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 19th and early 20th 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.
