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Recently, there has been increasing interest in the role of sports head injuries and subsequent cognitive decline. For instance, American football players are being scrutinized more closely because of new research suggesting close links between repeated concussion and decline in cognitive abilities.

Complaints by professional players are now being taken seriously, as associations all over the country begin to take action.

“I’ve had times where I walked up to the line, where I know the play, but don’t know what to do.” – Oakland Raiders tight end Tony Stewart

“I’ve known of players hiding concussions..Sometimes players aren’t real sure.  They hit their head, they get a little cuckoo for a little while.  It happens all the time.” – Kansas City Chiefs center Rudy Niswanger

Over the last three decades, there has been much work on the relationship between head injury (usually single head injury) and Alzheimer's disease (AD) and other dementias. Many well designed, population based studies have suggested a link between head injury and the development of AD and other dementias. However, there are many discrepancies between these studies and the risk attributed to head injury has varied widely between them. Several key factors are often examined in these studies to try to understand better the relationship between traumatic brain injury (TBI) and AD.

The following areas have been studied extensively:

1.      The Gender Effect:  Despite the many case control and cohort studies, none have shown an increased risk for AD after TBI for women. Although many TBI studies focus on the male population who are more at risk (for instance, in contact sports or in the military) the finding that women are at no increased risk of AD after TBI suggests that there may be a protective effect of female hormones against the development of AD after head injury.

2.      The degree of injury and subsequent development of AD or related disorders: Few studies have adequately assessed the degree of injury and so information in this area is limited but, the studies that have, in general, suggest that more moderate or severe injuries predispose to dementia later in life. For instance, one study divided TBI into mild, moderate, and severe categories:  injuries with loss of consciousness (LOC) or post-traumatic amnesia (PTA) of less than 30 minutes (mild); of more than 30 minutes but less than 24 hours (moderate); and of more than 24 hours (severe). Most studies suggested moderate and severe disease is more related to AD and that full recovery of cognitive loss can be regained after mild TBI.

3.      Time of injury to the development of subsequent dementia:  This relationship has been studied in large populations and there are good data to suggest that TBI in old age is associated with worsening of outcome compared to TBI at a younger age. Nevertheless, even individuals that have TBI in early adulthood (if the injury is severe enough) are at increased risk of AD and other dementias as many as five decades later.



One key question is how the brain "remembers" the injury for so many years and why there may be no signs of cognitive impairment soon after the injury for many decades until AD onsets. The question of the molecular underpinnings of TBI and how the brain continues to register that an injury has occurred is an area of intense study.

One such candidate for molecular memory is amyloid.  The amyloid molecule is increased in the brains of AD sufferers and occurs early in the pathological sequence that leads to full-blown AD. Most studies show that only about one-third of TBI victims have amyloid at autopsy.  Although amyloid is produced acutely after TBI, much of that amyloid does not stay in the brain but is degraded in the weeks and months following injury.

Another pathological molecule central to the AD process is tau.  Tau protein is formed when neurons die.  Although tau has been implicated in TBI, again, there are inconsistent data between studies -- some showing no increased involvement of tau while others show hyperphosphorylation and/or aggregation of tau. More recently in repetitive head injury (for instance, those occurring in American football) tau has been implicated as it has been seen particularly around blood vessels in the brain.

Whatever the ultimate underlying cause of the link between TBI and the subsequent development of AD, we can expect that once those links are fully uncovered, they will become new targets for the prevention of AD following TBI.

One other area that deserves attention is the genetic risk for poor recovery after TBI and subsequent risk for AD. Although it is generally accepted that APOE4 is a risk factor for AD, some studies of head injury have been equivocal in demonstrating that APOE4 acts synergistically with TBI to increase risk for AD.

However, given the plethora of data on the negative roles of APOE4 in the brain after TBI, it is safe to assume that individuals who carry the E4 are most probably at greater risk for developing AD than those who do not. It has been advocated that those individuals carrying an APOE4 allele should not engage in professions or pastimes with increased risk of TBI.

Much more work is needed in this area; but, at this stage, as a precaution, this is probably a position that can be easily endorsed.

Dr. Michael Mullan is the president of Sci-Brain. A company providing personalized program to reduce risk of Alzheimer's disease and improve your Brain Health.


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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
 
 
_ Two distinct patterns in of brain damage predicted by studies one studying how brain circuits wire up structurally in their natural manner and the other their functional connections, converged on a remarkably similar model which predicted the sites of degeneration in each forms of dementia .These studies have been proved significant since the models to predict and study the human neural degeneration has remained elusive.  Neurodegenerative process is thought to involve the accumulation of abnormal toxic proteins and the spread of these toxic proteins between neurons, which may be contagious through their synaptic connections.

http://www.todaysseniorsnetwork.com/diabetes_impact_dementia_brain_patterns.htm

http://www.ncbi.nlm.nih.gov/pubmed/17267521
 
 
_ The early ideas dealt with the antioxidant’s and CSF biomarkers have been proved wrong. Recent studies reveal that there is no association between an antioxidant combination of vitamin E, vitamin C and α-lipoic acid (E/C/ALA) and the changes Alzheimer’s related biomarkers in the cerebrospinal fluid. Oxidative impairment is linked to aging and is common in individuals with Alzheimer's disease but the risk can be reduced by diet rich in antioxidants.

http://www.medicalnewstoday.com/articles/243194.php
 
 
_  Studies on Brain imaging suggest that Alzheimer’s and other forms of most prevalent dementia’s may spread within nerve networks in the brain by moving directly between connected neurons, in a way  by propagating in all directions. Studies concluded that a nerve region's connectedness to a disease hot spot trumps overall connectedness, spatial proximity and loss of growth-factor support in predicting its vulnerability to the spread of Alzheimer’s.

http://memory.ucsf.edu/blog/alzheimer%E2%80%99s-disease-spreads-through-linked-nerve-cells-brain-imaging-studies-suggest-522/

 
 
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Model of Alzheimer's Amyloid Beta Peptide as done at Dr. Michael Mullan's research group.
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Roskamp Research Scientists Dr. Paris, Dr. Michael Mullan and others have discovered novel anticancer activity for a shortThe inhibition of angiogenesis is regarded as a promising avenue for cancer treatment. Although some antiangiogenic compounds are in the process of development and testing, these often prove ineffective in vivo, therefore the search for new inhibitors is critical. We have recently identified a ten amino acid fragment of the Alzheimer Abeta peptide that is anti-angiogenic both in vitro and in vivo. In the present study, we investigated the antitumoral potential of this decapeptide using human MCF-7 breast carcinoma xenografts nude mice. We observed that this decapeptide was able to suppress MCF-7 tumor growth more potently than the antiestrogen tamoxifen. Inhibition of tumor vascularization as determined by PECAM-1 immunostaining and decreased tumor cell proliferation as determined by Ki67 immunostaining were observed following treatment with the Abeta fragment. In vitro, this peptide had no direct impact on MCF-7 tumor cell proliferation and survival suggesting that the inhibition of tumor growth and tumor cell proliferation observed in vivo is related to the antiangiogenic activity of the peptide. Taken together these data suggest that this short Abeta derivative peptide may constitute a new antitumoral agent.

For more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

http://www.michaelmullan.us

www.rfdn.org