The Enigma of Alzheimer’s Disease: Studies Proving Positive for Brain Injury Patients

In an IDGA exclusive interview, Dr J Wesson Ashford, MD, PhD, explores the current research focus and insights the War Related Illness and Injury Study Center. Chris Archer (IDGA): Dr Ashford, can you start by telling me about your current research focus? Dr Ashford: During most of my career, the major focus of my research has been on the functions of the temporal lobe of the brain and memory mechanisms. After early interests in sleep, pain, and temporal lobe epilepsy, in 1978 I turned my attention to Alzheimer’s disease, which is primarily a disease of memory mechanisms and the temporal lobes of the brain. Much of my work has been on measuring memory function and dementia severity, diagnosis of Alzheimer’s disease including brain imaging and genetic factors, and considering approaches to prevention and treatment of this increasingly common condition. In 2007, I was asked to direct the War Related Illness and Injury Study Center at the VA Palo Alto Health Care System. Since that time, I have been working with Veterans from the First Gulf War and their multiple unexplained symptoms, evaluating Veterans with mild traumatic brain injury as a diagnostic problem, and studying post-traumatic stress disorder including the issues of cause and treatment. [eventPDF] Chris Archer: What has your research of memory screening and Alzheimer’s disease taught us about brain injuries and the need for improved post-combat screening? Dr Ashford: We have learned that the brain is primarily an organ for memory. New perceptions are all analyzed with respect to the entirety of a person’s memories, and if the information is new, it is stored in the memory banks of the brain. As we view the world, we are constantly reviewing our memories to understand what we perceive, and we then retrieve actions and ideas that we have learned in the past to develop new ideas and actions. Alzheimer’s disease, which ends up affecting over one in four individuals in the US, attacks our ability to store new information and eventually destroys our memory banks entirely. The initial signs of the Alzheimer-type dementia are usually impairments of the ability to learn new information and are specifically related to the appearance of Alzheimer pathology in the medial temporal lobe of the brain. This problem can be detected very quickly with simple memory tests. One of the main problems associated with traumatic brain injury is disruption of memory, and this memory problem is also likely due to disruption of the function of the medial temporal lobe, which coordinates the storage of new information. Accordingly, the memory screening tests developed for Alzheimer’s disease can be adapted to be a sensitive tool for detecting memory dysfunction associated with traumatic brain injury. Measurement of cognitive function should be done before entering combat and on return to determine whether any significant injury to brain or mental function has occurred during the combat experience. Chris Archer: Tell us about MemTrax.net – what are the main aims of the application? Dr Ashford: Since I began developing the thesis for my dissertation in 1979, while simultaneously managing geriatric in-patients with a likely diagnosis of Alzheimer’s disease, I sought to understand the aspect of memory disruption most specific to Alzheimer’s disease and develop a test for that specific type of memory process. Between 1985 and 1990, I developed a test that could be performed by both monkeys and presumed Alzheimer patients that involved the viewing of a complex picture and then recognizing that picture. The test was redesigned in 1999 to be a slide show in which the only required answer is the indication that a repeated slide is recognized. This test, referred to now as MemTrax, can be given as a slide show to an audience, administered by computer directly to a patient, or taken by anyone using the Internet. The test is very sensitive to memory problems, particularly those related Alzheimer’s disease. The test cannot be considered diagnostic since the specificity is lowered by many problems, including age related difficulties such as visual impairment and arthritis. The test is also available in more difficult forms on the web for younger individuals, and reaction-time measurements can give a clear indication of the efficiency of brain recognition mechanisms. As an "APP" for hand-held computers or cell-phones, this test can determine within two minutes if a person is having memory difficulties or has experienced a sudden decline of memory function, as might be caused by a traumatic brain injury. A major advantage of the MemTrax test is that it is as fun as many computer games, and subjects are willing to retake the test repeatedly, but show essentially no significant change in measurements under normal conditions. The MemTrax test/game can be found at: www.memtrax.net Chris Archer: At the conference you’re presenting on neuropsychiatric issues in the diagnosis, management, and rehabilitation of TBI – what are the main issues we’re seeing in post-combat patients? Dr Ashford: Correct, I will be discussing neuropsychiatric issues that are problematic for soldiers returning from combat. Combat stress – soldiers frequently experience fear and horror during combat. These experiences, particularly when severe and/or prolonged, can lead to Post-Traumatic Stress Disorder (PTSD). Traumatic brain injury – when soldiers are near a blast or strike their head, the brain can be damaged. The damage can cause: a variety of cognitive problems, including memory difficulties, attention deficits, language and other communication impairments, and disorders of visual-spatial cognition, several neurobehavioral problems, including mood dysregulation (depression, mania), PTSD, and psychosis, sensory losses, potentially affecting smell, vision, hearing, and balance, and somatic complaints, including pain (chronic headache), loss of libido (decreased sexual interest), fatigue, and sleep irregularities. Toxic exposures – industrial chemicals/solvents, environmental contaminants (burn pits), vaccinations, and chemical warfare agents (nerve gas) can cause unknown mental and cognitive problems. Infectious exposures – malaria (and the drugs used to prevent it), tropical diseases (leishmaniasis, Q-fever, sandfly fever, etc.), as well as diarrhea (and all of the possible long-term complications) can all have effects on the brain and cause long-term psychiatric and psychological problems. Non-neurologic injuries, including losses of limbs, vision, hearing, scars, and genital damage, can have major impacts on psychological function. Separation from social networks, family, and friends can lead to psychological reactions that can have long-term consequences. Suicidal ideations, intentions, and actions are experienced most frequently by young-adult males and these thoughts and acts are associated with particularly high lethality in soldiers returning from combat. Such problems are frequently associated with substance dependence. Chris Archer: How does your study of neuropsychiatry contribute to combating adverse effects of TBI? Dr Ashford: The adverse effects of TBI must be addressed by first understanding the nature of the brain injury. We are particularly interested in applying the latest brain imaging technology (many MRI scan techniques and PET scanning) to determine specific areas of the brain that are injured. Once a brain injury is precisely identified, then directed rehabilitation techniques can be applied to help the Veteran overcome the deficits caused by that brain injury. With all of these conditions, the important issue is to recognize the problems and find professional support, most readily available at VA hospitals and centers, to diagnose and manage conditions that are associated with impaired life function as well as substantial morbidity and mortality. In the VA and particularly at War Related Illness and Injury Study Center (with sites at East Orange, New Jersey, Washington, DC, and Palo Alto, California), we are expert in addressing the issues of combat Veterans and helping them to re-assimilate to a healthy civilian life.

The Enigma of Alzheimer’s Disease: Studies Proving Positive for Brain Injury Patients

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