Tuesday, 31 January 2017
Hospital-induced delirium may speed up dementia, study finds
![[older lady in hospital]](http://cdn1.medicalnewstoday.com/content/images/articles/315/315313/older-lady-in-hospital.jpg)
New research suggests that hospital-induced delirium may accelerate dementia.
Hospital-induced delirium is an often ignored or underdiagnosed illness affecting a large number of senior patients.
The condition is a temporary form of cognitive impairment that can last anywhere between a few days and a few weeks. It is believed to be caused by the changes that come with hospitalization, isolation, and overmedication.
Up to a third of patients over the age of 70 experience delirium, and those having surgery or in the intensive care unit are affected at a higher rate.
Until recently, the condition had been considered normal and simply put down to old age. More and more research, however, is showing that although common, the condition is not normal. It can have negative long-term cognitive effects and can sometimes lead to complications, such as blood clots or pneumonia.
Researchers from University College London (UCL) and the University of Cambridge, both in the United Kingdom, set out to investigate whether there was a link between post-delirium cognitive decline and the pathologic progress of dementia.
The scientists were led by Dr. Daniel Davis, from the MRC Unit for Lifelong Health and Aging at UCL, and the findings were published in the journal JAMA Psychiatry.
Examining the link between delirium and dementia
Davis and team examined the brains and cognitive abilities of 987 brain donors from three population-based studies in Finland and the U.K. The participants were aged 65 years and over.
The study included neuropathologic evaluations performed by investigators who were blinded to the clinical data.
Before death, the brain donors were followed up for an average of 5.2 years, during which time the researchers recorded each individual's experience of delirium using interviews.
They assessed the participants' cognitive abilities and cognitive decline by using the Mini-Mental State Examination score.
After death, researchers performed brain autopsies to look for neuropathologic dementia markers - such as neurofibrillary tangles and neocortical amyloid plaques, as well as vascular and Lewy body pathologic features - in the brain's substantia nigra.
Of the 987 participants, 279 (28 percent) had a history of delirium.
The researchers then examined the rate of cognitive decline and how it interacted with the dementia and delirium pathologic burden.
Treating delirium may 'delay or reduce' dementia
Overall, the slowest decline was observed in individuals with no history of delirium and the lowest dementia pathologic burden, while the fastest cognitive decline was seen in those with both delirium and dementia burden.
Interestingly, both delirium and dementia neuropathologic features taken together were associated with a much higher rate of cognitive decline than what is typically expected for delirium or dementia-related neuropathologic processes taken individually.
As the authors explain, "this means that delirium may be independently associated with pathologic processes that drive cognitive decline, which are different from the pathologic processes of classic dementia."
Although more research is needed to explain exactly how delirium may cause dementia, Dr. Davis emphasizes the importance of the study and its consequences on how we understand and treat this form of temporary mental impairment.
"Unfortunately, most delirium goes unrecognized. In busy hospitals, a sudden change in confusion [may] not be noticed by hospital staff [as] patients can be transferred several times and staff often switch over [...]. If delirium is causing brain injury in the short- and long-term, then we must increase our efforts to diagnose, prevent and treat delirium. Ultimately, targeting delirium could be a chance to delay or reduce dementia."
Learn how late-onset hypertension may lower the risk of dementia.
Can mushrooms help delay or prevent dementia and Alzheimer's disease?
Certain edible and medicinal mushrooms contain bioactive compounds that may enhance nerve growth in the brain and protect against neurotoxic stimuli such as inflammation that contribute to neurodegenerative diseases like dementia and Alzheimer's disease. The evidence supporting a potential role of mushrooms as functional foods to reduce or delay development of age-related neurodegeneration is presented in an article published in Journal of Medicinal Food, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers.
In "Edible and Medicinal Mushrooms: Emerging Brain Food for the Mitigation of Neurodegenerative Diseases," Chia Wei Phan, Pamela David, and Vikineswary Sabaratnam, University of Malaya, Kuala Lumpur, Malaysia, discuss the scientific findings related to the health benefits of edible and culinary mushrooms. The authors focus on the activity of bioactive components of mushrooms that may offer neuroprotective and cognitive benefits.
"In contrast to the body of literature on food ingredients that may benefit cardiometabolic diseases and cancer, very few studies have focused on food that may benefit neurodegenerative diseases," says Journal of Medicinal Food Editor-in-Chief Sampath Parthasarathy, MBA, PhD, Florida Hospital Chair in Cardiovascular Sciences and Interim Associate Dean, College of Medicine, University of Central Florida. "The current study might stimulate the identification of more food materials that are neuroprotective."
Article: Edible and Medicinal Mushrooms: Emerging Brain Food for the Mitigation of Neurodegenerative Diseases, Phan Chia-Wei, David Pamela, and Sabaratnam Vikineswary, Journal of Medicinal Food, doi: 10.1089/jmf.2016.3740, published 1 January 2017.
New PET imaging technique may help monitor neurological disease progression
Olfactory neurons in the nasal cavity are the primary source of our sense of smell. Unlike many types of neurons, olfactory neurons are continuously generated throughout the adult lifespan. This uniquely high rate of neuronal birth and death makes olfactory neurons particularly sensitive to the detrimental effects of progressive neurodevelopmental and neurodegenerative disease.
In Alzheimer's disease and Parkinson's disease, loss of the sense of smell often precedes classical symptoms of cognitive or motor dysfunction. Therefore, a technique that is able to non-invasively quantify the olfactory neuron population could provide important insights related to the diagnosis and progression of neurodevelopmental and neurodegenerative diseases. In work published in the JCI, a team led by Jacob Hooker at Harvard Medical School assessed GV1-57, a radiotracer that specifically binds to mature olfactory sensory neurons, as an approach for quantifying neuronal populations with PET imaging.
Using GV1-57, they were able to detect neuron generation during rodent postnatal development as well as neuron degeneration in rodent models of aging and neurodegenerative disease. In an additional proof-of-concept experiment, they showed that GV1-57 maintained saturable binding in non-human primate nasal cavity, suggesting that this radiotracer may be useful for evaluating neurological disease in clinical settings.
Article: Nasal neuron PET imaging quantifies neuron generation and degeneration, Jacob M. Hooker et al., JCI, doi: 10.1172/JCI89162, published 23 January 2017.
Commentary: Seeing how we smell, Helene Benveniste, Yuri Lazebnik, and Nora D. Volkow, JCI, doi: 10.1172/JCI91305, published 23 January 2017.
Alzheimer's protein buildup disrupts the brain's navigation center
![[Illustration of a brain map]](http://cdn1.medicalnewstoday.com/content/images/articles/315/315350/illustration-of-brain-gps.jpg)
Researchers suggest that a buildup of the protein tau may interfere with the brain's GPS.
The study reveals that the accumulation of a protein called tau, which is considered a hallmark of Alzheimer's disease, can damage nerve cells in the brain that help us to navigate our surroundings.
Co-study leader Dr. Karen Duff - of the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University Medical Center (CUMC) in New York - and colleagues publish their findings in the journal Neuron.
Alzheimer's disease is the most common form of dementia, accounting for around 60-80 percent of all cases.
The condition is characterized by a decline in cognitive functions, such as memory, learning, and problem-solving. People with Alzheimer's may also experience disorientation and behavioral changes, which can sometimes lead to wandering.
According to the Alzheimer's Association, approximately 6 in 10 people with the disease wander; they might have trouble recalling their name or address while out and about, or be unable to recognize their surroundings. This can put them at risk of injury.
Previous studies have suggested that wandering and other disoriented behaviors in Alzheimer's disease arise as a result of changes in the entorhinal cortex (EC), which is a brain structure involved in memory and navigation.
Dr. Duff and colleagues note that in Alzheimer's disease, the EC is one of the first areas of the brain to be affected by the buildup of tau - a protein that can twist and form "tangles" that are harmful to nerve cells.
However, precisely how tau can lead to problems with navigation has been unclear - until now.
Tau may reduce grid cells' ability to 'fire'
For their study, Dr. Duff and colleagues wanted to determine how tau affects grid cells, which are nerve cells in the EC that act as the brain's GPS. As we move through space, grid cells transmit electrical signals that create an internal map, helping us to navigate our environment.
To reach their findings, the researchers monitored the grid cells in two groups of older mice as they performed a series of spatial cognitive tasks. One group of mice had been genetically engineered to express tau in the EC, while the other group consisted of normal mice.
The researchers found that the tau-expressing mice were much less likely to be able to navigate their surroundings than the normal mice, indicating that tau interferes with grid cell function in the EC.
Further investigation of the rodents' brains showed that tau only destroyed or interfered with excitatory cells in the EC, not inhibitory cells. Excitatory cells are cells that transmit electrical signals, or "fire," while inhibitory cells suppress such signals.
According to the team, this finding suggests that tau reduces grid cells' ability to fire, making navigation difficult.
"It appears that tau pathology spared the inhibitory cells, disturbing the balance between excitatory and inhibitory cells and misaligning the animals' grid fields," says co-first study author Hongjun Fu, Ph.D., also of the Taub Institute.
Findings may advance Alzheimer's diagnosis and treatment
According to Dr. Eric Kandel, Kavli professor of brain science at CUMC, the team's study "clearly shows that tau pathology, beginning in the entorhinal cortex, can lead to deficits in grid cell firing and underlies the deterioration of spatial cognition that we see in human Alzheimer's disease."
He adds that this could further our understanding of the brain changes that arise in the early stages of Alzheimer's.
Furthermore, the researchers believe their findings indicate that deep brain stimulation and other therapies that target specific nerve cells have the potential to treat spatial disorientation in people with Alzheimer's.
However, study co-author Gustavo A. Rodriguez, Ph.D., also of the Taub Institute, notes that there is much more we need to learn about the role of grid cells in Alzheimer's.
"We don't yet know what percentage of healthy grid cells are needed for proper navigation or whether this system is rescuable once it has been compromised," he explains.
Still, Dr. Duff is confident that their discovery has the potential to benefit the millions of people living with Alzheimer's disease.
"[...] our findings suggest that it may be possible to develop navigation-based cognitive tests for diagnosing Alzheimer's disease in its initial stages. And if we can diagnose the disease early, we can start to give therapeutics earlier, when they may have a greater impact."
Dr. Karen Duff
Learn how a chicory compound could reduce memory loss for Alzheimer's patients.
Vitamin A deficiency may cause Alzheimer's to begin in the womb
![[beta amyloid plaques]](http://cdn1.medicalnewstoday.com/content/images/articles/315/315488/beta-amyloid-plaques.jpg)
New research shows that mice deprived of vitamin A in the womb may have higher levels of beta amyloid (here shown as plaque in the brain of an Alzheimer's patient).
Alzheimer's disease is estimated to affect more than 5 million people in the United States, and it ranks as the sixth leading cause of death in the country.
While researchers recognize that, being a neurodegenerative disease, Alzheimer's is caused by the progressive death of cells, the exact reasons for this remain unknown.
Previous research has associated low levels of vitamin A with cognitive impairment. Some studies have suggested that vitamin A may help to protect neurobiological functions indirectly using the glucocorticoid pathway.
Others have suggested that vitamin A contributes to healthy memory processes, and they recommended a supplemental intake to prevent age-related cognitive impairment.
In this context, researchers from the University of British Columbia (UBC) in Canada hypothesized that vitamin A deprivation might play a role in the development of Alzheimer's disease.
So they set out to examine the impact of prenatal and infancy vitamin A deficiency on the development of Alzheimer's disease in mice, as these early stages are key for brain development. Additionally, the study examined the link between vitamin A and dementia in humans.
The study was a collaboration with Dr. Tingyu Li and others from the Children's Hospital of Chongqing Medical University in China. The team was led by Dr. Weihong Song, a professor of psychiatry at UBC and Canada Research Chair in Alzheimer's Disease.
The findings were published in the journal Acta Neuropathologica.
Vitamin A-deprived mice showed signs of prenatal damage
The scientists used genetically modified mice. They deprived some of these mice of vitamin A when they were still in the womb, while others were deprived postnatally through their diet. Some of the prenatally deprived mice were fed a normal diet, while others received vitamin A supplements. All of the mice were tested for learning and memory abilities.
Dr. Song and team found that a mild deficiency of vitamin A increased the levels of a protein called amyloid beta, and that vitamin A-deprived mice performed significantly worse on memory and learning tests when they grew up, compared with their healthy counterparts.
The beta-amyloid protein is known to play a key role in the advancement of Alzheimer's disease; it builds up into a sticky plaque or forms clumps between the nerve cells. This blocks the neurotransmission and eventually leads to the death of brain cells.
Furthermore, when the prenatally deprived mice were placed on a healthy diet as infants, they still performed worse in cognitive tests than mice that received a normal intake of vitamin A in utero, but were deprived postnatally. This suggests that the neural damage had started in the womb.
"Our study clearly shows that marginal deficiency of vitamin A, even as early as in pregnancy, has a detrimental effect on brain development and has [a] long-lasting effect that may facilitate Alzheimer's disease in later life."
Dr. Weihong Song
Interestingly, some of the damage appeared to be reversible - at least to some extent. The mice that were deprived prenatally but were given supplements of vitamin A right after birth had better learning and memory processing skills than mice who did not receive the supplements.
"In some cases, providing supplements to the newborn Alzheimer's disease model mice could reduce the amyloid beta level and improve learning and memory deficits," says Song. "It is a matter of the earlier, the better."
The researchers also examined the vitamin A-dementia link in humans. They investigated 330 seniors in Chongqing, China, and they found that 75 percent of the elders who had mild or significant vitamin A deficiency were also cognitively impaired, compared with 47 percent of those with healthy levels of vitamin A.
Despite the compelling results of the study, Dr. Song warns against exaggerating their significance. He points out that vitamin A deficiency is not very common in North America, and cautions against the dangers of an excessively high vitamin A intake. He urges pregnant women not to take vitamin A supplements in excess, and reminds them that the best way to maintain an ideal level of the vitamin is by having a balanced diet.
Learn how frequent sauna use may decrease dementia risk in men.
UK health system not fit for people with dementia and other chronic conditions
The UK's current health and social care system isn't fit for purpose when it comes to caring for people living with dementia (PLWD) who also have other illnesses and chronic conditions.
That's according to a new research study by the University of Hertfordshire published in BMJ Open. It also found that the systems currently in place are not designed to sufficiently involve family carers in the way they should be.
One fifth of people living with dementia often have other medical conditions (comorbidities) such as diabetes, stroke and visual impairment. On average, PLWD have approximately five chronic illnesses in addition to their dementia.
But researchers at the University of Hertfordshire have found that services are not currently designed to provide adequate integrated care for people with dementia plus other conditions, which could be having adverse effects on their overall health.
Dr Frances Bunn, a Reader in Evidence Based Health Care at the University's Centre for Research in Primary and Community Care, and lead author of the study, explains: 'As the population ages, and the proportion of people with dementia and comorbidity increases, the delivery of healthcare becomes increasingly complex and challenging.
'Navigating the different systems of care is particularly difficult for people with dementia and comorbidity, not least because they receive advice and support from different sectors of health and social care and increasingly third sector providers.'
The study, which explores the impact of dementia on access to non-dementia services in the health system, recommends that more needs to be done to make sure that patients with dementia and comorbidity are receiving the proper care across the health service.
The prevalence of comorbidities in people living with dementia is significant but, prior to this study, little research had been done into the effects it can have on health organisations, their services and the patient experience.
Dr Bunn added: 'While there are policy and practice initiatives to improve healthcare for patients who have dementia, there is little evidence of how comorbidity is experienced by them and how this impacts on primary and secondary healthcare services. However, there are some immediate and simple changes that can be made to improve care for this vulnerable group.'
These are:
- Ensuring the impact of a diagnosis of dementia on pre-existing conditions is incorporated into care planning.
- Sharing vital information with family carers is the default option while the PLWD still has the capacity to decide.
- Giving longer appointments to PLWD so that all their conditions can be properly checked.
- Dementia-specific advice is included in guidelines for conditions such as diabetes and stroke.
The study, which involved interviewing people with dementia, family carers, and health professionals, shows that family play a significant role in coordinating their relative's care. For example, this can involve managing appointments, organising transport and keeping records of test results. However, whilst health professionals value the role family carers play, the study found there was little formal recognition of the carers' contribution, and no way of negotiating how or when a carers' views could be incorporated into care planning.
However, there are many challenges family carers face that also need to be taken into account. They sometimes have difficulty in understanding how health systems work or know who to contact. Many can also have their own health problems and may face practical challenges such as travel or combining caring responsibilities with jobs. That is why a more collaborative and joined up approach is needed between all parties involved.
Dr Bunn said: 'There is a need for coproduction of care in which health professionals, people living with dementia and family carers all work in partnership. The matching of management to the needs of the individual and improved collaboration across specialities and organisations is essential.
'Our study further highlights not only how family carers are often responsible for negotiating continuity and access for family members with dementia but also how care systems often hinder rather than support their efforts.'
Article: Healthcare organisation and delivery for people with dementia and comorbidity: a qualitative study exploring the views of patients, carers and professionals, Frances Bunn, Anne-Marie Burn, Louise Robinson, Marie Poole, Greta Rait, Carol Brayne, Johan Schoeman, Sam Norton, Claire Goodman, BMJ Open, doi: 10.1136/bmjopen-2016-013067, published January 2017.
People with dementia need more support to manage their medication
New research funded by Pharmacy Research UK and published in Health Expectations, reveals people with dementia may struggle with managing their medication - exposing them to side-effects, medication errors and an increased risk of non-adherence to drug treatment.
Researchers at Aston University, Hull University and the UEA interviewed family carers, people with dementia, nurses, GPs and community pharmacists for the project.
Their year-long research found that as dementia develops the person struggles to manage their own medication and increasingly relies on support from family carers. This is often their partner, who may also be taking many medicines and finding the carer role stressful, thus increasing the risk of medication error.
The study showed that for some carers this was a real burden of responsibility and that they hid their anxieties.
Lead researcher Dr Ian Maidment, Senior Lecturer in Clinical Pharmacy at Aston said: "Our study found incorrect dosing, forgetting to give the medication and taking medicines which should have been stopped."
Professor Chris Fox, Consultant Old Age Psychiatrist from UEA's Norwich Medical School said: "There can be severe health impact for both the patient and carer - too often in my clinical practice I come across patients and families overburdened and unclear about their medication regimes. This can result in more visits to their GP and hospital and is a cause of avoidable NHS admissions."
Dr Andrea Hilton from Hull University added: "There is a substantial role for community pharmacists and their teams to assist carers; many pharmacists have day-to-day contact both with carers and people with dementia. Community pharmacy is in a unique position to support and embrace patient-centred care and this is currently under-utilised. This research highlights that community pharmacists should be working more with GP practices and have full access to patients' medical records. Furthermore, home visits should be conducted for medication reviews."
Barbara Woodward-Carlton a former carer and a member of the Alzheimer's Society Research Network highlighted: "During the years I looked after my mother who had Alzheimer's disease I wish I had known what help I could have had from community pharmacists.
"My mother was an extremely pleasant person who always wanted to co-operate but found it incomprehensible that she should be taking any medication at all. At one point when she was very ill, I continued the medication she had been given including 'water tablets' without realising that she was dehydrated. I live with the shame of not knowing that as she was barely drinking and eating I should have stopped that medication. I welcome that community pharmacists are increasingly seen as those who can advise, educate and help those of us who care for others."
Dr Clare Walton, Research Manager at Alzheimer's Society said: "Seven in 10 people with dementia are also living with other health conditions and managing multiple medications which can be a tremendous challenge. Finding new and innovative ways to support people with dementia and their carers to safely and correctly age their medication is a focus for future research."
Ian Maidment added: "People with dementia are amongst the most vulnerable members of society and need more support with medication management. We need to develop new ways of supporting people with dementia manage their management and then test how well these new ways work."
Article: A qualitative study exploring medication management in people with dementia living in the community and the potential role of the community pharmacist, Ian D. Maidment PhD, Lydia Aston MA, Tiago Moutela MA, Chris G. Fox MBBS Bsc Mmmedsci MRCPsych MD, Andrea Hilton PhD, Health Expectations, doi: 10.1111/hex.12534, published 19 January 2017.
CardioBreak: Heart 'Hugger'; Watchman Without Warfarin; U.K. Rationing for Zetia?
Why heart failure is one of the roughly 10 diseases feasible for stem cell therapy: The New York Times interviewed leading researcher Shinya Yamanaka on the slow pace of progress.
A different approach to ventricular assist: A soft silicon robot that "hugs" the heart with its normal squeeze-and-twist motion. A prototype worked on pigs, Stat News reported.
ProPublica reported that Tom Price, nominated to be Health and Human Services secretary under the Trump administration, pressured the Agency for Healthcare Research and Quality to remove mention of a negative study of BiDil (the combination of hydralazine and isosorbide dinitrite) after receiving a campaign donation from the drug's manufacturer.
The Centers for Medicare and Medicaid Services approved an 888-patient study of the Watchman left atrial appendage closure device in non-valvular atrial fibrillation for patients who cannot take oral anticoagulants. (Cardiovascular Business)
The U.K. National Health Service, under budget pressures, is weighing rationing certain drugs, including ezetimibe (Zetia), starting in April 2017, The Times reported.
Expansion of Medicaid under the Affordable Care Act improved heart transplant wait listing rates for African Americans but not Hispanics, while rates for Caucasians stayed the same, according to a study in the Journal of the American Heart Association.
Hospitals that handle more deceased organ donors recover more organs per donor, according to another study in the same journal.
Implementing the Kidney Disease Improving Global Outcomes (KDIGO) guidelines to prevent cardiac surgery-associated acute kidney injury in patients with renal biomarker-defined risk worked to do just that in a single-center trial reported in Intensive Care Medicine.
Better diagnostic imaging to detect blunt cerebrovascular injury has cut stroke rates and related deaths among trauma patients, according to a study in the Journal of the American College of Surgeons.
Hemodialysis patients have a high prevalence of atrial fibrillation, but there's little consensus on stroke prevention for this population, according to practice patterns in a study in PLOS One.
Benzodiazepines and similar drugs are associated with stroke risk in Alzheimer's disease, researchers reported in International Clinical Psychopharmacology.
The FDA gave orphan drug status to glyburide for injection (Cirara) for severe cerebral edema in acute ischemic stroke. (Yahoo! Finance)
The HemoSphere hemodynamic monitor got CE Mark from European regulators, while that marketing clearance was expanded for the Tack endovascular system in arterial dissection repair after percutaneous transluminal angioplasty to include use below the knee. (Mass Device and Yahoo! Finance)
last updated
D.C. Week: Medicare: New Payment Plans for Hearts and Hips
WASHINGTON -- The Obama administration announced four new payment models for Medicare beneficiaries intended to improve cardiac and orthopedic care and to lower costs.
Medicare: New Payment Plans for Hearts and Hips
Physicians and hospitals will have more ways to participate in Medicare's new advanced alternative payment models (APMs) under programs announced Tuesday by the Centers for Medicare & Medicaid Services.
"The CMS innovation center is broadening the funnel so that more physicians can participate in advanced APMs, which are locally developed, physician-led models to [encourage] high quality of care," CMS acting administrator Andy Slavitt said on a conference call with reporters. "With today's announcement, we expect more than 70,000 new physicians to participate in advanced APMs and to qualify for the resulting bonuses."
The four models announced Tuesday are for cardiac and orthopedic care for Medicare beneficiaries -- specifically heart attack care, bypass surgery, and hip and femur procedures. The hospitals that beneficiaries are admitted to for these procedures will be held accountable for the quality and cost of care during both the inpatient stay and for 90 days afterward.
FDA: No Fingerstick Needed with Dexcom G5 CGM
The FDA has approved an expanded indication for Dexcom's G5 Mobile continuous glucose monitor, allowing it to be used alone without supplementary fingerstick glucose testing.
"This is the first FDA-approved continuous glucose monitoring system that can be used to make diabetes treatment decisions without confirmation with a traditional fingerstick test," the agency said in announcing the decision. Previously, the system had been approved as an adjunct to fingerstick testing.
But the new approval does not mean patients can forget about fingerstick testing entirely. "Users are warned that the system must be calibrated using a fingerstick blood sample at least once every 12 hours," the FDA stressed.
In deciding to expand the indication, the FDA relied on findings from two 7-day clinical trials involving a total of 130 adults and children as young as 2. Results from the continuous monitor were compared with those from standard fingerstick meters and from lab tests of blood glucose. Those studies indicated that the continuous monitor was accurate enough to be used alone to guide treatment.
Who Will Trump Pick to Helm the FDA?
President-elect Trump has yet to announce potential candidates to lead the FDA, but several health policy experts shared their picks with MedPage Today.
At least two names have been bandied about -- Scott Gottlieb, MD, a resident fellow with the conservative think tank, the American Enterprise Institute, and Jim O'Neill, a libertarian and managing director at global investment firm, Mithril Capital Management, co-founded by PayPal's Peter Thiel, a major Trump donor.
"The Trump Administration is looking for exceptionally strong, business savvy leaders who can hit the ground running, who are not ensnared by either the bureaucracy or the liberal status quo, and who can effect genuine change inside Washington. Both Scott Gottlieb, MD, and Jim O'Neill would certainly fit the bill and be huge assets to the Trump Administration, whether at FDA or another top spot," Kip Piper, MPA, wrote in an email to MedPage Today. Piper is a senior consultant with Sellers Dorsey, a healthcare consulting firm that specializes in Medicaid.
PARP Inhibitor Gets FDA Nod for Ovarian Cancer
The FDA, on Monday, granted accelerated approval to the PARP inhibitor rucaparib (Rubraca) for previously treated, BRCA-mutant ovarian cancer.
The agency stipulated that the approval applies to women whose disease has relapsed or progressed after at least two prior chemotherapy regimens. Additionally, the cancer's BRCA status must be confirmed by a companion diagnostic test that the FDA approved at the same time.
"Today's approval is another example of the trend we are seeing in developing targeted agents to treat cancers caused by specific mutations in a patient's genes," Richard Pazdur, MD, the FDA's director of hematology and oncology products, said in a statement.
Next Week
Congress is on recess. Happy Holidays.
Wednesday, 18 January 2017
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:
Could a chicory compound reduce Alzheimer's-related memory loss?
![[Red chicory]](http://cdn1.medicalnewstoday.com/content/images/articles/315/315183/red-chicory.jpg)
Researchers suggest that a compound found in chicory has the potential to reduce memory loss associated with Alzheimer's disease.
The study, recently published in The FASEB Journal, reveals that mice treated with chicoric acid displayed better memory in behavioral tests than rodents that did not receive the compound.
While further research is needed, study co-author Xuebo Liu, Ph.D., of the College of Food Science and Engineering at Northwest A&F University in China, and colleagues say that it is possible for chicoric acid to help maintain memory in patients with Alzheimer's and other neurodegenerative conditions.
Alzheimer's disease is the most common form of dementia, accounting for approximately 60-80 percent of all cases. It is estimated that every 66 seconds, somebody in the U.S. develops Alzheimer's disease, and it is currently the sixth leading cause of death in the country.
One of the earliest signs of Alzheimer's disease is memory loss. It is often mild in the early stages of the disease, with individuals potentially having problems recalling recent events, for example. In the later stages, a person may not recognize familiar faces, recall the names of loved ones, or recognize once familiar surroundings.
There is currently no way to halt Alzheimer's-related memory loss, though there are medications that might help to reduce its severity for a limited time. For example, cholinesterase inhibitors delay the worsening of memory and other cognitive symptoms for approximately 6-12 months in around 50 percent of patients who use them.
Now, Liu and colleagues suggest that chicoric acid has the potential to offer a more natural strategy to reduce memory impairment.
Assessing the effects of chicoric acid on memory in mice
Chicoric acid, also referred to as cichoric acid, is a chemical compound found in at least 63 types of plants and vegetables, including chicory, lettuce, and basil.
Previous studies have shown that chicoric acid has antioxidant properties, meaning that it can reduce or even prevent some types of cell damage caused by oxidative stress.
For their study, Liu and team set out to investigate whether chicoric acid might protect against memory impairment induced by lipopolysaccharides (LPS). These are molecules that have been linked to brain cell damage through oxidative stress and neuroinflammation.
The team used three groups of mice to reach their findings. One group was treated with LPS, one was treated with both LPS and chicoric acid, and one was a control group.
The memory and learning abilities of all groups were tested using two behavioral tests: the Y-maze, which assesses rodents' willingness to explore new surroundings, and the Morris water maze, which tests rodents' ability to recall and navigate their surroundings.
Chicoric acid 'a plausible therapeutic intervention' for Alzheimer's
The researchers found that mice treated with LPS took longer to complete the mazes than mice treated with both LPS and chicoric acid, suggesting that chicoric acid can reduce LPS-induced memory impairment.
The study also revealed that chicoric acid decreased the buildup of beta-amyloid proteins induced by LPS treatment. Beta-amyloid proteins are known to form "plaques" in brain cells that are considered a precursor to Alzheimer's.
Furthermore, the team found that chicoric acid reduced neuroinflammation triggered by treatment with LPS in both mouse brains and microglial cells.
According to the researchers, these results suggest that chicoric acid could be a "plausible therapeutic intervention for neuroinflammation-related diseases such as Alzheimer's disease."
While the current results are promising, further research is needed to determine the effects that chicoric acid may have on memory impairment for patients with Alzheimer's.
"These are provocative findings, but with the caveat that the LPS regime is not likely a model of long-term memory impairment. But the possibility remains that chicoric acid could prove to be a beneficial human nutraceutical for overall memory acuity."
Thoru Pederson, Ph.D., editor-in-chief of The FASEB Journal
Learn how statins might reduce the risk of Alzheimer's.
Late-onset hypertension may lower dementia risk, study finds
![[A man having his blood pressure taken]](http://cdn1.medicalnewstoday.com/content/images/articles/315/315294/a-man-having-his-blood-pressure-measured.jpg)
A new study suggests that developing hypertension late in life may lower the risk of dementia.
Dementia affects millions of people worldwide, and in the United States, it is estimated that 5 million people live with Alzheimer's disease - the most common form of dementia.
The illness, which manifests as a loss of cognitive function and behavioral abilities, affects 1 in 3 U.S. seniors.
A significant number of previous studies have suggested that hypertension in midlife can increase the risk of dementia in later years.
However, new research published in the journal Alzheimer's & Dementia suggests that the opposite may be true.
A team of researchers at the University of California-Irvine - led by Prof. Maria Corrada, a professor of neurology and epidemiology - set out to investigate the link between hypertension and dementia in patients aged 90 and above.
Analyzing the link between hypertension and dementia in older patients
Hypertension is commonly defined as having a blood pressure (BP) of 140/90 millimeters of mercury (mm Hg) or higher.
Prof. Corrada and team examined 559 patients from a long-term, population-based longitudinal study of people aged 90 and above, known as The 90+ Study.
The 90+ Study participants were mostly highly educated (75 percent), Caucasian (99 percent), and female (71 percent). They were selected from the survivors of the Leisure World Cohort Study, which comprised 13,978 members of a California retirement community.
At the start of The 90+ Study, the respondents - who, on average, were 93 years old - did not have dementia. The researchers followed the participants for 2.8 years, assessing them every 6 months to check if they developed the disease.
The assessment included neurological and neuropsychological examinations, as well as a review of their medical record to check for a hypertension diagnosis.
The researchers also measured their BP at the beginning of the study.
Prof. Corrada and team first examined the association between dementia risk and a history of hypertension, as reported by the participants.
Then, researchers estimated the link between the age of hypertension onset and dementia risk, using the "no hypertension" group as reference, and the association between baseline hypertension stage and risk of dementia, using normal BP as a reference.
Dementia risk lowest among those with hypertension at age 90 or above
Prof. Corrada and team adjusted all these measurements to account for antihypertensive medications.
In the follow-up period, 40 percent of the participants received a dementia diagnosis, and 61 percent reported a hypertension diagnosis.
Most participants reported having been diagnosed with hypertension after the age of 70, but 19 percent of participants said that the hypertension onset was at the age of 80 and above.
Overall, individuals in all stages of hypertension at baseline seemed to have a lower risk of dementia compared with those with normal BP, but these results were not statistically significant. However, the scientists noticed an inverse correlation between dementia risk and hypertension severity.
Patients who had been diagnosed with hypertension between the ages of 80-89 were at a significantly lower risk of developing dementia, compared with those with normal BP. Additionally, those who received their hypertension diagnosis at the age of 90 and over had the lowest risk of dementia.
The results stayed the same after the scientists adjusted for other parameters (including antihypertensive medication).
What could explain the findings?
As the authors note, this is the first time a study reports on the associations between dementia in "the oldest old" and age of hypertension onset.
"These new findings suggest some risk factors for dementia may change over the course of our lives," says Maria Carrillo, Ph.D., Alzheimer's Association chief science officer. "We have seen similar results in past studies comparing body mass in older adults with dementia risk."
Although the study is observational, Prof. Corrada and team ventured possible explanations for the results.
One reason for the association could be that in order to maintain normal cognition, the brain needs a certain blood flow level, which may change with age. According to this explanation, those who develop hypertension later in life may have developed a compensatory mechanism to keep the necessary blood flow level. The authors reference other studies showing that individuals with lower blood flow may have higher rates of cognitive decline.
Another possible but unlikely explanation includes antihypertensive medications, and the possibility of a certain class of medication lowering dementia risk. However, the authors explain that if this was the case, the lowest risk would have been noticed in those taking the medication for a long period of time - such as with hypertension onset earlier in life, not later.
Finally, a third possible explanation is a form of reversed causality; rather than lower BP causing poor cognition, a neurodegenerative process may cause a decline in BP. This way, those who have dementia as a consequence of the deterioration of brain cells would also have higher BP.
The authors concede that more studies are needed to explain their findings.
"Before we can make the leap to suggesting changes to blood pressure recommendations for reducing dementia risk in clinical care, we need more research to confirm and explain our findings. This includes investigations into the underlying biology of hypertension and brain function."
Prof. Maria Corrada
"We need to understand the bigger picture of what protects brain health throughout our entire lives, including our later years," adds Dr. Carrillo. "Looking at dementia in this group is critical since it is the fastest growing segment of the U.S. population with the highest rate of dementia."
Learn how ministrokes may cause dementia.
New research study creates new opportunities for treating brain diseases
Immunotherapy has proven to be effective against many serious diseases. But to treat diseases in the brain, the antibodies must first get past the obstacle of the blood-brain barrier. In a new study, a research group at Uppsala University describes their development of a new antibody design that increases brain uptake of antibodies almost 100-fold.
Immunotherapy entails treatment with antibodies; it is the fastest growing field in pharmaceutical development. In recent years, immunotherapy has successfully been used to treat cancer and rheumatoid arthritis, and the results of clinical studies look very promising for several other diseases. Antibodies are unique in that they can be modified to strongly bind to almost any disease-causing protein. In other words, major potential exists for new antibody-based medicines.
The problem with immunotherapy for diseases affecting the brain is that the brain is protected by a very tight layer of cells, called the blood-brain barrier. The blood-brain barrier effectively prevents large molecules, such as antibodies, from passing from the bloodstream into the brain. It has therefore been difficult to use immunotherapy to treat Alzheimer's and Parkinson's disease, which affect the brain, as well as cancerous tumours in the brain.
It has been known for a long time that some large proteins are actively transported across the blood-brain barrier. These include a protein called transferrin, whose primary task is to bind to iron in the blood and then transport it to the brain. The research group behind this new study has taken advantage of this process and modified the antibodies they want to transport into the brain using components that bind to the transferrin receptor. Then, like a Trojan horse, the receptor transports antibodies into the brain. The number of modifications to and placement of the antibodies have proven to be important factors for making this process as effective as possible.
"We've placed them so that each antibody only binds with one modification at a time, despite being modified in two places. Our design thus doubles the chances of the antibody binding to the transferrin receptor compared with only one modification. We've successfully increased the amount of antibodies in the brain almost 100-fold, which is the largest uptake improvement that has ever been shown," says Greta Hultqvist, researcher at the Department of Public Health and Caring Sciences at Uppsala University.
To try out the new format, researchers have used it on an antibody that binds to a protein involved in the course of Alzheimer's disease. Without the modification, they could only detect very small quantities of antibody in the brain in a mouse model of Alzheimer's disease, while they could detect high levels of the modified antibody in the same mice.
"From a long-term perspective, it's likely that the new format can be used to effectively treat not only Alzheimer's disease, but also other diseases affecting the brain," says Dag Sehlin, researcher at the Department of Public Health and Caring Sciences at Uppsala University.
Article: Bivalent Brain Shuttle Increases Antibody Uptake by Monovalent Binding to the Transferrin Receptor, Hultqvist G, Syvänen S, Fang XT, Lannfelt L, Sehlin D., Theranostics, doi:10.7150/thno.17155, published January 2017.
New guidelines could help improve research into vascular cognitive impairment
New guidelines have been developed that it is hoped will help to progress research into vascular cognitive impairment (VCI) following a study led by academics at the University of Bristol that brought together the views of over 150 researchers in 27 countries.
VCI refers to a decline in mental abilities, such as memory, thinking and planning, caused by problems with the blood supply to the brain. Vascular dementia, which is perhaps a more familiar term to most people, is recognised as a severe form of VCI. VCI is the second most common cause of dementia and gradual memory loss after Alzheimer's disease. Like Alzheimer's disease it does not have a cure and together both conditions contribute to the largest cause of death in England and Wales according to recent reports.
The Bristol team, led by Pat Kehoe, Gestetner Professor of Translational Dementia Research and Joint Head of the Dementia Research Group in the School of Clinical Sciences, invited researchers from around the world to participate in a project called the Vascular Impairment of Cognition Classification Consensus Study (VICCCS), which is funded by the Alzheimer's Society.
The international consortium has published their findings on what was agreed as a revised conceptual model of VCI and what should be considered to be its various subtypes. This new concept has built upon some key elements from sets of criteria that have been previously proposed but adopted to varying degrees. This lack of widespread adoption of any single criteria before now has proved to be a major stumbling block towards any progress in VCI research.
Professor Pat Kehoe, Chief Investigator for the study, said: "It may seem somewhat simplistic to some people that this study has been to get people to agree on how to view and name conditions that affects as many as 100,000 people in the UK alone.
"However, more than 20 years of research has been significantly hampered because numerous studies looked at this complicated group of related conditions in a large number of ways and under numerous different names. This has made the interpretation of any findings with other studies extremely difficult. For the field to move forward, and for us to successfully test potential therapies, there is a need for much greater clarity so that studies can be designed appropriately and meet with the latest requirements from regulatory bodies."
The project made use of an online consensus-building technique that uses recurring surveys, known as the Delphi method. The study was conducted in two parts and identified and addressed issues from the last two decades that have obstructed the progression of VCI research, which lags noticeably behind that of Alzheimer's disease.
Firstly, the surveys addressed what should be the guiding principles in defining a modern and workable concept of VCI and secondly, how the diagnosis of these conditions can be made in a more standardised way across the world. These surveys addressed issues and came up with consensus agreements in a step-by-step repetitive method that involved six phases of surveys over approximately two years.
Dr Olivia Skrobot, Research Associate in the School of Clinical Sciences, who coordinated the study, added: "This study was designed as a means to overcome the historical barriers to advance this area of research. The involvement of so many international researchers will, we hope, promote a new level of collaboration and togetherness and encourage significant progress for VCI research."
Dr Doug Brown, Director of Research and Development at Alzheimer's Society said: "Alzheimer's Society is thrilled to have funded this research as these guidelines will provide essential help to streamline research into vascular dementia. Historically, research in this area has lagged behind researchers' knowledge of Alzheimer's disease, despite vascular dementia being the second most common cause of the condition."
"Research relies on collaboration between experts in order to pool knowledge to further our understanding of the causes of health conditions and how to treat them. This research will allow us to work from the same understanding and criteria which will significantly speed up research in this vital area. As dementia is now the biggest killer in the UK, we need to bring researchers closer together to bring much-needed help to people with this condition as quickly as possible."
The paper, published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, describes the results of the first part of VICCCS, and the researchers hope the revised model of VCI will be widely adopted by the field. The team is currently preparing the second part of their findings from the study for publication, where challenges around diagnostic approaches and lack of standardisation have been addressed.
The aim of this part of the study is to provide guidelines to enable clearer diagnosis and also to simplify the eligibility for people to take part in specific research studies on VCI that have been relatively less common than other types of dementia and cognitive impairment.
Article: The Vascular Impairment of Cognition Classification Consensus Study, Olivia A Skrobot et al., Alzheimer's & Dementia, doi: 10.1016/j.jalz.2016.10.007, published online 10 December 2016.
Statins vs Alzheimer's; Marriage vs Fatal Stroke; Study by App
Statin use was associated with lower risk of Alzheimer's disease in a nearly 400,000-patient observational study using Medicare data.
High exposure to statins (defined by being above average in days of filled prescriptions for at least 2 years in a 3-year span) was associated with a significant 15% lower risk of Alzheimer's disease diagnosis for women and 12% lower risk among men relative to those who filled at least two prescriptions for a statin during that period but with lower exposure.
But the associations varied for particular statin drugs by sex and race or ethnicity. For example, the association of reduced risk with pravastatin and rosuvastatin (Pravachol and Crestor) was seen only among white women.
"Because statins may affect __alzheimer disease risk, physicians should consider which statin is prescribed to each patient," the researchers concluded.
However, the media watchdog site Health News Review called out the researchers for making too much of findings that cannot prove anything about causality, noting the "very small" absolute differences in Alzheimer's incidence and "healthy user bias" seen with statins.
That article pointed to a paper "in 2009 in Circulation which found that more 'adherent' patients (i.e., those who listen to their doctors and take statins) are less likely to be in car accidents than non-adherent patients, but it would be absurd to make any claim that statins prevent car crashes."
Marriage and Stroke Survival
Marital status may make a difference in stroke survival rates, an observational analysis of the Health and Retirement Study of middle age and older adults reported in the Journal of the American Heart Association.
During an average 5.3 years of follow-up of the participants, the risks of dying after a stroke compared with continuously married adults were:
- 71% higher for never-married people
- 23% higher for divorced and 25% higher for widowed participants
- 39% and 40% higher, respectively, for people divorced or widowed more than once -- a risk that remained even for those currently remarried
- Similar between men and women and across race or ethnic backgrounds
Adjustments for socioeconomic, psychosocial, behavioral, and physiological factors only partly explained the associations.
"Although marital events are not amenable to medical intervention or treatment, knowledge about the risks associated with marital life may be useful for personalizing care and improving prognoses for those who experience a stroke," the researchers suggested.
Mobile Health Studies
A smartphone-based study of cardiovascular health was feasible -- with consent and data collection done entirely through an app, reported researchers from the MyHeart Counts Cardiovascular Health Study.
Notably, the study online in JAMA Cardiology showed that in the relatively young population recruited (median age 36), "individuals' perception of their activity and risk bore little relation to sensor-estimated activity or calculated cardiovascular risk."
An accompanying editorial noted that the study succeeded as proof of concept but urged caution, too: "The inference that a lack of detectable smartphone motion indexes physical inactivity rests on the assumption that people carry their devices most of the time, a presumption that is untrue for many."
An editor's note likewise warned that "there is much work to be done to realize those" theoretical possibilities of more convenient, participant-centered research.
last updated
New insight into role of cell protein in learning ability and AIDS-related dementia
Researchers from the University of California (UCLA) and Cardiff University have made a breakthrough in the understanding of AIDS-related dementia, discovering the role of a neuron protein which was also found to affect learning abilities in healthy subjects.
Professor Kevin Fox who led the work at Cardiff University's School of Biosciences said: "Our work represents a major change in the understanding of how AIDS-related dementia works.
"Armed with the new knowledge that the CCR5 protein in neurons affects learning and plays a major role in AIDS-related dementia, we can now look at ways to suppress it for treatment of the disease and investigate whether its reduction can also benefit other forms of dementia and even aid recovery for stroke victims."
The new research started out as a random behavioural screen of mice at UCLA, revealing some mutant mice had better memory than others. Further tests revealed the mice with better memory lacked CCR5 proteins in their neurons. Conversely, animals that over-expressed CCR5 protein were slower to learn, revealing the impact of CCR5 on neurons and their ability to code memories.
The team already knew that the CCR5 protein was the receptor that AIDS uses to infect immune cells and that AIDS patients suffer from dementia. Having witnessed the link between CCR5 and learning in their behavioural screen of mice, they reasoned that activation of the protein in neuron cells by HIV infection might decrease neuron function and learning. When they introduced to the brain the part of HIV that attaches to CCR5 they found that learning and memory was decreased in normal mice, implying that HIV is likely to produce AIDS-related dementia by increasing the natural levels of CCR5 activity and restraining the cells from their usual plasticity function, resulting in a failure to code memories properly.
"I am still amazed that mice without CCR5 can have much better memory than normal mice. It is really exciting that drugs that inhibit CCR5, already on the market, could potentially be used to treat all sorts of memory deficits!" said Alcino Silva, professor of neurobiology and psychiatry at UCLA's David Geffen School of Medicine and Semel Institute for Neuroscience and Human Behavior.
Dr Stuart Greenhill, part of the Cardiff University team, added: "With the available CCR5 drugs on the market this work could have broad and immediate applicability across a range of neurological diseases."
Approximately 30% of HIV-positive adults and 50% of HIV-positive infants suffer from cognitive deficits - a significant clinical problem associated with HIV infection. It was previously thought that AIDS-related dementia was caused by the effects of HIV on immune cells, affecting the brain indirectly by attacking the immune system and creating inflammation.
"Our findings signal a major turnaround on how we imagine treating cognitive problems associated with AIDS," said UCLA scientist Miou Zhou.
Article: CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory, Miou Zhou Stuart Greenhill Shan Huang Tawnie K Silva Yoshitake Sano Shumin Wu Ying Cai Yoshiko Nagaoka Megha Sehgal Denise J Cai Yong-Seok Lee Kevin Fox Alcino J Silva, eLife, doi: 10.7554/eLife.20985, published 20 December 2016.
Concussion linked to brain changes in people at genetic risk for Alzheimer's
Researchers believe that the findings also highlight the importance of documenting concussion events and their associated symptoms.
Researchers, from Boston University School of Medicine (BUSM) in Massachusetts, and colleagues report their findings - which show promise for detecting the effect of concussion on neurodegeneration - in the journal Brain.
They suggest that their study shows that there is a need to record even mild head injuries because, when combined with genetic risk, they may lead to long-term health problems, such as brain diseases.
Alzheimer's is a disease that attacks the brain and gradually worsens. It is the most common form of dementia, a general term for mental decline that becomes serious enough to interfere with daily life.
It is the only disease among the top 10 causes of death in the United States that cannot be prevented, cured, or even slowed.
Currently, more than 5 million people in the U.S. are living with Alzheimer's disease. This number is expected to grow as more of the baby boom generation enters the age range at highest risk for the disease - 65 years and over.
In their study background, the researchers note that moderate-to-severe traumatic brain injury is one of the strongest environmental risk factors for late-onset Alzheimer's and other neurodegenerative diseases. However, it is not so clear whether the same applies to mild traumatic brain injury or concussion.
Concussion influences link to genetic risk
The team studied 160 war veterans between 19-58 years of age who had served in Iraq and Afghanistan, many of whom had been diagnosed with mild traumatic brain injury and post-traumatic stress disorder (PTSD).
Fast facts about Alzheimer's disease
- Every 66 seconds, someone in the U.S. develops Alzheimer's disease
- Alzheimer's and other forms of dementia cost the nation $236 billion in 2016
- The disease kills more U.S. adults than breast cancer and prostate cancer combined.
Learn more about Alzheimer's
The participants underwent MRI scans, from which the researchers could measure thickness in cortical brain regions known to deteriorate in early stage Alzheimer's disease and compare them with measurements of control regions.
Researchers also calculated a genetic risk score for Alzheimer's disease for each participant, by comparing results from their genotyping tests with information on risk genes from a large Alzheimer's disease genome-wide association study.
The results show that concussion appears to influence the link between genetic risk for Alzheimer's disease and cortical thickness. Participants with concussion and high genetic risk had reduced cortical thickness in Alzheimer's disease-vulnerable regions.
The researchers also found that concussion and high genetic risk "indirectly influenced episodic memory performance through cortical thickness, suggesting that cortical thinning in Alzheimer's disease-vulnerable brain regions is a mechanism for reduced memory performance."
'Document all concussion events'
First author Jasmeet P. Hayes, assistant professor of psychiatry at BUSM, says: "We found that having a concussion was associated with lower cortical thickness in brain regions that are the first to be affected in Alzheimer's disease."
Prof. Hayes - who is also a research psychologist at the National Center for PTSD, VA Boston Healthcare System - also points out that they found these brain abnormalities in a relatively young group of veterans, with an average age of 32 years.
She says that the findings show promise as a way to detect the potential brain deterioration that concussion might inflict early in one's lifetime.
The results also highlight the importance of documenting concussion events and their symptoms, "even if the person reports only having their 'bell rung' and is able to shake it off fairly quickly," Prof. Hayes notes.
The researchers hope other teams can now take their findings further and explore the mechanisms that accelerate the onset of brain deterioration - not only Alzheimer's disease, but also in other neurodegenerative disorders, such as Parkinson's disease and chronic traumatic encephalopathy.
"Treatments may then one day be developed to target those mechanisms and delay the onset of neurodegenerative pathology."
Prof. Jasmeet P. Hayes
Learn how traffic exposure may increase risk of dementia.
Sedentary behavior raises dementia risk as much as genetic factors
![[An older man watching television]](http://cdn1.medicalnewstoday.com/content/images/articles/315/315173/an-older-man-watching-television.jpg)
Researchers suggest that sedentary behavior puts older adults at just as much risk of developing dementia as those who are genetically predisposed to the disease.
Worldwide, there are around 47.5 million people living with dementia. By 2030, this number is expected to rise to approximately 75.6 million.
Alzheimer's disease is the most common form of dementia, accounting for about 60-80 percent of all cases. In the United States alone, an estimated 5.4 million people have Alzheimer's.
One of the biggest risk factors for Alzheimer's disease is the apolipoprotein E (APOE) e4 gene. According to the Alzheimer's Association, adults who possess one copy of the APOE e4 gene are three times more likely to develop the disease than those without the gene, while those with two copies are 8-12 times more likely to develop Alzheimer's.
However, the researchers of the new study - including Jennifer Heisz, an assistant professor in the Department of Kinesiology at McMaster University in Canada - suggest that the risk of dementia may be just as high for older adults exhibiting sedentary behavior.
Inactivity may 'negate the protective effects of healthy genes'
The Physical Activity Guidelines for Americans state that older adults should engage in around 150 minutes of moderate-intensity aerobic activity, or 75 minutes of vigorous-intensity activity, every week.
However, a 2015 review published in the Journal of Aging and Physical Activity found that adults aged 60 and older spend approximately 9.4 hours a day sedentary, which is equivalent to about 65-80 percent of their waking day.
For their study, Heisz and colleagues set out to investigate the association between physical activity and dementia risk among older adults with and without the APOE e4 gene.
The researchers came to their findings by analyzing the physical activity and dementia development of 1,646 older adults who were part of the Canadian Study of Health and Aging. All participants were free of dementia at study baseline and followed up for around 5 years.
Among adults who did not carry the APOE e4 gene, the researchers found that those who did not exercise were more likely to develop dementia than those who exercised.
For APOE e4 gene carriers, however, there was no significant difference in dementia risk between those who exercised and those who did not.
According to the researchers, these findings indicate that a lack of exercise may be just as risky for dementia development than carrying the APOE e4 gene.
"The important message here is that being inactive may completely negate the protective effects of a healthy set of genes."
Jennifer Heisz
Increasing exercise may protect against dementia
It is not all bad news; the study results also suggest that increasing physical activity may protect against the development of dementia in people without the APOE e4 gene.
"Although age is an important marker for dementia, there is more and more research showing the link between genetic and lifestyle factors," says study co-author Parminder Raina, a professor in the Department of Health Evidence and Impact at McMaster.
"This research shows that exercise can mitigate the risk of dementia for people without the variant of the apolipoprotein genotype," he adds. "However, more research is needed to determine the implications from a public health perspective."
Lead study author Barbara Fenesi, a postdoctoral fellow at McMaster, points out that further studies are needed in order to pinpoint the type of exercise that is most beneficial for brain health.
"A physically active lifestyle helps the brain operate more effectively. However, if a physician were to ask us today what type of exercise to prescribe for a patient to reduce the risk of dementia, the honest answer is 'we really don't know,'" she says.
Learn about how frequent sauna use may reduce men's risk of dementia.
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
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
High-Dose Omega-3 May Lower AD Risk in APOE4 Carriers
Action Points
- Docosahexaenoic acid (DHA), an essential long-chain, omega-3 polyunsaturated fatty acid, may reduce the risk for Alzheimer's disease, or delay the onset of symptoms, in carriers of the apolipoprotein E ε4 (APOE4) allele, according to a review of observational and clinical trials.
- Note that individuals with a single APOE4 allele are three to four times more likely to develop Alzheimer's as those without an E4 allele, and people with two E4 alleles have a 12-fold higher risk of developing AD.
Giving long-term high doses of docosahexaenoic acid to carriers of the apolipoprotein E ε4 (APOE4) allele before the onset of Alzheimer's disease (AD) dementia may reduce the risk for AD, or delay the onset of symptoms, and should be studied, according to an expert review.
While the review of landmark observational and clinical trials that assessed supplementation with ω-3 fatty acids such as docosahexaenoic acid (DHA),revealed it was not beneficial in symptomatic AD, several observational and clinical trials of ω-3 supplementation in the pre-dementia stage of AD suggested it may slow early memory decline in APOE4 carriers, reported Hussein Yassine, MD, of the Keck School of Medicine at the University of Southern California in Los Angeles, and colleagues.
Results were mixed in patients with mild or no cognitive impairment, they wrote in JAMA Neurology.
DHA is critical to the formation of neuronal synapses and membrane fluidity, the authors explained.
"We hypothesize that DHA supplementation in APOE4 carriers can result in beneficial outcomes if the timing of the intervention precedes the onset of dementia. Given the safety profile, availability, and affordability of DHA, refining an interventional prevention study in APOE4 carriers is warranted," they noted, adding that advanced brain imaging techniques could be used to identify optimal timing of DHA supplementation and treatment efficacy could be evaluated using specific biomarkers.
Their review of original articles, systematic reviews, and meta-analyses of ω-3 studies in AD showed that most associated higher levels of seafood, ω-3 consumption, or ω-3 blood levels with decreased incidence of AD, better cognitive measures, or preserved brain volume in AD-vulnerable regions.
One summary of 21 studies in a meta-analysis of of 181,580 participants, with 4,438 dementia cases identified over follow-up of 2 to 21 years, concluded that a single weekly serving of fish was associated with significantly lower risk for AD dementia.
A 2015 meta-analysis concluded that ω-3 supplementation significantly improved episodic memory in cognitively healthy older individuals.
"These studies indicate that APOE4 is a modifiable AD risk factor, and that the effect of APOE4 on AD pathologic changes can be attenuated with DHA supplementation," Yassine's group said.
Individuals with a single ε4 allele are three to four times more likely to develop AD as those without an ε4 allele, and people with two ε4 alleles have a 12-fold higher risk of developing AD, the researchers pointed out.
In an email to MedPage Today, Yassine stressed that the review was not intended to act as a recommendation for DHA supplementation. It was done "to stimulate interest in refining the role of high-dose DHA supplementation in a population at increased risk of AD using appropriately designed interventions. We think that long-term high-dose DHA supplementation in APOE4 carriers who are not avid seafood consumers may result in reducing AD incidence. This is evident from some of the epidemiology studies, but was difficult to demonstrate in randomized clinical trials given the limitations of trial designs."
His group proposed that APOE4 carriers be classified into three stages based on disease severity.
In the earliest pre-dementia phase of the disease (stage I), participants would have evidence of brain imaging changes in areas vulnerable to AD. However, no cognitive changes, or only subtle ones, would be detectable.
"In this stage, brain DHA metabolism is altered by APOE4, and brain imaging or CSF biomarkers can be used to select at-risk individuals and monitor the efficacy of supplementation," they explained.
It is for patients in an early prodromal stage of disease (stage II) that long-term high dose DHA supplementation could slow cognitive decline, the researchers stated. Patients in this group would have evidence of memory and/or executive decline but no significant impairment in activities of daily living.
Stage III would represent clinical AD with impairments in multiple cognitive domains. DHA supplementation would probably not be beneficial in this group.
Steven DeKosky, MD, of the McKnight Brain Institute in Gainesville, Fla., agreed that "it is almost surely correct that DHA won't help much if at all in people with full-blown disease."
But he cautioned that "the jury is still out on pre-AD. There isn't much to say to clinicians about how they should act on this information other than to know that we somehow have to get a trial going to prove if it does help or not," he told MedPage Today.
"This frequently gets translated into 'My doctor said I should take DHA supplements,'" noted DeKosky, who was not involved in the review.
Calling the hypothesis "thoughtful," DeKosky predicted that getting "evidence [of DHA supplementation's value] for the jury" would not be easy. Such a study would have to run long enough to demonstrate the DHA supplementation is effective in delaying onset or emergence of signs or symptoms of AD, he stated.
"Given that DHA is not patented, no pharma will fund a study that long since many companies could sell it," DeKosky said. "But that would be the evidence we would need."
Yassine's group plan to identify whether APOE4 carriers in the pre-dementia stage have measurable changes in brain DHA homeostasis, using novel imaging methods or cerebrospinal fluid DHA levels as an index of brain DHA. Then they will test to see whether high-dose DHA supplementation can offset these changes before the onset of AD dementia, Yassine explained.
The study was supported by the National Heart, Lung, and Blood Institute, the Alzheimer's Association, the National Institute on Aging, the LK Whittier Foundation, and Huntington Medical Research Institute.
Yassine disclosed no relevant relationships with industry. One co-author disclosed relevant relationships with Baxter, Eli Lilly, Forum, Lundbeck, Merck, Novartis, Roche/Genentech, TauRx, and Biogen, AC Immune, Accera, Avraham, Boehringer Ingelheim, Cerespir, Cognition, Forum, Merck, Neurim, Roche, Stemedica, Takeda, TauRx, vTv, and Toyama/FujiFilm.
- Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College and Dorothy Caputo, MA, BSN, RN, Nurse Planner
Primary Source
JAMA Neurology
Source Reference: Yassine HN, et al "Association of docosahexaenoic acid supplementation with __alzheimer Disease Stage in apolipoprotein E ε4 carriers: a review" JAMA Neurol 2016; DOI:10.1001/jamaneurol.2016.4899.
Friday, 6 January 2017
Could statins reduce the risk of Alzheimer's?
![[Statins and a stethoscope]](http://cdn1.medicalnewstoday.com/content/images/articles/314/314725/statins-and-a-stethoscope.jpg)
Researchers have found a link between high exposure to statins and a reduced Alzheimer's risk.
Published in JAMA Neurology, the study identifies a link between high statin use and a lower risk of Alzheimer's disease, though the reduced risk is dependent on sex, race/ethnicity, and the type of statin used.
While the study is purely observational, the research team - including Julie M. Zissimopoulos, Ph.D., of the University of Southern California in Los Angeles - and colleagues say that the findings should be further investigated in clinical trials.
Alzheimer's disease is the most common form of dementia, with around 5.2 million people in the United States aged 65 and older living with the disease. By 2050, this number could reach 13.8 million, unless new prevention or treatment strategies are found.
While great strides have been made in the search for ways to halt the development and progression of Alzheimer's in recent years, researchers are yet to jump the final hurdle.
Just last month, hopes of the first medication to slow Alzheimer's were dashed, after drug giant Eli Lilly announced that their promising drug candidate solanezumab had failed to reduce cognitive decline in a phase III trial of patients with the disease.
In the new study, Zissimopoulos and team suggest it might be worth investigating the feasibility of existing drugs for the prevention of Alzheimer's, after finding a link between high exposure to statins and reduced Alzheimer's risk.
Statins and Alzheimer's
Statins are often prescribed to lower levels of low-density lipoprotein cholesterol - "bad" cholesterol that can increase the risk of heart attack and stroke.
According to Zissimopoulos and colleagues, previous studies have shown that high cholesterol levels may be associated with the buildup of beta-amyloid plaques in the brain, which are considered to be a hallmark of Alzheimer's disease.
As such, the researchers hypothesized that cholesterol-lowering medications might influence the onset of Alzheimer's and its subsequent progression.
To investigate their theory, the team analyzed 2006-2013 Medicare data of 399,979 adults aged 65 and older who had used statins.
The researchers looked at how low and high statin use might be associated with risk of an Alzheimer's diagnosis between 2009-2013. High statin exposure was defined as "at least the 50th percentile of days of filled prescriptions in a given year for at least 2 years during 2006, 2007, and 2008."
Each year between 2009-2013, around 1.72 percent of women and 1.32 percent of men were diagnosed with Alzheimer's, with diagnosis lowest among white men, at 1.23 percent.
Overall, men and women with high exposure to statins were 15 percent and 12 percent less likely to be diagnosed with Alzheimer's, respectively, compared with men and women with low exposure to the drugs.
However, on closer investigation, the team found that the link between high statin use and lower Alzheimer's risk was dependent on sex, race/ethnicity, and the type of statin used.
Alzheimer's risk dependent on statin type, sex, race/ethnicity
High exposure to statins overall was only associated with a reduced risk of Alzheimer's for Hispanic men, black women, and white men and women, compared with low exposure to the drugs.
Breaking the data down further by statin type, the researchers found that:
- High atorvastatin exposure was linked to reduced Alzheimer's risk for white and black women, as well as for Hispanic men and women
- White, Hispanic, and black women had a lower Alzheimer's risk with high use of simvastatin, as did white and Hispanic men
- Pravastatin and rosuvastatin were linked to a reduced risk of Alzheimer's for white women.
For black men, the team identified no significant reduction in Alzheimer's risk with the use of any statin.
The researchers stress that their study is unable to prove cause and effect, so clinical trials are required - involving all racial and ethnic groups - to confirm their results.
Still, they believe their findings indicate that certain statins could be a feasible strategy to combat Alzheimer's disease:
"Our study identified the associations between AD [Alzheimer's disease] incidence and statin use by statin type, sex, and race/ethnicity. This suggests that certain patients, facing multiple, otherwise equal statin alternatives for hyperlipidemia treatment, may reduce AD risk by using a particular statin.
The right statin type for the right person at the right time may provide a relatively inexpensive means to lessen the burden of AD."
Read how statins could reduce the risk of death for some patients with arthritis.
Frequent sauna use may reduce dementia risk in men
![[A mature man in a sauna]](http://cdn1.medicalnewstoday.com/content/images/articles/314/314841/mature-man-in-a-sauna.jpg)
Men who used saunas frequently were found to be at lower risk of dementia in the new study.
Study leader Prof. Jari Laukkanen, of the University of Eastern Finland, and team recently published their findings in the journal Age and Ageing.
According to Alzheimer's Disease International, there are around 46.8 million people worldwide living with dementia. Unless new prevention and treatment strategies are found, this number is expected to reach 131.5 million by 2050.
Previous studies have suggested sauna use may benefit cardiovascular health, but Prof. Laukkanen and team note that no studies had investigated whether sauna use might benefit memory disorders.
To find out, the researchers analyzed the data of 2,315 apparently healthy men aged 42-60 who were part of the Kuopio Ischaemic Heart Disease Risk Factor Study.
The team divided the men into three groups based on their frequency of sauna use: once a week, two to three times a week, and four to seven times a week.
Participants were followed-up for a median of 20.7 years, during which time 204 cases of dementia and 123 cases of Alzheimer's disease - the most common form of dementia - were diagnosed.
Frequent sauna use lowered dementia risk by 66 percent
The researchers found that men who used a sauna more frequently were at lower risk of dementia, with the risk reducing further with more frequent sauna use.
Compared with men who used a sauna once a week, men who used a sauna four to seven times weekly were found to be at 66 percent lower risk of any dementia and had a 65 percent lower risk of developing Alzheimer's disease.
These results remained after accounting for a number of potentially confounding factors, including participants' age, alcohol intake, smoking status, body mass index, previous heart attack incidence, and diagnosis of type 2 diabetes.
Commenting on their findings, the authors write:
"In this male population, moderate to high frequency of sauna bathing was associated with lowered risks of dementia and Alzheimer's disease. Further studies are warranted to establish the potential mechanisms linking sauna bathing and memory diseases."
A previous study from Prof. Laukkanen and colleagues associated frequent sauna use with reduced risk of death from cardiovascular disease.
The researchers speculate that sauna use increases heart rate in a way that is comparable to exercise, which benefits heart health. This same mechanism could also be beneficial for memory, the team suggest.
"The sense of well-being and relaxation experienced during sauna bathing may also play a role," adds Prof. Laukkanen.
While the study results are certainly interesting, some glaring limitations should be noted. Firstly, the study only included men, so the results cannot be generalized to women. Additionally, very few participants reported never having used a sauna, so it is unclear how frequent sauna use might affect dementia risk in comparison to having never used one.
Read how a protein in urine might increase the risk of dementia.