Brain-imaging tool and stroke risk test help identify cognitive decline early

The connection between stroke risk and cognitive decline has been well established by previous research. Individuals with higher stroke risk, as measured by factors like high blood pressure, have traditionally performed worse on tests of memory, attention and abstract reasoning.

The current small study demonstrated that not only stroke risk, but also the burden of plaques and tangles, as measured by a UCLA brain scan, may influence cognitive decline.

The imaging tool used in the study was developed at UCLA and reveals early evidence of amyloid beta “plaques” and neurofibrillary tau “tangles” in the brain — the hallmarks of Alzheimer’s disease.

The study, published in the April issue of the Journal of Alzheimer’s Disease, demonstrates that taking both stroke risk and the burden of plaques and tangles into accout may offer a more powerful assessment of factors determining how people are doing now and will do in the future.

"The findings reinforce the importance of managing stroke risk factors to prevent cognitive decline even before clinical symptoms of dementia appear," said first author Dr. David Merrill, an assistant clinical professor of psychiatry and biobehavioral sciences at the Semel Institute for Neuroscience and Human Behavior at UCLA.

This is one of the first studies to examine both stroke risk and plaque and tangle levels in the brain in relation to cognitive decline before dementia has even set in, Merrill said.

According to the researchers, the UCLA brain-imaging tool could prove useful in tracking cognitive decline over time and offer additional insight when used with other assessment tools.

For the study, the team assessed 75 people who were healthy or had mild cognitive impairment, a risk factor for the future development of Alzheimer’s. The average age of the participants was 63.

The individuals underwent neuropsychological testing and physical assessments to calculate their stroke risk using the Framingham Stroke Risk Profile, which examines age, gender, smoking status, systolic blood pressure, diabetes, atrial fibrillation (irregular heart rhythm), use of blood pressure medications, and other factors.

In addition, each participant was injected with a chemical marker called FDDNP, which binds to deposits of amyloid beta plaques and neurofibrillary tau tangles in the brain. The researchers then used positron emission tomography (PET) to image the brains of the subjects — a method that enabled them to pinpoint where these abnormal proteins accumulate.

The study found that greater stroke risk was significantly related to lower performance in several cognitive areas, including language, attention, information-processing speed, memory, visual-spatial functioning (e.g., ability to read a map), problem-solving and verbal reasoning.

The researchers also observed that FDDNP binding levels in the brain correlated with participants’ cognitive performance. For example, volunteers who had greater difficulties with problem-solving and language displayed higher levels of the FDDNP marker in areas of their brain that control those cognitive activities.

"Our findings demonstrate that the effects of elevated vascular risk, along with evidence of plaques and tangles, is apparent early on, even before vascular damage has occurred or a diagnosis of dementia has been confirmed," said the study’s senior author, Dr. Gary Small, director of the UCLA Longevity Center and a professor of psychiatry and biobehavioral sciences who holds the Parlow–Solomon Chair on Aging at UCLA’s Semel Institute.

Researchers found that several individual factors in the stroke assessment stood out as predictors of decline in cognitive function, including age, systolic blood pressure and use of blood pressure–related medications.

Small noted that the next step in the research would be studies with a larger sample size to confirm and expand the findings.

Study Explains Why Fainting Can Result From Blood Pressure Drug Used In Conjunction With Other Disorders

A new study led by a Canadian research team has identified the reason why prazosin, a drug commonly used to reduce high blood pressure, may cause lightheadedness and possible fainting upon standing in patients with normal blood pressure who take the drug for other reasons, such as the treatment of PTSD and anxiety.

According to University of British Columbia researcher and study team leader Dr. Nia Lewis, the body is in constant motion leading to changes in blood pressure with every activity. For example, when standing, the body copes with the sudden drop in blood pressure by constricting peripheral vessels to concentrate the blood in the areas that help stabilize the body.

This study found that prazosin prevents this process by blocking the α1-adrenoreceptor, a critical pathway that allows the vessels to constrict. This physiological response is dangerous for individuals with normal blood pressure who take prazosin to treat the symptoms of PTSD and anxiety, for the act of standing up can cause light-headedness and/or fainting.

The study, entitled “Initial orthostatic hypotension and cerebral blood flow regulation: effect of α1-adrenoreceptor activity,” is published in the American Journal of Physiology–Regulatory, Integrative and Comparative Physiology.

Methodology

Eight males and four females, with an average age of 25, and all of whom had normal blood pressure, were enrolled in the cross-over trial.  On day one of the study, participants were weighed, measured, and familiarized with the blood pressure monitoring equipment and procedures that would be used.

On the next visit, participants stayed overnight at the research facility in order to control for activity and diet. The following morning they were given either prazosin (1mg/20kg body weight) or a placebo, and instructed to lie down.  After 20 minutes, they were told to rise in one smooth motion from the lying-down position to standing, and their blood pressure and cerebral blood flow was continuously monitored. They were required to remain standing for three minutes or until they felt severe lightheadedness and dizziness, or felt as if they were about to faint.

On their third and final visit the participants underwent the same procedure as on the second visit. At this visit, however, they received the placebo if they had previously been given the medication, and vice versa.

Results

The investigators found that:

• All but one of the 12 participants who took the medication experienced temporary dizziness or lightheadedness upon standing.
• All participants who took the placebo were able to complete the three-minute standing test. By contrast, only 2 of the 12 were able to complete the standing test after taking prazosin.
• After taking prazosin, none of the participants were able to attain normal blood pressure levels after standing. As a result, blood flow to the brain was reduced and subjects were unable to stand for 3 minutes as they began to experience the onset of fainting.
• When the participants had taken prazosin, mean arterial blood pressure and systolic blood pressure was significantly lower—by 15 percent— when lying down compared to when they took the placebo. Mean arterial blood pressure also fell for a longer period (11 seconds versus eight for placebo) after participants stood up following consumption of the medication, resulting in a lower arterial pressure levels.
• Blood flow to the brain, as measured by cerebral blood flow velocity, was not different when lying down. However, brain blood flow in the prazosin trial was reduced by 33 percent more than in than compared with the placebo trial.

Conclusions

“We were able to determine that, because prazosin shuts down a pathway that is critical to regulate blood pressure, the capacity to safely control blood flow to the brain was also reduced to a level that could induce fainting,” said Dr. Lewis. “No study has examined the effects of prazosin on the interaction between blood pressure and blood flow to the brain. The findings derived from this study show a mechanism of how prazosin causes fainting,” she explained.

Importance of the Findings

“This study highlights the importance of a key pathway in the body’s blood pressure system, known as the α1-adrenergic sympathetic pathway, in ensuring the recovery of blood pressure following standing and how important this pathway is in ensuring blood flow to the brain is not reduced to a level where fainting may occur,” said Dr. Lewis.

Additionally, this study provides a cautionary alert to those who are prescribed prazosin, for other conditions besides hypertension. 

Researchers look to breath to identify stress

According to a new pilot study, published in IOP Publishing’s Journal of Breath Research, there are six markers in the breath that could be candidates for use as indicators of stress.

The researchers hope that findings such as these could lead to a quick, simple and non-invasive test for measuring stress; however, the study, which involved just 22 subjects, would need to be scaled-up to include more people, over a wider range of ages and in more “normal” settings, before any concrete conclusions can be made, they state.

Lead-author of the study, Professor Paul Thomas, said: “If we can measure stress objectively in a non-invasive way, then it may benefit patients and vulnerable people in long-term care who find it difficult to disclose stress responses to their carers, such as those suffering from Alzheimer’s.”

The study, undertaken by researchers at Loughborough University and Imperial College London, involved 22 young adults (10 male and 12 female) who each took part in two sessions: in the first, they were asked to sit comfortably and listen to non-stressful music; in the second, they were asked to perform a common mental arithmetic test that has been designed to induce stress.

A breath test was taken before and after each session, whilst heart-rates and blood pressures were recorded throughout. The breath samples were examined using a technique known as gas chromatography-mass spectrometry, and then statistically analysed and compared to a library of compounds.

Two compounds in the breath – 2-methyl, pentadecane and indole – increased following the stress exercise which, if confirmed, the researchers believe could form the basis of a rapid test.

A further four compounds were shown to decrease with stress, which could be due to changes in breathing patterns.

“What is clear from this study is that we were not able to discount stress. It seems sensible and prudent to test this work with more people over a range of ages in more normal settings.

“We will need to think carefully about experimental design in order to explore this potential relationship further as there are ethical issues to consider when deliberately placing volunteers under stress. Any follow up study would need to be led by experts in stress,” Professor Thomas continued.

Breath profiling has become an attractive diagnostic method for clinicians, and recently researchers have found biomarkers associated with tuberculosis, multiple cancers, pulmonary disease and asthma. It is still unclear how to best manage external factors, such as diet, environment and exercise, which can affect a person’s breath sample.

“It is possible that stress markers in the breath could mask or confound other key compounds that are used to diagnose a certain disease or condition, so it is important that these are accounted for,” said Professor Thomas.

The researcher’s initial assumptions are that stressed people breathe faster and have increased pulse rates and an elevated blood-pressure, which is likely to change their breath profile. They emphasise, however, that it is too soon to postulate the biological origins and the roles of the compounds as part of a stress-sensitive response.

Mystery disease unraveled by Stanford neurologist

At first, Marc Laderriere thought that his decreasing energy was just age catching up to him — he was about to be 50. But something about that explanation didn’t sit right.

"At one point, one of my doctors said, ‘This is definitely a little strange. I don’t know what you have, but it could be nerves,’" Laderriere recalled.

He was experiencing a set of symptoms that were unusual but did not strike him as significant: Hot weather sapped his strength and made him dizzy, but he was sweating less. In cool weather, he never got goose bumps.

As a young man growing up in France, Laderriere had always been active. “I did a lot of skiing, a lot of swimming,” he said. When he came to work in the United States, as a director of wine sales for the Vina Robles Winery & Vineyards in Paso Robles, he said he became a workaholic. “I completely accepted that way of life,” he said.

The more he traveled for his job, the less time and attention he paid to his health until he recognized, with some discomfort, that he was not in such great shape any more. He knew he should add exercise to his daily routine, but the fatigue he felt was overwhelming.

Laderriere, who lives in Paso Robles, started first with visits to local doctors. He had a variety of standard tests, with the thought that he might have developed diabetes. That was not the case. When one physician suggested it could be nerves, he went to see a local neurologist who sent him back to his original physician, still without a diagnosis. His symptoms continued and, finally, a local doctor suggested Stanford Hospital & Clinics.

During his first visit, he met with a group of physicians who asked him a lot questions,. “They were picking my brain,” he said, “asking me, ‘What’s wrong with this?’ I did not think to mention to them that I wasn’t sweating, but my wife was with me and she did. One of the doctors said, ‘Hmm, I think you may want to meet Dr. Jaradeh.’”

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Can Blood Pressure Drugs Reduce the Risk of Dementia?

People taking the blood pressure drugs called beta blockers may be less likely to have changes in the brain that can be signs of Alzheimer’s disease and other types of dementia, according to a study released today that will be presented at the American Academy of Neurology’s 65th Annual Meeting in San Diego, March 16 to 23, 2013. The study involved 774 elderly Japanese-American men who took part in the Honolulu-Asia Aging Study. Autopsies were performed on the men after their death. Of the 774 men, 610 had high blood pressure or were being treated with medication for high blood pressure. Among those who had been treated (about 350), 15 percent received only a beta blocker medication, 18 percent received a beta blocker plus one or more other medications, and the rest of the participants received other blood pressure drugs.

The study found that all types of blood pressure treatments were clearly better than no treatment. However, men who had received beta blockers as their only blood pressure medication had fewer abnormalities in their brains compared to those who had not been treated for their hypertension, or who had received other blood pressure medications. The brains of participants who had received beta blockers plus other medications showed an intermediate reduction in numbers of brain abnormalities.

These included two distinct types of brain lesion: those indicating Alzheimer’s disease, and lesions called microinfarcts, usually attributed to tiny, multiple, unrecognized strokes. Study participants who had taken beta blockers alone or in combination with another blood pressure medication had significantly less shrinkage in their brains.

“With the number of people with Alzheimer’s disease expected to grow significantly as our population ages, it is increasingly important to identify factors that could delay or prevent the disease,” said study author Lon White, MD, of the Pacific Health Research and Education Institute in Honolulu. “These results are exciting, especially since beta blockers are a common treatment for high blood pressure.”

Earlier research has shown that high blood pressure in midlife is a strong risk factor for dementia.

Research offers new targets for stroke treatments

New research from the University of Georgia identifies the mechanisms responsible for regenerating blood vessels in the brain.

Looking for ways to improve outcomes for stroke patients, researchers led by the UGA College of Pharmacy assistant dean for clinical programs Susan Fagan used candesartan, a commonly prescribed medication for lowering blood pressure, to identify specific growth factors in the brain responsible for recovery after a stroke.

The results were published online Dec. 4 in the Journal of Pharmacology and Experimental Therapeutics

Although candesartan has been shown to protect the brain after a stroke, its use is generally avoided because lowering a person’s blood pressure quickly after a stroke can cause problems-like decreasing much-needed oxygen to the brain-during the critical period of time following a stroke.

"The really unique thing we found is that candesartan can increase the secretion of brain derived neurotrophic factor, and the effect is separate from the blood pressure lowering effect," said study coauthor Ahmed Alhusban, who is a doctoral candidate in the College of Pharmacy. "This will support a new area for treatments of stroke and other brain injury."

Alhusban and Fagan worked with Anna Kozak, a research scientist in the college, and Adviye Ergul, a professor and director of the physiology graduate program at Georgia Health Sciences University. They are the first to show that the positive effects of candesartan on brain blood vessel growth are caused by brain derived neurotrophic factor, or BDNF.

The research shows that when candesartan blocks the angiotensin II type 1 receptor, which lowers blood pressure, it stimulates the AT2 receptor and increases the secretion of BDNF, which encourages brain repair through the growth of new blood vessels.

"BDNF is a key player in learning and memory," said Fagan, the Albert W. Jowdy Professor. "A reduction of BDNF in the brain has been associated with Alzheimer’s disease and depression, so increasing this growth factor with a common medication is exciting."

AT2 is a brain receptor responsible for angiogenesis, or the growth of new blood vessels from pre-existing vessels. Angiogenesis is a normal and vital process in human growth and development-as well as in healing.

(Image: iStock)

High blood pressure damages the brain in early middle age

Uncontrolled high blood pressure damages the brain’s structure and function as early as young middle-age, and even the brains of middle-aged people who clinically would not be considered to have hypertension have evidence of silent structural brain damage, a study led by researchers at UC Davis has found.

The investigation found accelerated brain aging among hypertensive and prehypertensive individuals in their 40s, including damage to the structural integrity of the brain’s white matter and the volume of its gray matter, suggesting that vascular brain injury “develops insidiously over the lifetime with discernible effects.”

The study is the first to demonstrate that there is structural damage to the brains of adults in young middle age as a result of high blood pressure, the authors said. Structural damage to the brain’s white matter caused by high blood pressure previously has been associated with cognitive decline in older individuals.

Published online today in the medical journal The Lancet Neurology, the study will appear in print in the December 2012 issue. It emphasizes the need for lifelong attention to vascular risk factors for brain aging, said study senior author Charles DeCarli, professor of neurology and director of the UC Davis Alzheimer’s Disease Center.