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Thursday, February 04, 2016

UCLA Nursing Research Finds Possible Answer to Why Some Develop AD and Others Don’t

Dear Readers,

Alzheimer’s disease affects millions, but there is no cure and no real test for the diagnosis until death, when an examination of the brain can reveal the amyloid plaques that are a telltale characteristic of the disease.

Interestingly, the same plaque deposits have also been found in the brains of people who had no cognitive impairment, which has led scientists to wonder: Why do some develop Alzheimer’s and some do not?

Researchers at the UCLA School of Nursing, led by Professor Karen Gylys, may have just uncovered the answer. Their study, published in the January issue of the American Journal of Pathology, is the first to look at disease progression in the synapses — where brain cells transmit impulses.

The researchers analyzed autopsy tissue samples from different locations of the brains of patients who were considered cognitively normal and those who met the criteria for dementia. Using flow cytometry — a laser-based technology that suspends cells in a stream of fluid and passes them through an electronic detection apparatus — they measured the concentration of two of the known biochemical hallmarks of Alzheimer’s: amyloid beta and p-tau, proteins that when found in high levels in brain fluid are indicative of Alzheimer’s. This allowed the scientists to see large populations of individual synapses — more than 5,000 at a time — versus just two under a microscope.

They found that people with Alzheimer’s had elevated concentrations of synaptic soluble amyloid-beta oligomers – smaller clusters of amyloid-beta that are toxic to brain cells. These oligomers are believed to affect the synapses, making it harder for the brain to form new memories and recall old ones.

“Being able to look at human synapses has almost been impossible,” Gylys said. “They are difficult to get a hold of and a challenge to look at under an electron microscope.”

To overcome that challenge, the UCLA researchers cryogenically froze the tissue samples — which prevented the formation of ice crystals that would have otherwise occluded the synapses had the samples been conventionally frozen. Researchers also did a special biochemical assay for oligomers, and found that the concentration of oligomers in patients who had dementia was much higher than in patients who had the amyloid plaque buildup but no dementia.

Researchers also studied the timing of the biochemical changes in the brain. They found that the accumulation of amyloid beta in the synapses occurred in the earliest stages of the amyloid plaques, and much earlier than the appearance of synaptic p-tau, which did not occur until late-stage Alzheimer’s set in. This result supports the currently accepted “amyloid cascade hypothesis” of Alzheimer’s, which says that the accumulation of amyloid-beta in the brain is one of the first steps in the development of the disease.

The researchers now plan to examine exactly how soluble amyloid-beta oligomers lead to tau pathology and whether therapies that slow the accumulation of amyloid-beta oligomers in the synapses might delay or even prevent the onset of Alzheimer’s-related dementia.

“The study indicates there is a threshold between the oligomer buildup and the development of Alzheimer’s,” Gylys said. “If we can develop effective therapies that target these synaptic amyloid beta oligomers, even a little bit, it might be possible to keep the disease from progressing.”

Gylys said people can reduce their risk for Alzheimer’s through lifestyle and diet choices, but added that one solution is not going to be enough. “Alzheimer’s disease, like heart disease or cancer, is a lot of things going wrong,” she said. “But understanding this threshold effect is very encouraging.”

Other investigators involved in the study were Tina Bilousova, Harry Vinters, Eric Hayden, David Teplow, Gregory Cole and Edmond Teng of UCLA; Carol Miller of the University of Southern California; and Wayne Poon, Maria Corrada, Claudia Kawas, Charles Glabe and Ricardo Albay III of UC Irvine.

The research was supported by grants from the National Institutes of Health and National Institute of Aging.

by Laura Perry, UCLA School of Nursing
Author: Guest at 9:30 AM 0 Comments

Thursday, January 28, 2016

Slower Mental Decline Linked to Higher Amounts of Growth Factor in the Brain

Dear Readers,

Older people with higher amounts of a key protein in their brains also had slower decline in their memory and thinking abilities than people with lower amounts of protein from the gene called brain-derived neurotrophic factor, or BDNF, according to a study published in the Jan. 27, 2016, online issue of Neurology.

“This relationship was strongest among the people with the most signs of Alzheimer’s disease pathology in their brains,” said study author Aron S. Buchman, MD, of Rush University Medical Center in Chicago and a member of the American Academy of Neurology. “This suggests that a higher level of protein from BDNF gene expression may provide a buffer, or reserve, for the brain and protect it against the effects of the plaques and tangles that form in the brain as a part of Alzheimer’s disease.”

For the study, 535 people with an average age of 81 were followed until death, for an average of six years. They took yearly tests of their thinking and memory skills, and after death, a neurologist reviewed their records and determined whether they had dementia, some memory and thinking problems called mild cognitive impairment or no thinking and memory problems. Autopsies were conducted on their brains after death, and the amount of protein from BDNF gene expression in the brain was then measured. The participants were part of the Rush Memory and Aging Project and the Religious Orders Study.

The rate of cognitive decline was about 50 percent slower for those in the highest 10 percent of protein from BDNF gene expression compared to the lowest 10 percent. The effect of plaques and tangles in the brain on cognitive decline was reduced for people with high levels of BDNF. In the people with the highest amount of Alzheimer’s disease hallmarks in their brains, cognitive decline was about 40 percent slower for people with the highest amount of protein from BDNF gene expression compared to those with the lowest amount.

On average, thinking and memory skills declined by about 0.10 units per year on the tests. Higher levels of protein from BDNF gene expression reduced the effect of plaques and tangles in the brain on cognitive decline by 0.02 units per year.

The researchers found that the plaques and tangles in the brain accounted for 27 percent of the variation in cognitive decline, demographics accounted for 3 percent and BDNF accounted for 2 percent.

Michal Schnaider Beeri, PhD, of the Icahn School of Medicine at Mount Sinai in New York, noted in an accompanying editorial that exercise has been shown to increase levels of BDNF in the blood, but that the relationship between BDNF protein levels in the blood and in the brain is not clear.

“More research is needed to confirm these findings, determine how this relationship between protein produced by BDNF gene expression and cognitive decline works and see if any strategies can be used to increase BDNF in the brain to protect or slow the rate of cognitive decline,” said Buchman.

Buchman noted that the study does not prove that BDNF is the cause of a slower rate of cognitive decline; further work is needed to determine if activities which increase brain BDNF gene expression levels protect or slow the rate of cognitive decline in old age.

The study was supported by the National Institutes of Health, Illinois Department of Public Health and the Robert C. Borwell Endowment Fund.

“Higher brain BDNF gene expression is associated with slower cognitive decline in older adults” by Aron S. Buchman, Lei Yu, Patricia A. Boyle, Julie A. Schneider, Philip L. De Jager, and David A. Bennett in Neurology. Published online January 27 2016.

Thanks for reading,

Jeffree Itrich, M.J., M.S.W,
UC San Diego
Author: Jeffree Itrich at 11:20 AM 0 Comments

Wednesday, January 20, 2016

Is this the key to fighting Alzheimer’s?

Dear Readers,

Every four seconds, somewhere in the world, there is a new case of dementia. Alzheimer’s disease, which was considered rare 50 years ago, has today reached pandemic proportions, affecting some 45 million people globally. The cost of caring for Alzheimer’s has skyrocketed to more than $600 billion (about 1% of global GDP) and – if a breakthrough doesn’t come soon – those costs are projected to exceed $1 trillion by 2025.

Doctors have made significant progress towards understanding the causes of Alzheimer’s. For the first time, brain scans are revealing changes in the brains of living Alzheimer’s patients, allowing scientists to see how the disease develops. A disease in a dish model of Alzheimer’s is helping researchers efficiently and rapidly screen hundreds of drugs. New cognitive assessment tools and blood tests for early detection are in development. Experimental medicines targeting abnormal brain proteins are in clinical trials, and the first stem-cell trial for Alzheimer’s is about to begin in the United States. Meanwhile, a team of leading researchers recently published a roadmap for accelerating the testing phase of novel regenerative therapies. One of the most interesting areas is optogenetics, which uses light to activate brain cells, and has been shown to restore memories in amnesiac mice.

Despite these advances, there are still a lot of things we don’t know about dementia, and still room for research. We need better tools for detecting Alzheimer’s before it becomes full-blown, as well as new interventions that can delay the onset of disease in those at high risk, plus new treatments that can target tiny regions of the brain and boost memory. At a basic scientific level, we still need to gain clearer insight into what causes Alzheimer’s and the role played by proteins (such as amyloid and tau), as well as the immune system. It’s time for that to change, and a scientific competition with a lucrative prize could be just the thing to bring it about.

If there’s one thing stalling progress on Alzheimer’s, it’s a lack of resources. Our current investment levels remain modest: we spend 400 times less on research than the sum of the economic toll of the disease. More than 100 “promising” experimental medicines for Alzheimer’s have failed in clinical trials and no new treatments have come to market in the past decade. This failure rate also highlights the need to move from conventional thinking to new paradigms when it comes to dementia research.

The good news, however, is that today we are living in an extraordinary time, when technology is allowing small teams of individuals to accomplish what was once the province of only governments and the largest corporations. Empowered by machine learning, artificial intelligence, ubiquitous networks, cloud computing, robotics and digital manufacturing, small teams are building platforms and enterprises that are touching the lives of billions. If these creative and interdisciplinary teams begin to tackle Alzheimer’s, we may have a way forward. The challenge is to motivate them to do so.

Throughout history, our indomitable spirit of competition has brought about breakthroughs and solutions that once seemed unimaginable and impossible. In 1714, the British government’s Longitude rewards inspired a solution to the great scientific challenge of pinpointing a ship’s location at sea. The Apollo Project, to land a man on the moon, was spurred by intense competition between the US and USSR.

More recently, in 2004, a $10 million competition dubbed the Ansari XPRIZE challenged private entrepreneurs to build a spacecraft. The award spurred the advent of the private space industry and ushered in a new era of scientific prizes. Unlike awards given decades after a discovery, and often to an individual or small academic group (such as the Nobel or Lasker award) competition-based XPRIZEs offer a fast payout (two to seven years depending on the challenge) and revolve around narrowly defined, preset goals. Since the Ansari challenge began, XPRIZEs have led to the development of new oil-spill clean-up methods and a portable, real-life Star Trek Tricoder to diagnose disease. Prior XPRIZES have ranged from $2 million to $30 million.

Ken Dychtwald of Age Wave, a leading think tank on ageing, has co-conceived an Alzheimer’s XPRIZE. By offering a large monetary award, he hopes to inspire brilliant innovators who wouldn’t otherwise study Alzheimer’s to delve into the challenge. Whether they come from academia, industry or the general public, the hope is that new teams will look at dementia with fresh eyes and be able to see things that have been missed. A sponsor is now being sought to create the prize.

P. Murali Doraiswamy,MD,MBBS, FRCP, is Professor of Psychiatry and Medicine at Duke University and a leading researcher at the Duke Institute for Brain Sciences. He chairs the World Economic Forum’s Global Agenda Council for Brain Research and is a co-author of The Alzheimer’s Action Plan.

Peter H. Diamandis, MD, is the Chairman and Founder of the Xprize Foundation, which designs and launches large incentive prizes to drive radical breakthroughs for the benefit of humanity. He is Co-founder and Chairman of the Singularity University, which counsels the world’s top enterprises on how to utilize exponential technologies. He is the coauthor of BOLD: How to Go Big, Create Wealth and Impact the World.

Originally published in World Economic Forum.
Author: Guest at 9:41 AM 0 Comments

Friday, January 15, 2016

New Study Shows Connection Between Traumatic Brain Injury & Neurodegenerative Diseases Like AD

Dear Readers,

Researchers at the University of Texas in Galveston separated a toxic form of the tau protein in mice that had suffered a traumatic brain injury (TBI) and injected it into a group of healthy mice to see if they would develop dementia symptoms.

In previous research the same group found that this toxic form of tau, which traditionally increases after brain injury, could be why those who suffer TBIs develop chronic traumatic encephalopathy (CTE), a condition seen in many professional athletes and military personnel. They set out to test their theory that the toxic form of tau could be behind the condition.

In the second study the healthy animals that received the injections of toxic tau in the hippocampus, an area of the brain essential to memory, went on to develop the same cognitive impairments as seen in Alzheimer’s disease. The results suggest that the increased incidence of acquiring CTE and Alzheimer’s disease many years after the traumatic brain injury could be due to the seeding and dispersal of toxic tau following the brain injury. This has important implications for both TBI treatment and the prevention of brain degeneration in later life.

The group’s findings were published online in the January 5th, 2016 issue of Journal Neurotrauma. The study was headed up by Rakez Kayed in the department of neurology and the Mitchell Center for Neurodegenerative Diseases and Bridget Hawkins in the department of anesthesiology.

Thanks for reading,

Jeffree Itrich, M.S.W., M.J.
Manager, Recruitment & Communications
Alzheimer's Disease Cooperative Study
University of California San Diego
Author: Jeffree Itrich at 12:14 PM 0 Comments

Thursday, January 07, 2016

2015: The Year in AD Research

It is estimated that 5.3 million Americans and nearly 47 million worldwide have Alzheimer’s (AD). In the absence of a definitive treatment, the disease is pervasive and insidious, killing more people than breast cancer and prostate cancer combined. Due to the intense care that late-stage patients require, it’s also one of the most expensive—costing the U.S. $226 billion in 2015 alone. That figure is due to rise to $1.1 trillion (in 2015 dollars) by 2050. The sixth-leading cause of death, it’s the only one in the top 10 that cannot be cured, slowed, stopped, or prevented. Researchers are dutifully investigating every possible avenue to locate the underlying cause and find a possible treatment or prevention. Below are some of the more unconventional, non-drug studies that both made the news and provided a glimmer of hope in 2015.


In 2015 researchers presented additional evidence to support the ongoing theory that a Mediterranean style diet featuring olive oil may help protect the brain from Alzheimer’s disease. A nutritional epidemiologist at Rush University in Chicago, Martha Clare Morris, PhD, and colleagues developed the "Mediterranean-DASH Intervention for Neurodegenerative Delay" (MIND) diet. Study results were published in the journal Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association in March.

Over five years the researchers studied more than 900 middle-aged Americans on the MIND diet, which consists of foods like fish, grains, vegetables, and healthy fats. In those participants who followed the MIND diet “rigorously,” the researchers found that participants reduced their risk of developing AD by 53 percent. Those who did not follow it as stringently but still followed it “moderately well” presented a reduced risk of 35 percent.


There was great news for coffee drinkers this past year. Researchers came across evidence that coffee can help reduce the risk of AD. Part of a larger analysis of mortality by the Harvard School of Public Health, the study was published in the journal Circulation.

The researchers analyzed over 90,000 women and 40,000 men, finding that coffee consumption had a “significant inverse association” with death due to neurological diseases such as AD.

Coffee’s ability to possibly lower risk of death from AD wasn’t the only finding —researchers also discovered that regular coffee drinkers were less likely to die from a handful of other conditions as well, ranging from suicide to heart disease. The scientists hypothesized that coffee’s “bioactive compounds” coffee may be responsible, adding that further research should be conducted to verify this finding.


For decades doctors have observed a link between sleep problems and memory disorders. A lack of sleep is common in people with AD. And now, scientists at the University of California, Berkeley, have found convincing evidence that poor sleep, particularly a deficit of deep, restorative sleep, provides a conduit through which the beta-amyloid protein assaults the brain's long-term memories. The study was published in the journal Nature Neuroscience.

Using a combination of brain imaging and other diagnostic tools on 26 older adults without dementia, researchers looked for the link between bad sleep, poor memory and the toxic accumulation of beta-amyloid proteins. A buildup of beta-amyloid has been found in AD patients and, separately, in people reporting sleep disorders. A 2013 University of Rochester study showed that the brain cells of mice would shrink during non-rapid-eye-movement (non-REM) sleep to make space for cerebrospinal fluids to wash out toxic metabolites such as beta-amyloid. In short, sleep washes away toxic beta amyloid at night, preventing them from building up and destroying healthy brain cells. The researchers likened it to a brain power cleanse. The good news about the findings is that poor sleep can be treatable.


At the Alzheimer’s Association International Conference in July, Laura D. Baker, Ph.D., of Wake Forest School of Medicine, presented study findings suggesting that exercise may be able slow the progression of AD in people at high risk for developing the disease.

Her study demonstrated that after six months, participants who built up to exercising at an elevated heart rate for 30 minutes, four times a week, improved their cognition and had decreased levels of phosphorylated tau protein compared to those in a stretching-only control group. This is tremendous news because currently no approved drug has demonstrated that same effect. Tau protein levels are the measure scientists use to gauge AD disease progression. While the protein naturally increases with age in everyone, in people with AD, it increases significantly more. In Baker’s study, the exercise group saw a slight decrease in their levels after six months. Baker is embarking on a larger, similar study called EXERT that will enroll 300 subjects.


Newly published research out of the Yale School of Public Health revealed that people who sustain negative beliefs about aging are more likely to experience brain changes associated with AD. The study proposed that resisting negative beliefs about aging could possibly offer a way to reduce the incidence of AD.

Led by Becca Levy, associate professor of public health and of psychology, the study is the first to link a cultural-based psychosocial risk factor to the AD brain changes. The findings were published online Dec. 7 in the journal Psychology and Aging. Study authors examined healthy, dementia-free subjects from the Baltimore Longitudinal Study of Aging, the nation’s longest-running scientific study of aging. Based on MRIs, the researchers found that participants who held more negative beliefs about aging showed a greater decline in hippocampus volume. Reduced hippocampus volume is an indicator of AD.
Researchers also used brain autopsies to examine two other indicators of AD: amyloid plaques, and neurofibrillary tangles, which are twisted strands of protein that build up within brain cells. Participants holding more negative beliefs about aging had a significantly greater number of plaques and tangles.

Thanks for reading,

Jeffree Itrich, M.S.W., M.J.
Manager, Recruitment & Communications
Alzheimer's Disease Cooperative Study
University of California San Diego

Author: Jeffree Itrich at 9:45 AM 0 Comments

Thursday, November 05, 2015

Hope for Using Amyloid Pet Imaging in Clinical Care

Dear Readers,

Preclinical biomarkers that may predict progression from normal cognition to MCI and Alzheimer’s disease (AD) were included in the latest criteria and guidelines for the diagnosis of Alzheimer’s disease from the National Institute on Aging (NIA) and the Alzheimer’s Association (Sperling et al., 2011). One such biomarker is positron emission tomography (PET) amyloid imaging. When conducted according to established protocols, a positive PET scan is taken as consistent with moderate to frequent amyloid as visualized on a post-mortem exam, while a negative scan is consistent with sparse to no amyloid. Both positive and negative scans can be useful in the diagnosis of the cause of dementia (Zannas et al., 2014).

As with other biomarkers, amyloid PET imaging can be positive in the earliest disease stages, before clinical symptoms appear. As there is a developing consensus that early diagnosis and treatment may be essential for effective intervention, amyloid PET imaging is poised to have a significant impact in the clinic and in the selection of patients for clinical trials aimed at developing disease-specific therapies (Sperling et al., 2011).

In the fall of 2013, the Centers for Medicare & Medicaid Services (CMS) issued a decision memorandum stating that the evidence was insufficient to conclude that amyloid PET imaging was reasonable and necessary for the clinical diagnosis or treatment of AD. They ruled that Medicare would not cover the procedure as a routine clinical test. Other third-party payers followed Medicare’s lead. Thus, although the procedure has been approved by the FDA for clinical use and is widely available, in clinical practice it can be utilized only by those able to afford the approximately $3,000 out-of-pocket expense. CMS did make an exception for specific cases involving difficult differential diagnoses, such as AD versus frontotemporal dementia. In addition, CMS ruled that it would cover one amyloid PET scan per patient for CMS-approved clinical studies meeting specific criteria.

The CMS memorandum posed several questions meriting further study, including whether amyloid PET imaging leads to meaningfully improved health outcomes, including avoidance of futile treatment or tests, improving (or slowing the decline of) quality of life, and survival. Another question was whether specific variables could be identified - subpopulations, patient characteristics, or differential diagnoses – that predict enhanced health outcomes when management was guided by amyloid PET imaging. These questions have been addressed by several clinical investigations (Camus et al., 2012; Clark et al., 2012; Doraiswamy et al., 2014; Grundman et al., 2013) and case reports (Mitsis et al., 2014; Zannas et al., 2014). The following case series exemplifies the use of clinical amyloid PET imaging by specialists in dementia care. In each case, scan results were used to refine a diagnosis, change a treatment, avoid unnecessary tests and medications, encourage participation in clinical trials of anti-amyloid therapies, and/or facilitate personal planning, both legal and occupational.

Because there is an interest in utilizing the amyloid PET imaging as part of the diagnostic evaluation of Alzheimer’s dementia, CMS has agreed to support a demonstration grant called the IDEAs. In this study, over 18,000 amyloid PET scans will be acquired in people with Mild Cognitive Impairment or in dementias that are difficult to distinguish in order to determine if, after 3 and 12 months, clinical decision-making will be influenced by the acquisition of the PET scan. It is hoped by many researchers, including myself, that amyloid PET will be reimbursed so it can be used. In selected patients, it can be useful in excluding AD dementia or increasing the probability thus influencing clinical decision making and directing treatment.

Marwan Noel Sabbagh MD, FAAN
Professor of Neurology
Director, Alzheimer’s and Memory Disorders Division
Barrow Neurological Institute
Research Professor of Neurology, UA College of Medicine-Phoenix

Author: Guest at 2:07 PM 0 Comments

Tuesday, September 08, 2015

Age Dependence of Beta Amyloid Deposition in Down Syndrome

Dear Readers,

As more and more clinical trials are focusing on enrolling persons with various genetic susceptibility genes that put them at risk for developing Alzheimer’s disease, clarifying the relationship between Down’s syndrome and Alzheimer’s disease has been a recurrent theme discussed in my community presentations. Not only do I typically discuss the role of amyloid precursor protein to the development of clinical symptoms similar to that of Alzheimer’s disease in patients with Down’s syndrome, I am increasingly asked to comment on the various neuroimaging changes noted in patients with Down’s syndrome. Are the changes similar to those seen in patients with Alzheimer’s disease or are they different?

A recent paper by Jennings et al, examined whether 18F florbetaben PET imaging – commonly used in research studies - in patients with cognitive changes and Alzheimer’s disease could reliably detect amyloid in relatively young patients with Down’s syndrome.

In this study, individuals with Down’s syndrome (DS) were recruited from two centers and were atleast 40 years of age. Genetic testing noted that all of the patients had a triplication of chromosome 21 with no evidence of partial trisomy. All participants underwent a screening visit, including a history and physical examination, clinical assessments, and cognitive screening. PET imaging was performed within 12 weeks of the screening visit. Cognitive status of individuals with DS was evaluated using the Dementia Screening Questionnaire for individuals with disabilities (DSQIID). The scale includes questions on baseline “best ability,” on behaviors and symptoms suggestive of dementia, and current level of function to that of baseline ability.

PET acquisition with 18 F florbetaben was performed, and uptake was calculated for seven specific pre-identified brain volumes of interest (VOIs): frontal cortex, lateral temporal cortex, anterior cingulate cortex, posterior cingulate cortex, parietal cortex, occipital cortex, and cerebellum. Three independent readers blind to the clinical data performed a visual assessment of the PET scans.

The current sample included 39 DS subjects with a mean age of 46.3 years +/- 4.7 years (54% males, 95 % Caucasian). 18 F florbetaben uptake increased with age for all VOIs and increased by 2.88 % for each year of age above 40 years. When stratifying the subjects with DS on five year age intervals, those in the 50 years and older groups showed an increase in mean composite SUVR compared with the two younger subgroups. Multiple readers blinded to each other’s radiological evaluations showed good inter-rater reliability assessing the scans and no safety concerns were noted for administration of the tracer.

Cognitive testing noted a mean score of 6.4 +/- 8.0 (range 0-41) on the DSQIID with only two of the 34 participants considered to have dementia based on a DSQIID score >20. Those with a score of .0, had a higher composite SUVR compared to those with a DSQIID of 0.

In patients with DS, an increase in beta amyloid as measured by 18 F florbetaben was present, and the increase in 18 F florbetaben correlated with increasing age. Other important findings from this examination noted that less than 50% of subjects with DS between 40 and 50 years and 90% of those DS patients older than 50 years had an 18F florbetaben binding in a range that corresponded to the typical range noted in cases of Alzheimer’s disease. Consistent with earlier neuropathological autopsy studies, amyloid plaques localized in this study by PET, appeared to be localized in the medial temporal lobes. Finally, amyloid deposits were present in DS patients before they demonstrated signs/ symptoms consistent with dementia based on the DSQIID evaluation.

These results demonstrate that PET imaging in populations to visualize amyloid deposition can be performed reliably in special populations with a genetic risk for developing AD. Further, early detection of beta amyloid deposition before cognitive impairment in patients with DS, offers an opportunity for researchers to characterize the natural history of beta amyloid deposition, and potentially can inform drug development in disease modifying therapies.

Want to read more? Here are 3 articles you can refer to, to learn about the relationship between Down’s Syndrome and Alzheimer’s Disease.

1. Jennings D, Seibyl J, Sabbagh M et al. Age dependence of brain beta amyloid deposition in Down Syndrome. An 18F florbetaben PET study. Neurology 2015 84: 500-507

2. Deb S, Hare M, Prior L, Bhaumik S. Dementia screening questionnaire for individuals with intellectual disabilities. Br J Psychiatry 2007; 190: 440-444

3. Mann DM. Alzheimer’s disease and Down’s syndrome. Histopathology 1988: 13; 125- 137.

Thanks for reading,

Neelum T. Aggarwal, MD
Steering Committee Member, ADCS
Rush Alzheimer’s Disease Center
Chicago, IL

Author: Neelum Aggarwal MD at 8:14 AM 0 Comments

Friday, May 29, 2015

Imaging Dementia — Evidence for Amyloid

Dear Readers,

In a truly exciting development, the Centers for Medicare & Medicaid Services (CMS) has approved a four-year, $100 million study called Imaging Dementia—Evidence for Amyloid Scanning 'IDEAS'. The goal of the study is to better understand whether getting an amyloid PET scan can affect the diagnosis, management, and care of individuals whose cognitive symptoms cannot be diagnosed with current techniques. There will be approximately 18,500 patients enrolled from over 200 imaging centers around the country. CMS will reimburse for one amyloid scan for each cognitively impaired person taking part in a clinical trial, if that trial collects data about how the scan subsequently affected the patient’s health outcomes. As readers of this blog will recall, amyloid PET scans, though FDA approved, are not currently covered by any insurance.

The participants in the IDEAS study will be Medicare beneficiaries aged 65 and older. Before a patient gets a scan, the clinician will complete a case report form with the diagnosis and treatment plan. Patients will then undergo amyloid PET imaging and three months after the referral, the clinician will submit a second, updated report that details any change in diagnosis and/or treatment plan resulting from the amyloid PET scan. Participants will learn the results of the amyloid scan.

Perhaps the greatest impact of the IDEAS study will be on patients with the syndrome called Mild Cognitive Impairment (MCI), which presents with symptoms of memory loss and can result from multiple causes, including AD, about half of the time. In a patient with MCI, where the amyloid scan is negative, a diagnosis of AD is essentially ruled out. This type of information will help clinicians tailor diagnostic work-ups and treatment plans more clearly with a better sense of the patient's amyloid status in hand.

Thanks for reading,

Michael Rafii, MD, PhD
Director, Memory Disorders Clinic
Medical Core Director
Alzheimer’s Disease Cooperative Study
University of California San Diego
Author: Michael Rafii MD, PhD at 1:59 PM 0 Comments

Tuesday, May 05, 2015

Aducanumab’s Extraordinary Results

Dear Readers,

At the recent AD/PD meeting held in March, results were presented from an AD clinical trial that for the first time clearly showed a drug could significantly reduce beta-amyloid in the brain while also slowing cognitive decline. The drug, aducanumab, is yet another anti-amyloid antibody that was tested in 166 patients with prodromal or mild dementia due to AD. An Alzheimer’s diagnosis was confirmed using amyloid PET scans. Participants were given either 3 mg/kg or 10 mg/kg of the immunotherapy by monthly intravenous infusion. The researchers reported results on two measures: CDR (Clinical Dementia Rating) scale and MMSE (Mini Mental State Exam). Both scales are used to objectively measure memory and cognitive function. On the CDR scale, patients on placebo declined by an average of 2.04 points at one year, compared with 0.59 for the 10 mg/kg , which was statistically significant. On the MMSE scale, patients taking placebo declined an average of 3.14 points at one year compared with a decline of 0.75 points in the 3 mg/kg dose, and 0.58 points in the 10 mg/kg, both of which are statistically significant.

Partway into the trial, Biogen followed a recommendation of its data safety-monitoring board and added a third cohort of 6 mg/kg because the highest dose was showing more ARIA-E (Amyloid-Related Imaging Abnormalities (ARIA)) on brain MRI, a closely watched side effect of anti-amyloid therapy. The ARIA-E side effect was seen more often in patients with ApoE4, a gene variant associated with AD. On the highest dose (10 mg/kg), 55 percent of ApoE4 carriers developed ARIA-E versus 17 percent for non- ApoE4 carriers. The study also showed patients on the drug had headaches more frequently; 22 percent for those receiving aducanumab versus 5 percent on placebo.

So, what do these results mean? First, they lend further support to the idea that clinical trials for AD should utilize Amyloid PET to confirm the patient population. Second, it furthers the idea that earlier treatment with anti-amyloid therapies is likely critical for efficacy. And finally, it sets the stage for a large phase III study to confirm the findings and make dose adjustments to get maximal efficacy with minimal adverse effects. As readers might recall, all three of these features are integrated into the ADCS’ Anti-Amyloid for Asymptomatic Alzheimer’s (A4) clinical trial.

Thanks for reading,

Michael Rafii, MD, PhD
Director, Memory Disorders Clinic
Medical Core Director
Alzheimer’s Disease Cooperative Study
University of California San Diego
Author: Michael Rafii MD, PhD at 3:00 PM 0 Comments

Monday, March 30, 2015

The Mediterranean-DASH Intervention for Neurodegenerative Delay – The MIND Diet and AD

Dear Readers,

Information on the role of diet and physical activity to cardiovascular health has been reported in the literature for many years. Recently, the focus has shifted to brain health; what is the role of nutrition to brain health? Are there certain foods that would prevent cognitive decline or Alzheimer’s disease (AD) or enhance cognition? A recent paper by Morris et al. sought to examine the relationship between diet and developing AD, from a well established longitudinal study of persons in Chicago participating in the Memory and Aging Project (MAP).

The Memory and Aging Project is a cohort study of people aged 65 years and older living in retirement communities and senior public housing units in the Chicago area. The cohort study began in 1997 and includes annual cognitive testing and clinical neurological examinations. From 2004 - February 2013, the MAP study participants were invited to complete food frequency questionnaires. Over the course of the diet study, 1,545 older adults enrolled in the MAP study and 1,068 completed the dietary questionnaires. A total of 923 had at least two neuropsychological assessments and were clinically determined not to have AD at baseline. All data derived was based on this group of people. The food questionnaire asked participants to report usual frequency of intake over the previous 12 months of 144 food items. Nutrient levels and total energy for each food item were based either on portion sizes (e.g. slice of bread) or according to age- and sex-specific portion sizes from national dietary surveys.

The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet score has 15 dietary components including 10 brain healthy food groups (green leafy vegetables, other vegetables, nuts, berries, beans, whole grains, fish, poultry, olive oil and wine) and five unhealthy food groups (red meats, butter and stick margarine, cheese, pastries and sweets, and fried/fast food) (1) . The total MIND diet score was determined by summing up all 15 of the component scores. The DASH diet scoring, was based on seven food groups and three dietary components (total fat, saturated fat and sodium).(2) The Mediterranean Diet Score includes 11 dietary components, and was computed based on scoring as established scoring scales (3). Over the course of 4.5 years, a total of 144 people developed AD. The MIND diet score was linearly associated with a lower risk of developing AD - people with the top MIND diet scores had a 53% reduction in the rate of developing AD compared with participants with the lowest. Even those participants in the middle range of the MIND diet scores had a statistically significant 35% reduction in AD rate compared with those with the highest scores. Consider how this compares to results from two other diets, the Mediterranean and DASH. Only the highest levels of the Mediterranean and DASH diet scores were significantly associated with reduction of incident AD. (54% reduction in AD for Mediterranean diet and 39% reduction for the DASH diet).

Interestingly, the MIND diet and relationship to developing AD was not modified by age, sex, education, physical activity, obesity, low BMI, or histories of stroke, diabetes, or hypertension. Thus this diet appears to be a more “realistic” type of diet that many adults can apply and derive benefits. Future studies in larger community based populations and populations that are racially / ethnically diverse are needed to examine whether this diet offers the same beneficial effects.

Want to read more? Here are three articles you can review to learn about the diet, nutrition and Alzheimer’s Disease.

1) Morris MC, Tangney CC, Wang Y, Sacks FM, Bennett DA, Aggarwal NT. MIND diet associated with reduced incidence of Alzheimer's disease. Alzheimer’s Dement. 2015 Feb 11.S1552-5260(15)

2) Folsom AR, Parker ED, Harnack LJ. Degree of concordance with DASH diet guidelines and incidence of hypertension and fatal cardiovascular disease. Am J Hypertens 2007; 20:225-232.

3) Panagiotakos DB, Pitsavos C, Arvaniti F, Stefanadis C. Adherence to the Mediterranean food pattern predicts the prevalence of hypertension, hypercholesterolemia, diabetes and obesity, among healthy adults; the accuracy of the MedDietScore. Prev Med 2007; 44:335-340.

Thanks for reading.

Neelum T. Aggarwal, MD
Steering Committee Member, ADCS
Rush Alzheimer’s Disease Center
Rush Institute for Aging
Chicago, IL

Author: Neelum Aggarwal MD at 2:00 PM 0 Comments

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The Alzheimer's Disease Cooperative Study (ADCS) was formed in 1991 as a cooperative agreement between the National Institute on Aging (NIA) and the University of California, San Diego. The ADCS is a major initiative for Alzheimer's disease (AD) clinical studies in the Federal government, addressing treatments for both cognitive and behavioral symptoms. This is part of the NIA Division of Neuroscience's effort to facilitate the discovery, development and testing of new drugs for the treatment of AD and also is part of the Alzheimer's Disease Prevention Initiative.

The ADCS was developed in response to a perceived need to advance research in the development of drugs that might be useful for treating patients with Alzheimer's disease (AD), particularly drugs that might not be developed by industry.