Changing stroke rehab and research worldwide now.Time is Brain! trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.

What this blog is for:

My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.My back ground story is here:

Thursday, April 2, 2020

For stroke survivors, light physical activity linked to better daily function

Is this your hospitals 'Get out of jail free' card? Allowing them to declare rehab a success if you can do light physical activity? I would be screaming at my providers if this crapola is the best they are trying for.  You need to demand 100% recovery.

For stroke survivors, light physical activity linked to better daily function

Kinesiology and community health professor Neha Gothe and her colleagues examined the relationship between physical activity and physical function in stroke survivors. They found that those who engaged in more light physical activity also reported fewer functional limitations.
Kinesiology and community health professor Neha Gothe and her colleagues examined the relationship between physical activity and physical function in stroke survivors. They found that those who engaged in more light physical activity also reported fewer functional limitations.
Photo courtesy Neha Gothe

  • Editor’s notes:
    To reach Neha Gothe, email
    The paper “Associations between physical activity intensities and physical function in stroke survivors” is available online and from the U. of I. News Bureau.
    DOI: 10.1097/PHM.0000000000001410

Contemporary Bobath Part 3: Scoping review of Bobath studies

I'm not going to read it but just in case your therapist still uses it even after it was proven not to work since 2003. You'll have to ask your therapist why it is still in use. And ask your stroke hospital why the fuck they are still allowing therapy that doesn't work. People need to be fired, starting with the board of directors. Unless you prefer incompetent hospitals.

Physiotherapy Based on the Bobath Concept for Adults with Post-Stroke Hemiplegia: A Review of Effectiveness Studies 2003

The latest here:

Contemporary Bobath Part 3: Scoping review of Bobath studies

State of the Art and Future Directions for Lower Limb Robotic Exoskeletons

3 years old. Your doctor is responsible for KNOWING AND USING THE STATE OF ART TODAY!

State of the Art and Future Directions for Lower Limb Robotic Exoskeletons

Some Coronavirus Patients Show Signs of Brain Ailments

Doctors have observed neurological symptoms, including confusion, stroke and seizures, in a small subset of Covid-19 patient.

Credit...Francisco Seco/Associated Press

Neurologists around the world say that a small subset of patients with Covid-19 are developing serious impairments of the brain.
Although fever, cough and difficulty breathing are the typical hallmarks of infection with the new coronavirus, some patients exhibit altered mental status, or encephalopathy, a catchall term for brain disease or dysfunction that can have many underlying causes, as well as other serious conditions. These neurological syndromes join other unusual symptoms, such as diminished sense of smell and taste as well as heart ailments.
In early March, a 74-year-old man came to the emergency room in Boca Raton, Fla., with a cough and a fever, but an X-ray ruled out pneumonia and he was sent home. The next day, when his fever spiked, family members brought him back. He was short of breath, and could not tell doctors his name or explain what was wrong — he had lost the ability to speak.
The patient, who had chronic lung disease and Parkinson’s, was flailing his arms and legs in jerky movements, and appeared to be having a seizure. Doctors suspected he had Covid-19, and were eventually proven right when he was finally tested.
Continue reading the main story
On Tuesday, doctors in Detroit reported another disturbing case involving a female airline worker in her late 50s with Covid-19. She was confused, and complained of a headache; she could tell the physicians her name but little else, and became less responsive over time. Brain scans showed abnormal swelling and inflammation in several regions, with smaller areas where some cells had died.
Physicians diagnosed a dangerous condition called acute necrotizing encephalopathy, a rare complication of influenza and other viral infections.
“The pattern of involvement, and the way that it rapidly progressed over days, is consistent with viral inflammation of the brain,” Dr. Elissa Fory, a neurologist with Henry Ford Health System, said through an email. “This may indicate the virus can invade the brain directly in rare circumstances.” The patient is in critical condition.
These domestic reports follow similar observations by doctors in Italy and other parts of the world, of Covid-19 patients having strokes, seizures, encephalitis-like symptoms and blood clots, as well as tingling or numbness in the extremities, called acroparesthesia. In some cases, patients were delirious even before developing fever or respiratory illness, according to Dr. Alessandro Padovani, whose hospital at University of Brescia in Italy opened a separate NeuroCovid unit to care for patients with neurological conditions.
The patients who come in with encephalopathy are confused and lethargic and may appear dazed, exhibiting strange behavior or staring off into space. They may be having seizures that require immediate medical care, and experts are warning health care providers who treat such patients to recognize that they may have Covid-19 and to take precautions to protect themselves from infection.

Eating three to six eggs a week could cut your risk of heart disease

What does your doctor say? I wouldn't necessarily trust the analysis, can the poorest people in China afford eggs?

Eating three to six eggs a week could cut your risk of heart disease

A new Chinese study has found that eating eggs several times a week could be linked with a lower risk of cardiovascular disease and death.
Carried out by researchers from Fuwai Hospital, Chinese Academy of Medical Sciences, the new study looked at 102,136 participants from 15 provinces across China, who were all free of cardiovascular disease (CVD) and cancer at the start of the study.
The participants completed food-frequency questionnaires to assess their egg consumption and were then followed for 17 years.
The findings, published in the journal Science China Life Sciences, showed that participants who ate three to six eggs per week had the lowest risk of CVD and death among the group.
However, a low or high intake of eggs appeared to be associated with a higher risk of CVD and death, with eating less than one egg a week linked with a 22 percent higher risk of CVD and a 29 percent higher risk of death, and eating ten or more eggs per week linked with a 30 percent higher risk of CVD and a 13 percent higher risk of death.
The researchers also found that egg consumption appeared to have a different effect on different types of CVD. While those who ate more eggs had a higher risk of coronary heart disease (CHD) and ischemic stroke, those who ate fewer eggs had a higher risk of hemorrhagic stroke.
Eggs are known to be a quick and affordable source of high-quality proteins, packed with nutrients that are beneficial for health. However, they are also high in cholesterol, meaning there has been some uncertainty as to whether consuming them could also increase cholesterol levels and the risk of CVD. The researchers say that up until now the findings from most studies looking at this association have been inconsistent, and no consensus has been reached about recommendations on egg intake. They also add that their findings highlight that moderate egg consumption of three to six eggs a week should be recommended for CVD prevention in China.
A large-scale US study published in The BMJ just last month also found that, despite previous concerns, eating an egg a day is not linked with a higher risk of CVD, compared to eating less than one egg per month. After investigating further and carrying out a meta-analysis of 28 observational studies, the team again failed to find a link between eating eggs and CVD risk among participants in the US and European studies.

Study Shows Choline Benefits for Your Brain RSS

Read and ask your doctor about this. 

Study Shows Choline Benefits for Your Brain

A new study shows that taking in choline throughout your life helps keep your brain young and protects against Alzheimer's disease. Keep reading to find out more about the study, what choline is, its benefits, and how to get choline in your diet.
[Disclaimer: This post is not meant to be medical advice. I am summarizing and passing on information based on my research and experience. Check with your own medical providers for personalized guidance.]

What is Choline?

Choline is an essential nutrient. That means that you have to have it.
It was only added to the US list of required nutrients in 1998, so recognition of its importance is relatively new.
It is similar to B vitamins but it is not a vitamin.
Your body can produce a small amount of choline, but you need to eat or take in the bulk of it from diet or supplements.

Choline Benefits

Choline is vital to the structure of cells throughout your body and is of particular importance for liver and nervous system function. It helps lift mood, boost memory and energy, and reduce inflammation.
Adequate amounts of choline are important to your brain for several reasons.
  1. Choline is used by your body to make fats and move fats to where they are needed. (Your brain cells are largely made up of fats, so this is a key nutrient for a healthy brain.)
  2. It is used to make the neurotransmitter acetylcholine. Acetylcholine is used for muscle control, memory, and other brain functions. 

Choline Research Study

Researchers at Arizona State University studied the effect of lifetime choline supplementation on mice who were bred to develop Alzheimer's-like symptoms (AD mice) and mice who did not have the Alzheimer's gene (non-AD mice) against control groups of both types of mice who were not supplemented.
The mice were repeatedly placed in a maze to test their memory. The AD mice that were given choline supplements throughout their life had better memory capability than AD control mice that were not supplemented.
Examining brain tissue from the mice showed less microglia activation in the supplemented groups for both AD and non-AD mice compared to their control groups. Activated microglia are associated with neurodegenerative diseases such as Alzheimer's, traumatic brain injury, multiple sclerosis, and Parkinson's disease.
The researchers concluded that their results suggest that "additional dietary choline may be an avenue to reduce brain inflammation in both neurodegenerative disease and the nondiseased aging brain."
To read the study: Velazquez R, Ferreira E, Knowles S, et al. Lifelong choline supplementation ameliorates Alzheimer’s disease pathology and associated cognitive deficits by attenuating microglia activation. Aging Cell. September 2019:e13037. 

Recommended Amounts of Choline

The minimum amount of choline that you should be getting is the Recommended Adequate Intake (AI):
  • 550 mg/day for adult males
  • 425 mg/day for adult females
For maximizing the benefits of choline, you need to be getting more than the minimum.  
There also is a Tolerable Upper Limit (UL) established for choline. It is recommended that you don't go over this amount with supplements:
  • 3,500 mg/day

Choline and Folate

Choline and folate play well together. To optimize your use of choline, make sure you are getting enough folate also. (Folic acid is sometimes included in supplements instead of folate, but it is not really what your body needs. If you want to boost your folate using supplements, look for those that say folate on the nutrient breakdown.)

Choline Rich Food Sources

Choline can be found naturally in some foods. The best food sources of choline include:
  • pasture-raised eggs,
  • liver (chicken or beef),
  • grass-fed beef and pastured pork, 
  • wild salmon,
  • dairy products, and 
  • cruciferous vegetables (cauliflower, broccoli, cabbage, bok choy, kale, Brussel's sprouts). 
These foods are also good sources of folate.
What is choline, Choline foods sources, Choline rich foods

Choline Supplements

Some experts recommend CDP choline, also called Citicoline, or Alpha GPC choline. When I looked on Amazon, they are either extremely expensive or have quite a lot of bad reviews where people are talking about experiencing negative side effects like headaches.
Personally, I have used Thorne Research's Phosphatidyl Choline for many years. (Thorne is a high-quality supplement company that stays away from GMO sources. This is particularly important with choline supplements as they are most often sourced in soybeans and most soybeans are now GMO.) It seems to me that my brain is sharper when I use it. I also eat many choline-rich foods.

Scientists Confirm: Herpes Virus Implicated in Alzheimer’s Disease

You'll want your doctor to know what to do with this to prevent your getting dementia.

Your chances of getting dementia.

1. A documented 33% dementia chance post-stroke from an Australian study?   May 2012.

2. Then this study came out and seems to have a range from 17-66%. December 2013.

3. A 20% chance in this research.   July 2013.

4. Dementia Risk Doubled in Patients Following Stroke September 2018 

5. Parkinson’s Disease May Have Link to Stroke March 2017 

The latest here:

Scientists Confirm: Herpes Virus Implicated in Alzheimer’s Disease

A coalition of scientists from the Icahn School of Medicine in New York City and Arizona State University, collected over 2,000 post-mortem tissue samples from 944 brains held at several brain banks funded by the US National Institute of Aging, which also provided money for the study. Some of the brain samples had the tell-tale amyloid plaques and tau buildups found in Alzheimer’s disease and some had signs of other cognitive impairments. Others were “control” patients with healthy brain function. What they discovered is groundbreaking news for scientists and any lives touched Alzheimer’s disease. They published their results in the science journal, Neuron, last week.
The herpes viruses
There are 9 herpes viruses known to man but when people think of herpes, they usually think of sexually transmitted diseases and unsightly cold sores erupting from infected lips. Those are the herpes viruses, HSV1 and HSV2. The peculiar thing about any herpes virus is its ability to go dormant in the body only to reawaken later and begin reproducing all over again causing diseases like shingles. In fact, the name herpes is derived from the Greek word meaning, “to creep” because of their ability to creep up nerves and plant themselves on our spines and in some instances, even our brains, probably having an effect on Alzheimer’s disease.
Although the research team found over 500 types of viruses present in those 2,000 brains, the two forms of herpes virus – HHVA6 and 7 – were found in particularly high concentrations in the brains of individuals with Alzheimer’s. After their dormant stage, they start actively reproducing and appear to speed up the Alzheimer’s-related protein build ups that ultimately lead to the brain’s system failure. Although not causative, they are described as “putting gas on the flame,” by Joel Dudley, a geneticist at the Icahn School of Medicine at Mt. Sinai in New York City, who described the virus as accelerating the disease. The study offers strong evidence that viral infections can influence its course.
Just an accident
Like the discovery of penicillin, many scientific discoveries are made by accident and this discovery is no different. The goal for this study was to identify new targets for drugs by using genetic data to look for differences between healthy brain tissue and brain tissue from those who had developed Alzheimer’s. Dudley says that, “Viruses were the last thing we were looking for.” But when they began to analyze the differences, “it just sort of came screaming out at us from the data.” The two human herpes viruses HHV6 and HHV7 were twice as high in brain tissue from people with Alzheimer’s!
Once they knew this, the next step was to find out how the viruses could affect the course of a brain disease. In order to do this, they set about identifying interactions between virus genes and other genes in the brains cells by mapping out a kind of social network between the two. Dudley wanted to know, “If the viruses are tweeting, who’s tweeting back?”
What they found were that the herpes virus genes were interacting with genes known to both increase a person’s risk for Alzheimer’s and to make a person’s brain more vulnerable to infection with HHV6 and HHV7. Just having the virus present in the brain isn’t enough to cause Alzheimer’s. Something needs to activate the virus out of its dormancy. To date, that activating factor has not been found but Dudley is hopeful and suspects some internal function of the brain cells is the cause. Still, because of the importance of this finding, we are two steps closer to finding a way to slow and maybe even stop the progression of the disease.

1. Multiscale Analysis of Independent Alzheimer’s Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus. Neuron.
2. Herpes Viruses Implicated in Alzheimer’s Disease. The Scientist. June, 21, 2018
3. Researchers Find Herpes Viruses In Brains Marked By Alzheimer’s Disease. NPR. June 21, 2018.

Defining the relationship between hypertension, cognitive decline, and dementia: a review

Way beyond my pay grade, ask your doctor for what this means in 8th grade language. And then ask for EXACT PROTOCOLS THAT PREVENT THESE PROBLEMS. 

Defining the relationship between hypertension, cognitive decline, and dementia: a review


Hypertension is a highly prevalent condition which has been established as a risk factor for cardiovascular and cerebrovascular disease. Although the understanding of the relationship between cardiocirculatory dysfunction and brain health has improved significantly over the last several decades, it is still unclear whether hypertension constitutes a potentially treatable risk factor for cognitive decline and dementia. While it is clear that hypertension can affect brain structure and function, recent findings suggest that the associations between blood pressure and brain health are complex and, in many cases, dependent on factors such as age, hypertension chronicity, and antihypertensive medication use. Whereas large epidemiological studies have demonstrated a consistent association between high midlife BP and late-life cognitive decline and incident dementia, associations between late-life blood pressure and cognition have been less consistent. Recent evidence suggests that hypertension may promote alterations in brain structure and function through a process of cerebral vessel remodeling, which can lead to disruptions in cerebral autoregulation, reductions in cerebral perfusion, and limit the brain’s ability to clear potentially harmful proteins such as β-amyloid. The purpose of the current review is to synthesize recent findings from epidemiological, neuroimaging, physiological, genetic, and translational research to provide an overview of what is currently known about the association between blood pressure and cognitive function across the lifespan. In doing so, the current review also discusses the results of recent randomized controlled trials of antihypertensive therapy to reduce cognitive decline, highlights several methodological limitations, and provides recommendations for future clinical trial design.
Keywords: Hypertension, Hypotension, Blood Pressure, Cognition, Cognitive Impairment, Dementia


Hypertension is a highly prevalent condition, occurring in one-third of the world’s adults and two-thirds of adults over age 65 [,]. Already an established risk factor for cardiovascular and cerebrovascular disease [], emerging evidence suggests that hypertension may also play an important role in the development of cognitive decline, Alzheimer’s disease, and vascular dementia []. Because hypertension is a modifiable risk factor, it represents a potentially important mechanism through which the prevention or delay of age-related cognitive disorders may be possible. For this reason, understanding hypertension’s role in the development and progression of age-related cognitive decline and dementia has been a research priority over the last two decades. Although a great deal has been learned from epidemiological studies, there is still little consensus about the effectiveness of treating hypertension to prevent or slow cognitive decline. What is clear, however, is that the connection between blood pressure (BP) and cognitive function is biologically complex and still not fully understood.
The goal of this review is to provide an overview of the research that has contributed to the understanding of the connection between BP and cognitive function, paying particular attention to recent findings. In doing so, this review will first provide an overview of what is known about the connection between hypertension, cognitive function, Alzheimer’s disease, and vascular dementia. Second, the neurobiological changes associated with hypertension will be described, and the research that demonstrates how these biological processes influence neuronal function will be highlighted. Lastly, the findings from clinical trials designed to assess the effectiveness of antihypertensive agents for the prevention or delay of cognitive decline will be summarized. Methodological considerations and specific recommendations for future research will also be discussed. Although this review focuses on the topic of hypertension and cognitive function, the link between low BP and cognition will also be discussed.

Hypertension and cognitive function

Cross-sectional and longitudinal observational studies

Over the last several decades the link between hypertension and cognitive function has been examined across many age groups. Although much of this research has focused on understanding the relationship between BP and cognition in older adults, the group most likely to experience cognitive decline, studies which assess BP starting in middle-age and follow participants forward until they reach older ages have also been especially informative. Multiple epidemiological studies have demonstrated that elevated BP in the 4th and 5th, decade of life, particularly untreated hypertension, increases the risk for cognitive impairment 20–30 years later (see Table 1) []. These findings have been further supported by longitudinal studies which show that high midlife BP is associated with increased cognitive decline over time []. Because confounding variables, such as education and socioeconomic status, are less likely to affect cognitive change (compared to baseline cognitive abilities) [], studies which show an increased rate of cognitive decline over time among hypertensive adults provide especially strong evidence for the deleterious effects of high BP. As will be discussed below, several studies have also identified hypertension duration and the trajectory of BP levels over time as important determinants of cognitive function later in life [,].

Table 1.

Epidemiologic studies of early- and midlife hypertension and cognition
StudyStudy Design Duration
Age at BP AssessmentBP MeasureAge at
Cognitive Assessment
Cognitive Domains
Major Findings
NHANES III, USA []Cross-sectional
n = 5,077
6-16SBP, DBP6-16Arithmetic Reading
Working memory
Elevated SBP, but not DBP, was associated with poorer working memory.
Normative Aging Study, USA []Cross-temporal a
29 years
n = 758
37 (5)
(BP measured every 3-5 years for up to 44 years)
HTN66 (5)Multi-domain composite scoreHTN at any point during follow-up and greater duration since onset of HTN were associated with lower cognitive functioning later in life, independent of age at onset.
NHLBI Twin Study, USA []Cross-temporal a
25 years
10 years
n = 392
43-53SBP, DBPT1: 59-69
T2: 68-79
Processing speed
Verbal fluency Visual memory
Elevated SBP at baseline was associated with declines in processing speed over a period of 10 years.
Honolulu-Asia Aging Study, USA []Cross-temporal a
25 years
n = 3,735
53 (5)SBP, DBP78 (5)Cognitive Abilities Screening Instrument (CASI)Elevated SBP at baseline was associated with poorer cognitive functioning in late-life.
Xi’an, China []Cross-sectional
n = 1,799
40-85SBP, DBP, MAP40-85MMSEElevated SBP, DBP, and MAP were associated with cognitive impairment among 40-60 year-olds, but this was not the case for older participants.
Whitehall II, UK []Cross-temporal a
12 years
n = 5,838
44 (6)SBP, DBP56Memory
Verbal fluency
Elevated SBP at baseline was associated with poorer baseline memory and reduced verbal fluency at follow-up, especially among women.
Cross-temporal a
3 years
n = 17,630
64 (9)HTN67Multi-domain composite scoreHTN was not associated with the development of cognitive impairment over a span of 40 months.
Framingham Heart Study, USA []Cross-temporal a
12 years
n = 1,814
40-69HTNT1: 52 (8)
T2: 64
Executive function
HTN was associated with worse performance on measures of executive functioning and visual memory.
NHANES III, USA []Cross-sectional
n = 3,270
30-59HTN30-59Processing speed Reaction time
Working memory
HTN and DM, but not HTN alone, was associated with worse reaction time, processing speed, and working memory.
EVA Study Group, France []Longitudinal
4 years
n = 1,373
59-71HTNT1: 59-71
T2: 63-75
MMSEBaseline HTN was associated greater MMSE declines over 4 years. This relationship was stronger among participants who were untreated for hypertension.
ARIC, USA []Longitudinal
6 years
n = 10,963
47-70HTNT1: 47-70
T2: 53-76
Processing speed
Verbal fluency
Baseline HTN was associated with greater decline in processing speed over a 6-year period.
ARIC, USA []Longitudinal
14 years
n = 12,702
59 (4)HTNT1: 59 (4)
T2: 62
T3: 65
T4: 73
Processing speed
Verbal fluency
Baseline HTN was associated with greater declines in verbal fluency over a 14-year period.
ARIC, USA []Longitudinal
20 years
n = 13,476
45-64Pre-HTN, HTNT1: 48-67
T2: 54-73
T3: 70-89
Processing speed
Verbal fluency
Verbal memory
Baseline HTN was associated with greater declines in processing speed, verbal fluency, and a global composite score of cognitive functioning over a 20-year period.
Western Collaborative Group Study, USA []Cross-temporal a
25-30 years
n = 717
(BP measured approximately 10 times over 30 years)
SBP75 (4)Executive function
Processing speed
Compared to participants who maintained a normal SBP over 30 years, participants who had persistently high SBP had poorer verbal memory in late-life. Participants who displayed a significant decrease in SBP over 30 years performed more poorly on measure of processing speed.
Male Cohort in Uppsala, Sweden []Cross-temporal a
20 years
n = 999
50SBP, DBP72Multi-domain composite scoreElevated DBP at baseline was associated with reduced cognitive functioning in late-life. This relationship was stronger among participants who were untreated for hypertension.
Male Cohort in Uppsala, Sweden []Cross-temporal a
20 years
n = 502
72 (1)Memory
Processing speed
Verbal fluency
Working memory
Elevated DBP at baseline was associated with poorer performance on measures of working memory, processing speed, and verbal fluency in late-life. Participants with DBP ≤ 70mg Hg at baseline demonstrated highest levels cognitive functioning in late-life.
Framingham, USA []Cross-temporal a
28 years
n = 1,993
(BP measured biennially over 28 years)
HTN, SBP, DBP55-89Attention
Among participants untreated for hypertension, the proportion of visits during which HTN was present and the average SBP and DBP were inversely associated with cognitive functioning.
ARIC, USA []Cross-sectional
n = 13,840
45-69HTN45-69Processing speed
Verbal fluency
Verbal memory
HTN among women, but not men, was associated with poorer performance on all cognitive measures.
ARIC = Atherosclerosis Risk in Communities; BP = blood pressure; DBP = diastolic blood pressure; EVA = Epidemiology of Vascular Aging; HTN = hypertension; MAP = mean arterial pressure; MMSE = Mini Mental Status Exam; NHANES III = National Health and Nutrition Examination Survey; NHLBI = National Heart, Lung, and Blood Institute; REGARDS = Reasons for Geographic and Racial Differences in Stroke; SBP = systolic blood pressure
aCross temporal: a study design in which the exposure variable (e.g., hypertension) and the outcome variable (e.g., cognition) are measured distict time points.
Hypertension in the 6th and 7th decade has been associated with poorer overall cognitive function and cognitive decline (see Table 2) []. Hypertension among individuals in their 70s has also been identified as a risk factor for mild cognitive impairment (MCI) – a state of subtle cognitive decline that is believed to precede the onset of dementia [,]. In contrast, studies that include individuals in their 8th, 9th, and 10th decade of life have largely either failed to find such an association [,] or have found high BP to be protective against cognitive impairment [,]. Together, these results suggest that the relationship between cognition and BP in late-life may be age dependent []. Inverted U- or J-shaped curves may most accurately represent the relationship between BP and cognition among octogenarians and nonagenarians, as both low BP and extremely high BP (systolic blood pressure (SBP) >160mmHg) have been linked to cognitive impairment in this age group [,].

Table 2.

Epidemiologic studies of late-life hypertension and cognition
StudyStudy Design Duration
Age at BP AssessmentBP MeasureAge at
Cognitive Assessment
Cognitive Domains AssessedMajor Findings
n = 1,579
71 (7)HTN, SBP, DBP, PP, MAP71 (7)MMSEHTN and antihypertensive medication noncompliance were associated with lower MMSE scores.
Kungsholmen Project, Sweden []Longitudinal
3 years
n = 1,736
75-101SBP, DBPT1: 75-101
T2: 78-104
MMSEHigher SBP and DBP at baseline were associated with better MMSE score at baseline and 3-year follow-up. Baseline SBP < 130 mmHg was associated with increased risk of cognitive impairment at follow-up.
REGARDS, USA []Cross-sectional
n = 14,566
65 (9)HTN65 (9)Six-item ScreenerHTN was not associated with risk of cognitive impairment.
Framingham Heart Study, USA []Cross-temporal a
13 years
n = 1,702
67 (8)HTN80Abstract reasoning
Verbal fluency
Working memory
Baseline HTN was associated with poorer working memory, visual memory, and verbal memory at follow-up among participants not on antihypertensive medication.
Framingham Heart Study, USA []Cross-temporal a
4-6 years
n = 1,423
66 (7)HTN71Abstract reasoning
Executive function
Baseline HTN was associated with greater memory impairment 4-6 years later in men, but not in women.
Northern Manhattan Study, USA []Longitudinal
6 years
n = 4,337
76 (6)HTNT1: 78
T2: 80
T3: 81
Executive function
Baseline HTN was associated with declines in executive functioning, but not memory or language.
REGARDS USA []Cross-sectional
n = 19,836
65 (10)SBP, DBP, PP65 (10)Six-item ScreenerHigher DBP was associated with greater risk of cognitive impairment.
Indo-US Cross National Dementia Epidemiology Study, India/USA []Cross-sectional
n = 4810
n = 636
67 (7)
82 (4)
67 (7)
82 (4)
MMSEHigher SBP and DBP were associated with increased risk for cognitive impairment in the younger Indian cohort. No association between BP and cognitive impairment was found in the older American cohort.
Osservatorio Geriatrico Regione Campania, Italy []Cross-sectional
n = 1,229
74 (6)SBP, DBP74 (6)MMSEHigher DBP, but not SBP, was associated with cognitive impairment in participants > 75, but not in participants 65-74 years of age.
Baltimore Longitudinal Study of Ageing, USA []Longitudinal
11 years
n = 847
71 (9)SBP, DBP82Attention
Executive function
Processing speed
High SBP was associated with memory declines among older participants. Cross-sectional analyses demonstrated that both high and low diastolic BP were associated with poorer executive functioning, processing speed, and naming among participant groups.
Chicago Health and Aging, USA []Cross-sectional
n = 5,816
65-104SBP, DBP65-104MMSEParticipants with SBP < 100 mm Hg and SBP > 140 mm Hg had lower MMSE scores.
Chicago Health and Aging, USA
6 years
n = 4,284
74 (6)SBP,
Processing speed
BP was not associated with cognitive change over the span of 6 years.
The Italian Longitudinal Study on Aging, Italy []Cross-sectional
n = 3,425
65-84HTN65-84MMSEHypertension was not associated with MMSE score.
Men Born in 1914, Sweden []Cross-sectional
n = 500
68HTN68Processing speed
Verbal abilities
Visual memory
HTN (SBP 140-159 mm Hg) was associated with better visuospatial and verbal abilities. Severe HTN (SBP ≥ 180 mm Hg) was associated with poorer performance on measures of memory and processing speed.
Cardiovascular Health Study, USA
7 years
n = 5,888
≥ 65SBP≥ 72Modified MMSE
Processing speed
SBP Elevated SBP was associated with a decline in MMSE and processing speed over a period of 7 years.
East Boston cohort study, USA []Longitudinal
9 years
n = 3,657
74 (6)SBP, DBP83Memory
A U-shaped relationship between SBP and cognition was found whereby SBP < 130mm Hg or ≥ 160mm Hg was associated with a higher rate of errors on a mental status questionnaire (SPMSQ).
Duke Population Studies of the Elderly, USA []Longitudinal
3 years
n = 3,202
73 (6)SBP, DBP76SPMSQAmong white participants, a U-shaped relationship between SBP cognitive decline was found whereby SBP < 110 mm Hg and SBP > 165 mm Hg was associated with 3-year cognitive decline. No association between BP and cognition was found in black participants.
East Boston Study, USA []Cross-sectional
n = 3,627
≥ 65SBP, DBP, HTN≥ 65Attention
BP was not associated with cognitive functioning.
BP = blood pressure; COGNIPRES = Cognitive function and blood pressure control; DBP = diastolic blood pressure; HTN = hypertension; MAP = mean arterial presure; MMSE = Mini Mental Status Exam; PP = pulse pressure; REGARDS = Reasons for Geographic and Racial Differences in Stroke; SBP = systolic blood pressure; SPMSQ = Short Portable Mental Status Questionnaire
aCross temporal: a study design in which the exposure variable (e.g., hypertension) and the outcome variable (e.g., cognition) are measured distict time points.
While individuals who develop hypertension earlier in life are likely to be subjected to the deleterious neurological effects of hypertension for many decades, this is not the case for individuals who develop hypertension much later. The strong associations found between midlife hypertension and late-life cognitive abilities supports the notion that hypertension duration and chronicity in adulthood may be especially important determinants of cognitive impairment in elderly individuals. Perhaps the strongest support for this hypothesis comes from a longitudinal study which found that a longer duration of time between hypertension initiation and cognitive testing is associated with reduced cognitive abilities independent of age []. In particular, longitudinal studies suggest that middle-aged adults with prolonged hypertension and elevated systolic blood pressure (SBP) over a period of 25–30 years are at an exceptionally high risk for cognitive impairment later in life [,]. Thus, studies with a longer period between the initiation of BP monitoring and subsequent cognitive assessment may be better able to detect the effects of high BP on neurocognitive outcomes. The trajectory of blood pressure changes from midlife into older age may also be important, as the combination of hypertension in midlife and low diastolic blood pressure (DBP) in late-life has been associated with smaller brain volumes and poorer cognitive outcomes among older adults []. Individuals who develop hypertension before middle adulthood may also be at particularly high risk for cognitive impairment, as a number of studies have found associations between high BP, cognitive deficits, and reduced academic functioning in children, adolescents, and young adults []. Irrespective of age, the cognitive domains that appear most vulnerable to hypertension are executive functioning and information processing speed. Both cognitive processes rely heavily on the integrity of frontal and subcortical brain structures which may be most vulnerable to the effects of hypertension.

Blood pressure variability

BP fluctuates substantially over a 24-hour period as a result of factors such as postural change, circadian rhythm, and general physiologic variability [,]. Fluctuations in BP associated with autonomic dysfunction, such as orthostatic hypotension, become more prevalent with increasing age and may be associated with cognitive deficits [,,]. Although a number of studies have demonstrated a connection between orthostatic hypotension and cognitive function, with worse performance in the setting of orthostasis [], others have failed to replicate this finding []. Ambulatory blood pressure measurement (ABPM) has been used in a number of studies to more accurately capture short-term, daily BP variability, which may reflect autonomic dysfunction or increased arterial stiffness, among other etiologies. Using ABPM, elevated 24-hour mean BP, 24-hour BP variability, and reduced nocturnal dipping (a natural reduction of night-time BP) have each been identified as potential risk factors for cognitive impairment [,]. Because autonomic dysfunction occurs in the early phase of several neurodegenerative disorders [], it is difficult to determine whether cognitive deficits found in individuals with potential sequelae of autonomic dysfunction (e.g., BP variability and orthostatic hypotension) are the result of underlying neurodegenerative changes or the direct effect of transient drops in BP.

Genetic factors

Additional insights into the relationship between hypertension and cognition have emerged through genetic studies. A polymorphism in the ACE gene, a gene which regulates BP through its effects on angiotensin converting enzyme (ACE) activity [], has been linked to both cognitive function [] and the presence of neuroimaging abnormalities [,]. Middle-aged and older adults who carry an allele that codes for the high activity variant (D) of the ACE I/D polymorphism show greater levels of cognitive impairment and cognitive decline [,]. Unexpectedly, other studies have found the low activity allele (I) of the ACE I/D polymorphism to confer increased risk for dementia [,]. Polymorphisms in another gene, AGTR1, which codes for the angiotensin-II type 1 receptor, also an important part of the regulation of BP, have been associated with reduced prefrontal and hippocampal volume [], reductions in hippocampal volume over time, and poorer memory in older adults []. Additional evidence suggests that specific genetic variants may interact with hypertension to promote or buffer against the effects of elevated BP on cognitive function and brain structural integrity. Two Alzheimer’s disease risk genes that have also been associated with cognitive function in nondemented individuals, Apolipoprotein E (APOE) and Clusterin (CLU), appear to modify the effect of hypertension on cognitive function []. For example, multiple studies have found that hypertension is only associated with cognitive deficits in individuals who possess a copy of the ε4 allele of the APOE gene [,].

Dementia risk and hypertension

Alzheimer’s disease

Several forms of cardiovascular disease have been identified as risk factors for both Alzheimer’s disease and vascular dementia [], which together account for the majority of dementia cases worldwide [,]. Alzheimer’s disease, cerebrovascular disease, and cardiovascular disease have shared genetic contributions [,], and approximately 50% of individuals diagnosed with Alzheimer’s disease display significant cerebrovascular pathology on autopsy [,]. Together, these findings suggest that cardiovascular disease, Alzheimer’s disease, and vascular dementia may have an overlapping pathophysiology [].
Despite significant evidence for the role of cardiovascular disease in the pathogenesis and progression of Alzheimer’s disease, the association between hypertension and Alzheimer’s disease is still not well understood. Although a consistent relationship between elevated DBP at midlife and incident Alzheimer’s disease has been demonstrated [,,], evidence for an association between midlife SBP and incident Alzheimer’s disease has been conflicting []. What is clear is that late-life hypertension does not appear to be a risk factor for incident Alzheimer’s disease [,]. In fact, multiple studies suggest that abnormally low DBP in late-life may increase one’s risk for Alzheimer’s disease [,]. Some, but not all, have argued that this inverse relationship between late-life DBP and Alzheimer’s disease risk results from a tendency for BP to decline concurrently with the onset and progression of dementia [,,]. Together, previous findings suggest that the combination of high BP in midlife followed by low BP in late-life may place individuals at especially high risk of developing Alzheimer’s disease. However, few studies have examined this hypothesis directly [].

Vascular dementia

Because hypertension is a known risk factor for cerebral small vessel disease [] and stroke [], hypertension is often considered a risk factor for vascular dementia, a form of cognitive decline resulting from small- or large-vessel cerebrovascular disease [,]. However, only a handful of studies have directly examined the relationship between hypertension and vascular dementia. Although previous research supports the relationship between midlife hypertension and the development of vascular dementia [,,,], it is unclear whether there is an association between late-life hypertension and vascular dementia, as findings have thus far been conflicting [,,,]. Compared to the associations between midlife hypertension and incident Alzheimer’s disease, the associations found between midlife hypertension and incident vascular dementia tend to be more robust and consistent [,,]. However, because patients are more likely to develop mixed Alzheimer’s and vascular dementia than pure forms of one or the other, this distinction may not be meaningful.

Pathophysiology of hypertension as it relates to cognitive decline

Evidence from neuroimaging and biomarker studies

Neuroimaging has played a pivotal role in advancing the understanding of how BP influences cognitive function and underlying brain structure. Results from studies that have examined the relationship between BP and brain volume are largely consistent with findings from the BP and cognition studies. High SBP has been associated with smaller regional and total brain volumes [] and reductions in brain volume over time []. The relationship between high DBP and brain volume is less consistent, however [,,,]. In elderly populations, low SBP [,] and low DBP [,] have been associated with reduced brain volume and cortical thickness, suggesting that the relationship between BP and brain volume may age-dependent [,,]. A pattern of hypertension in midlife followed by hypotension in late-life appears to be especially harmful [], particularly in brain regions affected in the earliest phase of Alzheimer’s disease [].
An association between hypertension and the development of Alzheimer’s disease has also been supported by research that examines Alzheimer’s disease biomarkers directly. Compared to the brains of normotensive individuals, the brains of individuals with a history of hypertension show greater levels of β-amyloid plaques, atrophy, and neurofibrillary tangles [,]. Similarly, hypertension has been identified as a risk factor for cortical fibrillar β-amyloid deposits [,,] and reduced glucose metabolism in Alzheimer’s disease-specific brain regions [,] using positron emission tomography (PET) in the brains of cognitively normal middle-aged and older adults. Consistent with these findings, one study found that individuals with abnormal plasma β-amyloid levels and elevated BP at midlife have an especially high risk of developing Alzheimer’s disease later in life [].
Hypertension has also been associated with several defining features of vascular dementia and cerebral small vessel disease, including WMH volume [,], WMH progression [,], lacunar infarcts, and cerebral microbleeds [,]. Supporting the relationship between high BP and white matter pathology, findings from observational studies [] and clinical trials [,] suggest that treatment of hypertension reduces WMH progression. Even before the development of overt neuroimaging abnormalities, hypertension appears to be associated with reduced white matter microstructural integrity in both young and old individuals, suggesting white matter may be especially vulnerable to the deleterious effects of hypertension [].

Hypertension and vascular remodeling

Emerging evidence suggests that sustained elevations in BP may cause cerebral vessel remodeling in a manner which promotes pathological brain changes and subsequent cognitive decline. To preserve the steady low-pressure blood supply to the periphery and protect end organ microcirculation from pulsatile stress associated with hypertension, a rearrangement in vessel wall material in the form of hypertrophic remodeling of the media and vascular smooth muscle cells occurs []. This enlargement in media size causes a reduction in lumen diameter, leading to increased vascular resistance and vessel wall stiffening []. Arterial stiffening, in turn, increases arterial pulse wave velocity and pulsatile pressure, which over time causes rarefaction of downstream capillaries and further inward remodeling of vessel walls []. Hypertension promotes intracranial atherosclerosis in large intracranial arteries [,] and arteriolosclerosis in smaller arterioles supplying subcortical white matter and deep gray matter brain structures []. Arteriolosclerosis is a process characterized by a loss of tunica media smooth muscle cells, fibro-hyaline deposits, and thickening of the vessel wall, resulting in increased microvascular resistance. Because the brain requires high levels of continuous perfusion throughout systole and diastole [], increases in vascular resistance leave cerebral arterioles vulnerable to hypoperfusion when systemic BP is reduced [,]. As described below, hypoperfusion has been associated with several neurovascular changes [], which together may disrupt cognition [].

Autoregulation and cerebral perfusion

The brain requires a high volume of consistent blood flow to sustain adequate perfusion. However, the brain’s ability to maintain steady low-pressure blood flow in the context of changing systemic BP – a process known as cerebral autoregulation – can be disrupted as a result of chronic hypertension [,]. After prolonged exposure to high BP and elevated pulsatility, a shift occurs in the brain’s autoregulatory capacity whereby higher systemic BP is required to maintain the same level of cerebral perfusion []. Hypertension is believed to alter cerebral autoregulation by inducing changes in arteriole endothelial and vascular smooth muscle cells that diminish cerebrovascular reactivity [] and increase myogenic tone, respectively []. Not only do these vascular changes shift the cerebral autoregulatory curve in a manner which reduces resting cerebral blood flow, but the brain also becomes more susceptible to hypoperfusion during periods of low systemic BP [] or during periods of normal BP in chronically hypertensive individuals []. These hypertension-induced changes to cerebral autoregulation and perfusion may explain why individuals with chronic hypertension in midlife and low BP in late-life show significant reductions in brain volume [,] and greater levels of cognitive deficits [].
While ischemia may occur in some cases, the brain is more likely to be subjected to chronic oligemia (i.e., mild reductions in blood flow) as a result of hypertension. Chronic oligemia may, in turn, lead to endothelial dysfunction, acidosis, oxidative stress, and unmet metabolic energy demands that can impair neuronal function [,,]. Oligemia may also down-regulate the synthesis of proteins necessary for synaptic plasticity and memory formation [], and promote neuronal tau phosphorylation, β-amyloid oligomerization, and the upregulation of amyloidogenic APP []. Each of these neurophysiological changes likely contributes to the development of Alzheimer’s disease and cerebral amyloid angiopathy (CAA). Evidence suggests that β-amyloid accumulation may also occur as a result of hypertension-induced up-regulation of the receptor for advanced glycation end products (RAGE), which controls the shuttling of β-amyloid from the blood across the endothelial barrier into the brain [].

Endothelial dysfunction, altered functional hyperemia & Oxidative stress

By promoting endothelial dysfunction, hypertension is also believed to disrupt the coordinated coupling among neurons, glia, and cerebral blood flow in the microvasculature []. Uncoupling of this system, known collectively as the neurovascular unit, can impair the homeostatic process of functional hyperemia, whereby increases in CBF occur in coordination with increases in neuronal activity to ensure the delivery of adequate levels oxygen and glucose and facilitate the removal of metabolites []. Support for these findings comes from animal research, which has demonstrated that hypertension-induced vascular oxidative stress resulting from up-regulation of reactive oxygen species (ROS)-producing enzyme NADPH oxidase impairs the endothelium-dependent expression of vasodilators and vasoconstrictors necessary to maintain neurovascular coupling [,,].

Antihypertensive clinical trials to improve cognition

Given the apparent association between BP and cognitive function, efforts have been made to determine whether improved BP control can be used to delay cognitive decline and reduce dementia risk. To date, evidence from large placebo-controlled, randomized clinical trials (RCTs) has been conflicting [,]. A 2009 Cochrane Review of randomized, double-blind, placebo-controlled trials concluded that there is currently no convincing evidence for the protective effects of antihypertensive use in late-life []. Although several large placebo-controlled RCTs, such as the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) [], the Systolic Hypertension in Europe (SYST-EUR study) [], and the Heart Outcomes Prevention Evaluation (HOPE) study [] have found antihypertensive agents to be protective against cognitive decline and dementia, just as many trials have failed to replicate this finding []. Thus, it is unknown whether BP control alone is enough to reduce the risk of cognitive decline. It is possible that the neuroprotective effects of antihypertensive agents may result from drug-specific neurobiological changes as opposed to (or in addition to) BP lowering [,]. In support of this idea, a meta-analysis of RCTs which compared the neuroprotective properties of different antihypertensive drug classes found angiotensin receptor blockers (ARBs) to be superior to β-blockers, diuretics, and ACE inhibitors for preventing cognitive decline [].

The ability to draw conclusions about the effectiveness of BP interventions for the reduction of cognitive decline has been limited by brief study durations and insufficient power to detect effects. Cognitive decline, even in the course of neurodegenerative disease, is a relatively gradual process, and, as described above, elevated BP in midlife may be the most important determinant of risk for subsequent cognitive and decline and dementia. Thus, midlife may be the most critical window during which BP control must begin. Extended treatment and follow-up periods and larger sample sizes will likely be needed to reliably detect the effects of BP lowering on cognitive measures. By comparison, neurodegenerative and dementia-specific biomarkers (e.g., hippocampal atrophy and CSF-tau) may be more sensitive to treatment-related effects, but their validity as intermediate endpoints remains a subject of debate [,]. Future studies may also benefit from making use of a more comprehensive cognitive battery. The Mini-Mental State Examination (MMSE), which has been used to assess cognitive abilities in the majority of previous trials, is notoriously insensitive to cognitive change, especially in domains of executive functioning and processing speed, making it an especially poor choice for detecting cognitive change in this context [,]. Additionally, effect sizes in previous BP lowering trials may have been attenuated because participants receiving antihypertensive medication often saw only minor reductions in BP compared to participants given placebo. This limitation is addressed in an ongoing trial (SPRINT-MIND) to evaluate the neuroprotective effects of reducing BP to below a specific level (i.e., below 120mm Hg) using one or more antihypertensive agent []. The parent trial to this study (SPRINT) has already demonstrated improved cardiovascular outcomes in the setting of this tighter blood pressure control []. However, the ability of this trial to show benefit in cognitive outcomes will be limited by short follow-up.

Conclusions and future directions

It is clear that hypertension can affect brain structure and function in a manner that increases one’s risk of cognitive decline and dementia. Hypertension, high SBP, and high DBP during midlife have been most consistently linked to late-life cognitive decline and incident dementia. However, hypertension has been associated with early-life and midlife cognitive deficits as well. Although the association between late-life hypertension and cognitive function is less clear, particularly among octogenarians and nonagenarians, limited evidence suggests that mildly elevated BP in late life may be protective against cognitive decline, especially for individuals with a history of longstanding hypertension. Hypertension duration may be an especially important determinant of cognitive decline, as evidence suggests that the damaging neurological effects of hypertension may be cumulative. Few studies have assessed BP longitudinally, and even fewer have attempted to retrospectively determine how lifetime duration of hypertension relates to cognitive function. Given the increasing prevalence of hypertension among younger individuals [], assessing the cumulative effects of elevated BP over the lifespan will be especially important to understanding how BP may influence neurodevelopment and neurodegeneration [].
Recent advances in neuroimaging and physiologic and hemodynamic monitoring have allowed for an improved understanding of the mechanisms through which hypertension affects neurocognitive function. Hypertension, especially in midlife, has been identified as a risk factor for cerebral atrophy, white matter microstructural damage, and cerebral small vessel disease. Evidence suggests that hypertension contributes to the development and progression of such neurological changes by promoting vessel wall remodeling and endothelial dysfunction, which results in autoregulatory deficits. These changes to the neurovascular unit leave the brain vulnerable to hypoperfusion resulting from drops in systemic BP. Although evidence exists to support this model of hypertension-induced cerebrovascular changes, much is still unknown about how these pathophysiological processes directly influence cognitive function and promote Alzheimer’s and vascular dementia in humans.
Additional insights into the role circulatory changes play in cognitive decline will likely come from the study of other markers of vessel function. For example, pulse pressure, a measure of arterial stiffening, which increases with age and exposure to hypertension [], can be used as an additional method to quantify the effects of vascular pathology resulting from chronic hypertension. Elevations in pulse pressure have been associated with cognitive impairment [,], cognitive decline [], cerebral small vessel disease [,], and Alzheimer’s disease biomarkers []. Compared to BP, pulse pressure is believed to more precisely quantify the exposure of target organs such as the brain to potentially harmful pulsatile energy resulting from arterial stiffening [].
A more nuanced understanding of the relationship between BP and neural function will likely be needed before antihypertensive therapies can be effectively employed as an intervention to reduce cognitive decline. Given that many individuals who develop hypertension do so before late-life and experience the harmful effects of hypertension for decades, it is unclear whether specific antihypertensive agents will be able to modify the trajectory of cognitive decline within the span of a multi-year trial. If the effects of hypertension on the brain are cumulative, interindividual differences in the duration and severity of previous hypertension must be considered in future trial design. Because the effects of BP on cognition appear to differ with age, future clinical trials may also benefit from limiting enrollment to specific age groups. Other factors such as race, sex, genetics, and the presence of cerebrovascular morbidity have each been identified as effect modifiers in observational studies and should, therefore, be considered when designing future antihypertensive trials.