How Sensory Stimulation Can Help Alzheimer’s

Originally used as a therapy in Europe, sensory stimulation has gained prominence in the United States as a treatment for Alzheimer’s disease.

Using everyday objects, therapists can trigger emotions and memories in seniors who have lost their ability to connect with the world around them.

Sensory Stimulation Therapy

Sensory stimulation uses everyday objects to arouse one or more of the five senses (hearing, sight, smell, taste and touch), with the goal of evoking positive feelings.

Used in Europe since the 1960s, this therapy was originally designed to help people with learning disabilities. It was a way for them to explore a safe, stimulating environment that provided age-appropriate and enjoyable activity.

Since then, the therapy has become widely used to treat other conditions, including:

• Alzheimer’s
• Autism
• Brain injuries
• Chronic pain
• Other forms of dementia

Ways Sensory Stimulation Can Affect Alzheimer’s

As Alzheimer’s progresses, a senior’s ability to communicate and perform everyday activities declines. Giving these seniors means to express themselves, when they can no longer do so with words, can help them feel safe and relax. This can improve their:

1. Mood
2. Self-esteem
3. Well-being

Additionally, by drawing attention to a particular item, sensory stimulation encourages memories and responses from seniors suffering from Alzheimer’s:

For instance, art or photos can trigger emotions and memories for seniors who no longer speak. A senior who has not expressed a word in months might suddenly smile or want to pick up a pencil and draw. That art form eventually can become a means for the senior to communicate, either through personal works of art or simply by sharing the experience.

Ways Sensory Stimulation Engages Seniors

Sudden drops in blood pressure may increase risk of dementia

Dementia affects tens of millions of people in the United States. New research suggests that those who experience sudden blood pressure drops in their middle age may be more likely to develop dementia in old age.

New research finds long-term link between sudden drops in BP and the risk of dementia in later life.

Alzheimer's disease, the most common form of dementia, currently ranks as the sixth leading cause of death in the U.S. In fact, it is estimated that 1 in 3 U.S. elders dies with a form of dementia.

New research indicates that middle-aged people who experience sudden drops in their blood pressure (BP) may be at risk of developing dementia and serious cognitive decline when they reach old age.

The study was conducted by researchers from the Johns Hopkins Bloomberg School of Public Health in Baltimore, MD, and the findings were presented at the American Heart Association's Epidemiology and Prevention/Lifestyle 2017 Scientific Sessions in Portland, OR.

Chronically low BP may cause dizziness, fatigue, nausea, or fainting. Temporary, rapid drops in BP bear the name "orthostatic hypotension" (OP) and may cause serious damage; they stop the necessary blood flow from reaching the brain.

Previous studies have indicated a link between OP and cognitive impairment in seniors, but the new Johns Hopkins study - led by Andreea Rawlings, Ph.D., a post-doctoral researcher in the Department of Epidemiology at the Bloomberg School - is the first to examine the long-term correlations between the two.

The researchers examined clinical data from the Atherosclerosis Risk in Communities study, which collected information on 15,792 participants aged between 45 and 64 in 1987, the year of enrollment.

Patients with OP are 40 percent more likely to have dementia

For the new study, Rawlings and team isolated the data on 11,503 patients who had no history of heart disease and visited the hospital for the first time. Scientists took the patients' BP after they had lay down for 20 minutes.

The researchers defined OP as a rapid drop of 20 millimeters of mercury (mm Hg) or more in systolic BP, or 10 mm Hg or above in diastolic BP.

Approximately 6 percent of the participants, or 703 individuals, met these criteria.

The team clinically followed the participants for the following two decades or more.

They found that people with OP upon their first visit had a 40 higher risk of developing dementia than their OP-free counterparts. Patients with OP also had 15 percent more cognitive decline.

"Even though these episodes are fleeting, they may have impacts that are long lasting. We found that those people who suffered from orthostatic hypotension in middle age were 40 percent more likely to develop dementia than those who did not. It is a significant finding and we need to better understand just what is happening."

Andreea Rawlings, lead author

As this is an observational study, researchers cannot establish causality or explain whether OP is an indicator of another disease responsible for the cognitive decline. However, they speculate that the decrease in the blood flow to the brain may play a role.

The lead author of the study also acknowledges the study's limitation that arises from not knowing whether the patients had a singular episode of OP, or whether they had lived with the recurring symptoms over time.

"Identifying risk factors for cognitive decline and dementia is important for understanding disease progression, and being able to identify those most at risk gives us possible strategies for prevention and intervention," Rawlings says. "This is one of those factors worth more investigation."

Learn how high BP is linked to a lower risk of Alzheimer's.

Written by Ana Sandoiu

Seniors Load Up on Psych Meds (JAMA Internal Medicine)

Older Americans are being over-prescribed, suggested new research finding that the percentage of people over 65 taking three or more mind-altering drugs has more than doubled in the past decade.

What's more, nearly half of these patients were not formally diagnosed with mental health issues, insomnia, or pain conditions.

Researchers found that 1.4% of doctor visits by seniors involved three or more central nervous system-affecting medication in 2013 compared to 0.6% in 2004, meaning 3.68 million doctor visits a year involve older patients taking three or more brain-altering drugs.

The authors said the latest findings are "concerning" as combining multiple drugs such as opioids, antidepressants, tranquilizers, and antipsychotics are associated with serious risks, particularly in seniors.

"We hope that the newer prescribing guidelines for older adults encourage providers and patients to reconsider the potential risks and benefits from these combinations," said lead author Donovan Maust, MD, MS, of the University of Michigan.

2017-02-15T15:30:00-0500

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FDA Clears App to Screen for Cognitive Impairment

The FDA recently granted UK-based Cambridge Cognition Holdings 501(k) clearance to market CANTAB Mobile as a device that can detect early stages of clinically relevant mental impairment in older adults.

For older adults, early detection of dementia and Alzheimer's is crucial for receiving timely treatment and planning the future. The Cambridge Neuropsychological Test Automated Battery (CANTAB) was developed initially more than 30 years ago as a group of tests for use in neurologic and psychiatric research. The Paired Associates Learning (PAL) test is one of the tests to detect features of cognitive impairment that could be signs of early Alzheimer's disease.

CANTAB Mobile translates the relatively complex, specialist-administered PAL test into a self-guided, iPad-based exam that can be administered at a larger scale, such as in a primary care office or as part of large clinical studies.

Assessment via the medical app is a simple, 10-minute, point-of-care exam anyone can use anywhere. CANTAB Mobile's platform includes three tests focused on episodic memory, mood, and the ability to perform regular, daily activities. The test also takes age, gender, and education into consideration, and results, in the form of a 1-page physician's report, can reassure the user or refer patients to next steps.

We've seen some other examples of neurologic and psychiatric assessment tools being translated into mobile platforms. One example is the HAND in HAND ResearchKit app from the University of Nebraska, which focused on the cognitive impacts of chronic HIV. In that study, a platform called Brain Baseline was used to offer plug-and-play neurologic assessments.

According to a description of CANTAB Mobile in Translational Neuropsychopharmacology (Robbins et al, Springer, 2016) by researchers from Cambridge Cognition Holdings, about 25% of ~10,000 patients screened in the UK were identified as having clinically significant memory problems. Hopefully, we'll see more data on the real-world accuracy of large-scale screening using CANTAB Mobile, and the downstream effects of that.

This post originally appeared on iMedicalApps.com.

2017-03-10T15:00:00-0500

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ACC: FOURIER Substudy May Help Refute 'Dr. Google'

WASHINGTON -- Reaching very low LDL levels with a PCSK9 inhibitor was not associated with any increase in neurocognitive adverse events, according to the largest and most rigorous study to assess the topic to date.

Small and preliminary studies have raised concerns over the possibility of the neurocognitive effects of statins. Though most clinicians and scientists have not shared these concerns, consumers and patients have expressed broad suspicions about statins.

"In my office every day my patients say that statins make them dumb. I can comfortably tell my patients that we actually studied whether this makes you dumb, and it didn't," said Sandra Lewis (Oregon Health and Science University).

The new study, called EBBINGHAUS, was a substudy of the enormous FOURIER trial, published Friday, which compared the cardiovascular event impact of PCSK9 inhibition with evolocumab (Repatha) or placebo. EBBINGHAUS tested the hypothesis that "the addition of evolocumab to statin therapy in patients with clinically evident vascular disease does not adversely affect cognitive function."

The results were presented at the American College of Cardiology meeting here by Robert Giugliano (Brigham & Women's Hospital). "We all need your help to combat Dr. Google," he told the media at a press conference.

EBBINGHAUS enrolled 1,974 patients from the FOURIER trial. The primary analysis was based on the cohort of 1,204 patients who had baseline and follow-up cognitive testing, consisting of a battery of tests, patient surveys, and investigator-reported adverse events. There were no significant differences between the groups in the primary endpoint, the spatial working memory strategy index, or any of the other measures in the study.

"It's out there on the internet that statins make people stupid," said Roger Blumenthal (Johns Hopkins), a trial discussant. EBBINGHAUS "advanced the field by showing that pharmacologically achieved low levels of LDL are safe," he said. But Giugliano and others acknowledged that the trial tested the effect of a PCSK9 inhibitor and did not assess the effects of statins, which are much more widely used. But the lack of adverse effects in patients reaching extremely low LDL levels (30 mg/dL) in the FOURIER trial will likely add much reassurance.

Giugliano reported that there were no differences between older and younger patients in EBBINGHAUS. But the trial did not address the concerns that have been raised about the effects of very long-term lipid-lowering therapy for primary prevention.

2017-03-19T10:18:13-0400

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NeuroBreak: Opioid Scripts Down at the VA; Paxil on Trial

The VA's "Opioid Safety Initiative" reduced the number of veterans who were given a prescription for opioids by a quarter, and almost half as many vets were getting opioids and benzodiazepines concomitantly after the policy was implemented. Also, more than a third fewer patients were getting high doses of opioids. Now, more VA patients are getting non-opioid therapies, naloxone, and treatment for substance use disorders. "The VA provides an example of how technology, data, and organizational leadership can make a difference in improving opioid prescribing," Walid Gellad, MD, MPH, of the VA, and colleagues write. (JAMA Internal Medicine)

A trial begins today in Chicago around the potential role that paroxetine (Paxil) played in the suicide of a 57-year-old lawyer who was taking the antidepressant. The lawsuit alleges that drugmaker GlaxoSmithKline failed to adequately warn Dolin's doctor about an increased risk of suicidal behavior in adults with the drug. The only other Paxil suicide case to go to trial was in 2001 in Cheyenne, Wyo., and resulted in a multi-million dollar verdict against GSK. In that case, Donald Schell shot and killed his wife, his daughter, his granddaughter, and then himself while under the influence of Paxil. (Law360)

The FDA has warned against transvascular autonomic modulation (TVAM) for neurological disorders. In a safety communication, the agency cautioned that at least one practitioner is using the procedure -- which is essentially balloon angioplasty of the jugular vein -- to treat a wide range of neurological disorders. In 2012, the FDA warned against using the same procedure to treat so-called chronic cerebrospinal venous insufficiency (CCSVI) in multiple sclerosis patients. (MedPage Today)

While many recent reports have indicated falling dementia rates around the world, a new report from the Netherlands says the prevalence is on the rise in that country. Dutch researchers found a 2% rise each year over the last 23 years -- but the data come from an analysis of primary care records, leaving plenty of room for caveats. (Alzforum)

2017-03-14T12:00:00-0400

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Encouragement to consult GPs for memory concerns did not ensure earlier dementia diagnosis

Encouraging patients with potential memory deficits to seek early advice from a general practitioner (GP) empowered more of them to consult their GP, but GPs did not change their behavior and refer more to memory services or for earlier overall diagnosis of dementia, according to a trial publishing in PLOS Medicine by Gill Livingston, of University College London, and colleagues.

Early diagnosis of dementia allows patients and families to plan for the future, receive symptomatic treatment, access social and voluntary care, and delays care home entry, with few negative effects. To determine whether reaching out directly to patients could lead to earlier diagnoses of dementia, Livingston and colleagues conducted a cluster-randomized controlled trial in 22 general practices in South-East England. Eligible patients from 11 practices assigned to the intervention (6387 patients who were >70 years old, living in their own homes and without known diagnosis of dementia) received a personally signed letter and information leaflets with information about overcoming common barriers to accessing dementia diagnosis and care, while patients in 11 control practices (8171 patients who met the same criteria) received usual care. Compared to control, the intervention had no significant effect on the primary outcome, earlier dementia diagnosis at memory clinics, as measured by the Mini Mental State Examination. There was a significant increase in the proportion of patients in the intervention practices consulting their GPs with suspected memory problems compared to control practices, but no difference in proportion of patients who were referred to memory specialist clinics by the GPs.

The authors note that it is unclear why additional patients presenting to GPs did not lead to earlier overall diagnosis of dementia, though they speculate that some patients may have been "worried well", or that early memory problems were not recognized by the GPs.

The authors suggest that to increase early diagnosis it may be necessary to inform both sides of the doctor-patient relationship: "Interventions likely to be successful in decreasing cognitive severity at diagnosis will need to target both the public and practitioners and particularly concentrate on the benefits of earlier diagnosis."

This article appears in the PLOS Medicine Special Issue on Dementia, publishing every week throughout March.

Article: Effectiveness of an intervention to facilitate prompt referral to memory clinics in the United Kingdom: Cluster randomised controlled trial, Gill Livingston , Gianluca Baio, Andrew Sommerlad, Simon de Lusignan, Spyridon Poulimenos, Steve Morris, Greta Rait, Juanita Hoe, PLOS Medicine, doi: 10.1371/journal.pmed.1002252, published 14 March 2017.

New Workplace Violence Guidelines: Psychiatric Times & Neurology Times

The Occupational Safety and Health Administration has issued revised guidelines regarding workplace violence in the healthcare setting.

Looking for a good neurology app? Here's one physician's top 10 list.

Two recent studies explore the link between sleep dysfunction and cognitive impairment in elderly individuals.

In this editorial, a psychiatrist discusses the importance of mental health policies.

Cardio workouts may enhance functional ability in older adults with mild cognitive impairment, according to a recent pilot study.

This weekly news roundup is brought to our readers by our partners at Psychiatric Times & Neurology Times, which is a part of UBM Medica. (Free registration is required.)

2017-03-07T18:30:00-0500

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Pearls from: Ronald Petersen, MD, PhD

Questions have been raised about the amyloid hypothesis since several therapeutics aimed at the protein have failed. But Ronald Petersen, MD, PhD, of the Mayo Clinic, argues that the amyloid hypothesis isn't dead yet.

The following is a transcript of the discussion:

I think the amyloid hypothesis is still well, alive, and kicking. It's been challenged along the way because of some of the treatment failures aimed at amyloid itself. Nevertheless, I think there are certain reasons why those trials may have failed, and so the underlying hypothesis that amyloid may be the initiating event in a cascade of events that leads to maybe tau abnormalities, metabolic abnormalities, inflammation, and ultimately clinical changes down the road, I think that is still a viable hypothesis and certainly being investigated by many people. Now with some of our new imaging techniques, we can follow the deposition of amyloid, the deposition of tau in the brain over time and track clinical progression.

Now, we can see those same two entities, the plaques and the tangles, in the living individual using PET imaging. So now we can track people who are clinically normal, and as they progress on to cognitive impairment, we can see if the amyloid precedes the clinical impairment. We can see the amyloid develop. We can also use them, then, as targets of treatment and indices of whether the treatment is working.

So if we have an amyloid-based therapy, we image somebody at the outset of the trial, see if they have the plaques in the brain. We treat them for a year, year and a half, whatever it takes, and measure the amount of amyloid in the brain again at the end of the therapeutic trial with PET imaging and see if, in fact, we have been successful at removing the amyloid from the brain.

We can do the same thing with tau now. Tau is relatively new on the scene, but we can also measure tau presence at the beginning of a trial and tau presence at the end of a trial, and correlate it with any clinical changes, hopefully stabilization or maybe even improvement in cognitive function over the course of the trial.

Ultimately in the field of treatment of Alzheimer's disease, we're moving toward earlier and earlier identification of the disease process with the thought of intervening earlier rather than later. Ultimately, of course, we'd really like to prevent the disease. So what if we're able to image somebody who's clinically normal, find that they have, say, the amyloid protein in the brain, treat that, try to remove that protein from the brain to prevent them from becoming clinically impaired down the road? So, I think the underlying thought is that the earlier we intervene, the better we will be and perhaps we can even prevent the disease.

Amyloid is still the primary target of therapy currently being developed by most pharmaceutical companies, but there certainly are other targets. The other major feature of the disease, of course, is the neurofibrillary tangle comprised of tau. So, tau is actively being pursued as another therapeutic target. Antibodies against it. Anti-aggregation against it to see if, in fact, we can have an impact on that aspect of the disease.

In addition to amyloid and tau, of course, there are other features. There's inflammation. There are other neuropathologic deposits in the brain such as alpha-synuclein, TDP-43, and these may certainly cause clinical symptoms as well. So they're actively being pursued as possible targets for treatment. So while we focus on amyloid now, we're stretching it to tau. There certainly are other aspects of the disease, oxidation, neuroinflammation, that might be feasible targets as well.

2017-02-21T14:00:00-0500

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Low levels of glucose in the brain may trigger Alzheimer's

Our brain runs on sugar, and new research links the lack of glucose with cognitive impairment typical of Alzheimer's disease and dementia. Additionally, researchers may have identified a new drug target for treating the neurodegenerative disease.

Using a mouse model, researchers have uncovered the mechanism by which glucose deprivation in the brain leads to cognitive impairment.

More than 5 million people in the United States live with Alzheimer's disease. Before they develop the full-blown illness, many of these patients start experiencing a mild form of cognitive impairment.

This can include problems with their reasoning, judgment, or memory that are greater than normal, yet do not interfere with daily functioning.

As recent studies have suggested, even before the first signs of cognitive impairment, the levels of glucose in the brain begin to decline.

Glucose is crucial for good cognitive functioning. In fact, our brains rely heavily on this source of energy, using half of all the sugar in our body to fuel reasoning, memory, and learning.

New research - led by Dr. Domenico Praticò, a professor at the Center for Translational Medicine at the Lewis Katz School of Medicine at Temple University in Philadelphia, PA - investigates more deeply the impact that glucose deprivation has on the brain.

The findings were published in the Nature journal Translational Psychiatry.

Studying the impact of glucose deprivation on the brain

Dr. Praticò has shown in a previous study that, to make up for glucose deprivation, the brain builds up the protein called phosphorylated tau.

The tau protein then creates so-called tangles - "gridlocks" of twisted fibers of tau that block the transportation of nutrients through to the neurons. Eventually, these tangles cause the brain cells to die. A larger number of tau tangles is usually associated with an increased severity of Alzheimer's and dementia.

The previous study by Dr. Praticò investigated this mechanism in vitro and showed that tau buildup occurs using the P38 kinase pathway.

In this new research, the team has examined the mechanism of tau phosphorylation as a response to glucose deprivation in vivo, using a mouse model.

Dr. Praticò and colleagues used mice that have been genetically modified in a way that replicates memory problems and tau pathology typical of Alzheimer's disease.

When the mice were 4 or 5 months old, some of them were administered 2-deoxyglucose (DG) - a chemical compound that prevents glucose from entering the cell and being processed into energy.

The mice were injected with the substance over several months, and at the end they were tested for cognitive function using maze tests to evaluate memory and learning.

P38 kinase directly associated with memory impairment

The glucose-deprived mice performed much worse in the cognition tests than those that had not received DG.

Additionally, a microscopic evaluation of the mice's brains revealed that neurons in the glucose-deprived mice had abnormal synaptic functioning. Memory encoding and storage were impaired because the interneural synapses were unable to communicate properly with each other.

Furthermore, the researchers also found high levels of phosphorylated tau and high numbers of dead cells in the brains of DG-treated mice.

Following up on Dr. Praticò's previous research, the team examined P38 activation and found it to be directly associated with memory deficits.

"The findings are very exciting," says Dr. Praticò. "There is now a lot of evidence to suggest that P38 is involved in the development of Alzheimer's disease."

According to him, the findings support the fact that even small episodes of chronic glucose deprivation can damage the brain. "There is a high likelihood that those types of episodes are related to diabetes, which is a condition in which glucose cannot enter the cell. Insulin resistance in type 2 diabetes is a known risk factor for dementia," Dr. Praticò explains.

The authors conclude by noting that this is the first time that a study has offered "in vivo experimental evidence" that glucose deprivation in the brain - by activation of the P38 kinase pathway - triggers memory and cognitive impairment, synaptic miscommunication between neurons, and neuronal death.

They also comment on the possibilities for treatment, as this is the first time that P38 has been identified as a potential new drug target for Alzheimer's disease:

"Drugs targeting this kinase in the brain may represent a suitable therapeutic approach for the treatment of both AD [Alzheimer's disease] and related tauopathies for which impaired glucose utilization is an established risk factor."

"It is an exciting avenue of research," Dr. Praticò adds. "A drug targeting this protein could bring big benefits for patients."

Learn how scientists can stop and reverse Alzheimer's-related brain damage in mice.

Written by Ana Sandoiu

A glitch in 'gatekeeper cells' slowly suffocates the brain

Abnormality with special cells that wrap around blood vessels in the brain leads to neuron deterioration, possibly affecting the development of Alzheimer's disease, a USC-led study reveals.

"Gatekeeper cells" called pericytes surround blood vessels, contracting and dilating to control blood flow to active parts of the brain.

"Pericyte degeneration may be ground zero for neurodegenerative disorders like Alzheimer's disease, ALS and possibly others," said Berislav Zlokovic, senior author of the study and director of the Zilkha Neurogenetic Institute at the Keck School of Medicine of USC. "A glitch with gatekeeper cells that surround capillaries may restrict blood and oxygen supply to active areas of the brain, gradually causing neuron loss that might have important implications for Alzheimer's disease."

Published in Nature Neuroscience, this was the first study to use a pericyte-deficient mouse model to test how blood flow is regulated in the brain. The goal was to identify whether pericytes could be an important new therapeutic target for treating neuron deterioration.

"Vascular problems increase the risk of cognitive impairment in many types of dementia, including Alzheimer's disease," said Kassandra Kisler, co-first author and a research associate at the Zilkha Neurogenetic Institute. "Pericytes play an important part in keeping your brain healthy."

A closer look at the mouse models

Pericyte dysfunction suffocates the brain, leading to metabolic stress, accelerated neuronal damage and neuron loss, said Zlokovic, holder of the Mary Hayley and Selim Zilkha Chair in Alzheimer's Disease Research.

To test the theory, researchers stimulated the hind limb of young mice deficient in gatekeeper cells and monitored the global and individual responses of brain capillaries, the smallest blood vessels in the brain. The global cerebral blood flow response to an electric stimulus was reduced by about 30 percent compared to normal mice, denoting a weakened system.

Relative to the control group, the capillaries of pericyte-deficient mice took 6.5 seconds longer to dilate. Slower capillary widening and a slower flow of red blood cells carrying oxygen through capillaries means it takes longer for the brain to get its fuel.

As the mice turned 6 to 8 months old, global cerebral blood flow responses to stimuli progressively worsened. Blood flow responses for the experimental group were 58 percent lower than that of their age-matched peers. In short, with age, the brain's malfunctioning vascular system exponentially worsens.

"We now understand the function of blood vessel gatekeeper cells is to ensure adequate oxygen and energy supply to brain cells," said Amy Nelson, co-first author and a postdoctoral scholar at the Zilkha Neurogenetic Institute. "Prior to our study, scientists knew patients with Alzheimer's disease, ALS and other neurodegenerative disorders experience changes to the blood flow and oxygen being supplied to the brain and that pericytes die. Our study adds a new piece of information: Loss of these gatekeeper cells leads to impaired blood flow and insufficient oxygen delivery to the brain. The big mystery now is: What kills pericytes in Alzheimer's disease?"

The research was supported by the National Institutes of Health, the National Natural Science Foundation of China and the American Heart Association.

Scientists at the Zilkha Neurogenetic Institute, the USC Mark and Mary Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine and other collaborators are already working to further this line of research, scanning the brains of people who are genetically at risk for Alzheimer's. They are also collecting cerebral spinal fluid and blood for analysis of vascular damage, including injury to pericytes.

Article: Pericyte degeneration leads to neurovascular uncoupling and limits oxygen supply to brain, Kassandra Kisler, Amy R Nelson, Sanket V Rege, Anita Ramanathan, Yaoming Wang, Ashim Ahuja, Divna Lazic, Philbert S Tsai, Zhen Zhao, Yi Zhou, David A Boas, Sava Sakadžić & Berislav V Zlokovic, Nature Neuroscience, doi:10.1038/nn.4489, published online 30 January 2017.

As Presidents Get Older, Worries About Dementia Risk Grow (NPR)

Donald Trump, age 70, is the oldest president ever to take office, and also has a family history of dementia. Should he undergo at least a baseline cognitive test?

In fact, some physicians have argued that all presidents should have to undergo regular neuropsychiatric exams, NPR reports.

"Only a generation ago, our political leaders -- like the rest of us -- were likely to die of heart disease or cancer in their 60s and 70s, what we now think of as late middle age," said one psychiatrist.

And, said bioethicist Art Caplan, "I think we're about 50 years overdue for having some sort of annual physical for the president and vice president, the results of which should be reported publicly," he says. "Part of this should be psychiatric and cognitive testing."

But political resistance to the idea may be insurmountable, the NPR report suggested.

2017-02-17T15:00:00-0500

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Is it depression or dementia? Brain SPECT imaging helps distinguish them

Neuroimaging of decreased blood flow in specific regions of the brain can differentiate between depression and cognitive disorders, according to a new report in the Journal of Alzheimer's Disease.

Does a patient have depression or a cognitive disorder (CD) such as Alzheimer's disease or both? Since both disorders have overlapping symptoms, how can a clinician tell them apart to make an appropriate diagnosis? In a new article published in the Journal of Alzheimer's Disease, researchers have found that single photon emission computed tomography, or SPECT, can help to distinguish between these diagnostic categories.

In one of the largest studies of its kind, 4541 subjects were examined, 847 of whom had been diagnosed with dementia, 3269 with depression, and 425 with both conditions. Using brain SPECT imaging, a nuclear medicine study that measures blood flow and activity, researchers found that people with cognitive disorders had reduced blood flow in multiple brain areas compared to those with depression, particularly in the hippocampus, temporal, and parietal lobes. They also found that SPECT could distinguish depression from CDs with 86% accuracy. In addition, brain SPECT imaging showed the ability to distinguish depression or dementia in people with both with 83% accuracy.

"This is a critical clinical question that has practical implications for patient management and treatment," explained lead researcher and psychiatrist Daniel G. Amen, MD. "These disorders have very different prognoses and treatments and being able to improve diagnostic accuracy can improve outcomes for some patients."

The authors write, "Cognitive impairment is present in approximately half of persons who have late onset depression and depression is evident in 9-65% of individuals with dementia. Studies have indicated that the prevalence of depression in patients with mild cognitive impairment is 25%. Consequently, it is often challenging to diagnostically disentangle depression and cognitive disorders from one another."

Traditionally, depression can be diagnosed using tools such as the Beck Depression Inventory. However, there was no statistically significant difference in the burden of depression symptoms on this inventory between persons with both depression and CDs compared to persons with either condition. This increases the difficulty of distinguishing these disorders on the basis of depression symptom severity alone.

"One of the greatest new insights of the past decade is the linkage of depression to the psychology of late life cognitive decline. Raji and coworkers extend the approach to the biological substrate by an elegant imaging approach. These studies further place brain aging on a firm biological basis," added George Perry, PhD, Editor-in-Chief of the Journal of Alzheimer's Disease and Dean and Professor of Biology University of Texas at San Antonio.

Article: Classification of Depression, Cognitive Disorders and Co-Morbid Depression and Cognitive Disorders with Perfusion SPECT Neuroimaging, Daniel G. Amen, MD, Pavitra Krishnamani, BA, MS, Somayeh Meysami, MD, Andrew Newberg, MD, and Cyrus A. Raji, MD, PhD, Journal of Alzheimer's Disease, doi: 10.3233/JAD-161232, published 10 February 2017.

D.C. Week: Dems, GOP Squabble over CMS Nominee

WASHINGTON -- At a nomination hearing for President Trump's appointee to lead the Centers for Medicare & Medicaid Services (CMS), Democrats and Republicans once again clashed over potential changes to Medicare and Medicaid reform.

Mixed Reception for CMS Pick at Senate Hearing

Republicans on the Senate Finance Committee praised the performance Thursday of Seema Verma, MPH, President Trump's nominee to head CMS, while Democrats decried what they said was her lack of answers to their questions.

"You have acquitted yourself very well," committee chair Sen. Orrin Hatch (R-Utah) said to Verma, a healthcare consultant from Indianapolis who helped Indiana redesign its Medicaid program. "I look forward to this [nomination] being reported out of this committee, and my goal is for it to all happen very expeditiously."

But Sen. Ron Wyden (D-Ore.), the committee's ranking member, begged to differ: "For questions I thought were appropriate for a job like this, we're not getting much of a sense of how you'd approach it," he said. "I think this committee needs answers, and the public needs answers."

The Finance Committee will vote at an unspecified later date on whether to send Verma's nomination to the full Senate.

CMS Projects U.S. Health Spending to Reach 19.9% of GDP by 2025

Overall health spending is expected to account for 19.9% of the total U.S. economy by 2025, versus a 17.8% share in 2015, according to a CMS report published in Health Affairs.

Health spending is projected to grow annually at a rate of 5.6% on average from 2016 to 2025, surpassing the average projected growth in gross domestic product (GDP) by 1.2%, according to Sean Keehan, of the CMS Office of the Actuary in Baltimore, and colleagues.

"After an anticipated slowdown in health spending growth for 2016, we expect health spending growth to gradually increase as a result of faster projected growth in medical prices that is only partially offset by slower projected growth in the use and intensity of medical goods and services," Keehan said in a press release.

Policy Experts View HHS Rules as 'Underwhelming'

As the Trump administration begins to grapple in earnest with the nitty-gritty of health insurance regulation, it appears responsive to insurers' concerns -- but outside observers say the moves seen so far won't fix the system's problems.

An early step by the administration came Wednesday with issuance of draft regulations seemingly aimed at bringing more certainty to insurance markets and stopping companies from dropping out of the Affordable Care Act's exchanges. But it came too late for many carriers that had already abandoned these markets, and another big one, Humana, announced it would exit the exchanges at the end of 2017.

Another exchange participant hinted Thursday that it was losing patience: Molina Health Care, an insurer focused on Medicaid plans, reported a loss of $91 million that led to a 13% drop in shares.

"We are clearly disappointed in these results," said the company's CEO, J. Mario Molina, MD, who blamed the ACA.

Shulkin Vote Unites Senate

The Senate confirmed David Shulkin, MD, as the next Secretary of the Department of Veterans Affairs in a unanimous vote, Monday evening.

"Dr. Shulkin is the right man at the right time for the Veterans Administration," said Sen. Johnny Isakson (R- Ga.), Chairman of the Senate Committee on Veterans' Affairs, in a speech prior to the vote.

"We don't want to privatize the VA, we don't want to reorganize the VA, we want to make the VA work -- give our veterans access to every bit of care they can possibly get," Isakson said.

Monday's blanket endorsement by the full Senate, 100-0, was not a surprise. A week earlier, the Senate Committee on Veterans' Affairs voted unanimously to approve Shulkin, sending his nomination to the Senate floor. And at a hearing before the Senate VA committee in early February, Shulkin also received a generally warm reception.

Senators Ponder Mental Health Funding

In a rare display of comity Wednesday, Democratic and Republican senators alike discussed which mental health and substance abuse programs should receive funding in the next appropriations cycle, and how those programs could be run more efficiently.

"I don't know anybody that wants to deny healthcare to people who need it," said Sen. John Kennedy (R-La.) at a hearing held by the Senate Appropriations Subcommittee on Labor, Health and Human Services, Education, and Related Agencies. "If you're hungry, we'll feed you; if you're homeless, we'll house you; if you're too poor to be sick, we'll pay for your doctor."

However, he added, "I think most right-thinking people are concerned about the cost, because most people have to work for their money."

Next Week

Congress is on recess.

On Wednesday, Health Affairs will host a briefing in San Francisco on the Work/Health Relationship (the event will be live-streamed ).

And America's Health Insurance Plans will hold a congressional briefing on developments in Medicare Advantage.

On Thursday, the FDA's Circulatory System Devices Panel of the Medical Devices Advisory Committee will meet to discuss "the de novo request for the Sentinel® Cerebral Protection System."

On Friday, The Center for Strategic International Studies will host a conversation with U.S. Surgeon General Vivek Murthy, MD, focused on addressing the opioid epidemic.

2017-02-18T12:00:00-0500

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People who sleep longer twice as likely to develop dementia

Alzheimer's disease affects millions of Americans, and the numbers are expected to grow. New research suggests there may be a link between prolonged sleep and the risk of dementia.

New research suggests those who sleep for more than 9 hours each night are at a higher risk of developing dementia.

Over 46 million people are living with dementia worldwide, and the number is expected to almost triple by 2050.

In the United States, over 5 million people are currently estimated to have Alzheimer's disease. The disease risk increases with age, as 1 in 3 seniors die with Alzheimer's or another form of dementia.

The financial burden of the disease is also great. American families are believed to spend over $5,000 yearly on caring for someone with Alzheimer's, and the national economic burden is estimated at $236 billion.

A new, large-scale study suggests people with prolonged sleeping patterns may have an increased risk of developing dementia.

The research was led by Dr. Sudha Seshadri, professor of neurology at Boston University School of Medicine (BUSM), and the findings were published in the journal Neurology.

Researchers examined data from the Framingham Heart Study (FHS). FHS is a large cohort study that started in 1948 by enrolling 5,209 men and women aged between 30 and 62 living in the town of Framingham, MA. The original purpose of the study was to identify risk factors for cardiovascular disease.

Sleeping 9 hours or more linked to greater dementia risk

For this study, a large number of adults enrolled in the FHS were asked to report how long they usually slept per night. The researchers then clinically followed the participants for 10 years to see who developed Alzheimer's disease and other forms of dementia.

BUSM researchers then examined the data collected on sleep duration and calculated the risk of developing dementia.

The team found that people who sleep regularly for 9 hours or more were twice as likely to develop Alzheimer's within 10 years, compared with those who consistently slept less than 9 hours.

Additionally, as the study's lead author explains, education seems to be playing a role in staving off the risk of dementia.

"Participants without a high school degree who sleep for more than 9 hours each night had six times the risk of developing dementia in 10 years as compared [with] participants who slept for less. These results suggest that being highly educated may protect against dementia in the presence of long sleep duration."

Dr. Sudha Seshadri

The study also found that people who slept longer seemed to have smaller brain volumes. Being observational, the study cannot establish causality, but the researchers suspect excessive sleep is probably a symptom rather than a cause of the neuronal changes that come with dementia. As a consequence, they speculate, reducing sleep duration is not likely to lower the risk of dementia.

The authors believe the findings may inform future dementia and cognitive impairment detection practices. Co-corresponding author Matthew Pase, Ph.D., who is a fellow in the department of neurology at BUSM and investigator at the FHS, weighs in on the significance of the findings.

"Self-reported sleep duration may be a useful clinical tool to help predict persons at risk of progressing to clinical dementia within 10 years," he says. "Persons reporting long sleep time may warrant assessment and monitoring for problems with thinking and memory."

The sooner a patient is diagnosed with dementia, the more time they and their families have to plan ahead and make crucial healthcare decisions.

Learn how scientists stopped and reversed Alzheimer's-related brain damage in mice.

Written by Ana Sandoiu

Shaggy Dog Stories May Signal Future Alzheimer's (The Guardian)

When people lose the ability to stay focused when talking, it might be an early indication of Alzheimer's disease, The Guardian reported from a recent study.

A series of verbal exercises showed that individuals with mild cognitive impairment "were much less concise in conveying information, the sentences they produced were much longer, they had a hard time staying on point and I guess you could say they were much more roundabout in getting their point across," a researcher told the newspaper.

The finding surprised the researchers, who expected to find that sophisticated vocabulary was the first to go when a patient's mental faculties started to fail.

2017-02-21T15:00:00-0500

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Human neurons in mouse brains are more susceptible to Alzheimer's pathology

Cells behave differently when removed from their environments, just as cells that develop in cultures do not behave like cells in living creatures. To study the effects of Alzheimer's disease in a more natural environment, scientists from the lab of professor Bart De Strooper (VIB-KU Leuven, Dementia Research Institute-UK) in collaboration with scientists from ULB (profs Pierre Vanderhaeghen and Jean-Pierre Brion) successfully circumscribed this challenge by transplanting human neural cells into mouse brains containing amyloid plaques, one of the hallmarks of Alzheimer's disease. The results of their research showed that, unlike mouse neurons, human neurons that developed in this environment were extremely susceptible to Alzheimer's disease. Their high-impact results are published in leading academic journal Neuron.

The study of the development of Alzheimer's disease on a molecular level presents unique challenges, as neurons behave differently in vivo vs. in vitro. Using mice as models presents useful insights, but mouse models never fully develop the disease, despite the fact that their brains and neurons share many similarities with those of humans.

A new, humanized model

A team of researchers has now transplanted human neurons into mouse brains which mimick some of the hallmarks of Alzheimer's disease, including the presence of amyloid plaques. They found that, compared to mouse neurons, human neurons were much more sensitive to amyloid plaque pathology. This novel model allows for a better characterization of the disease processes that actually take place in the brain of human patients.

Much of the work was performed in close cooperation with prof. Pierre Vanderhaeghen (ULB-WELBIO, VIB-KU Leuven), whose lab previously pioneered the technology to differentiate human pluripotent stem cells into neural cells in vitro, and then transplant them in the mouse brain, generating a human/mouse chimera.

Prof. Bart De Strooper (VIB-KU Leuven, Dementia Research Institute-UK): "We relied heavily on the insights and expertise of Pierre Vanderhaeghen and his lab to set up this new AD model. With this novel experimental technique, we can study how different cell types in the human brain respond to the __alzheimer pathology, hopefully unraveling the link between amyloid and tau protein pathology - which leads to neuron death and is the holy grail of current Alzheimer's research."

Prof. Pierre Vanderhaeghen (ULB-WELBIO and VIB): "While many features of the brain are conserved between different species such as humans and mice, the human brain displays a number of characteristics, which make us what we are, as a species and as individuals. However, studying this human-specific part remains a big challenge in neuroscience. This study is exciting because it constitutes a first proof of principle that stem cell-based models of transplanted human neurons can be applied to study an important neurological disease."

Identifying genetic components

Moving forward, Prof. De Strooper and his team are already planning a screen to identify human genes that protect against cell death associated with Alzheimer's disease.

Prof. Bart De Strooper (VIB-KU Leuven, Dementia Research Institute-UK): "Now that we are able to investigate the disease by observing human cells directly, we can make progress in this field of research at a considerably faster pace. The eventual end goal of the screening is to identify new drug targets within human cells themselves, something that was never possible before."

Article: Hallmarks of Alzheimer's Disease in Stem-Cell-Derived Human Neurons Transplanted into Mouse Brain, Bart De Strooper et al., Neuron, doi: 10.1016/j.neuron.2017.02.001, published 23 February 2017.

Dementia risk reduced by eating 'five-a-day'

Dementia is estimated to affect around 47.5 million people worldwide, and this number is expected to more than triple by 2050. But according to new research, there is one simple thing older adults can do to help reduce their risk of dementia: eat their "five-a-day."

Researchers say eating five portions of fruits and vegetables daily could reduce older adults' dementia risk.

In a study published in the journal Age and Ageing, researchers found that eating at least three portions of vegetables and two servings of fruits daily was associated with lower risk of dementia in older adults.

The World Health Organization (WHO) recommend that adults should consume at least 400 grams of fruits and vegetables daily - the equivalent to around five servings - in order to improve overall health and lower the risk of chronic diseases, such as heart disease and cancer.

Previous research has indicated that fruit and vegetable intake may also reduce the risk of Alzheimer's disease and other dementias, but the precise amounts that should be consumed to pose such benefits have been unclear.

For this latest study, co-author Linda Lam - of the Department of Psychiatry at the Chinese University of Hong Kong - and colleagues set out to investigate whether adhering to the five-a-day recommendation is associated with reduced dementia risk.

Lower dementia risk for adults who ate at least five-a-day

The researchers came to their findings by analyzing the health and diet of 17,700 older Chinese adults.

All adults were free of dementia at study baseline. The researchers followed the participants for an average of 6 years to see whether they developed the condition, and whether dementia development might be associated with fruit and vegetable intake.

Compared with adults who did not adhere to WHO recommendations for fruit and vegetable intake, adults who consumed three servings of vegetables and two servings of fruits daily were found to be at lower risk of dementia development over 6 years.

Dementia risk was further reduced for adults who consumed an additional three portions of vegetables each day, the team reports.

The results remained after accounting for a number of confounding factors, including age, smoking status, and the presence of other chronic diseases.

Findings highlight importance of fruit and veg intake for older adults

The study was not designed to pinpoint the reasons why fruits and vegetables might lower dementia risk, but the researchers speak of one hypothesis.

They explain that oxidativestress - an imbalance between free radical production and the body's ability to counteract the toxic effects - and inflammation is believed to play a role in dementia.

Fruits and vegetables contain vitamin B, vitamin E, and other nutrients with antioxidant and anti-inflammatory properties that could help prevent such processes.

Further research is needed to explore precisely how fruits and vegetables might lower dementia risk, but this current study sheds light on how much we need to consume to reap the rewards.

"The findings of our study not only highlight the importance of consuming both fruits and vegetables in dementia prevention among older people, but also provide some insight into the daily amount of fruits and vegetables required for cognitive maintenance.

As a public health promotion strategy, the need for a balanced diet on cognitive health should be duly emphasized in the older population."

Linda Lam

Read about how eating 10 portions of fruits and vegetables a day is best for health.

Written by Honor Whiteman

Dementia Risk Up with Autoimmunity

Action Points

• Patients with various types of autoimmune disease were at small but significantly increased risk for dementia, according to a retrospective study of hospitalization records from England.
• Note that there are suggestions that Alzheimer's disease may have an autoimmune component, and that autoimmune and inflammatory mechanisms may play a role in the development of dementia.

Patients with various types of autoimmune disease were at increased risk for dementia, a retrospective study in England found.

Among patients whose medical records included hospitalization for an autoimmune disease, the likelihood of subsequent hospitalization for dementia was 20% higher than for controls (RR 1.20, 95% CI 1.19-1.21), according to Clare J. Wotton, BSc, and Michael Goldacre, BM BCh, of the University of Oxford.

And in particular, the risk for vascular dementia was elevated (RR 1.28, 95% CI 1.26-1.31) more than the risk for Alzheimer's disease (RR 1.06, 95% CI 1.04-1.08), the researchers reported in the Journal of Epidemiology and Community Health.

"There are suggestions that Alzheimer's disease may have an autoimmune component, and that autoimmune and inflammatory mechanisms may play a role in the development of dementia," Wotton and Goldacre wrote.

Other hints of potential links between dementia and autoimmunity have included the female predominance of both conditions, a relationship between the presence of antithyroid antibodies and Alzheimer's disease, and a decreased risk for Alzheimer's in individuals who use nonsteroidal anti-inflammatory drugs (NSAIDs) -- such as patients with rheumatoid arthritis.

To examine the possibility of this association in a large population, the authors used England's Hospital Episode Statistics database to look for cases from 1998 to 2012 in which a patient was admitted to a National Health Service hospital for any of 25 autoimmune diseases, and later was hospitalized with a diagnosis of dementia.

Their analysis included 1,833,827 individuals with admissions for autoimmune diseases, with specific diagnoses ranging from 316,043 for rheumatoid arthritis to 1,019 with Goodpasture's syndrome. Approximately 7 million individuals were included as controls.

Most patients were in their 50s or 60s at the time of entry into the autoimmune cohort, the majority were women, and mean follow-up was about 5 years.

Among the 25 autoimmune diseases, 18 had significant positive associations for dementia (P for all <0.001):

• Addison's disease, RR 1.48 (95% CI 1.34-1.64)
• Multiple sclerosis, RR 1.97 (95% CI 1.88-2.07)
• Psoriasis, RR 1.29 (95% CI 1.25-1.34)
• Systemic lupus erythematosus, RR 1.46 (95% CI 1.32-1.61)
• Thyrotoxicosis, RR 1.31 (95% CI 1.27-1.34)

Of the 81,502 patients with autoimmune disease who also developed dementia, the subtype of dementia was identified in 42,568 -- 20,032 with Alzheimer's and 22,536 with vascular dementia.

Risks for vascular dementia but not Alzheimer's disease were increased for idiopathic thrombocytopenia purpura, pemphigus, scleroderma, Sjogren's syndrome, systemic lupus erythematosus, and most notably, for polyarteritis nodosa, with a rate ratio of 2.12 (95% CI 1.42-3.05, P<0.001).

"The associations with vascular dementia might reflect associations between autoimmune disease and risk factors for cardiovascular and cerebrovascular diseases more generally," Wotton and Goldacre noted.

In contrast, risks were elevated for Alzheimer's disease but not vascular dementia in Addison's disease, myxoedema, pemphigoid, pernicious anemia, psoriasis, and thyrotoxicosis, although the risks were less pronounced than for vascular dementia, with rate ratios ranging from 1.08 to 1.30.

For rheumatoid arthritis, the overall adjusted rate ratio was 1.13 (95% CI 1.11-1.15, P<0.001), the risk for vascular dementia was 1.16 (95% CI 1.12-1.20, P<0.001), but the risk for Alzheimer's was decreased (RR 0.89, 95% CI 0.86-0.93, P<0.001).

"A previous admission with rheumatoid arthritis seemed to protect against Alzheimer's disease, but elevated the risk of vascular dementia. Although evidence that NSAIDs reduce the risk of Alzheimer's disease is not conclusive, our findings might add circumstantial evidence to the data supporting the hypothesis that NSAIDs protect against Alzheimer's disease," the authors wrote.

If there indeed is a protective effect for NSAIDs for some autoimmune conditions, and if the effect is through anti-inflammatory mechanisms, then corticosteroids might have similar effects, they pointed out.

Limitations of the study included its focus solely on patients with hospital admissions and a lack of information on potential confounding factors.

The authors also cautioned that the effect sizes seen in the study were small. Nonetheless, "the findings may be relevant to furthering understanding of the pathogenesis of Alzheimer's disease and of vascular dementia. Studies should be considered to confirm or refute our findings, and if confirmed, to explore possible mechanisms mediating the associations," they concluded.

The authors reported no competing interests.

• Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College and Dorothy Caputo, MA, BSN, RN, Nurse Planner

2017-03-01T18:30:00-0500

• Primary Source

  Journal of Epidemiology and Community Health

  Source Reference: Wotton C, Goldacre M "Associations between specific autoimmune diseases and subsequent dementia: retrospective record-linkage cohort study, UK" J Epidemiol Community Health 2017; doi:10.1136/jech-2016-207809.

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Heart risks in middle age boost dementia risk later in life

Smoking, high blood pressure and diabetes were all dementia risks, with diabetes in middle age raising the risk almost as much as a genetic risk factor for Alzheimer's disease. Some risk factors had a different impact in black and white participants, while genetics and smoking had a greater impact in whites.

People who have heart disease risks in middle age - such as diabetes, high blood pressure or smoking - are at higher risk for dementia later in life, according to research presented at the American Stroke Association's International Stroke Conference 2017.

"The health of your vascular system in midlife is really important to the health of your brain when you are older," said Rebecca F. Gottesman, M.D., Ph.D., lead researcher and associate professor of neurology and epidemiology at the Johns Hopkins University in Baltimore.

In an ongoing study that began in 1987 and enrolled 15,744 people in four U.S. communities, the risk of dementia increased as people got older. That was no surprise, but heart disease risks detected at the start of the study, when participants were between 45-64 years of age, also had a significant impact on later dementia, researchers noted. Dementia developed in 1,516 people during the study, and the researchers found that the risk of dementia later in life was:

• 41 percent higher in midlife smokers than in non-smokers or former smokers;
• 39 percent higher in people with high blood pressure (≥140/90 mmHg) in middle age, and 31 percent higher in those with pre-hypertension (between 120/80 mmHg and 139/89 mmHg) compared to those with normal blood pressure; and
• 77 percent higher in people with diabetes in middle age than in non-diabetics.

"Diabetes raises the risk almost as much as the most important known genetic risk factor for Alzheimer's disease," Gottesman said.

Overall, the risk of dementia was 11 percent lower in women. The risk was highest in individuals who were black, had less than a high school education, were older, carried the gene known to increase Alzheimer's risk, or had high blood pressure, diabetes or were current smokers at the time of initial evaluation.

Smoking and carrying the gene known to increase the chance of Alzheimer's were stronger risk factors in whites than in blacks, the researchers noted.

"If you knew you carried the gene increasing Alzheimer's risk, you would know you were predisposed to dementia, but people don't necessarily think of heart disease risks in the same way. If you want to protect your brain as you get older, stop smoking, watch your weight, and go to the doctor so diabetes and high blood pressure can be detected and treated," said Gottesman.

Because Atherosclerosis Risk in Communities is an observational study, the current study could not test whether treating heart risk factors will result in a lessened dementia risk later in life.

"The benefit is that this is a long-term study and we know a lot about these people. Data like these may supplement data from clinical trials that look at the impact of treatment for heart disease risks," Gottesman said.

Co-authors include Marilyn Albert, Ph.D.; Alvaro Alonso, M.D., Ph.D.; Laura H. Coker, Ph.D.; Josef Coresh, M.D., Ph.D.; Sonia M. Davis, Dr.P.H.; Jennifer A. Deal, Ph.D.; Guy M. McKhann, M.D.; Thomas H. Mosley, Ph.D.; A. Richey Sharrett, M.D., Dr.P.H.; Andrea L.C. Schneider, M.D., Ph.D.; B. Gwen Windham, M.D., M.H.S.; Lisa M. Wruck, Ph.D. and David S. Knopman, M.D.

The study was funded by the National Heart, Lung and Blood Institute and the National Institute of Neurological Disorders and Stroke.

Reference: American Stroke Association Meeting Report - Session A14 - Abstract 98 - Heart disease risk factors in middle age were associated with an increased risk of dementia in later years.

Alzheimer's disease: Molecular study clarifies potential link to high blood sugar

A new molecular study reveals for the first time that high blood sugar or glucose damages an important enzyme that is involved with how the immune system responds in the early stages of Alzheimer's disease. The researchers say the findings will help map the progression of the devastating disease to better identify those at risk and perhaps find new ways to treat or prevent it.

Many experts believe the damage to brain cells caused by Alzheimer's disease starts 10 years or more before symptoms of mental decline appear.

Abnormally high blood sugar, or hyperglycemia, is a well-known characteristic of diabetes and obesity.

However, apart from the fact that people with diabetes have a higher risk of developing Alzheimer's disease, the link between hyperglycemia and this common cause of dementia has been less clear.

Now, researchers show that macrophage migration inhibitory factor (MIF) - an enzyme that plays an important role in immune function and insulin regulation - undergoes damage associated with high glucose in early Alzheimer's disease.

The team - from the University of Bath and King's College London, both in the United Kingdom - describes the findings in a paper published in the journal Scientific Reports.

Toxic changes in the brain

Alzheimer's is a progressive brain-wasting disease that erodes people's ability to remember, think, perform daily tasks, and lead an independent life.

Fast facts about Alzheimer's disease

• Experts suggest there are more than 5 million people with Alzheimer's disease in the United States.
• The first symptoms of the disease vary from person to person.
• Genetic mutation is usually the cause of early-onset Alzheimer's.

Learn more about Alzheimer's

Among older adults, Alzheimer's disease is the most common cause of dementia, a condition that affects 46 million people worldwide.

As more studies are done, scientists are gradually unraveling the complex changes that happen in the brain during the onset and development of the disease.

Many experts believe the damage caused by Alzheimer's disease starts 10 years or more before the cognitive decline becomes apparent.

During this preclinical stage, when people appear symptom-free, toxic changes are taking place in the brain.

One of the main changes occurring in the brain is the accumulation of abnormal proteins into toxic plaques and tangles, causing once-healthy cells to stop working, lose connections with other cells, and die.

Scientists already knew that glucose and its metabolic byproducts can damage proteins through a reaction called glycation, which has also been linked to Alzheimer's disease, and is a known feature of the hyperglycemia induced by diabetes.

For the new study, the researchers used a sensitive technique to detect glycation in brain samples from people with and without Alzheimer's disease.

Sugar damage to enzyme could be 'tipping point'

The team found evidence that the enzyme MIF undergoes glycation damage in the early stages of the disease. It also seems that the extent of MIF glycation increases as the disease progresses.

MIF is involved in how brain cells called glia respond to the buildup of the abnormal proteins during Alzheimer's disease.

The team suggests that sugar damage to MIF reduces some of the enzyme's functions and blocks others completely, and this could be the "tipping point" that allows Alzheimer's to develop.

"We've shown that this enzyme is already modified by glucose in the brains of individuals at the early stages of Alzheimer's disease," says Jean van den Elsen, one of the senior investigators and professor in biology and biochemistry at Bath.

He and his colleagues are now investigating if they can detect similar changes in the blood.

"Excess sugar is well known to be bad for us when it comes to diabetes and obesity, but this potential link with Alzheimer's disease is yet another reason that we should be controlling our sugar intake in our diets."

First author Dr. Omar Kassaar, University of Bath

Learn how concussion is linked to brain changes in people at genetic risk for Alzheimer's.

Written by Catharine Paddock PhD

CCB Doesn't Help Cognition After Stroke

HOUSTON -- Nimodipine didn't improve cognition when ischemic stroke patients with vascular mild cognitive impairment (MCI) started taking the calcium channel blocker within a week of their event, researchers reported here.

In a randomized controlled trial from 23 sites in China, patients had no differences in change in Mini-Mental State Exam (MMSE) scores at 6 months whether they were on the drug or placebo, Huaguang Zheng, MD, of Beijing Tiantan Hospital in China and colleagues reported at the International Stroke Conference meeting here.

"In our trial, we found that nimodipine didn't benefit vascular MCI patients, but it may have marginal positive effects on specific cognitive domains, such as executive function, and it won't increase the risk of stroke or other adverse events," Zheng said during a press briefing.

More than half of stroke patients develop vascular MCI during the first three months of follow-up, he explained, and about 30% to 50% will develop dementia within 5 years.

While there are currently no effective therapies for vascular MCI and dementia, some studies have suggested that nimodipine may have cognitive benefits, he said.

To assess whether that's the case, Zheng and colleagues randomized 654 patients to either placebo or to 30 mg nimodipine three times a day. The primary endpoint was the change in cognition function on the MMSE and on the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) over 6 months.

Overall, outcomes were similar between the two groups, with no significant advantage for nimodipine, Zheng said.

There was, however, an advantage for nimodipine in terms of the proportion of patients who had an ADAS-Cog score of 0 or greater at 6 months (34% versus 47%), and there was some indication that the drug may benefit specific brain areas, particularly executive function, he noted.

Zheng added that nimodipine didn't increase the risk of stroke and other adverse events.

He acknowledged that the study was limited because it didn't evaluate Global Cognitive Index scores, neurological outcome, or subcortical dementia, and the sample size was too small.

Mark Alberts, MD, of Hartford Healthcare, said it was "reasonable to investigate" nimodipine given that it's been shown to potentially have neuroprotective effects. But the problem of cognitive decline following stroke is a "vexing issue" because the pathophysiology is so complicated.

"If you have a stroke, and you develop dementia after the stroke, is that vascular dementia related to the stroke? Having a stroke, you take out millions of neurons," he told MedPage Today. "Most people, including myself, think it's a combination, that there's some underlying degenerative process, and vascular disease on top of that is just accelerating it perhaps."

Alberts said it's best to focus on risk factor control in patients with cognitive impairment after a stroke -- treating diabetes, hypertension, and hypercholesterolemia, for instance. For patients who progress to dementia, he offers rehabilitation programs or the cholinesterase inhibitor donepezil (Aricept).

Amytis Towfighi, MD, of the University of Southern California and director of neurological services at the Los Angeles County department of health, agreed that risk factor control is the main therapeutic strategy for cognitive impairment following stroke.

"Currently there are no proven treatments. We don't know if medications that have been tested in Alzheimer's would be effective," she told MedPage Today. "Generally we recommend lifestyle changes -- the same things you would recommend to prevent stroke. Prevention is the key."

The study was supported by the National Key Technology Research and Development Program of the Ministry of Science and Technology of China. Bayer provided additional support.

Zheng disclosed no financial relationships with industry.

1969-12-31T19:00:00-0500

last updated 02.27.2017

• Primary Source

  International Stroke Conference

  Source Reference: Zheng H, et al "Efficacy and safety of nimodipine in vascular mild cognitive impairment: a randomized placebo controlled trial" ISC Meeting 2017; Abstract LB7.

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