypertension results in dementia so I will not comment on the differential diagnosis of stroke.  Elevated blood pressure can also cause blood vessel damage that is not due to a rupture or embolism.  Prolonged hypertension can cause inflammation in long blood vessels supplying the striatum and periventricular white matter in the brain.  The specifics of that process are being actively studied at this point but damaged is hypothesized to occur because of endothelial cel dysfunction as well as compromise of elastin a connective tissue protein in blood vessels leading to inflammation and narrowing or expansion of blood vessels.  The inflammatory process can lead to further changes and result in a compromised blood-brain barrier and progressive narrowing of those blood vessels.  Eventually the circulation is compromised resulting in the death of neurons visualized as volume loss and white matter changes on imaging studies.   

There seems to be very little work done on the actual pressure signaling at the level of the blood vessel.  Many physiological studies and reviews are focused on overall blood pressure effects and the effect of pressure waves within the vascular system. There are other determinants of endothelial dysfunction including the effects of aging, toxins like tobacco smoke, intercurrent diseases, and metabolic/nutritional factors like blood glucose, lipids, and uric acid.  Epidemiological data supports resting blood pressure and pulse pressure as being significant factors leading to endothelial dysfunction and atherosclerosis.

The modern approach to treating the problem of endothelial dysfunction leading to cardiovascular and cerebrovascular disease is to address all the risk factors.  Hypertension, smoking, diabetes mellitus, metabolic syndrome and obesity, dyslipidemia, and substance use including alcohol all need to be addressed. Many psychiatrists might see this as a primary care problem – but given the way health care is rationed these days a psychiatrist may be the only physician that the patient is seeing on a regular basis.    

That provides the opportunity to collect data like weight, blood pressure and pulse, as well as metabolic parameters if needed. One of my previous posts discusses the issue of blood pressure parameters and white coat effect, and white coat hypertension. The previous thinking was that a lot of people get hypertensive just from the stress of being in a physician’s office.  Some research backed that up showing no difference in outcomes. That research had the same design problems as research about the safety of alcohol.  The control group contained people with cardiovascular diseases and treatment for hypertension. The practical way to address this issue is to advise the patient to check their blood pressure at home with an approved device. Many of these devices can download data into a smartphone app for easy storage.  Home blood pressure monitoring is also useful to detect Transient blood pressure increases due to physical or emotional stress. Although it has not been well studied – this kind of blood pressure reactivity probably needs to be addressed since acute and chronic increases irrespective of etiology are a problem.  

Age is one of the most significant risk factors for dementia. As the incidence of dementia increases with more survivors into old age – there are early interventions that can prevent it from happening.  Good blood pressure control happens to be one of them. 

George Dawson, MD, DFAPA

Supplementary on Binswanger:

Otto Binswanger (1852-1929) was a Swiss physician.  Like many brain specialists of the day he was variously described as a psychiatrist, neurologist, and neuropathologist. He identified as being a psychiatrist primarily but in those days before board certification psychiatry was a much broader field. Both Freud and Meyer had similar qualifications. He is sometimes confused with his nephew Ludwig Binswanger (1881-1966) who was one of the leading researchers of the existential psychiatry movement.  He described “encephalitis subcorticalis chronica progressive” while attempting to differentiate types of dementia from dementia caused by tertiary syphilis that was called general paresis of the insane or GPI at the time.  GPI was a very common reason for institutionalization at the time accounting for 20% of admission and 34% of the death in asylums in the 19^th and early 20^th century before the advent of antibiotics.

Binswanger’s description was controversial up to modern times and I will try to capture that in the graphic below.  The original description was published in 3 issues of a trade paper rather than a medical journal.  It is often critiqued as being long, rambling, and not publishable by today’s standards.  I think that criticism has the benefit of the retroscope since most papers at the time would have similar difficulties.  

Supplemental references on the Binswanger graphic according to those dates:

1894:  Blass JP, Hoyer S, Nitsch R. A translation of Otto Binswanger's article, 'The delineation of the generalized progressive paralyses'. 1894. Arch Neurol. 1991 Sep;48(9):961-72. doi: 10.1001/archneur.1991.00530210089029. PMID: 1953422.

1910:  Dening TR.  Stroke and other Vascular Disorders – Clinical Section.  In: A History of Clinical Psychiatry. Berrios G, Porter R (eds). New Brunswick.  The Athlone Press. 1995: 72-85.

1910:  Nicolson M.  Stroke and other Vascular Disorders – Social Secition. In: A History of Clinical Psychiatry. Berrios G, Porter R (eds). New Brunswick.  The Athlone Press. 1995: 86-94

1986:  Esiri MM, Oppenheimer DR.  Diagnostic Neuropathology. Blackwell Scientific Publications, London, 1896.

1994:  Hansen LA. Pathology of Other Dementias.  In:  Alzheimer Disease.  Terry RD, Katzman R, Bick KL (eds). New York. Raven Press. 1994: 167-196.

The discussion of neuropathology in this text and the subsequent edition is superior to what is seen in general pathology texts and some neuropathology texts.

Román GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH, Amaducci L, Orgogozo JM, Brun A, Hofman A, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology. 1993 Feb;43(2):250-60. doi: 10.1212/wnl.43.2.250. PMID: 8094895. 

2025:  Bir SC, Khan MW, Javalkar V, Toledo EG, Kelley RE. Emerging Concepts in Vascular Dementia: A Review. J Stroke Cerebrovasc Dis. 2021 Aug;30(8):105864. doi: 10.1016/j.jstrokecerebrovasdis.2021.105864. Epub 2021 May 29. PMID: 34062312.

 

References:

1:  He J, Zhao C, Zhong S, Ouyang N, Sun G, Qiao L, Yang R, Zhao C, Liu H, Teng W, Liu X, Wang C, Liu S, Chen CS, Williamson JD, Sun Y. Blood pressure reduction and all-cause dementia in people with uncontrolled hypertension: an open-label, blinded-endpoint, cluster-randomized trial. Nat Med. 2025 Apr 21. doi: 10.1038/s41591-025-03616-8. Epub ahead of print. PMID: 40258956.

2:  Supplementary Information for Reference 1 (see Supplementary Table 7. Meta-Analysis of Randomized Controlled Trials of Antihypertensive Treatment on Dementia) for results of 5 additional RCTs of hypertension treatment in dementia.  https://www.nature.com/articles/s41591-025-03616-8#Sec23

3:  Franklin SS, Thijs L, Hansen TW, O'Brien E, Staessen JA. White-coat hypertension: new insights from recent studies. Hypertension. 2013 Dec;62(6):982-7. doi: 10.1161/HYPERTENSIONAHA.113.01275. Epub 2013 Sep 16. PMID: 24041952.

4:  Lockhart SN, Schaich CL, Craft Set al. Associations among vascular risk factors, neuroimaging biomarkers, and cognition: Preliminary analyses from the Multi-Ethnic Study of Atherosclerosis (MESA). Alzheimers Dement. 2022 Apr;18(4):551-560. doi: 10.1002/alz.12429. Epub 2021 Sep 5. PMID: 34482601; PMCID: PMC8897510.

Blood Pressure

Blood pressure is an important topic for psychiatrists and all physicians.  The prevalence of blood pressure problems especially hypertension is high in the United States and has significant associated mortality and morbidity.  Many psychiatric medications affect blood pressure and some blood pressure medications like beta adrenergic receptor blockers, central alpha adrenergic receptor agonists, and alpha-1 adrenergic receptor inverse agonists have psychiatric applications.  In addition, blood pressure irregularities are noted in major toxic reactions to psychiatric medications like serotonin syndrome and neuroleptic malignant syndrome.  Hypertension is a contraindication to the use of some psychiatric medications and parameters need to be placed for their use.  All of these considerations would seem to make it obvious that frequent and consistent blood pressure measurements should be a part of psychiatric practice - but they are not.

Various problems with obtaining blood pressures occur in psychiatric practice.  Practice settings are part of the problem.  In some clinics, depending on the resources blood pressures may not be measured at all. I have received patients from some of these clinics who were treated with medications that cause hypertension or hypotension and found that their blood pressures were never checked.  I have worked in clinics where the only way that I could obtain a blood pressure or pulse reading was if I took it myself.  I have worked in other settings where blood pressures were taken, but I had no confidence in the numbers.  I found myself interviewing the patient and trying to piece together why their blood pressure and heart rates were elevated at some times but normal in others.  The only adequate assessment of the situation is that attention to blood pressure and its measurement in psychiatric settings is uneven and may be uniformly poor.

That is why an article in The Journal of Clinical Hypertension (1) caught my eye.  In the student the authors looked at 159 medical students and how they measured the blood pressure of a simulated patient against an 11-element skillset on BP measurement.  Only one student out of the 159 demonstrated all 11 skills in simulation.  The specific tasks are listed in the article and have to do with patient preparation, positioning, and the actual measurement task itself.  Some common errors in any of these areas can lead to significant differences in systolic and diastolic blood pressure measurements.  Those errors alone especially those in cuff size selection, arm positioning and patient readiness can lead to consistent false measurements in blood pressure.  As an example, I have assessed a week or two of blood pressure measurements in the mild hypertension range and after correcting the measurement techniques found that the subsequent week was all in the normal range.  This study illustrates an unacceptably high variation in these skillsets in medical students.  I am not aware of similar studies in practicing physicians.

The second article (2) is an encyclopedic reference that is a scientific consensus statement by the American Heart Association on High Blood Pressure Research.  This reference will answer any possible question about blood pressure measurement. A valuable resource from this site was a resource that provides a very extensive list of validated home blood pressure devices. It is possible to make recommendations for accurate and cost effective devices or provide the link to patients who want to explore the possibilities.

I encourage psychiatrists everywhere to make sure that blood pressures and pulses are being taken regularly and accurately.  The buck stops with the physician doing the assessment and treatment and in my opinion it is impossible to practice psychiatry without regular blood pressure measurements.  In addition to monitoring the cardiovascular status of the patient and the response to prescribed medications it provides the opportunity to diagnose a disorder that causes significant cardiovascular and cerebrovascular disease and reverse that process.

Know the 11-element skillset on blood pressure measurement.


George Dawson, MD, DFAPA


References:

1: Rakotz MK, Townsend RR, Yang J, Alpert BS, Heneghan KA, Wynia M, Wozniak GD.Medical students and measuring blood pressure: Results from the American Medical Association Blood Pressure Check Challenge. J Clin Hypertens (Greenwich). 2017 Jun;19(6):614-619. doi: 10.1111/jch.13018. Epub 2017 Apr 28. PubMed PMID: 28452119

2: Pickering TG, Hall JE, Appel LJ, Falkner BE, Graves J, Hill MN, Jones DW,Kurtz T, Sheps SG, Roccella EJ; Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Recommendations for blood pressure measurement in humans and experimental animals: Part 1: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Hypertension. 2005 Jan;45(1):142-61. Epub 2004 Dec 20. PubMed PMID: 15611362

Both of the above links are full text.