A new study by researchers at the Albert Einstein School of Medicine dramatically underscores the potential role of the NF-kB protein in aging. NF-kB is a master protein which controls many inflammatory chemicals throughout the body. Researchers at the Roskamp Institute have studied NF-kB for many years as a potential way of controlling chronic inflammation which accompanies aging and underlies conditions such as Alzheimer’s disease. This new study points to a part of the brain as regulating the aging process. The current view of aging generally suggests that enzymes, DNA, proteins and other constituents of the body essentially “wear out” with age, accumulating damage due to environmental insults until they no longer function properly. This new study suggests something quite different, namely that a part of the brain called the Hypothalamus deliberately induces aging throughout the body. It has been suggested that one reason why the brain might take such drastic action is to inhibit reproduction past a certain age. This suggestion is highly speculative at this stage, but the data offered by the Albert Einstein researchers suggests that, with age, increased NF-kB activity triggers degeneration in both the brain and other areas of the body. The researchers showed that as mice aged, they increasingly expressed NF-kB in the part of the brain that is normally responsible for the production of reproductive and growth hormones. The researchers artificially manipulated NF-kB activity using genetic techniques and showed that reducing NF-kB activity was associated with better performance in cognitive tests, greater muscle strength and greater bone mass and skin thickness. Conversely, exacerbation of NF-kB activity increased all of these peripheral signs of aging, as well as reducing cognitive abilities. Furthermore the research suggested that microglia (the inflammatory cells resident in the brain) are the originators of the NF-kB activity and this spreads to nearby neurons, including those responsible for growth and reproductive hormones. These findings are of direct significance to work at the Roskamp Institute as researchers there have shown that increased NF-kB collates strongly with Alzheimer’s pathology and pathology of other central nervous system disorders. Moreover, they have worked extensively on ways to reduce NF-kB activation, particularly using the naturally occurring compound Anatabine.  Roskamp Institute researchers have shown in multiple preclinical studies of neuroinflammation (such as Alzheimer's, traumatic brain injury and Multiple Sclerosis) that Anatabine (supplied by RockCreek Pharmaceuticals) has potent anti-inflammatory properties. This new finding suggests that NFKB inhibitors might also have a role in decelerating aging. In fact,  preliminary studies at the Roskamp Institute suggest that mortality in mice with Alzheimer pathology is reduced by Anatabine treatment. Additional studies are needed to clarify whether Anatabine might reduce the Hypothalamic inflammation and increase the release of hormones that oppose aging.

Dr. Michael Mullan M.D., Ph.D
President & CEO
Roskamp Institute
 
 
A recent study suggests that consuming cocoa flavanols as part of a regulated diet could improve cognitive function. This study, conducted by researchers at the University of L’Aquila in L’Aquila, Italy, was published on August 14 in Hypertension.

Flavanols are a class of flavonoids (plant secondary metabolites with medicinal properties) that are abundant in teas, berries, apples, grapes, red wine, and chocolate. Flavanols can work as an antioxidant. This study involved 90 elderly participants with mild cognitive impairment (MCI), a condition that increases the risk of developing Alzheimer’s or some other form of dementia. The 90 patients were each randomized to consume a dairy-based cocoa flavanol drink of different amounts (990 milligrams, 520 milligrams, or 45 milligrams) for eight weeks. Their diet was cut off of other sources of flavanols. After eight weeks, they participated in neuropsychological tests, and results showed that those in the groups who drank higher levels of cocoa performed significantly higher in the tests than those who drank lower levels of cocoa. Those given the drinks with higher flavanol content also had decreased insulin resistance, blood pressure, and oxidative stress. The decreased insulin resistances levels contributed to 40 percent of the higher results in the cognitive tests.

However, the researchers acknowledge that this was just a small preliminary study that requires larger long-term studies before the results can be confirmed. They still need to determine the amount of cocoa flavanols needed to obtain the benefits and how long these benefits will last. While flavanols has the potential to help improve cognitive function as part of a healthy diet, it is discouraged that people should consume chocolate everyday because of this study.

Sources: http://www.healthcare-today.co.uk/news/cocoa-could-keep-dementia-at-bay/22509/

               http://www.alzheimers.org.uk/site/scripts/news_article.php?newsID=1295

Keywords: cocoa; flavanols; mild cognitive impairment (MCI); research

Wendy Liu

August 14, 2012

 
 
The Roskamp Institute researchers are in search of new treatments for traumatic brain injury (TBI) to help out the veterans of the country. An article in the New England Journal of Medicine has called attention to the number of medical aftereffects of TBI in the American soldiers returning from Iraq. This was revealed through a survey of more than 2,500 soldiers returning from Iraq. Five percent of them stated that they suffered injuries with loss of consciousness, while ten percent said they had injuries that resulted in changed mental status, and another seventeen percent reported other injuries during their deployment. Of the five percent who reported loss of consciousness and of the ten percent who reported altered mental status, 45 percent and 27 percent met the criteria for Post Traumatic Stress Disorder (PTSD), respectively.

The conclusion of the article revolved around the close link between mild TBI, experienced by the veterans from Iraq, with PTSD and physical health problems three to four months after the soldiers come home. In addition, both PTSD and depression serve as mediums for the relationship between mild TBI and physical health issues.

TBI initiates degenerative pathways; researchers at Roskamp are using this knowledge to discover which genes and proteins are connected with these pathways to seek for new treatments for TBI.

For the original article, please visit http://www.roskampinstitute.us/articles/archives/27.

For more information on TBI, please visit

http://www.rfdn.org
http://www.roskampinstitute.us
http://www.michaelmullan.us
http://www.michaelmullangroup.com

Wendy Liu

July 30, 2012

 
 
With Alzheimer’s disease (AD) being the most common type of dementia among the 35 million patients suffering from dementia cases worldwide, the battle to find a drug to at least slow down this disease is becoming more urgent each day. While current medicines do ease the symptoms of AD, none of them delay, stop, or reverse the cognitive and behavioral decline of AD. In recent news, a drug called bapineuzumab, that hoped to improve the cognitive and life functions of the patients participating in the trial, has failed its first of four clinical trials. The 1,100 patients in this late-stage study have mild to moderate cases of Alzheimer’s, and each has a variation of the gene, ApoE4, which increases the chances of developing AD. About half of AD patients have this gene. Bapineuzumab is an antibody based drug that targets beta-amyloid, a protein which scientists believe to be the cause of AD. The failure of this trial may be due to the high risk patients, as well as the fact that the drug is being tested too late into the disease. Jointly created by Pfizer and Johnson & Johnson, it has been announced that Johnson & Johnson will carry out the remaining three clinical trials, with one involving ApoE4 and the other two with patients without the gene. The results of these remaining trials will be presented at a neurology conference in Sweden this September. For more details and news about this study as well as Alzheimer’s disease, please visit:

http://www.washingtonpost.com/business/pfizer-alzheimers-disease-drug-fails-in-1-study-2nd-study-in-different-patients-continues/2012/07/23/gJQAB7K64W_story_1.html

http://www.rfdn.org
http://www.roskampinstitute.us
http://www.michaelmullan.us
http://www.michaelmullangroup.com

Keywords: Alzheimer’s disease; bapineuzumab; ApoE4

Sources: http://www.washingtonpost.com/business/pfizer-alzheimers-disease-drug-fails-in-1-study-2nd-study-in-different-patients-continues/2012/07/23/gJQAB7K64W_story_1.html

http://www.nytimes.com/2012/07/24/business/alzheimers-drug-fails-its-first-clinical-trial.html

You can follow updates on clinical trials at the Roskamp Institute Website: http://www.rfd

Wendy Liu

July 24, 2012

 
 
Research has shown that nearly two-thirds of dementia cases of patients over 60 in the Western Hemisphere are cases caused by Alzheimer’s disease.  This correlation with age continues as the frequency of Alzheimer’s nearly doubles by five year increments after the age of 65.To gain a better understanding of this prevalence, scientists are looking into the amyloid-b precursor protein (APP) gene which has shown to have a significant effect in those with Alzheimer’s disease.  Through their research, derived from 1,795 Icelandic citizens, scientists have discovered a mutation in the APP gene that safeguards individuals from cognitive deterioration and Alzheimer’s disease. Because mutations on this site (A673T allele) also prevents cognitive decline in patients without Alzheimer’s, this suggests that the two conditions may be controlled by or related through the same mechanisms. 

Patients enrolled in this study were registered through the Memory Clinic at Landspitali University Hospital and the cognitive condition was assessed through the Minimum Data Set (MDS) for nursing homes.  Genotypic data was then collects for the APP site A673T for all 1,763 patients.  This data reveals that this site on APP is vital to the production of amyloid plaque, making it able to protect patients from the cognitive decline seen in Alzheimer’s and non-Alzheimer’s patients.  These results make this mutation the first genetic variant discovered that can create a strong shield from Alzheimer’s disease.  It also confirms  the hypothesis that the pathogenesis of regular cognitive deterioration and Alzheimer’s disease may be partially related, suggesting that Alzheimer’s disease may be the driving force of the correlation between age and decline in cognitive function.

By Alec Waid, Intern Roskamp Institute