Blood pressure drugs shown to decrease risk of Alzheimer's disease dementia. A Johns Hopkins Medicine-led analysis of data previously gathered on more than 3,000 elderly Americans strongly suggests that taking certain blood pressure medications to control blood pressure may reduce the risk of dementia due to Alzheimer's disease (AD), says an October 16, 2013 news release, "Blood pressure drugs shown to decrease risk of Alzheimer's disease dementia." After all, high blood pressure may be linked to dementia. See, "High Blood Pressure Linked to Dementia - Mercola. "But older adults don't develop dementia as a deficiency or lack of blood pressure drugs. Another study says the opposite, that blood pressure drugs can lead to dementia. See, "What's Causing Your Memory Loss? It's Not Necessarily Alzheimer's." And not all people with normal or low blood pressure are immune from dementia. Some types of drugs given for high blood pressure might also cause mental confusion in the elderly. See, "When Patients Suddenly Become Confused - Harvard Health."
An older person may not associate any given drug with brain confusion or other symptoms such as delirium. Many drugs that act on the brain can cause delirium, including narcotic painkillers, sedatives (particularly benzodiazepines), stimulants, sleeping pills, antidepressants, Parkinson's disease medications, and antipsychotics. Beta blockers sometimes prescribed for high blood pressure can be associated with pseudodementia in some older adults. See, "Definition of Drug-Induced Cognitive Impairment in the Elderly." At least knowing the possibilities can bring up questions between patient and doctor. See, "Drug-induced cognitive impairment in the elderly." Histamine H2 receptor antagonists, cardiac medications such as digoxin and beta-blockers, corticosteroids, non-steroidal anti-inflammatory agents and antibiotics can all cause acute, and, less commonly, chronic confusion. Some doctors prescribe certain beta blockers for high blood pressure control. The issue is how they affect elderly patients.
Other medications that may cause delirium are corticosteroids, cimetidine, digoxin, and muscle relaxants. Besides nifedipene and tolterodine (mentioned above), anticholinergic drugs that can cause delirium include antihistamines and some drugs for digestive problems, allergies, and acute asthma attacks. Because there are so many potential culprits (some available over the counter) and because the effects of medications are sometimes additive, an older person may risk delirium even if she or he is taking each drug at the recommended dose.
Toxic reactions to drugs
Medications are common culprits in mental decline. With aging, the liver becomes less efficient at metabolizing drugs, and the kidneys eliminate them from the body more slowly. As a result, drugs tend to accumulate in the body. Elderly people in poor health and those taking several different medications are especially vulnerable. The list of drugs that can cause dementia-like symptoms is long. It includes cardiovascular drugs. Also check out the site, "Drugs That Cause Dementia - HealthCentral." Vitamin B12 deficiency could also cause symptoms mistaken for dementia.
Now in a new study, a report published in a recent edition of the journal Neurology, explains how a team of researchers found that people over the age of 75 with normal cognition who used diuretics, angiotensin-1 receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors showed a reduced risk of AD dementia by at least 50 percent. In addition, diuretics were associated with 50 percent reduced risk in those in the group with mild cognitive impairment.
Beta blockers and calcium channel blockers did not show a link to reduced risk, the scientists reported
"Identifying new pharmacological treatments to prevent or delay the onset of AD dementia is critical given the dearth of effective interventions to date," says the author, Sevil Yasar, M.D., Ph.D., assistant professor of medicine in the Department of Geriatric Medicine and Gerontology at the Johns Hopkins University School of Medicine, according to an October 16, 2013 news release, Blood pressure drugs shown to decrease risk of Alzheimer's disease dementia. "Our study was able to replicate previous findings, however, we were also able to show that the beneficial effect of these blood pressure medications are maybe in addition to blood pressure control, and could help clinicians in selecting an antihypertensive medication based not only on blood pressure control, but also on additional benefits."
Alzheimer's disease is a rapidly increasing clinical and public health issue in the United States' aging population, and the most common cause of intellectual and social decline.Yasar and her colleagues conducted a "post-hoc" analysis of information gathered originally in the so-called Ginkgo Evaluation of Memory Study (GEMS) study, a six-year effort to determine whether use of the herb ginkgo biloba reduced Alzheimer's disease risk.
That study , a double-blind, randomized, controlled clinical trial of 3,069 adults without dementia, aged between 75 and 96 years, began in 2000 and recruited participants from four U.S. cities: Hagerstown, Md.; Pittsburgh, Pa.; Winston-Salem/Greensboro, N.C.; and Sacramento, California.
Yasar said that while the GEMS trial showed no benefit of ginkgo biloba in reducing incidence of dementia, information was also available among the study participants related to their use of several classes of antihypertensive drugs. Extensive studies suggest that high blood pressure is a major risk factor for dementias including AD, and there had been suggestions that drugs used to control blood pressure conferred a protective effect on the brain in addition to controlling blood pressure.
The question, Yasar said, was which ones were associated with reduced AD dementia risk, and which were not
Yasar and colleagues looked at 2,248 of the GEMS subjects, of them 351 reported use of a diuretic, 140 use of ARBs, 324 use of ACE inhibitors, 333 use of calcium channel blockers and 457 use of beta blockers. The average age of this group was 78.7 years, and 47 percent were women. "We were able to confirm previous suggestions of a protective effect of some of these medicines not only in participants with normal cognition, but also in those with mild cognitive impairment," says Yasar in the news release.
"Additionally, we were also able to assess the possible role of elevated systolic blood pressure in AD dementia by placing those within each medication group in categories above and below systolic blood pressures of 140 mmHg, the standard cut-off reading for a diagnosis of hypertension," she explains in the news release.
Yasar cautioned that the analysis had its limitations, owing mostly to the fact that the data collected by the GEMS trial were not gathered to directly measure the effect of the drugs, and by the fact that it was impossible to tell with certainty how well each group of participants complied with their drug treatments. Nor did the research team have information on subjects' use of drugs prior to the study period.
But, she states in the news release, "the consistent pattern we saw of reduced risk of AD dementia associated with these medications warrants further studies, including the use of brain imaging, to better understand the biologic basis of these associations." Such studies, she added, "could lead to identification of new pharmacologic targets for preventive interventions to slow cognitive decline and possibly delay progression of AD dementia."
Other Johns Hopkins investigators who authored the study include Jin Xia, M.S.; Wenliang Yao, Ph.D.; Qian-Li Xue, Ph.D.; and Michelle C. Carlson, Ph.D. Additional researchers include Curt D. Furberg, M.D., Ph.D.; Carla I. Mercado, Ph.D.; Annette L. Fitzpatrick, Ph.D.; Linda P. Fried, M.D.; Claudia H. Kawas, M.D.; Kaycee M. Sink, M.D.; Jeff D. Williamson, M.D.; and Steven T. DeKosky, M.D. The research team included scientists from Wake Forest School of Medicine (Winston-Salem, N.C.), University of Washington (Seattle, Wash.), Columbia University (New York, N.Y.), University of California, Irvine (Irvine, Calif.), University of Pittsburgh (Pittsburgh, Pa.) and University of Virginia (Charlottesville, Va.).
The study was supported by the Ginkgo Evaluation of Memory (GEM) Study; the National Center for Complementary and Alternative Medicine (NCCAM); the Office of Dietary Supplements; the National Institute on Aging; the National Heart, Lung, and Blood Institute; the University of Pittsburgh Alzheimer's Disease Research Center; and the National Institute of Neurological Disorders and Stroke.
Yasar has been funded by NIH and received research support from the John A. Hartford Foundation, the Nathan Shock Memorial Fund, the drug company Sanofi and families of grateful patients. She served as a consultant for the Charles River Company. For more information, check out the Johns Hopkins Department of Geriatric Medicine and Gerontology.
Even for elderly people with no signs of dementia, those with hardening of the arteries are more likely to also have the beta-amyloid plaques in the brain that are a hallmark of Alzheimer's disease, according to a study published in the Oct. 16, 2013, online issue of Neurology®, the medical journal of the American Academy of Neurology. In elderly, hardening of the arteries is linked to plaques in the brain
"This is more evidence that cardiovascular health leads to a healthy brain," said study author Timothy M. Hughes, PhD, of the University of Pittsburgh, according to the October 16, 2013 news release, "In elderly, hardening of arteries linked to plaques in brain." The study involved 91 people with an average age of 87 who did not have dementia. Researchers took scans of the participants' brains to measure any plaques in the brain. The amount of stiffness in the participants' arteries was measured about two years later.
Half of all participants had beta-amyloid plaques
People with beta-amyloid plaques were more likely to have high systolic blood pressure, higher average blood pressure and higher arterial stiffness as measured with the brachial-ankle method. For every unit increase in brachial-ankle arterial stiffness, people were twice as likely to have beta-amyloid plaques in the brain. Arterial stiffness was highest in people who had both amyloid plaques and white matter hyperintensities in the brain, or brain lesions.
"These two conditions may be a 'double-hit' that contributes to the development of dementia," Hughes said in the news release. "Compared to people who had low amounts of amyloid plaques and brain lesions, each unit of increase in arterial stiffness was associated with a two- to four-fold increase in the odds of having both amyloid plaques and a high amount of brain lesions."
Hughes noted that the relationship between arterial stiffness and amyloid plaque was not changed when regular resting blood pressure was taken into account. "This study adds to growing evidence that hardening of the arteries is associated with cerebrovascular disease that does not show symptoms. Now we can add Alzheimer's type lesions to the list," Hughes said. The National Institutes of Health and the National Institute on Aging supported the study. To learn more about brain health, please visit the American Academy of Neurology (AAN) patient information website. http://www.aan.com/patients.
The American Academy of Neurology, an association of more than 26,000 neurologists and neuroscience professionals, is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer's disease, stroke, migraine, multiple sclerosis, brain injury, Parkinson's disease and epilepsy.
Finding Alzheimer's disease before symptoms start, Johns Hopkins researchers identify biomarkers in spinal fluid
You may also want to see another study about finding Alzheimer's disease before symptoms start. Johns Hopkins School of Medicine researchers say that by measuring levels of certain proteins in cerebrospinal fluid (CSF), they can predict when people will develop the cognitive impairment associated with Alzheimer's disease years before the first symptoms of memory loss appear.
Identifying such biomarkers could provide a long-sought tool to guide earlier use of potential drug treatments to prevent or halt the progression of Alzheimer's while people are still cognitively normal. To date, medications designed to stop the brain damage have failed in clinical trials, possibly, many researchers say, because they are given to those who already have symptoms and too much damage to overcome.
"When we see patients with high blood pressure and high cholesterol, we don't say we will wait to treat you until you get congestive heart failure. Early treatments keep heart disease patients from getting worse, and it's possible the same may be true for those with pre-symptomatic Alzheimer's," says Marilyn Albert, Ph.D., according to the October 16, 2016 news release, "Finding Alzheimer's disease before symptoms start." Albert is a professor of neurology at the Johns Hopkins University School of Medicine. She is primary investigator of the study whose results are published in the Oct. 16 issue of the journal Neurology. "But it has been hard to see Alzheimer's disease coming, even though we believe it begins developing in the brain a decade or more before the onset of symptoms," she adds.
For the new study, the Hopkins team used CSF collected for the Biomarkers for Older Controls at Risk for Dementia (BIOCARD) project between 1995 and 2005, from 265 middle-aged healthy volunteers. Some three-quarters of the group had a close family member with Alzheimer's disease, a factor putting them at higher than normal risk of developing the disorder. Annually during those years and again beginning in 2009, researchers gave the subjects a battery of neuropsychological tests and a physical exam.
The researchers found that particular baseline ratios of two proteins — phosphorylated tau and beta amyloid found in CSF — were a harbinger of mild cognitive impairment (often a precursor to Alzheimer's) more than five years before symptom onset
They also found that the rate of change over time in the ratio was also predictive. The more tau and the less beta amyloid found in the spinal fluid, the more likely the development of symptoms. And, Albert says, the more rapidly the ratio of tau to beta amyloid goes up, the more likely the eventual development of symptoms.
Researchers have known that these proteins were in the spinal fluid of patients with advanced disease. "But we wondered if we could measure something in the cerebral spinal fluid when people are cognitively normal to give us some idea of when they will develop difficulty," Albert says in the news release. "The answer is yes."
Alzheimer's disease disrupts critical metabolic processes that keep neurons healthy
These disruptions cause neurons to stop working, lose connections with other nerve cells, and finally die. The brains of people with Alzheimer's have an abundance of two abnormal structures — amyloid plaques and "tangles" made of tau.
The plaques are sticky accumulations of beta-amyloid that build up outside of the neurons, while the tangles form inside the neurons. When there are too many tangles inside the cells, the cells start to die. In a normal brain, tau helps the skeleton of the nerve cell maintain itself. When too many phosphate groups attach themselves to tau, too much of the protein develops and tangles form.
Albert says researchers believe that the relative amount of beta-amyloid in the spinal fluid decreases as Alzheimer's progresses because it is getting trapped in the plaques and therefore isn't entering the fluid
Though the BIOCARD study has been going on for nearly two decades, this is some of the first predictive data to come out of it, Albert says, owing to the length of time it takes for even high-risk middle-aged people to progress to dementia. Only 53 of the original patients have progressed to mild cognitive impairment or dementia, giving a sample size just large enough to draw some preliminary conclusions. These first symptoms include memory disruptions such as repeating oneself, forgetting appointments, and forgetting what others have said.
Albert cautions that the biomarker ratio at this point is not accurate enough to precisely predict whether a particular individual is progressing to dementia, and further analysis of information about the group over time is needed.
However, she says, if the findings prove valid, they not only could guide the use of early treatments with drugs that become available, but also may also help test new drugs by seeing if they alter the rate at which the proteins change over time.
The research was supported by grants from the National Institutes of Health's National Institute on Aging (U01-AG03365 and P50-AG005146). Other Johns Hopkins researchers involved in the study include Abhay Moghekar, M.B.B.S.; Shanshan Li; Yi Lu; Ming Li; Mei-Cheng Wang, Ph.D.; and Richard O'Brien, M.D., Ph.D. Albert reports that she serves on scientific advisory boards for Eli Lilly, Eisai, Genentech, Biogen and AgeneBio, and receives research support from GE Healthcare. For more information on Albert, click here.