Could marijuana use increase vulnerability to Alzheimer's?

A new study warns that marijuana use may increase susceptibility to Alzheimer's disease, after finding the drug severely reduces blood flow in an area of the brain affected by the illness.

Researchers suggest marijuana use may increase susceptibility to Alzheimer's by reducing blood flow in the hippocampus.

Published in the Journal of Alzheimer's Disease, the study reveals that individuals with a marijuana use disorder showed reduced blood flow in nearly all areas of the brain, compared with healthy controls.

What is more, the research team - including co-author Dr. Elisabeth Jorandby of Amen Clinics Inc. in California - found that the hippocampus saw the largest reduction in blood flow with marijuana use.

The hippocampus is the brain region associated with learning and memory, and it is the first region to be affected in patients with Alzheimer's disease.

In the United States, marijuana is becoming increasingly legalized for recreational and/or medicinal use.

With this in mind, researchers are in agreement that it is more important than ever to understand the possible harms of marijuana use, and Dr. Jorandby and colleagues caution that reduced brain blood flow may be one such effect.

Almost every brain region affected by marijuana use

When blood flow in the brain is reduced, this causes a reduction in the amount of oxygen that reaches brain cells, which can cause brain tissue damage and death.

According to the authors, few previous studies have assessed the effects of marijuana use on blood flow in the brain.

To address this research gap, the team used single photon emission computed tomography (SPECT) to measure the blood flow and brain activity of 982 individuals who had been diagnosed with a marijuana use disorder, alongside 92 healthy controls.

SPECT was used to measure participants' brain blood flow and activity during a mental concentration task and when at rest.

Compared with the healthy controls, the researchers found that subjects with marijuana use disorders showed significantly reduced blood flow in almost all brain regions, but the hippocampus fared worst.

In particular, the team identified abnormally low blood flow in the right hippocampus of subjects with marijuana use disorders as they completed the concentration task.

Talking to Medical News Today, study co-author Dr. Cyrus Raji, of the University of California-San Francisco, said the team was surprised by just how much marijuana use affected brain blood flow.

"Prior papers have suggested that marijuana can damage the brain. What surprised [us] was how low blood flow was in the brains of our cohort - virtually every brain area had reduced blood flow on perfusion imaging in relation to marijuana use," he told us.

Findings suggest marijuana has 'damaging influences in the brain'

The researchers note that marijuana use is believed to impede activity in this brain region to disrupt memory formation, and previous studies have associated weakened blood flow in the hippocampus with Alzheimer's disease.

"As a physician who routinely sees marijuana users, what struck me was not only the global reduction in blood flow in the marijuana users' brains, but that the hippocampus was the most affected region due to its role in memory and Alzheimer's disease," says Dr. Jorandby.

"Our research has proven that marijuana users have lower cerebral blood flow than nonusers. Second, the most predictive region separating these two groups is low blood flow in the hippocampus on concentration brain SPECT imaging.

This work suggests that marijuana use has damaging influences in the brain - particularly regions important in memory and learning and known to be affected by Alzheimer's."

Dr. Elisabeth Jorandby

Study co-author Dr. Daniel Amen, founder of Amen Clinics Inc., believes the team's findings should act as a word of caution for marijuana users.

"Our research demonstrates that marijuana can have significant negative effects on brain function. The media has given the general impression that marijuana is a safe recreational drug, this research directly challenges that notion," he says.

Based on their results, Dr. Raji told MNT that frequent cognitive testing for patients prescribed medical marijuana is something that is "certainly worthy of careful consideration."

He added that the team now plans to conduct further research with the aim of pinpointing "actual risk levels of dementia" for individuals who use marijuana.

Read how marijuana may lower dopamine levels to trigger mental illness.

Written by Honor Whiteman

NeuroBreak: Ocrevus Delay; Pregnancy Brain; Fentanyl Menace

The FDA has delayed the PDUFA date for ocrelizumab (Ocrevus) by three months. Drugmaker Genentech says it's for review of additional data on the drug's manufacturing process, not concerns about safety or efficacy. (Press Release)

Many mothers will argue that "pregnancy brain" is real -- and a new study finds a loss of grey matter in brain regions involved in social cognition, specifically those dealing with the ability to register how other people perceive things. But the authors of the Nature Neuroscience paper suggest that brain volume loss in this case is not necessarily a bad thing. It may actually represent pruning or other cellular adaptation that is helpful for raising a child: for instance, streamlining certain brain areas to be more efficient at "mothering" skills such as nurturing and teaching. (New York Times)

More women are using marijuana during pregnancy now than they were a decade ago (rising from about 2% to 4% for past-month use), most likely to ease nausea. Commenting on the findings, NIDA chief Nora Volkow warned that the fetal endocannabinoid system forms about 2 weeks into pregnancy, and substances that interact with it could affect fetal brain neurodevelopment. (MedPage Today)

Opioid overdose deaths rose for yet another year, topping 33,000 in 2015, according to the latest CDC data. Findings from a follow-up National Center for Health Statistics study found similar increases, and both studies revealed big jumps in deaths due to fentanyl -- mostly illicitly made stuff, not prescriptions, federal researchers suggested. (MedPage Today, LiveScience)

Wholesalers flooded the state of West Virginia with 780 million hydrocodone and oxycodone pills over a six-year period -- enough to give every man, woman, and child 433 pills. (Charleston Gazette-Mail)

Meanwhile, Purdue is still trying to push its products -- now on a global scale. A network of companies owned by the Sackler family is moving rapidly into Latin America, Asia, the Middle East, and Africa, advocating the use of its painkillers in places that aren't prepared to handle an epidemic of opioid abuse and addiction. (Los Angeles Times)

The FDA said quit-smoking drugs varenicline (Chantix) and bupropion (Zyban) can drop their black-box warnings about serious neuropsychiatric risks. (MedPage Today)

An early phase I study finds a "favorable safety profile and excellent immunogenicity" for an anti-tau vaccine, AADvac1. More information is needed on CSF tau and other Alzheimer's biomarkers, as well as a signal of brain atrophy, editorialists warned. (Lancet Neurology)

A large observational study generated emphatic headlines that statins may reduce the risk of Alzheimer's, but this Health News Review story warns why the association is likely just that.

Nurse anesthetists won't be able to administer anesthesia by themselves under a new rule from the Department of Veterans Affairs. (MedPage Today)

FDA has granted breakthrough status to neridronic acid for the treatment of complex regional pain syndrome (CRPS), the first of its kind in the disease, said manufacturer Gruenenthal.

Celgene is wading into the neurodegeneration space, signing a deal with Evotec for a discovery program aimed at a wide range of neurodegenerative conditions. (Endpoints News)

2016-12-20T13:00:00-0500

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Alzheimer's: Are we on the right path to new drugs?

With the number of people living with Alzheimer's disease expected to almost triple by 2050, the race is on to find a treatment that can prevent or slow the condition. But last week saw another crack emerge in the already rocky path toward an effective Alzheimer's medication; pharmaceutical giant Eli Lilly announced the failure of what had previously been hailed a "breakthrough" in the treatment of the most common form of dementia.

Last week, Eli Lilly announced that the drug solanezumab had failed to slow cognitive decline in patients with mild Alzheimer's.

In a statement released last Wednesday, Eli Lilly revealed that their drug solanezumab failed to slow cognitive decline in a phase III clinical trial of more than 2,000 patients with mild Alzheimer's disease.

Solanezumab is a monoclonal antibody that aims to slow Alzheimer's progression by targeting and breaking down beta-amyloid plaques in the brain, which are clumps of protein thought to play a significant role in the disease.

While there are a number of other drugs in development that work in a similar way, none had come as far as solanezumab; it is the first medication of its kind to reach the last stage of testing prior to being eligible for license application, and researchers were optimistic that the drug would yield success.

In 2012, early data from the trial suggested solanezumab could slow disease progression by around 34 percent for a subset of patients in the earliest stages of Alzheimer's.

And last year, Medical News Today reported on further results from the trials that revealed the earlier solanezumab is given to patients with mild Alzheimer's, the greater the chance of success.

The failure of solanezumab

Though these early results were met with caution, there were high hopes that solanezumab would become the first drug to slow Alzheimer's disease. However, it seems these hopes have now been dashed.

Eli Lilly report that in the final stage of their trial - called EXPEDITION3 - patients with mild Alzheimer's who were treated with solanezumab "did not experience a statistically significant slowing in cognitive decline compared to patients treated with placebo."

"Lilly will not pursue regulatory submissions for solanezumab for the treatment of mild dementia due to Alzheimer's disease," the drug giant said in their statement.

Alzheimer's organizations across the globe have spoken of their sadness following the trial results.

"After positive news last summer we had high hopes for this drug to become the first to slow down Alzheimer's disease," says Jeremy Hughes, chief executive of the Alzheimer's Society in the United Kingdom. "It's extremely disappointing to learn that it hasn't delivered a meaningful change for people living with dementia, when the need is clearly so great."

In a statement, the Alzheimer's Association in the United States say they are "disappointed" with the results, but they add that there are other beta-amyloid targeting drugs in development that show promise.

However, many researchers claim the failure of solanezumab begs the question: is targeting beta-amyloid really a feasible way to treat Alzheimer's disease?

Beta-amyloid and Alzheimer's

Beta-amyloid is a "sticky" protein fragment produced by a molecule called amyloid precursor protein (APP). Beta-amyloid can accumulate between nerve cells - or neurons - in the brain, clumping together to form so-called plaques.

According to the National Institute on Aging, some individuals will develop these plaques as they age, but they are much more abundant in certain regions of the brain in people with Alzheimer's disease, including the hippocampus - the region associated with learning and memory.

Beta-amyloid plaques are believed by many to play a key role in Alzheimer's disease.

As such, beta-amyloid is considered a hallmark of Alzheimer's disease. However, precisely how it contributes to the condition is a topic of debate.

In fact, scientists remain unclear about whether beta-amyloid plays a role in the development of Alzheimer's disease, or whether it is a byproduct of Alzheimer's pathology. In other words, is beta-amyloid a cause or a symptom of Alzheimer's?

The former is the more widespread theory. A study published in 2013 in the journal Science, for example, used mouse models to show how beta-amyloid destroys the connections between brain cells - called synapses - before forming plaques to cause nerve cell death.

However, other studies have suggested a protein called tau - which forms twisted strands known as "tangles" inside nerve cells - may be a primary cause of Alzheimer's.

One such study - published earlier this year in the journal Science Translational Medicine - found that a greater abundance of tau in the brain's temporal lobe was linked to poorer memory.

While Alzheimer's researchers have increasingly looked to tau as a target for new drugs in recent years, the focus is still very much on beta-amyloid. But given the number of beta-amyloid-targeting drugs that have failed in testing, optimism for these types of medication is gradually dwindling.

Is the beta-amyloid theory dead?

Alzheimer's disease has one of the highest drug failure rates. According to a 2014 study published in the journal Alzheimer's Research & Therapy, of 244 compounds tested in Alzheimer's clinical trials between 2000-2012, only one was approved by the Food and Drug Administration (FDA), representing a 99.6 percent failure rate.

Fast facts about Alzheimer's

• Alzheimer's is the most common form of dementia, affecting more than 5.4 million Americans
• In the U.S., someone develops Alzheimer's every 66 seconds
• This year, Alzheimer's will cost the U.S. around $236 billion.

Learn more about Alzheimer's

The vast majority of these clinical trials were for therapies that target beta-amyloid, accounting for 70 of 146 compounds tested. In comparison, only 13 of the compounds tested targeted the tau protein.

Looking at the overall statistics, it is hard not to question the feasibility of beta-amyloid-targeting drugs for the treatment of Alzheimer's, and it seems the latest report of solanezumab's failure has done nothing to quash this doubt.

Talking to BBC News, Prof. Peter Roberts, of the University of Bristol in the United Kingdom, said he was not surprised solanezumab failed to yield positive results for Alzheimer's patients.

"The problem, to my mind, is completely fundamental. There is still no convincing evidence that shows a clear relationship between amyloid deposition and deficits in cognition in humans," he said. "All we really know is that evidence of amyloid deposition begins up to maybe 20 years before the onset of Alzheimer's disease."

Some researchers believe solanezumab's failure is further confirmation that beta-amyloid is simply the wrong target for an Alzheimer's treatment.

"The amyloid hypothesis is dead," George Perry, a neuroscientist at the University of Texas at San Antonio, told Nature News. "It's a very simplistic hypothesis that was reasonable to propose 25 years ago. It is not a reasonable hypothesis any longer."

"We're flogging a dead horse," added Peter Davies, an Alzheimer's researcher at the Feinstein Institute for Medical Research in Manhasset, New York. "There's no sign of anybody getting better, even for a short period, and that suggests to me that you have the wrong mechanism."

A different approach to beta-amyloid may be needed

Many scientists, however, remain optimistic that beta-amyloid is the right target for Alzheimer's drug development, but some suggest the way the protein is targeted may need to be reassessed.

In the case of solanezumab, the drug binds to beta-amyloid plaques in the brain and breaks them down. However, Prof. Roxana O'Carare, a professor of clinical neuroanatomy at the University of Southampton in the U.K., speculates that the protein may need to be removed from the brain completely.

"The brain is not equipped with lymph vessels as other organs have. Instead fluid and waste are eliminated from the brain along very narrow pathways that are embedded within the walls of blood vessels," she explained to BBC News.

"These pathways change in composition and fail in their function with increasing age and with the risk factors for Alzheimer's disease, resulting in the buildup of amyloid in the walls of blood vessels."

"When a vaccine such as solanezumab is administered," Prof. O'Carare added, "the sticky plaques of amyloid from the brain break down, but the excess waste and fluid is unable to drain along the already compromised drainage pathways."

There might still be hope for solanezumab

While Eli Lilly say they will no longer seek regulatory approval for solanezumab, the drug continues to be tested in a number of clinical trials.

The Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease study, or the A4 study, is one such trial. Initiated in 2014, the phase III trial is testing the safety and efficacy of solanezumab in 1,150 patients at risk of Alzheimer's due to beta-amyloid buildup.

Although solanezumab fell at the last hurdle in Eli Lilly's trial, some Alzheimer's researchers and organizations believe it is not necessarily the end of the road for the drug.

"We sincerely hope that the ongoing Alzheimer's prevention trials (A4 study, Alzheimer's Prevention Initiative, DIAN-TU) that are testing solanezumab and other anti-amyloid agents will continue," say the Alzheimer's Association in a statement.

"These other programs have different ways of acting on the amyloid pathway and some are also addressing the disease at a much earlier stage when these drugs may still prove to be effective."

'Dementia can and will be beaten'

Researchers are keen to point out that there are a number of other drug compounds being tested that have shown promise against Alzheimer's in early trials.

The Alzheimer's Association note that one therapeutic strategy being investigated is alleviating inflammation of the brain, or neuroinflammation, which some researchers have suggested may play a role in Alzheimer's disease.

Earlier this year, the Alzheimer's Association announced that four new phase I and phase II trials will each be receiving $1 million in funding to further investigate the link between neuroinflammation and Alzheimer's.

"Increasing evidence suggests neuroinflammation plays an important role in the brain changes that occur in Alzheimer's and other neurodegenerative diseases," says Maria Carrillo, Ph.D., chief science officer of the Alzheimer's Association.

"By further understanding the role and the timing of neuroinflammation and immune responses, we will be able to further accelerate novel candidate Alzheimer's therapies," she adds.

So it seems that in the wake of the disappointing news about solanezumab, it is certainly not time to give up on the prospects of new treatments that can prevent, slow, or halt Alzheimer's disease.

"Dementia is society's biggest health challenge - and we've seen time and again that developing effective treatments is incredibly difficult. This is only one drug of several in the pipeline and they aim to tackle dementia in different ways, so we should not lose hope. Dementia can and will be beaten."

Jeremy Hughes, chief executive of the Alzheimer's Society

Written by Honor Whiteman

Aerobic exercise improves cognition in old age

A significant number of people aged 65 and over are affected by mild cognitive impairment. New research suggests aerobic exercise can have remarkably beneficial effects on these patients.

Aerobic exercise may improve cognition in seniors with mild cognitive impairment.

Mild cognitive impairment (MCI) refers to the slightly decreased cognitive abilities in individuals of 65 years of age and over. Such people may experience minor cognitive decline in memory or reasoning, but not to an extent where it interferes significantly with daily activities.

Studies report that anywhere between 5-20 percent of the older population have MCI.

MCI often leads to Alzheimer's disease (AD). Some studies have shown that 80 percent of patients with MCI have developed AD after 6 years.

Previous research has suggested exercise training may increase the volume of some brain areas and improve memory.

Now, new research confirms it may not only increase brain size, but could also improve cognition in patients with MCI.

Studying the effects of exercise on patients with MCI

Researchers examined 35 adults with MCI in a randomized, controlled trial of physical exercise. The team was led by Laura D. Baker, Ph.D., from Wake Forest School of Medicine (WFSM) in Winston-Salem, NC.

Researchers divided the participants in two groups: one group of 16 adults averaging 63 years of age, and a control group of 19 adults with the mean age of 67.

The former group participated in a range of aerobic activities, including treadmill, stationary bike, and elliptical training. They trained four times per week for 6 months. The control group engaged in stretching exercises at the same rate.

Scientists took magnetic resonance scans of all of the participants' brains before and after the 6-month period.

The brain images were compared using conventional and biomechanical metrics to measure the changes in brain volume and shape.

"We used high-resolution MR [magnetic resonance] images to measure anatomical changes within areas of the brain to obtain both volumetric data and directional information," says co-author Jeongchul Kim, Ph.D., of WFSM.

The results of the study have been presented today at the annual meeting of the Radiological Society of North America.

Executive function improved with aerobic activity

At the end of the 6-month period, participants were tested to see the effects of aerobic exercise on cognitive function.

"Even over a short period of time, we saw aerobic exercise lead to a remarkable change in the brain," says Baker.

Those who took part in the aerobic program had improved significantly more in executive function than the stretching group.

In both the aerobic and the control group, researchers noticed a volume increase in most gray matter areas of the brain, including the temporal lobe, which is responsible for short-term memory.

"Compared with the stretching group, the aerobic activity group had greater preservation of total brain volume, increased local gray matter volume, and increased directional stretch of brain tissue," adds Kim.

In the stretching group, researchers noticed a local atrophy within the white matter tracts, also known as connecting fibers. Kim notes that such a deformation is most of the time related to brain volume loss, but not always.

"Directional changes in the brain without local volume changes could be a novel biomarker for neurological disease. It may be a more sensitive marker for the tiny changes that occur in a specific brain region before volumetric changes are detectable on MRI."

Jeongchul Kim, Ph.D.

Kim explains that the treatment of AD and MCI requires tracking changes in the brain while patients undergo changes in diet and exercise. Therefore, both MRI measures are important to the treatment of these conditions.

"Any type of exercise can be beneficial," he adds. "If possible, aerobic activity may create potential benefits for higher cognitive functioning."

Read about how stronger muscles may lead to a stronger brain.

Written by Ana Sandoiu

Morning Break: Weight-Shaming Suicide; Faith Moves Brains; Diabetes Capital

Cyberbullying and weight shaming got the blame for a Texas teenager's decision to commit suicide, witnessed by her family. (CNN)

People who are "feeling the spirit" of a religious experience show it in their brains. (Fox News)

A new study put a $411 billion price tag on the adverse effects that lack of sleep has on health and productivity. (VOA News)

Cancer patients reported feeling less anxiety and depression during treatment with the psychedelic component of "magic mushrooms." (CBS News)

A drug company CEO warned industry colleagues that pushback against high drug prices did not end with the defeat of Hillary Clinton. (Fierce Pharma)

Mobile, Ala., won the dubious title of "Diabetes Capital of America," with an estimate diabetes prevalence of almost 18%, followed closely by Charleston, W.Va. (17.6%), and Corpus Christi, Texas (16.9%). (Market Watch)

Alcohol intake, particularly white wine, had a significant association with the risk of invasive melanoma. (American Association for Cancer Research)

A jury in Dallas awarded a total of $1 billion to six plaintiffs who said they were injured by hip implants manufactured by a division of Johnson & Johnson. (Reuters)

Bacteria in the digestive system may play a role in symptom severity in Parkinson's disease, according to a study in mice. (NBC News)

A group of Australian high school students created a generic version of the antiparasitic drug Daraprim for $2 a pill, the same pill Martin Shkreli wanted to sell for $750. (Washington Post)

Will President-elect Trump make fast food fashionable at the White House? (CNN)

A strategy of alternately starving and flooding prostate cancer cells with testosterone yielded "unexpected and exciting" results in a preliminary study. (EORTC-NCI-AACR)

Morning Break is a daily guide to what's new and interesting on the Web for healthcare professionals, powered by the MedPage Today community. Got a tip? Send it to us: MPT_editorial@everydayhealthinc.com.

2016-12-02T09:30:00-0500

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Eli Lilly Alzheimer's drug fails to show benefits in final stage clinical trial

Eli Lilly and Company has announced that their drug solanezumab has failed to meet its primary endpoint of slowing cognitive decline in people with mild Alzheimer's disease.

The phase III trial, called EXPEDITION 3, was started in 2013 after the same drug failed to meet its primary endpoints in two earlier clinical trials in mild to moderate Alzheimer's. However, further analysis of the earlier trials showed a slowing of cognitive decline in only those volunteers with mild Alzheimer's. The findings at that time were encouraging enough to support the drug going back into another phase III trial in people only in the mild stages of the disease. Unlike previous trials with the drug, EXPEDITION 3 used amyloid PET brain scans or spinal fluid tests to select only those patients with high levels amyloid who were most likely to respond to the drug.

Solanezumab is one of several drugs in development that are designed to target amyloid - a key protein that builds up into 'plaques' early in the brain in Alzheimer's disease. The drug is a monoclonal antibody designed to tag single amyloid molecules circulating in the blood and the brain, mopping them up to prevent more plaques forming.

EXPEDITION 3 was a multinational, 18-month placebo-controlled trial in over 2,100 people with mild Alzheimer's disease.

The headline results shows that the drug did not cause a statistically significant slowing in memory and thinking decline compared to a placebo treatment, as measured by a cognitive test called ADAS-Cog14. While Lilly reports that several of the secondary measurements being taken in the trial showed a signal in the right direction, these were much smaller than hoped for.

As a result, Lilly will not be submitting the drug for regulatory approval for the treatment of mild Alzheimer's. However, the drug is currently planned to enter another phase III trial in people at an even earlier stage of the disease called 'prodromal Alzheimer's'. This term describes people with early memory and thinking problems not severe enough to be classed as dementia, but who have signs of amyloid on PET scans and in spinal fluid. If it continues, this trial is expected to report results in 2021.

Dr David Reynolds, Chief Scientific Officer at Alzheimer's Research UK, said: "Our 15-year wait for a new Alzheimer's drug does not end today, but we shouldn't view this setback as the end of the line - the journey towards a new treatment can and will continue. It's very disappointing that solanezumab has not shown benefit for people with mild Alzheimer's and will no doubt trigger important debate within the research community. We only have headline information today, so we'll need to see the full data to understand why solanezumab didn't show benefits and what researchers must learn from the findings.

"Solanezumab is designed to mop up amyloid protein - a key hallmark of Alzheimer's - and is the result of years of development based on the concept that this protein is a central driver of the disease. While today's results are a setback for the amyloid hypothesis, there are several other anti-amyloid drugs still in clinical trials that work in different ways, some of which are being tested even earlier in the disease process than solanezumab. We can't disregard these ongoing trials and their findings will now be more important than ever in shaping the search for disease-modifying treatments for Alzheimer's.

"Today is undoubtedly a set-back for people with Alzheimer's and their families, and highlight the ongoing importance of drug discovery efforts into other aspects of the biology of Alzheimer's. Our understanding of the biology of Alzheimer's is expanding and with it are our approaches for improving the lives of those with the disease. Alzheimer's Research UK is already supporting millions of pounds of treatment research taking place in labs around the country today, including our pioneering Drug Discovery Alliances, to ensure that this hard work continues."

The physics of caffeine extraction now provides solutions for nerve stimulation

Researchers at Karolinska Institutet have developed a method for producing flexible plastic electrodes capable of releasing the neurotransmitter acetylcholine upon an electrical trigger. This technology has applications in the treatment of Alzheimers's Disease or muscular disorders where today, hard metal electrodes are used to stimulate nerves to restore muscle function.

Using flexible plastics instead of metal is an advantage because it will cause less damage to the surrounding brain tissue. By stimulating brain regions the physiological way, with neurotransmitters instead of electricity, the researchers claim that the effect will be much more specific and will allow treatments that were not previously possible.

Impregnating conducting plastics with sufficient amounts of neurotransmitters, so that release is only possible due to an electronic trigger is difficult under normal conditions. The multidisciplinary team therefore used the unique properties of a supercritical fluid to achieve the desired effect.

They took carbon dioxide gas and put it under pressure while at the same time, increasing the temperature. At a specific point under these conditions, the carbon dioxide will take on the properties of both a liquid and a gas. The researches found that acetylcholine with a co-solvent would dissolve in supercritical carbon dioxide and penetrate into the conducting plastic material.

"This approach has additional benefits." said Professor Agneta Richter-Dahlfors, the lead investigator of the study. "Supercritical carbon dioxide is good sterilization method for sensitive materials, so when we impregnate the plastic with this method, we are also preparing it for use in the clinic, you get two for one."

In the second part of the research article the researchers showed that they could then release the acetylcholine on demand by stimulating the conducting plastic with an electrical signal. This caused the polymers of the plastic to expand, allowing the trapped acetylcholine to diffuse out into the surroundings. This could be used for treating muscular disorders where the motor neurons are damaged.

"We are very excited about the results. The field of Organic Bioelectronics is expanding and every way we turn we find new and exciting applications in medicine. There are many important neurotransmitters which we can use with this method to stimulate nerve cells specifically," said Dr. Susanne Löffler.

This work was published in the Journal for Controlled Release and was carried out with financial support Vinnova and Carl Bennet AB.

Article: Electrochemically triggered release of acetylcholine from scCO2 impregnated conductive polymer films evokes intracellular Ca2+ signaling in neurotypic SH-SY5Y cells, Susanne Löffler, Silke Seyock, Rolf Nybom, Gunilla B. Jacobson & Agneta Richter-Dahlfors, Journal for Controlled Release, doi: 10.1016/j.jconrel.2016.10.020, published online 26 October 2016.

NeuroBreak: Amyloid Rollercoaster; Opioid Deaths Still Rising

Although the investigational Alzheimer's drug solanezumab disappointed those at the CTAD meeting last week, extended results from an early study of aducanumab quickly boosted spirits. Following concerns about ARIA, Biogen added a titration arm to the study, and this group had less ARIA and good efficacy when compared with a steady higher dose of the drug. The field isn't letting go of the amyloid hypothesis just yet. (Endpoints News, FierceBiotech)

Heroin deaths have surpassed gun homicides for the first time ever. The opioid epidemic continues to surge in the U.S., topping 30,000 deaths in 2015. (Washington Post)

Teen use of illicit substances continues to drop -- with the exception of marijuana. (STAT News)

Governments should call on naloxone drugmakers to drop prices and increase transparency about the generic drug's costs, researchers argue in the New England Journal of Medicine.

Endo has sold the rights to the opioid chronic pain drug Belbuca back to BioDelivery Sciences. (Philly.com)

A diagnostic algorithm involving cerebrospinal fluid and nasal samples had excellent sensitivity and specificity for diagnosing Creutzfeldt-Jakob disease. (JAMA Neurology)

A higher exposure to statins was tied to a lower incidence of Alzheimer's disease compared with lower exposure, but that reduction varied by race/ethnicity and type of statin. (JAMA Neurology)

Rates of neonatal abstinence syndrome in rural areas jumped more than 500% from 2004 to 2013, far outpacing urban areas. (MedPage Today)

Bristol-Myers Squibb is paying nearly $20 million to settle charges that it improperly promoted Abilify for children and older patients with dementia and Alzheimer's disease. (Reuters)

The nation's largest statewide effort to track concussions among youth athletes is under way in Texas. UTSouthwestern launched the ConTex registry, run by Munro Cullum, PhD, to assess the prevalence of brain injuries in high school sports.

2016-12-13T12:00:00-0500

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Dementia: Protein in urine may put people at greater risk

New research - published in Neurology, the medical journal of the American Academy of Neurology - suggests that people who have protein in their urine might have higher odds of developing problems with memory and thinking down the line, and they may even develop dementia.

Protein in urine may be associated with an increased risk of cognitive impairment or dementia.

Researchers trawled through all available publications focused on kidney problems and the development of cognitive impairment or dementia, in order to summarize the best available evidence and connect the dots between the two conditions.

Protein in urine is a sign of kidney problems, which have been deemed a possible risk factor for cognitive impairment and dementia in several studies.

The brain and kidneys are both end organs and share similar structural and mechanical features, which makes them susceptible to vascular damage. Several pathways might link chronic kidney disease (CKD) and cognitive impairment, including the shared vascular factors.

"CKD and dementia share many risk factors, such as high blood pressure, diabetes and high cholesterol, and both show similar effects on the brain, so they may have shared vascular factors or there may even be a direct effect on the brain from kidney problems," says Kay Deckers, of Maastricht University in the Netherlands, author of the systematic review and meta-analysis.

Around 10 percent of the global population is affected by CKD, and the condition is more likely to occur in older people. The study notes that: "Both CKD and dementia are important public health problems with associated poor health outcomes and rising healthcare costs for our society."

According to the World Health Organization (WHO), there are currently 47.5 million people worldwide who have dementia, and that number continues to rise, with 7.7 million new cases every year. Identifying the factors that may cause dementia is important given the lack of effective treatments.

The authors of the study say that the exact mechanisms relating kidney impairment to dementia are not entirely understood. However, traditional risk factors and other factors that they have in common may play a part.

The authors write: "Traditional risk factors include cardiovascular disease (e.g., myocardial infarction, atrial fibrillation), stroke, type 2 diabetes mellitus, isolated systolic hypertension, age, smoking, and hypercholesterolemia."

"Other factors include anemia, albumin, and hyperhomocysteinemia, whereas inflammation, oxidative stress, cerebral small vessel disease, silent brain infarcts, microbleeds, and white matter lesions are possible underlying mechanisms leading to cognitive impairment or dementia."

Kidney dysfunction potential risk factor for dementia

Out of 8,494 studies on the conditions, 22 of these met the criteria to be included in the systematic review. Five of the studies - that included a total of 27,805 people - were evaluated in the meta-analysis of the protein that sometimes emerges in urine, called albuminuria or proteinuria.

The analysis found that, compared with individuals without the protein in their urine, people with the urine protein were 35 percent more likely to develop cognitive impairment or dementia.

Deckers and team say that their large population-based study adds to the growing evidence that kidney dysfunction is an independent risk factor for cognitive impairment or dementia.

However, limitations of the study include the fact that most of the studies used different methods for estimating renal function and this was only tested once, usually at the start of the study.

"Protein in the urine was associated with a modestly increased risk of cognitive impairment or dementia. More research is needed to determine whether the kidney problems are a cause of the cognitive problems or if they are both caused by the same mechanisms."

Kay Deckers

In addition to examining the association of albuminuria, Deckers and colleagues also observed other markers of kidney function. The first marker analyzed was estimated glomerular filtration rate. The results from this marker were mixed and showed no significant relationship with cognitive impairment or dementia.

Analysis of the other three other markers of kidney function - cystatin C, serum creatinine, and creatinine clearance - could not be completed due to too many variations in the approach of the studies, which made them incomparable.

Learn how light therapy could be a promising noninvasive therapy for Alzheimer's disease.

Written by Hannah Nichols

PodMed: A Medical News Roundup From Johns Hopkins

PodMed is a weekly podcast from Johns Hopkins Medicine. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week.

This week's topics include statins and Alzheimer's, teen substance use, national mortality data, and psychiatric drug use in American adults.

Program notes:

0:33 Cause specific mortality in the US

1:35 At over 80 million deaths

2:32 Not terribly surprising to see risk factors

3:00 How many US adults take a psychiatric drug

4:01 Only 9% of Hispanics

5:03 Statins and Alzheimer's disease

6:06 Fat or lipid soluble?

7:03 Personalized medicine approach

7:31 Teen drug and substance use

8:31 Marijuana use continues apace

9:30 Kids are smart and paying attention

10:41 End

2016-12-17T14:00:00-0500

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Year in Review: Psychiatry

The nation's addiction to prescription opioid painkillers dominated headlines in psychiatry once again.

In July, President Obama signed into law the Comprehensive Addiction and Recovery Act (CARA), which expanded medication-assisted treatment and access to treatment programs.

Other agencies developed their own plans aimed at stemming the crisis. For example, in March, the CDC issued guidelines that strongly recommended against using opioids for chronic pain. The U.S. Department of Health and Human Services increased the number of addiction patients that a physician can treat with buprenorphine from 100 to 275.

The FDA took up the gauntlet by advancing its own opioid "action plan," focusing on support for development of abuse-deterrent opioids and increased access to the overdose reversal agent naloxone.

Finally, the U.S. Surgeon General weighed in with a landmark report on addiction that calls for an evidence-based public health response.

Stimulant Addiction

While public health officials have been focusing on the nation's opioid addiction problems, some have expressed concerns about increased use of medications that treat attention deficit-hyperactivity disorder (ADHD) in adults.

Since 2013, the FDA has received 19,000 reports of complications from ADHD drugs, most of which are stimulants like Adderall (amphetamine and dextroamphetamine), Concerta (methylphenidate), Ritalin (methylphenidate), and Vyvanse (lisdexamfetamine), according to a MedPage Today/Milwaukee Journal Sentinel analysis.

Federal statistics are showing that recreational use of Adderall in particular is increasing among those ages 26 or older, rising nearly four-fold from 2006 t0 2014. National emergency department data showed that cases involving Adderall and Ritalin quintupled over 7 years.

"Amphetamines are grossly overused," Nicolas Rasmussen, PhD, MPH, a medical historian who has studied the history of amphetamines in the U.S., told reporters.

Depression Screen for Teens

The U.S. Preventive Services Task Force called for routine screening of major depressive disorder (MDD) in adolescents.

Overall, the task force found "adequate" evidence that screening can identify depression in adolescents, and that treatment of MDD in adolescents is linked to "moderate" benefit, such as improved depression severity, depression symptoms, or global functioning scores. There were no studies that directly evaluated whether this screening led to improved health outcomes.

The panel noted that there's still insufficient evidence to recommend routine screening for younger children.

Pot and Psychosis Relapse

Two big studies tied marijuana use to psychosis recurrence. A meta-analysis reported in January found that continued use of cannabis after being diagnosed with psychosis was associated with more relapses compared with both discontinued use and never having used cannabis at all. The study also found an association between extended hospital stays and continued cannabis use.

"What it essentially shows us is that if you continue to use cannabis, it's definitely bad for your psychosis because you continue to have relapses and get admitted to the hospital," lead author Sagnik Bhattacharyya, MBBS, MD, PhD, of King's College in London, told MedPage Today. "If you stop using cannabis, then it's not as bad."

Meanwhile, a quasi-experimental investigation within an observational study showed a higher risk of psychosis relapse while using marijuana. The researchers wrote that these results suggest "that it is more likely than not that continued cannabis use after onset of psychosis is causally associated with increased risk of relapse of psychosis, resulting in psychiatric hospitalization."

Alzheimer's Roller Coaster

The investigational anti-amyloid drug solanezumab failed to meet its primary endpoint in the EXPEDITION3 trial, raising questions for some about the soundness of the amyloid hypothesis in Alzheimer's disease.

But lead investigator Paul Aisen, MD, of the University of Southern California in Los Angeles, said the negative results are the "strongest confirmation to date" of the theory, given that the drug appeared to slow cognitive decline even though the findings weren't significant, and many other secondary endpoints favored the drug.

Indeed, a different anti-amyloid drug, Biogen's aducanumab, showed positive results in an early phase Ib study. The drug's mechanism is different from solanezumab's, which may account for the difference.

Much can change between phase I and phase III, but researchers aren't ready to give up on the amyloid hypothesis just yet.

Boost for CBT

Long-term findings from the COBALT trial showed that cognitive behavioral therapy offered both clinical benefit and bang-for-the-buck in treatment-resistant depression in the long haul. CBT improved quality of life to a greater extent than usual care over nearly 4 years, and that benefit came at an annual cost of about $500, researchers found.

"In view of this robust evidence of long-term effectiveness and the fact that the intervention represented good value for money, clinicians should discuss referral for CBT with all those for whom antidepressants are not effective," the investigators wrote.

Initial results from that trial provided the first evidence of the sustained effectiveness of CBT.

Here are more of this year's top headlines:

Aisen: Negative Study Confirms Amyloid Hypothesis

Surgeon General: Addiction Not a 'Moral Failing'

White House Puts Mental Health Parity in the Spotlight

Pot Use Up as Perceived Risk Falls

HHS Awards $53 Million to Fight Opioid Abuse Epidemic

CDC Issues Warning on New Opioid Substitute

Suboxone Underused, Opioids Overused in Medicare

U.S. Shrink Supply May be Shrinking

Opioid Bill Overwhelmingly Approved by Senate

FDA Chief Criticizes Industry for Inaction on Opioids

HHS Eases Buprenorphine Prescribing

Implant for Opioid Addiction Wins FDA Approval

FDA Warns of Skin Reaction with Olanzapine

FDA Warning: Abilify Tied to Impulse Control Problems

ACP: Choose CBT Before Drugs for Insomnia Tx

APA Urges Cautious Use of Antipsychotics in Dementia

CDC Comes Down Hard on Opioids for Chronic Pain

USPSTF Backs Screening Teens for Major Depression

CBT Works Long-Term in Tough Cases

2016-12-16T12:30:00-0500

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Diogenes Syndrome: Symptoms and Treatment

Diogenes syndrome is a poorly understood behavioral condition typically associated with other conditions, such as dementia.

People with Diogenes syndrome often show a severe self-neglect, social isolation, hoarding, and may live in unsanitary conditions.

A person with Diogenes syndrome can develop a skin condition called dermatitis passivata, where a horny crust develops over the skin. This is usually due to a lack of regular washing.

As Diogenes syndrome is normally linked to other conditions and is not fully understood, it is not listed as a psychiatric disease in the current Diagnostic and Statistical Manual of Mental Disorders 5th Edition, (DSM V).

Contents of this article:

1. What is Diogenes syndrome?
2. Signs and symptoms
3. Treatment for Diogenes syndrome

What is Diogenes syndrome?

Diogenes syndrome may typically, but not always, affect older and isolated people.

Diogenes syndrome is typically observed as a behavioral disorder of the elderly, but it can affect men or women of any age and socioeconomic status.

However, Diogenes syndrome is most common among people with above average intelligence, who are over 60 years, and who live alone.

Approximately 0.05 percent of Americans aged 60 years and older may have Diogenes syndrome. It is considered rare, but there is a lack of research about its prevalence.

There are two forms of Diogenes syndrome: primary and secondary.

In primary cases, the syndrome is not triggered by other medical conditions that an individual already has. In secondary cases, the syndrome is the result of other mental health disorders.

Diogenes syndrome is also known as senile or severe social breakdown syndrome, self-neglect syndrome, senile squalor syndrome, and messy house syndrome.

Signs and symptoms

Symptoms of the condition vary, but there is a cluster of common features that may be present.

These include:

• Poor insight or comprehension of self-hygiene, public health, or safety
• Distrust of society or strangers
• Paranoia or general suspiciousness
• Aloofness or detachment
• Extreme social anxiety
• Obsessive compulsive tendencies
• Excessive hoarding or collecting of household items and waste
• Unsanitary or unsafe living conditions
• Poor nutrition or diet
• Unwillingness to accept outside help or intervention
• Fear or distrust of medical professionals and settings
• Hostility and aggression towards others
• A distorted concept of reality
• Skin conditions due to uncleanliness, such as dermatitis passivata

The signs and symptoms of Diogenes syndrome are often difficult to distinguish from those of other medical conditions such as:

Diogenes syndrome may be difficult to identify from depression

• Syllogomania (hoarding)
• Schizophrenia
• Mania
• Frontotemporal dementia
• Depression
• Obsessive-compulsive personality disorder
• Alcoholism

Research is still being conducted to improve understanding of Diogenes syndrome.

Most of what is known about the condition is based on psychological case studies. Some sources estimate that at least half of all cases occur in patients without prior mental health conditions.

When not associated with another medical condition, Diogenes syndrome may be brought on by a traumatic or stressful event, such as the death of a loved one.

During such periods, everyday activities like personal care tend to be disrupted or overlooked. Lack of self-care, extreme social isolation, and neglect tend to distinguish Diogenes syndrome from syllogomania.

Because little specific research is available, the health, social, and mental complications related to Diogenes syndrome are poorly understood.

However, the syndrome is thought to increase the likelihood of death.

Treatment for Diogenes syndrome

There is no formal diagnosis or treatment plan for Diogenes syndrome.

Some studies recommend compiling a patient's complete medical and psychological history and performing a physical exam, blood screening, and organ function tests to work out a baseline of health.

Bereavement may be a trigger for Diogenes syndrome.

Some doctors may also do imaging tests to rule out the presence of other conditions that may cause similar symptoms. Other doctors conduct personality assessments, which may shed light on the root cause of the syndrome.

Currently, there are no medications or therapy options recognized or recommended specifically for managing Diogenes syndrome. Medications designed or prescribed to treat other medical conditions may help alleviate symptoms, such as paranoia or mania.

Psychological factors must also be taken into consideration, as they often lead to the development or continuation of the syndrome. Aggressive psychological therapy or counseling is sometimes necessary.

These treatments work best alongside other support systems designed to treat the underlying cause of the syndrome. For example, cleaning and personal care services can help decrease the severity of symptoms.

As people with Diogenes syndrome are frequently fearful of medical establishments, treatment is often carried out by home health or community care workers. Ethical and legal complications can complicate treatment as patients may persist in refusing medical intervention.

Because views on matters like self-hygiene and safety vary between people and cultures, many of the symptoms of Diogenes syndrome can also be difficult to objectively assess and treat.

Cases of Diogenes syndrome should be handled with extreme sensitivity by all involved. If a patient feels attacked, judged, or unsafe as the result of intervention, they are more likely to refuse further aid and to return to prior behaviors.

Tips for caregivers

Helping a person who has Diogenes symptom can be a challenge.

Most people who have the condition refuse help even from family members and close friends.

The tendency towards isolation and social anxiety means that many cases of Diogenes syndrome take a long time to identify and to treat.

People with immediate or forced interactions are often the first to spot cases of the condition. These include neighbors, close family members, and mental healthcare workers.

Written by Jennifer Huizen

Among antidementia drugs, memantine is associated with the highest risk of pneumonia

A recent study from the University of Eastern Finland shows that among users of antidementia drugs, persons using memantine have the highest risk of pneumonia. The use of rivastigmine patches is associated with an increased risk as well.

The study found that persons using donepezil or galantamine had the lowest risk of pneumonia. However, persons using memantine or rivastigmine patches had a 1.6 and 1.15 times higher risk of pneumonia, respectively, but no elevated risk was observed among patients using rivastigmine in capsule form. The real risk increase may be even higher, as only cases of pneumonia leading to hospitalisation or death were taken into account.

The study is the first to compare the risk of pneumonia associated with different antidementia drugs and drug forms. The results are not likely to be explained by differences between drug molecules, as rivastigmine was associated with an increased risk of pneumonia in patch form only. The increased pneumonia risk among persons using memantine or rivastigmine patches may be explained at least partly by the fact that these medications are often used in more advanced states of dementia. However, all participants were home-dwelling persons.

The study is based on data from a nationwide register-based study (MEDALZ) conducted at the University of Eastern Finland. The risk of pneumonia was compared among users of different antidementia drugs. The study population consisted of 65,481 persons diagnosed with Alzheimer's disease during 2005-2011 in Finland.

No cure for Alzheimer's diseases currently exists, but the progression of the disease can be slowed down by antidementia drugs, such as memantine and acetylcholinesterase inhibitors such as donepezil, galantamine, and rivastigmine. Persons with Alzheimer's disease have an elevated risk of pneumonia, and it is one of the most common causes of hospitalisation among persons with Alzheimer's disease. Pneumonia is also a common cause of death in this population.

The findings published in the Annals of Medicine. In addition to researchers from the University of Eastern Finland, also researchers from the University of Turku and Karolinska Institutet participated in the study.

Article: Use of antidementia drugs and risk of pneumonia in older persons with Alzheimer's disease, Lampela P, Tolppanen AM, Tanskanen A, Tiihonen J, Lavikainen P, Hartikainen S, Taipale H, Annals of Medicine, doi: 10.1080/07853890.2016.1254349, published online 27 October 2016.

Football players 'not at higher risk of neurodegenerative disease'

The risk of traumatic brain injury is particularly high among football players. A new study sets out to investigate if football players are also at a higher risk of developing degenerative brain diseases later in life.

Compared with other athletes, American football players do not seem to be at a higher risk of neurodegenerative disease, researchers say.

Traumatic brain injuries (TBI) are defined by the American Association of Neurological Surgeons (AANS) as "a blow or jolt to the head, or a penetrating head injury that disrupts the normal function of the brain."

All athletes are at risk of TBI, but the risk is especially high among cyclists and football players.

According to the AANS, out of 446,788 cases of sports-related brain injuries treated in American emergency rooms in 2009, 46,948 were reported by football players.

Some researchers have hypothesized a link between TBI and the onset of neurodegenerative diseases, such as Parkinson's and dementia, in professional athletes.

A new Mayo Clinic study examines the long-term risk of developing degenerative brain diseases in people who played American football in high school.

Examining the risk of brain degenerative disease in varsity athletes

A team of researchers in Rochester, MN, led by Mayo Clinic neurologist Dr. Rodolfo Savica, set out to examine the risk of neurodegenerative disease among high-school football players and other varsity athletes.

Researchers used the medical records linkage system of the Rochester Epidemiology Project to study comparatively the risk of developing neurodegenerative diseases in football players, swimmers, basketball players, and wrestlers.

Scientists reviewed all the yearbooks and documented team rosters for Mayo High School and John Marshall High School - formerly called Rochester High School - between 1956 and 1970. The students were followed for a total of 40 years after participating in high-school sports.

The findings were published in the journal Mayo Clinic Proceedings.

The study examined a total of 486 students, 296 of whom were football players, and the remaining 190 were non-football athletes.

The neurodegenerative diseases considered were dementia and Parkinson's disease. Researchers also examined cases of mild cognitive impairment (MCI).

MCI is considered to be a set of symptoms rather than a disease in itself. It refers to the slightly decreased cognitive abilities in individuals who are 65 years of age and over. The minor cognitive decline these patients report does not interfere significantly with daily activities, but studies have shown an increased risk of dementia in people with MCI.

Increased TBI risk among football players

The study did find a suggestive increased risk of TBI among the football players, and the risk was higher for the 153 students who played for more than one season.

However, the study did not find an increased risk of degenerative brain diseases among football players, compared with the other athletes.

Among the 296 football players, 34 - a little over 11 percent - had reported head trauma.

Only five football players had developed MCI, three had an onset of Parkinson's disease, and two were reported to have dementia. No cases of amyotrophic lateral sclerosis (ALS) were reported among football players.

Comparatively, 14 cases of head trauma were reported among the 190 non-football athletes, amounting to just over 7 percent.

Of the non-football athletes, four had developed MCI, three reported having Parkinson's disease, and one case of dementia was reported. No cases of ALS were reported among football players.

Overall, 1.68 percent of the football players developed a form of neurodegenerative disease, compared with 2.1 percent in non-football players.

Another 2.1 percent of the non-football athletes developed MCI, compared with 1.68 percent in football players.

Football-related head trauma risk should not be underestimated

Despite the proven physical fitness benefits of varsity sports on cardiovascular and overall health, the authors warn against the serious issue of brain trauma risks in football.

As mentioned by the authors, in the decades between 1956 and 1970, football-related head trauma was still minimized, with coaches and industry professionals referring to it as "getting your bell rung."

Furthermore, a previous Mayo Clinic study conducted between 1946 and 1956 did not find an increased risk of degenerative brain disease among football players. The previous research compared 438 male football players with 140 non-football-playing classmates.

Despite the optimistic findings, Dr. Savica and team caution against underestimating the risk of traumatic brain injury:

"This study should not be interpreted as evidence that football-related head trauma is benign. The literature on chronic traumatic encephalopathy in college and professional football players seems irrefutable, with reports of devastating outcomes. However, there may be a gradient of risk, with low potential in high-school football players that played in the study period."

Although football between 1956 and 1970 was largely similar to football today, the researchers highlight the need for more current football studies.

The authors concede that between then and now, football has evolved, with changes in safety measures - such as headgear design. But although helmets once made of leather now come in hard plastic shells, Dr. Savica says the headgear still does not protect against concussions and gives players a false sense of protection.

Learn how early return to play after concussion may be harmful for young athletes.

Written by Ana Sandoiu

More Health Systems Can Mean More Problems for VA Patients

Using more than one health system can have a negative effect on patient safety, according to a study published Monday in the Annals of Internal Medicine.

Specifically, the study found that rates of potentially unsafe medication prescribing were significantly higher among veterans using more than one health provider.

Those rates were significantly higher among veterans with dementia using more than one health system compared to those using only the Department of Veterans Affairs providers.

According to the study, the average dementia patient has four co-morbid conditions and receives care from five different providers annually. Medication management is particularly challenging because the average patient takes five different drugs, and 16% of patients take nine or more.

Provision of highly coordinated care is fundamental to prescribing safety in dementia patients, the study suggests.

The research originated in the Center for Health Equity Research and Promotion at the Veterans Affairs' Pittsburgh Healthcare System, and the Center for Health Services Research in Primary Care at the Durham Veterans Affairs Medical Center, in Durham, NC.

"Recent federal policy changes to expand access to care may have unintended consequences that thwart the VA's efforts to enhance care coordination," the study states.

In 2006, the introduction of the Medicare Part D prescription drug program expanded veterans' access to medications through non-VA health care systems, in which eligibility for Part D is independent of VA benefits.

Subsequent legislation further expanded veterans' ability to seek care outside the VA system.

Although this study claims to be the first to focus on prescribing quality and safety with patients seeking care in both VA and non-VA systems, previous studies show such use lead to duplication and overuse of other health services, and worse health outcomes.

"Successful co-management requires that health information exchange between systems -- currently the responsibility of veterans and caregivers -- needs to improve," the report states. Pilot programs, such as the VA Virtual Lifetime Electronic Record, show "great potential" to facilitate health information sharing between VA and non-VA providers.

This report is brought to you by HealthLeaders Media.

2016-12-11T10:00:00-0500

• Primary Source

  Annals of Internal Medicine

  Source Reference: Thorpe JM, et al "Dual health care system use and high-risk prescribing in patients with dementia: a national cohort study" Ann Intern Med 2016. DOI: 10.7326/M16-0551.

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Amyloid Hypothesis: Yay or Nay?

Since the poll posted, almost 75% of responders said "Yes" to the question, "Do you think the Trump administration will weaken mandatory vaccination programs?"

Some experts believe the amyloid hypothesis is valid, despite recent drug trial results.
Now, MedPage Today asks:

2016-12-16T09:00:00-0500

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Immune cells identified as the culprit linking hypertension and dementia

Hypertension is a leading risk factor for dementia and other disorders associated with cognitive decline. Blood flow to the brain is tightly controlled by several mechanisms that malfunction when blood pressure is abnormally high. Better understanding of how these mechanisms become disrupted in individuals with hypertension may help identify preventative therapies to reduce their risk of developing dementia.

A team led by Costantino Iadecola at Weill Cornell Medical College found that hypertension activates immune cells in the brain called perivascular macrophages, leading to increased oxidative stress in the brain's blood vessels that is linked to dementia. They determined that when angiotensin II, a hormone linked to high blood pressure, activates the macrophages, it causes increases in oxidative stress that are linked to disruptions in blood flow as well as cognitive dysfunction.

Selectively removing these immune cells from the brain reduced damage to blood vessels and reduced signs of cognitive decline in mouse models of hypertension. These findings suggest that targeting activators of perivascular macrophages is a potential approach for preventing dementia in individuals with high blood pressure.

Article: Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension, Giuseppe Faraco, Yukio Sugiyama, Diane Lane, Lidia Garcia Bonilla, Haejoo Chang, Monica M. Santisteban, Gianfranco Racchumi, Michelle Murphy, Nico Van Rooijen, Joseph Anrather, and Costantino Iadecola, JCI, doi: 10.1172/JCI86950, published 14 November 2016.

Commentary: Macrophages come to mind as keys to cognitive decline, D.G. Harrison and Tomasz J. Guzik, JCI, doi: 10.1172/JCI91277, published 14 November 2016.

Women with dementia receive less medical attention

Women with dementia have fewer visits to the GP, receive less health monitoring and take more potentially harmful medication than men with dementia, new UCL research reveals.

The study, published in Age and Ageing, also found that only half of all dementia patients had a documented annual review even though GP surgeries are offered financial incentives to carry these out. Women were found to be at particular risk of staying on antipsychotic or sedative medication for longer. This might be because they have fewer appointments where their treatment can be reviewed.

"As women tend to live longer than men, they are more likely to live alone without a family carer to help them access healthcare," says Dr Claudia Cooper (UCL Psychiatry) who led the research. "Perhaps because of this, they are more at risk of missing out on medical help that might help them stay well for longer. We found that women were more likely to be on psychotropic drugs - sedatives or anti-psychotics - which can be harmful in the long term and may not be appropriate. Women tended to stay on such drugs for longer, perhaps because they have fewer check-ups to see if the drugs were still needed.

"Women with dementia who live on their own may need additional support accessing healthcare services. We should ensure GPs have the resources to proactively engage with these patients and review their condition regularly to make sure their treatment plan, including any drugs, are appropriate. Improving access to healthcare and reducing psychotropic drug use in people with dementia, especially women, could help them to live well with dementia for longer."

The researchers analysed the records of 68,000 dementia patients and 259,000 people without dementia to compare their access to healthcare services, using The Health Improvement Network (THIN) database. Overall, people with dementia received less medical care than those without even though they are more vulnerable to physical and mental illnesses.

"Dementia can cause a wide range of physical complications, including difficulties swallowing and mobility problems," says Dr Cooper. "People with dementia are particularly susceptible to malnutrition, as they may have difficulties eating, preparing food or remembering to eat. Previous research has shown that up to 45% of dementia patients experience clinically significant weight loss¹, which can lead to further physical problems and frailty. However, despite this high risk, less than half of dementia patients are currently receiving an annual weight check-up. The good news is that things seem to be improving: only 24% of patients had their weight monitored in 2002 compared with 43% in 2013."

Improvements may be linked to the government's National Dementia Strategy which launched in 2009. Around the time this was launched, GP surgeries were offered additional financial incentives through the NHS Quality and Outcomes Framework to review dementia patients annually. However, the latest study suggests that there is still more work to be done to ensure that people with dementia, particularly women, are able to access the services they need.

Article: Inequalities in receipt of mental and physical healthcare in people with dementia in the UK, Cooper et al., Age and Ageing, doi: 10.1093/ageing/afw208, published online 4 December 2016.

Understanding psychological dimensions of dementia can improve care, says new British Psychological Society report

To help people live well with dementia we need a better understanding of its psychological impact, according to a new British Psychological Society report (BPS).

The report stresses that dementia affects a person's sense of identity, how they think and behave, their mood and their personal relationships.

So improving people's experience of dementia means improving the support they receive to process how they feel and how they understand the condition, their future and their relationships.

Dr Linda Clare, Chair of the BPS Dementia Advisory Group, said: "Maintaining a sense of control, identity and connection is a key focus as dementia progresses. Without it there is a risk that the person will experience a sense of isolation and dislocation at a time when the resources to protect against this threat are lacking.

"That's why we say putting the person at the centre of care is vital to help people to live well with dementia."

The BPS report 'Psychological Dimensions of Dementia: Putting the person at the centre of care'highlights a number of areas where action is needed to improve understanding and care, and makes recommendations for commissioning services.

The recommendations include:

• People with dementia should be supported in making their own decisions as far as possible.
• Care and treatment should be individually tailored to each person's needs and circumstances.
• Dementia care plans must cover all the person's needs, including equal access to the right healthcare for other mental or physical health needs.
• Families and carers should be included in care planning at all times and have access to psychological support.

Dr Clare continued: "The rights of people with dementia must be respected. We need to ensure their active and meaningful involvement in decisions about their own lives and in planning and evaluating the services they receive.."

Aisen: Negative Anti-Amyloid Trial Confirms Amyloid Hypothesis

SAN DIEGO -- Although the amyloid-scavenging drug solanezumab failed to slow Alzheimer's disease progression significantly in the phase III EXPEDITION3 trial, investigator Paul Aisen, MD, of the University of Southern California, insisted that the amyloid hypothesis remains alive and well.

"We have a negative study that confirms a beneficial effect," Aisen said during the presentation of the results at the Clinical Trials in Alzheimer's Disease (CTAD) meeting here Thursday night. "Two other studies [EXPEDITION and EXPEDITION2] have shown a small benefit. They all show a very consistent story that treatment with solanezumab slows disease progression."

"This is not a refutation of the amyloid hypothesis," he continued. "I think this is a confirmation of the amyloid hypothesis. I think it is the strongest confirmation to date."

At least one audience member reminded Aisen that "not everyone on Twitter agrees with your interpretation" -- not least because both the drug and placebo groups continued to worsen, and questions have long been raised as to whether the benefit would be detectable clinically.

Anton Porsteinsson, MD, of the University of Rochester School of Medicine, told MedPage Today that he's staking out a middle ground regarding the study findings and the hypothesis: "I don't think they dispute it, and I don't think they necessarily affirm it either," he said.

He acknowledged the small effect size is fairly consistent across measurements, and that it only looks at patients who've already developed plaques, raising the question about whether the drug could have an effect earlier in the amyloid build-up process. That possibility is currently being tested in an ongoing trial called A4.

David Knopman, MD, of the Mayo Clinic in Rochester, Minn., had a similar perspective. He told MedPage Today that the study added "a great deal more negative" to the debate over the hypothesis, but noted that "this was not a failure of amyloid beta but of this particular drug."

Indeed, one of the big questions was whether the solanezumab results would spell the end for another anti-amyloid drug under investigation -- Biogen's aducanumab. Since solanezumab targets monomeric forms of soluble amyloid beta, most researchers agreed that the findings shouldn't have an effect on aducanumab because that drug targets an insoluble form that's already gunked up in the brain as plaques.

"Not all monoclonal antibodies are created equal," Alzheimer's Association chief science officer Maria Carillo, PhD, said during a panel discussion following the presentation of the findings. "This is not the time for companies to sit back and say, we need to drop this [amyloid] pathway."

Solanezumab drugmaker Eli Lilly reported the top-line results of the highly anticipated EXPEDITION3 trial in a press release last month. There was an 11% slower decline in disease progression for those on the drug, but the difference on the ADAS-Cog₁₄ wasn't significant at 80 weeks (P=0.095).

At the meeting, researchers released additional details from the study, which randomized 2,129 patients to either 400 mg of solanezumab infusion every 4 weeks for 80 weeks, or to matching placebo. All patients had to be amyloid-positive on either a PET scan or on cerebrospinal fluid (CSF) analysis.

About 85% of patients in each group completed the trial, which was conducted at 210 sites in 11 countries.

Although the ADAS-Cog14 wasn't significant, another measure of cognition -- the Mini-Mental State Examination (MMSE) -- did show a significant difference of 13% less decline with the drug, they reported (P=0.014).

The researchers also saw better results on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) scale: a significant 15% smaller decline for those on the drug (P=0.004).

There were similar significant reductions in decline in function, with 14% less decline on the ADCS-iADL (P=0.019) and 15% less decline on the ADCS-ADL (P=0.009) -- although there was no difference in function as measured by the FAQ (7% less decline, P=0.14).

It did appear that the drug does what it's supposed to do, clearing soluble, monomeric forms of beta amyloid as confirmed by a rise in plasma concentrations of the protein, the researchers said.

But there were no differences between groups in terms of amyloid plaque burden in PET scans or in CSF total tau or p-tau levels or on tau PET scans. Nor were there any differences in MRI whole brain atrophy between groups.

There were similar rates of adverse events, with serious AEs occurring in about 17% of the solanezumab group and 19% of the placebo group.

Larry Honig, MD, PhD, of Columbia University, who delivered the main findings, concluded that solanezumab missed its primary endpoint in mild Alzheimer's disease, and that while several secondary endpoints favored the monoclonal antibody, the magnitude of treatment differences were small.

He noted that factors "possibly relevant to interpretation of study results include drug target, disease stage studied, and dosage of drug delivered" -- and several commenters said that since the drug has shown such good safety, perhaps a larger dose would provide different results.

Although Eli Lilly said it won't pursue an indication for solanezumab in mild Alzheimer's, it hasn't ruled out continued development for other indications. The A4 trial, which is looking at solanezumab in early stages of disease -- asymptomatic patients who have amyloid deposits in the brain confirmed on PET scans -- is still enrolling patients.

"Obviously we're very disappointed that we didn't reach our primary outcome," said Eric Siemers, MD, of Eli Lilly. "We didn't expect solanezumab to be the cure for this disease, but we hoped it would be the first to slow down the progression."

"It's been a rough time," Siemers said.

The study was supported by Eli Lilly.

The authors reported financial conflicts with several drugmakers.

2016-12-09T09:33:20-0500

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  Clinical Trials in Alzheimer's Disease meeting

  Source Reference: Honig LS, et al "EXPEDITION 3: A phase 3 trial of solanezumab in mild dementia due to Alzheimer's disease" CTAD Meeting 2016.

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Sense of smell may predict Alzheimer's risk

New research published in the journal Annals of Neurology suggests an individual's sense of smell could be useful in determining whether they are likely to develop Alzheimer's disease.

Researchers suggest sense of smell could be used to predict a person's risk of Alzheimer's.

Principal investigator Dr. Mark Albers, of the Department of Neurology at Massachusetts General Hospital (MGH), and team found that by assessing the ability to recognize, recall, and distinguish different odors, they could accurately identify individuals who were at greater risk of Alzheimer's disease.

Alzheimer's is the most common form of dementia, with around 5.4 million adults in the United States living with the disease. By 2050, this number is expected to reach 13.8 million, unless new preventive and treatment strategies are found.

As with any illness, the earlier Alzheimer's is detected, the greater the chance of treatment success. However, at present, Alzheimer's can only be identified through a series of medical and cognitive assessments, and it can often take years to receive a clinical diagnosis.

According to Dr. Albers and colleagues, it is known that Alzheimer's disease can negatively impact the brain circuits that control sense of smell, or olfaction, and studies have suggested that such neurodegeneration can arise more than a decade before the onset of memory problems.

With this in mind, the researchers set out to investigate whether testing a person's sense of smell could be an effective way to predict Alzheimer's disease.

Olfactory recognition and recall assessed with four tests

Dr. Albers and team included 183 older adults in their study, all of whom were part of ongoing studies taking place at the Massachusetts Alzheimer's Disease Research Center, based at MGH.

Of these participants, 70 had normal cognitive functioning, 74 had subjective cognitive impairment (whereby a person reports memory and thinking problems, but these cannot be verified with cognitive tests), 29 had mild cognitive impairment (MCI), and 10 had Alzheimer's disease.

Fast facts about Alzheimer's

• Alzheimer's is the sixth leading cause of death in the U.S.
• Every 66 seconds, someone in the U.S. develops Alzheimer's
• This year, Alzheimer's will cost the U.S. $236 billion.

Learn more about Alzheimer's

All participants had undergone in-depth medical and neurological assessments, as well as brain imaging to pinpoint features associated with Alzheimer's disease.

Each subject took part in four separate tests created by the MGH team that assessed their sense of smell: the Odor Percept IDentification-10 (OPID-10) test, the Odor Awareness Scale (OAS), the OPID-20 test, and the Odor Discrimination (OD) test.

The OPID-10 test requires participants to smell 10 different odors - including menthol, clove, strawberry, smoke, and lemon - for 2 seconds and report whether each scent is familiar. They are then asked to choose one of four words that best describes each odor.

In the OPID-20 test, subjects are asked to smell the same 10 odors from the OPID-10 test, as well as a further 10, which include banana, garlic, cherry, peach, and chocolate. Participants are asked whether they were presented with any of these odors in the OPID-10 test, as a way of determining their olfactory recall. Based on their answers, they are given a percepts of odor episodic memory (POEM) score.

The OAS is a questionnaire used to determine participants' attention to odors in the environment and how scents affect their behavior and emotions, while the OD test assesses subjects' ability to repeatedly distinguish between two different odors.

Poorer sense of smell linked to features of Alzheimer's

Using the four tests, the researchers found they could accurately distinguish between each of the four groups of study participants.

In detail, participants who performed poorly on the OPID-20 test were more likely to show thinning in two regions of the brain: the hippocampus and the entorhinal cortex. Such brain changes have been associated with Alzheimer's disease.

What is more, the researchers found they could differentiate between participants with normal cognitive functioning and those with Alzheimer's using POEM scores, with lower scores associated with greater cognitive decline.

The team notes that in adults with normal cognitive functioning, the ability to recognize and distinguish scents can vary widely.

To account for this variance, the researchers compared the POEM scores of the groups with normal cognitive function and subjective cognitive impairment with predicted scores, based on their results in the OD and OAS tests. This, they say, enabled better identification of which individuals were good or bad at recalling and recognizing odors.

From this, the team found that adults who had poorer POEM performance were more likely to possess a variation of the APOE gene - known as APOE e4 - that is linked to increased risk of Alzheimer's. These adults also demonstrated thinning of the entorhinal cortex.

While these results need to be validated in a larger group, the team believes these early findings suggest testing an individual's sense of smell may be useful for earlier detection of Alzheimer's disease.

"It is well recognized that early diagnosis and intervention are likely to produce the most effective therapeutic strategy for Alzheimer's disease - preventing the onset or the progression of symptoms.

If these results hold up, this sort of inexpensive, noninvasive screening could help us identify the best candidates for novel therapies to prevent the development of symptoms of this tragic disease."

Dr. Mark Albers

Read how probiotics could improve cognitive functioning for patients with Alzheimer's.

Written by Honor Whiteman

Targeted preventive measures for hip fracture are needed for persons with Alzheimer's disease

The hip fracture risk factors are generally similar among those with and without Alzheimer's disease, according to a recent study from the University of Eastern Finland. However, the incidence of hip fracture is higher among those with Alzheimer's disease, regardless of other characteristics. Alzheimer's disease itself appears to be such a significant risk factor for hip fracture that the relative impact of other risk factors is considerably smaller among those with Alzheimer's disease.

Older persons, men, and those with mental and behavioural disorders or using antipsychotics or antidepressants had a higher hip fracture risk both among persons with and without Alzheimer's disease, but the relative risk increase was higher among persons without Alzheimer's disease. Stroke, diabetes, active cancer treatment, and the use of proton pump inhibitors, antiepileptics or opioids were associated with a higher hip fracture risk only in those without Alzheimer's disease.

The findings are based on the MEDALZ study, including all community-dwellers of Finland who received a clinically verified diagnosis of Alzheimer's disease in 2005-2011 and had no history of previous hip fracture (N=67,072) and a matched cohort of persons without Alzheimer's disease.

Previously, many risk factors for hip fracture, including dementia, had been identified. It was not known whether the same factors predict hip fracture risk in persons with and without Alzheimer's disease, which is the most common form of dementia. However, it is known that the consequences of hip fracture are even more devastating for a person with dementia.

The new findings underline the importance of developing and implementing preventive interventions that are suitable for persons with dementia. Different preventive interventions such as exercise, medications, home safety assessment and modification interventions, as well as medication reviews have already been proposed but few studies have explored the applicability of these measures to persons with dementia. Regular assessments of medication are one feasible approach, as an association was found between various medications and hip fracture risk.

Article: Comparison of predictors of hip fracture and mortality after hip fracture in community-dwellers with and without Alzheimer's disease - exposure-matched cohort study, Anna-Maija Tolppanen, Heidi Taipale, Antti Tanskanen, Jari Tiihonen, Sirpa Hartikainen, BMC Geriatrics, doi: 10.1186/s12877-016-0383-2, published 1 December 2016.

Study challenges model of Alzheimer's disease progression

Alzheimer's disease is a neurodegenerative disorder for which, despite years of research, there are no effective treatments or cures.

However, recent breakthroughs in molecular genetics have shown that the disease may spread, like an infection, across closely connected areas of the brain. These findings underscore the need for research aimed at tracking its spread to the earliest points of origin in the brain, so therapies that target those areas can be developed.

An international collaboration between Nathan Spreng, Cornell assistant professor of human development and the Rebecca Q. and James C. Morgan Sesquicentennial Faculty Fellow in the College of Human Ecology, and Taylor Schmitz of the University of Cambridge's Cognitive Brain Sciences Unit, sheds light on the basal forebrain region, where the degeneration of neural tissue caused by Alzheimer's disease appears even before cognitive and behavioral symptoms of the disease emerge.

Their paper, "Basal forebrain degeneration precedes and predicts the cortical spread of Alzheimer's pathology," is published in Nature Communications. Data used for their work were obtained from the Alzheimer's Disease Neuroimaging Initiative database.

The basal forebrain contains very large and densely connected neurons that are particularly vulnerable to the disease. Schmitz and Spreng show that, as Alzheimer's progresses, degeneration of the basal forebrain predicts subsequent degeneration in temporal lobe areas of the brain involved in memory. This pattern is consistent with other research showing that Alzheimer's indeed spreads across brain regions over time, but the study challenges a widely held belief that the disease originates in the temporal lobe.

"We're hoping that this work pushes a bit of a reorganization of the field itself, to reappraise where the disease originates," Spreng said. "That could open up new avenues for intervention; certainly it would for detection."

Their report is the product of a two-year study of a large sample of age-matched older adults. Within this sample, one group was cognitively normal, according to standard tests, while others were characterized by different levels of cognitive impairment:

• individuals with mild cognitive impairment (MCI) who did not progress to Alzheimer's disease;
• MCI individuals who progressed to Alzheimer's after one year; and
• individuals classified as having Alzheimer's throughout the duration of the study.

Through analysis of high-resolution anatomical magnetic resonance imaging of brain volumes, taken three times over the two-year study period, the researchers were able to determine that individuals with MCI or Alzheimer's showed greater losses in gray matter volume in both the basal forebrain and temporal lobe, compared with cognitively normal controls. Intriguingly, they showed that over the two-year period, degeneration of neural tissue in the basal forebrain predicted subsequent tissue degeneration in the temporal lobe, but not the other way around.

A sampling of spinal fluid from healthy adults can detect an abnormal level of beta amyloid, indicative of Alzheimer's, Spreng said. Test results showed that temporal lobes looked the same regardless of amyloid level, but the basal forebrain showed notable degeneration among those seemingly healthy adults with abnormal amyloid levels.

Spreng admits that being able to predict who will get the disease doesn't mean a lot without a protocol to treat and, ultimately, cure the disease. "And it might induce more anxiety," he said. But the more knowledge that can be gained now, he said, the better.

"Future molecular genetics work holds strong promise for developing therapeutic strategies to prevent the spread of pathology at stages of Alzheimer's preceding cognitive decline," Schmitz said. "Our clarification of an earlier point of Alzheimer's propagation is therefore of utmost importance for guiding endeavors to combat this devastating disease."

This work was funded by grants from the National Institutes of Health and the Alzheimer's Association.

Article: Basal forebrain degeneration precedes and predicts the cortical spread of Alzheimer's pathology, Taylor W. Schmitz, R. Nathan Spreng & The Alzheimer's Disease Neuroimaging Initiative, Nature Communications, doi: 10.1038/ncomms13249, published online 4 November 2016.