Sirion Therapeutics, Inc., an
ophthalmic-focused biopharmaceuticals company, announced today that it has
begun enrollment of a phase II clinical trial, which will evaluate
fenretinide in the treatment of Geographic Atrophy (GA) in patients with
age-related macular degeneration.

The newly initiated phase II trial is a proof of concept trial being
performed as a multicenter, randomized, double-masked, placebo controlled,
dose-comparison trial in up to 225 patients at approximately 20 sites in
the United States. The fenretinide compound was acquired by Sirion in July
of this year through an acquisition of Sytera, Inc., a San Diego
biopharmaceutical company.

“Initiating patient enrollment in our phase II proof of concept trial
is an important milestone for Sirion,” said Barry Butler, President and
Chief Executive Officer of Sirion Therapeutics, Inc. “Fenretinide is a good
strategic fit with our company mission of finding treatments for sight
threatening disease. We hope that fenretinide will offer help to the almost
1 million people in the U.S. that currently suffer from GA,” concluded
Butler.

About Sirion Therapeutics, Inc.

Sirion Therapeutics is a Tampa, Florida based biopharmaceutical
company, with additional offices in La Jolla, California, dedicated to the
development and commercialization of innovative ophthalmic products. For
more information regarding Sirion and the matters announced in this press
release, please visit Sirion’s website at siriontherapeutics/.

About Geographic Atrophy (GA)

Geographic atrophy (GA) is the advanced form of atrophic AMD. According
to data published in Archives of Ophthalmology, approximately 973,000
people in the US had GA in at least one eye as of 2004. This number is
expected to increase by more than 50% by 2020. There is currently no
therapeutic treatment for GA.

Forward-Looking Statements

This press release may contain forward-looking statements relating to
our ability to develop viable drug product candidates. Any such
forward-looking statements are only predictions, and involve known and
unknown risks, uncertainties and other factors which may cause actual
results to differ materially. Please see our public filings with the
Securities and Exchange Commission for detailed risks, uncertainties and
cautionary statements regarding our business and any forward-looking
statements.

Sirion Therapeutics, Inc.
siriontherapeutics/

UroToday – Almost 40 years ago, Donald F. Gleason pioneered his well acknowledged grading system of prostate adenocarcinoma. In the ensuing years, the reliability of the Gleason system in predicting the outcomes of patients with prostate cancer (PCa) undergoing surgery, radiation therapy or surveillance has been proven in several single and multi-institutional studies. In its original version, the Gleason system considered only the two most predominant Gleason patterns.

Although it has been acknowledged that a substantial number of radical prostatectomy (RP) specimens contain more than two different Gleason grades, a third or fourth potentially present Gleason pattern did not contribute to the Gleason-score, regardless of its magnitude or state of aggressiveness. Recently, a handful of studies have been published, which uniformly demonstrated that the presence of a tertiary Gleason grade is significantly associated with adverse disease at the time of RP. Moreover, a tertiary Gleason grade was a statistically significant predictor of biochemical failure after RP in some of the studies.

Limitations, however, arise in consideration of these study designs, which were nearly all retrospective and were often limited by low statistical power due to small study populations. Furthermore, the data were derived from time intervals when pathological reporting of a tertiary Gleason grade might not have been mandatory. Consequently, prevalence and definition of the reported TGG differed substantially in the above-mentioned studies, ranging from 13 to 50%, which might hamper the assessment of their clinical impact.

Due to the paucity of available contemporary data addressing this issue, we decided to conduct the presented study.

Results and future aspects

As shown in the abstract, we found that the presence of a tertiary Gleason grade in RP-specimen was statistically significantly associated with all the addressed adverse pathological features, namely presence of extracapsular extension, seminal vesicle invasion, positive surgical margins, and presence of lymph node metastases (p

It is common knowledge that smoking is a health risk but why do teens become addicted to smoking more easily than adults? In an evaluation for Faculty of 1000 Biology, Neil Grunberg looks into why adolescents are more prone to substance abuse.

Grunberg describes the study, published by Natividad et al. in Synapse journal, as “fascinating” and suggests it “may have implications to help understand why adolescents are particularly prone to drug abuse”.

Nicotine increases the level of dopamine in the brain, a neurotransmitter that is responsible for feelings of pleasure and wellbeing. The study looked at dopamine levels in adolescent and adult rats after nicotine withdrawal. The authors found that the withdrawal signs (physical and neurochemical) seen in adolescent rats were fewer than those observed in adults.

The study provides previously unknown mechanisms as to why there are differences in nicotine withdrawal between adolescent and adult rats. The key here, as stated by Grunberg, is “age alters [neurological] systems and interactions relevant to nicotine”.

The reason that adolescents are prone to drug abuse (in this case, nicotine) is that they have increased sensitivity to its rewarding effects and do not display the same negative withdrawal effects as adults do, due to an underdeveloped dopamine-producing system.

Since rats are not subject to cultural influences, “rat studies of nicotine … have provided valuable insights that have led to practical behavioural and pharmacological interventions”, says Grunberg.

The results of this study may not stop at nicotine. Grunberg continues, “these findings might also be relevant to other addictive and abuse drugs”.

The full text of this article is available free for 90 days at f1000biology/article/d43fbwjsqtzb3f1/id/1166360

An abstract of the original article Nicotine withdrawal produces a decrease in extracellular levels of dopamine in the nucleus accumbens that is lower in adolescent versus adult male rats is at ncbi.nlm.nih/sites/entrez/19771590

Source: Steve Pogonowski

Faculty of 1000: Biology and Medicine

A constellation of different stem cell populations within our skin help it to cope with normal wear and tear. By constantly proliferating, the stem cells allow skin to replenish itself, allowing each cell to be replaced by a new one about once a month. But the normal cycle of division and death within one or more of these stem cell types can sometimes be derailed by genetic mishaps. Such events are believed to spawn carcinomas and other deadly skin cancers, which are the mostly frequently diagnosed cancers in the United States.

Researchers at Cold Spring Harbor Laboratory (CSHL) led by Associate Professor Alea A. Mills, Ph.D., have now unmasked a long sought stem cell origin of carcinoma and identified the genetic lesions occurring within these cells that spur them on to malignancy. Her team has found that increased activity of a powerful oncogene called Ras combined with overly exuberant activity of a protein called ANp63О±, stimulates the population of skin stem cells that produce keratin 15 – one of many keratin proteins found in the skin – promoting carcinoma development. These findings are online in the journal Cell Stem Cell.

When cells in the skin or anywhere else in the body sense a potentially cancer-causing threat such as an activated oncogene like Ras – which speeds up cell division – the cells cope by slamming on the brakes to trigger a process called senescence. This is a tumor-suppressive mechanism that halts cell division while allowing cells to stay metabolically active.

“Unfortunately there are a number of genetic events that can bypass senescence and push a cell down the road towards cancer,” says Mills. The loss of a gene called p53, a powerful tumor suppressor, in senescent cells is one such event.

Mills’s group has long focused on p53′s sister gene p63, which she discovered during her postdoctoral years. As Mills found subsequently, adult mice that lack p63 age faster, implicating this gene in aging-related processes. Like the other genes in its family, p63 has the ability to produce different protein versions or isoforms. Each of the six p63 isoforms is prevalent in different tissues and performs different functions.

In the skin, for example, TAp63 isoforms are predominantly found within the inner layers known as the dermis, where they guard against the formation of cancers known as sarcomas. The ANp63О± isoform, on the other hand, is found within stem cells of the skin’s outer layers – the epidermis – where it is essential for the cell proliferation needed for skin replenishment.

ANp63О± has gained notoriety in recent years because it has been found to be present at very high levels in some types of human cancer, particularly squamous cell carcinoma, but is absent in other types of tumors, such as sarcomas. “This p63 isoform has been very perplexing,” comments Mills.

“It was well known that Ras activation drives cells into senescence, but we found that as it does so, it exterminates levels of ANp63О±. So we wondered what would happen if instead, there were excessive levels of ANp63О± – a situation akin to that observed in the clinic in human carcinomas.”

ANp63О± obliterates oncogene-induced senescence

Mills’ team investigated this question both in cultured cells – cells that they prepared from mouse skin and propagated in the lab – as well as in living mice. When cultured cells in which the Ras oncogene was switched on were also made to produce high levels of ANp63О±, the cells overcame senescence and started dividing. Transplanting these cells from the lab dish to the skin of live mice caused robust carcinoma formation.

To test ANp63О±’s cancer-causing role in vivo, the scientists induced Ras mutations in living mice by painting their skin with a carcinogenic compound called DMBA. The mice soon developed papillomas – harmless, pre-malignant lesions that resemble warts. The cells within these lesions were arranged into two zones: a layer of proliferating, healthy cells; and a region of senescent cells that formed when Ras mutations accumulated and caused levels of ANp63О± to be driven down.

But eventually, the levels of ANp63О± were beefed up in cells within the senescent zone, and as a result, provided a way to escape from senescence. Armed with ample ANp63О±, these cells divided rampantly, eroding the senescent zone and turning lesions that were once harmless into malignant carcinomas.

Although the reason for the eventual increase in ANp63О± levels in senescent cells remains unknown, the team was able to elucidate the mechanistic basis of ANp63О±-triggered bypass of senescence. The culprit is a protein called LSH, which is known to regulate gene activity by controlling the way the cell’s DNA is packaged.

“It appears that ANp63О± is unshackling the cell from senescence by turning loose LSH, which in turn sets the stage for tumor progression,” explains Mills. “Our experiments explain why ANp63О± and LSH are both present at higher levels in human carcinomas.”

ANp63О± maintains the keratin 15-positive stem cell population

“A clue to its cancer-causing potential was that when ANp63О± was turned on in the context of activated Ras, the cells took on ‘stem-like’ features, which was especially intriguing because this does not happen when senescence is bypassed by other means such as p53 depletion,” according to Bill Keyes, Ph.D, a former postdoc in the Mills lab who is first author of this work and who now has his own research group at the Center for Genomic Regulation in Barcelona.

Following up on this stem cell link using cells from the skin of living mice that had been engineered to have their different skin stem cell populations tagged with different fluorescent colors, Keyes found that combined expression of activated Ras and ANp63О± triggered abnormal proliferation of the stem cell population that produces the keratin 15 protein, while not affecting other stem cell populations.

“The net effect was to maintain this epithelial stem cell population over a longer period of time,” says Mills. “This suggests that when present at high levels, ANp63О± equips these cells with stem cell-like features, thereby giving them time to transform into cancerous cells.”

ANp63О± is already being used as a pathological marker in the clinic to distinguish between cancer subtypes. “This study adds a new dimension to what we know about p63′s role in stem cell function and the contribution of its various isoforms in cancer,” says Mills. “It also adds new insight to the role of stem cells in cancer by showing that when more mature progenitors or committed cells accumulate genetic lesions that make them more stem-like, they tend to promote cancer.”

Notes:

“ANp63О± Is an Oncogene that Targets Chromatin Remodeler Lsh to Drive Skin Stem Cell Proliferation and Tumorigenesis” appears in Cell Stem Cell on February 4. The full citation is William M. Keyes, Matteo Pecoraro, Victoria Aranda, Emma Vernersson-Lindahl, Wangzhi Li, Hannes Vogel, Xuecui Guo, Elvin L. Garcia, Tatyana V. Michurina, Grigori Enikolopov, Senthil K. Muthuswamy and Alea A. Mills.

Source:
Cold Spring Harbor Laboratory

Scientists from Chimerix, Inc. presented in vitro data demonstrating that the company’s lipid-conjugated drugs, CMX001 and CMX157, are not substrates for the human Organic Anion Transporters (hOATs) and thus have significantly reduced potential to cause nephrotoxicity via this mechanism. These data, presented at the International Pharmaceutical Federation (FIP) Pharmaceutical Sciences World Congress (PSWC 2010) and American Association of Pharmaceutical Sciences (AAPS) Annual Meeting, provide a mechanistic explanation for the observed absence of nephrotoxicity in human clinical testing of both compounds to date. Nephrotoxicity is a significant dose-limiting factor for several comparable therapies.

Chimerix is applying its powerful PIM (Phospholipid Intramembrane Microfluidization) Conjugate Technology to existing antiviral compounds to create new chemical entities with improved pharmaceutical attributes. The PIM Conjugate Technology is used to modify a drug molecule so that it mimics a naturally occurring phospholipid. The lipid mimic can then utilize natural uptake pathways enabling oral bioavailability and altering drug distribution profiles. Chimerix’s lead clinical candidate CMX001 applies Chimerix’s PIM Conjugate Technology to the antiviral agent cidofovir, while the second clinical stage compound, CMX157, is the company’s proprietary lipid conjugation of tenofovir. Both cidofovir and tenofovir are known to cause nephrotoxicities, and the severity of nephrotoxicities associated with cidofovir in particular have substantially limited its use. Chimerix has created CMX001 and CMX157 with the intent of minimizing this serious side effect while enhancing drug bioavailability and antiviral activity.

The study reported at the World Congress was designed to evaluate whether CMX001 and CMX157 are substrates of human Organic Anion Transporter 1 (hOAT1) and hOAT3, which are both linked to kidney excretion of endogenous substances and certain drugs. Researchers noted that net uptake of CMX001 and CMX157 was not enhanced in OAT-expressing cells. These data provide evidence that CMX001 and CMX157 are not substrates of human OAT1 and OAT3 and therefore have a low potential to cause OAT-mediated nephrotoxicity. In contrast, uptake of cidofovir and tenofovir was enhanced in in vitro cells expressing OAT1, consistent with previous literature reports.

“Nephrotoxicity is a serious and potentially life-threatening adverse effect associated with the antiviral agents cidofovir and tenofovir. Through the application of our proprietary PIM Conjugate Technology we are able to dramatically alter drug distribution and thereby potentially avoid nephrotoxicity,” said George Painter, Ph.D., Chief Scientific Officer of Chimerix. “Our animal and clinical studies of CMX001 and CMX157, in which both compounds have demonstrated a positive safety profile, are consistent with our in vitro observations that CMX001 and CMX157 are not metabolized in the kidney. Furthermore, these data are consistent with, and provide a mechanistic explanation for, data presented at the recent ICAAC meeting that CMX001 was well tolerated in 46 patients with compromised renal function.”

Chimerix is developing CMX001 for dual-use as a broad-spectrum antiviral for the treatment of life-threatening viruses in immunocompromised transplant and cancer patients and as a medical countermeasure in the event of a smallpox release. CMX001 is currently in Phase 2 clinical trials for the prophylaxis and treatment of human cytomegalovirus infection. CMX157 is currently in Phase 1 clinical testing for the treatment of HIV infections.

Cidofovir and tenofovir are polar, acyclic nucleoside phosphonates that are FDA-approved as Vistide® (cidofovir injection) for the treatment of cytomegalovirus retinitis, and as Viread® (tenofovir disoproxil fumarate) for the treatment of HIV.

These data were presented in a poster titled “Lipid Conjugates of Cidofovir and Tenofovir, CMX001 and CMX157, Are Not Substrates of Human Organic Anion Transporters hOAT1 and hOAT3″ (Abstract T3396) at the FIP Pharmaceutical Sciences World Congress and AAPS Meeting being held in New Orleans, LA.

Source: Chimerix, Inc

View drug information on Viread; Vistide.

University of Utah researchers have found that delayed-enhancement magnetic resonance imaging (DE-MRI) holds promise for predicting treatment outcomes and measuring disease progression for patients with atrial fibrillation (AF), a little known heart rhythm disorder that affects more than 3.5 million Americans and causes more than 66,000 deaths a year. Their latest study on a novel application of this technology for AF appears in the April 7 issue of the journal Circulation.

AF is a misfiring of the electrical signals of the heart, which causes rapid and/or irregular heartbeats and is associated with fibrosis (scar tissue) in the left atrium. Although DE-MRI is an established method for visualizing tissue damage in cardiac disease processes, the study assessed its use in a protocol developed to detect fibrosis in AF patients before they underwent radiofrequency (RF) ablation. This procedure involves the use of catheters that emit mild, painless radiofrequency energy to destroy carefully selected heart muscle cells to stop them from conducting extra electrical impulses.

In this study, the University of Utah colleagues developed a protocol using DE-CMRI to create 3-D images of the left atrium before RF ablation, which were processed and analyzed with custom software tools and computer algorithms to calculate the extent of left atrium wall injury. Patients were then assessed at least six months after the procedure, and the researchers found that only 14 percent classified as having minimal fibrosis had suffered AF recurrence compared to 75 percent recurrence for the group that had extensive scar tissue damage.

“Our results indicate that DE-MRI provides a noninvasive means of assessing left atrial myocardial tissue in patients suffering from AF, and that those who do have tissue damage may be at greater risk of suffering AF recurrence after treatment with RF ablation,” said lead author Nassir F. Marrouche, M.D., assistant professor of internal medicine in the University of Utah School of Medicine and director of the Atrial Fibrillation Program. “Our findings also present a disease progression model that supports the importance of early intervention.”

In addition to its noninvasive nature, DE-MRI offers other advantages over commonly used invasive electroanatomic mapping studies to assess tissue health. For example, while other such diagnostic mapping studies have been associated with a high degree of spatial error, three-dimensional DE-MRI provides information on both the anatomy and the location of pathology without spatial distortion. Marrouche and his colleagues also have developed methods of processing the MRI images in order to visualize the entire volume of left atrium wall injury in 3-D.

“Until now, there has not been an accurate, non-invasive way to assess left atrium scar formation, which studies show is linked to AF disease severity,” said Marrouche. “If substantiated, our DE-MRI visualization technique and analysis would provide guidance in determining appropriate candidates for AF catheter ablation as well as in identifying the heart muscle cells that need to be destroyed.”

Last fall, the University of Utah Atrial Fibrillation program became the first in the world to be able to ablate using a catheter custom-made to be compatible with MRI. Next month, University Health Care will open a new multimillion dollar clinical and research lab, which will be the first in North America to provide real-time DE-MRI for treating patients with AF.

Source: University of Utah Health Sciences

The transplant community was largely unaware of sub-standard transportation practices for donor organs until a number of fatal air crashes took the lives of transplant personnel, calling attention to procurement aviation safety. A new report highlighting the need for improved safety measures in organ procurement travel appears in the December issue of Liver Transplantation, a peer-reviewed journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases (AASLD).

In the U.S., the Organ Procurement and Transplantation Network (OPTN) is responsible for maintaining the national transplant waiting list which currently has more than 72,000 patients on the active wait list and only 8,477 donors. Given the scarcity of donor organs the need to quickly expedite their recovery and delivery to intended transplant patients is apparent. Many times procurement by air transport is necessary and at times dangerous due to nonstandard practices as John Renz, M.D., Ph.D., from the University of Chicago points out in his report.

Dr. Renz evaluated fatal and non-fatal procurement air accidents in the U.S. which were reported to the National Transportation Safety Board (NTSB). He found in one incident, a surgeon who was not licensed to fly at night attempted to do so and crashed on take-off, killing himself and a physician’s assistant. Other accidents involved pilot error such as runway overrun, mismanagement of an abnormal flight control situation, and lack of flight crew coordination. “No accident was associated with the processes of procurement,” said Dr. Renz. “It was the tolerance of dangerous operational practices, not found in commercial airline service, which contributed to the incidents.”

A prior study by Englesbe and Merion calculated that the procurement air travel fatality rate is 1000 times higher than commercial aircraft, speculating the “riskiest job in medicine” belongs to transplant surgeons involved in procurement transport. In his editorial also published in this month’s issue, Dr. Robert Merion, Professor of Surgery at the University of Michigan Health Systems and President of Arbor Research Collaborative for Health, adds, “We need better data on organ procurement travel and a commitment to zero tolerance policy for procurement-related travel accidents.” Dr. Merion, who lost four colleagues in a 2007 procurement flight crash which also claimed the lives of the two pilots, suggests the outcome of each procurement flight or ground transport be reported to the OPTN.

In his report, Dr. Renz also presents measures to create a “culture of safety” among those involved with organ transportation. He cites the use of quality aircraft, two-pilot crews, and aviation safety consultants as methods to improve safety. “Mandating turbine-powered, fixed wing aircraft, operated by reference to instruments under commercial flight regulations, to airports with continuous radar surveillance by two qualified pilots would ensure a level of competence and safety we expect with scheduled airline service,” concluded Dr. Renz.

While both the study and editorial stress a need for procurement travel standards, the two doctors disagree on feasibility and cost of implementation. The authors do agree that further evaluation is necessary and should ultimately result in national procurement transportation standards that will ensure the safety of those involved in the travel and continued service for transplantation patients awaiting donor organs.

Sources: Wiley – Blackwell, AlphaGalileo Foundation.

Just as the site for the 2013 America’s Cup has been announced, a study from Rhode Island Hospital highlights that the sport isn’t always smooth sailing. The study was published recently in the journal Wilderness and Environmental Medicine.

Through an on-line survey completed by sailors, researchers at Rhode Island Hospital have pieced together a report of the injuries that occur on two types of boats — dinghies (small boats with crews of one or two) and keel boats (larger boats like those used in the America’s Cup races with a crew of up to 16).

With a total of 1860 respondents, there were a total of 1715 injuries reported, with 79 percent of the sailors reporting at least one injury in the prior 12 months. Of the injuries reported, a large majority (71 percent) occurred on keel boats. The most common types of injuries on both keel boats and dinghies were contusions, lacerations and sprains. On keel boats, the upper and lower extremities accounted for 78 percent of all injuries, with another 11 percent occurring on the trunk. For dinghies, the upper and lower extremities again were most commonly injured sites, while the head and neck also accounted for 12 percent of the injuries.

The study, led by emergency medicine physician Andrew Nathanson, MD, of Rhode Island Hospital, found the most common causes of the injuries were trips and falls, being hit by an object, or being caught in the lines. The “objects” most frequently cited were the boom, spinnaker pole, sail clew (bottom rear corner) and collisions with fellow crew members. Tacking and jibing maneuvers also played a role in about a third of the injuries on both dinghies and keel boats. The most commonly cited activities that preceded the injury were crossing from one side of the boat to the other during a tack, changing the sails, operating a winch and steering.

Nathanson says, “It’s important to note that nearly half of the injuries reported were minor and required no treatment. Only four percent of the injuries were considered serious, and resulted in evacuation from the vessel and/or hospitalization.” Twenty-six percent of the injured sailors reported receiving first aid onboard while 33 percent sought medical care after the injury (although these groups are not mutually exclusive).

Of the 70 most serious injuries reported, 25 percent were fractures, 16 percent were torn tendons or cartilage, 14 percent were concussions and 8 percent were dislocations. The majority of severe injuries were to the head, knee, leg and arm. Three eye injuries were also reported that resulted in permanent loss of vision. Heavy weather was considered a contributing factor in 36 percent of the severe injuries.

Nathanson says, “What is most alarming about this survey is the fact that only 30 percent of the sailors who responded reported wearing a life jacket. According to the United States Coast Guard, two thirds of recreational boating deaths are caused by drowning. Lifejacket use rates can be increased not only by education but also by improving the aesthetics and comfort of jackets, and by enforcing use at regattas and sailing schools.”

Also of note, seven percent of the injured sailors reported that they consumed alcohol within two hours of sustaining an injury. Nathanson says, “While the effects of alcohol are dose-dependent, even low levels of alcohol use while boating is a potential problem.”

Nathanson reports that the survey also indicates falls while on board boats can likely be reduced by improved footwear and better anti-skid deck surfaces, less cluttered and more ergonomic deck layouts and adherence to the sailing maxim “one hand for the boat, and one hand for yourself.” The researchers also recommend protective head gear, padded spars and higher boom clearance as potential changes that can reduce sailing injuries.

Also of concern in the results of the survey is that 16 percent of the sailors reported having suffered a sunburn while sailing in the year prior. Nathanson says, “Sunscreen utilization was low, particularly in sailors less than 30 years old. Focused educational interventions should be developed aimed at sailors, particularly those in the younger age group, in order to reduce the risk of skin cancer. Participants in water sports have been shown to be at increased risk of skin cancer because of their prolonged exposure to solar radiation.”

The study was funded by the Bonnell Cove Foundation. Nathanson is an associate professor at The Warren Alpert Medical School of Brown University and also a physician with University Emergency Medicine Foundation. Other researchers involved in the study with Nathanson include Janette Baird, PhD and Michael Mello, MD, MPH, of Rhode Island Hospital’s Injury Prevention Center and Alpert Medical School.

Source:
Nancy Cawley Jean

Lifespan

The number of people with Alzheimer’s and dementia – both new cases and total numbers with the disease – continues to rise among the very oldest segments of the population in contradiction of the conventional wisdom, according to research reported today at the Alzheimer’s Association 2009 International Conference on Alzheimer’s Disease (ICAD 2009) in Vienna.

Previous epidemiological studies have suggested that the number of people with Alzheimer’s and dementia begins to level off and perhaps even go down a bit in people age 90 and above, known as the “oldest old.” This is the fastest growing segment of the population in western countries.

“The number of people affected by Alzheimer’s and dementia is growing at an epidemic pace, and the skyrocketing financial and personal costs will devastate the world’s economies and healthcare systems, and far too many families,” said William Thies, Ph.D., Chief Medical & Scientific Officer at the Alzheimer’s Association. “We must make the fight against Alzheimer’s a priority before it’s too late.”

“However there is hope. There are many drugs in late stage clinical trials for Alzheimer’s that show promise to slow or stop the progression of the disease. This, combined with advancements in early detection, has the potential to change the landscape of Alzheimer’s in our lifetimes. But we need more funding for research to see these possibilities through to completion,” Thies said.

The research reported at ICAD 2009 includes a study of more than 2,100 individuals age 80 years or older in eight municipalities of Varese province, Italy, and a systematic review and collaborative analysis of studies reporting the prevalence of dementia in Europe.

The Monzino 80-plus Study – Dementia Risk Continues to Rise in the “Oldest Old”

Ugo Lucca, head of the Laboratory of Geriatric Neuropsychiatry at the Mario Negri Institute for Pharmacological Research in Milano, Italy, and colleagues conducted a prospective, door-to-door, population-based study of all people age 80 years or older in eight municipalities of Varese province, Italy, roughly 30 kilometers (20 miles) north of Milan (known as the Monzino 80-plus Study). Their goal was to estimate the prevalence (total number with the disease) and incidence (new cases of the disease) of dementia in this population.

The researchers were able to gather information and an initial dementia evaluation for 2,138 individuals. The mean age of the population at that first evaluation was 87.5 years; 74.1% were women. Mean education was 5.1 years, and mean MMSE score was 21.4. After an average follow-up period of three years, of the 1,085 survivors non-demented at baseline, 995 were re-evaluated for dementia.

Prevalence of dementia standardized on the 2008 Italian population was 22.9% and was higher in women (25.8%) than in men (17.1%). Prevalence increased with advancing age:
13.5% at 80-84 years

30.8% at 85-89

39.5% at 90-94

52.8% over 94

The estimated annual incidence of dementia standardized on the 2008 Italian population was 8.6% and was higher in women (9.2%) than in men (7.2%). Incidence also rose with increasing age:
6.0% at 80-84 years

12.4% at 85-89

13.1% at 90-94

20.7% over 94

“Gathering reliable information on such a large number of the ‘oldest old’ makes this one of the largest studies investigating dementia in this age segment of the population,” Lucca said. “This study’s results confirm that Alzheimer’s and dementia are very common among the oldest people in society. We believe this strengthens the need to shift more of the focus of clinical research to this segment of the elderly population.”

According to the researchers, though the rate of women who developed dementia during the follow-up period was higher than in men in this study, no definite conclusion can be drawn about this difference because the number of men in the oldest ages became very small.

Systematic Review of Dementia in Europe – Higher Prevalence in Female “Oldest Old”

The goal of Dr. Emma Reynish, a consultant geriatrician and coordinator of the European Alzheimer’s Disease Consortium from the Victoria Hospital, Kirkcaldy, Scotland, UK, and colleagues at the EuroCoDe (European Collaboration on Dementia) project, was to determine the prevalence of dementia in Europe based on up to date research findings and including data from Eastern Europe. They conducted an extensive literature search using Cochrane review methodologies and compiled a database of all European epidemiological studies in the field up to the present date. 194 articles were identified by the review and 26 studies met inclusion criteria to participate with raw data in the collaborative analysis.

According to the researchers, while dementia prevalence rates for all men and for women up to age 85 confirmed previous findings, age-specific prevalence rates were higher than previously documented in the female “oldest old” age groups, rising to over 50% in those over 95 years.

“Our key findings confirmed that age remains as the single most important risk factor for dementia,” Reynish said. “Nevertheless, due to the lack of data in the oldest old in previous prevalence studies, the prevalence of dementia of women over the age of 85 had been underreported.”

About ICAD 2009

The 2009 Alzheimer’s Association International Conference on Alzheimer’s Disease (ICAD 2009) brings together more than 3,000 researchers from 70 countries to share groundbreaking research and information on the cause, diagnosis, treatment and prevention of Alzheimer’s disease and related disorders. As a part of the Association’s research program, ICAD 2009 serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community. ICAD 2009 is being held in Vienna, Austria at Messe Wien Exhibition and Congress Center from July 11.

About the Alzheimer’s Association
The Alzheimer’s Association is the leading voluntary health organization in Alzheimer care, support and research. Our mission is to eliminate Alzheimer’s disease through the advancement of research, to provide and enhance care and support for all affected, and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer’s.

Ugo Lucca, et al – Risk of dementia continues to rise in the oldest old: The Monzino 80-plus Study (Funder: Fondazione Italo Monzino (Milano, Italy))

Emma Reynish, et al – Systematic Review and Collaborative Analysis of the Prevalence of Dementia in Europe (Funder: European Commission, coordinated by Alzheimer Europe)

Control #: 09-A-1144-ALZ P3 – Tuesday Posters – Presentation #P3-168; Speaking Time: 7/14/2009, 12:30 – 3:00 PM

Risk of dementia continues to rise in the oldest old: The Monzino 80-plus Study

Ugo Lucca, Mariateresa Garrì, Alessandro Nobili, Luca Pasina, Francesca Gandini, Emma Riva, Mauro Tettamanti Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.

Disclosure Block: U. Lucca, None; M. Garrì, None; A. Nobili, None; L. Pasina, None; F. Gandini, None; E. Riva, None; M. Tettamanti, None.

Background: Most dementia sufferers are eighty years or older, the fastest growing segment of the elderly population in western countries. Because of the small number of persons in this age class usually included in population-based studies, prevalence and incidence estimates fluctuate widely in the oldest old, making it hard to establish whether the risk of dementia (and Alzheimer’s disease) continues to rise also at very high ages.

Objective: To estimate the prevalence and incidence of dementia (mild+) in a prospective, door-to-door population-based study of all eighty years or older residents in eight municipalities of Varese province, Italy (the Monzino 80-plus Study).

Methods: Among the 2,436 eligible residents, information could be gathered for 2,138 individuals (response rate: 87.8%). Of the 1,085 survivors non-demented at baseline, 995 (91.7%) were re-evaluated after an average follow-up period of 3 years. Diagnosis of dementia was based on DSM-IV criteria.

Results: Mean age of the population at baseline evaluation was 87.5 (SD: 4.8) years and 74.1% were women. Some 32% lived alone and 11.5% in an institution. In the whole population, mean education was 5.1 (2.5) years, mean MMSE score 21.4 (7.6), and mean percentage of dependence on IADL 48.5% (36.9%). Prevalence of dementia standardized on the 2008 Italian population was 22.9% (95% CI: 21.1-24.7) and was higher in women 25.8% (95% CI: 23.7-28.1) than in men 17.1% (95% CI: 14.0-20.5). Prevalence increased with advancing age: 13.5% at 80-84 years, 30.8% at 85-89, 39.5% at 90-94, and 52.8% over 94. The number of person-years of observation was 3,110. The estimated annual incidence of dementia standardized on the 2008 Italian population was 8.6% (95%CI: 7.6-9.7) and was higher in women 9.2% (95% CI: 8.0-10.6) than in men 7.2% (95% CI: 5.5-9.2). Incidence as well rose with increasing age: 6.0% at 80-84 years, 12.4% at 85-89, 13.1% at 90-94, and 20.7% over 94.

Conclusions: Although not exponentially, the overall prevalence and incidence rates of dementia continue to rise also in very old age.

Control #: 09-A-1781-ALZ P3 – Tuesday Posters – Presentation #P3-168, Speaking Time: 7/14/2009, 12:30 – 3:00 PM

Systematic Review and Collaborative Analysis of the Prevalence of Dementia in Europe

Emma Reynish1,2, Horst Bickel3, Laura Fratiglioni4, Andrzej Kiejna5, Martin Prince6, Jean Georges7, EUROCODE Prevalence Group

1Victoria Hospital, Kirkcaldy, United Kingdom; 2Toulouse University Hospital, Toulouse, France; 32 Klinik und Poliklinik fГјr Psychiatrie und Psychotherapie der Technischen, Munich, Germany; 4Karolinska Institute, Stockholm, Sweden; 5Department of Psychiatry, Wroclaw, Poland; 6Institute of psychiatry, London, United Kingdom; 7Alzheimer Europe, Luxembourg, Luxembourg.

Disclosure Block: E. Reynish, None; H. Bickel, None; L. Fratiglioni, None; A. Kiejna, None; M. Prince, None; J. Georges, None.

Background: An accurate estimate of the numbers of individuals affected with dementia is essential. Previous collaborative work from Europe is based on studies performed 20 years ago. This current project aims to determine the prevalence of dementia in Europe based on up to date research findings and includes data from Eastern Europe.

Methods: A systematic review followed by collaborative analysis of studies reporting the prevalence of dementia in Europe. Medline and Embase searches were performed using the search terms “Dementia / Prevalence / Incidence / Epidemiology” and/or “Alzheimer’s Disease / Vascular dementia, Lewy-body disease / Fronto-temporal dementia / Incidence / Prevalence / Epidemiology. A database of studies was compiled and those fulfilling predetermined quality criteria were invited to submit data for collaborative analysis. Age and sex specific prevalence’s were calculated using the total number of prevalence cases from all studies as the numerator and total population examined as the denominator.

Results: A total of 194 articles were identified by the review and 26 studies met inclusion criteria to participate with raw data in the collaborative analysis. Calculated age specific prevalence rates for men confirmed previous findings with rates rising from 1.8% in the 65-69 years age range up to 30% in the over 90 years age group. For women confirmation of previous findings was also true for the 65 to 85 years age ranges with 5 year age specific rates rising from 1.5% to 30% respectively. Age specific prevalence rates were however higher than previously documented in the female oldest old age groups rising to over 50% in those over 95 years.

Conclusions: Epidemiological studies of dementia prevalence in Europe continue to show constant rates in all age ranges with the female oldest old being the exception. Here estimates show a higher than previously reported prevalence in females.

Source:
Niles Frantz

Alzheimer’s Association

In a feature article in The New Republic, Daniel Callahan and Sherwin Nuland propose a radical reinvention of the American medical system requiring new ways of thinking about living, aging, and dying. They argue that a sustainable-and more humane- medical system in the U.S. will have to reprioritize to emphasize public health and prevention for the young, and care not cure for the elderly.

An interesting twist on their argument, which would aim to bring everyone’s life expectancy up to an average age of 80 years but give highest priority for medical treatment to those under 80, is that Callahan and Nuland are themselves 80 years old. Daniel Callahan, Ph.D., is cofounder and president emeritus of The Hastings Center and author most recently of Taming the Beloved Beast: How Medical Technology Costs Are Destroying Our Health Care System. Sherwin Nuland, M.D., is a retired Clinical Professor of Surgery at the Yale School of Medicine and author of How We Die and the Art of Aging. He is also a Hastings Center Fellow and Board member.

“The real problem is that we have medicine excessively driven by progress, which aims to rid us of death and disease and treats them as the targets of unlimited medical warfare,” said Callahan and Nuland. “That warfare, however, has come to look like the trench warfare of World War I: great human and economic cost for little progress. Neither infectious disease nor the chronic diseases of an aging society will soon be cured. Cancer, heart disease, stroke, and Alzheimer’s disease are our fate for the foreseeable future. Medicine and the public must adapt it to that reality, one that has mainly brought us lives that end poorly and expensively in old age.”

The article notes that the Affordable Care Act might ease the financial burden of this system, but not eliminate it. It reports, for example, that the cost of Alzheimer’s disease is projected to rise from $91 billion in 2005 to $189 billion in 2015, and to $1 trillion in 2025 – twice the cost of Medicare expenditures for all diseases now.

“We need to change our priorities for the elderly. Death is not the only bad thing that can happen to an elderly person,” the authors write. “An old age marked by disability, economic insecurity, and social isolation are also great evils.” They endorse a culture of care, not cure, for the elderly, with a stronger Social Security program and a Medicare program weighted toward primary care that supports preventative measures and independent living.

Callahan and Nuland point the way to a more sustainable path that reprioritizes the entire system. Among their recommendations:

– improve medicine at the level of public health and primary care, while reducing its use for expensive high-tech end-of-life care;

– shift resources for the elderly to greater economic and social security and away from more medical care;

– subsidize the education of physicians, particularly those who go into primary care, and decrease medical subspecialization;

– train physicians better to tell the truth to patients about the way excessively aggressive medicine can increase the likelihood of a poor death;

– shift the emphasis in chronic disease to care rather than cure;

– conduct a top-down, bottom-up, long-range study of the entire American system of health care, including the training of physicians, with a view toward reconstituting it along systematic lines that take science, humanistic concerns, economics, and social issues into account.

Source:

The Hastings Center