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Can a Blow to the Head Cause Alzheimer's Disease?

By Samuel A. Scott, Ph.D.*
(Reprinted with permission from the Winter 2001 T.I.E.S Newsletter from the Omaha and Eastern Nebraska , also serving Southwestern Iowa, Chapter of the Alzheimer's Association - now known as the Midlands Chapter.)
Head trauma is viewed by many as another potential contributing factor in this disorder ..."


Chronic traumatic brain encephalopathy, or dementia pugilistica ("punch drunk syndrome"), has long been known to occur in athletic boxers and, to a lesser extent, in soccer players. Owing to the delayed dementia in a subset of individuals who fist fight for a living, the American Medical Association (AMA) recommended a ban on boxing over a decade ago. Obviously, the sport continues.

This particular cause of head trauma, or traumatic brain injury (TBI), also appears to cause some of the brain abnormalities observed in individuals who die with Alzheimer's disease (AD) - in particular neurofibrillary tangles; b-amyloid-containing senile plaques; loss of cholinergic basal forebrain cells (such as the target of all three current Food and Drug Administration-approved drugs used to treat the disorder).

In general, Traumatic Brain Injury (TBI) is viewed as a risk factor for Alzheimer's based on studies revealing a higher incidence in individuals pre-exposed to head trauma. In many such individuals, the brain contains "diffuse plaques," such as those without a compact amyloid core but containing b-amyloid fibrils. This type of plaque is thought by some to be an "early" form of amyloid deposit in Alzheimer's. Diffuse plaques typically occur in one out of three individuals who expire due to head trauma. Furthermore, the neurofibrillary tangles in individuals who die from the acute or prolonged effects of head trauma are identical to those suffering from Alzheimer's disease, suggesting a similar etiology (cause) among the two lesions. Therefore, at least some cases of head injury may disrupt the brain such that it resembles that of a patient who died from Alzheimer's disease "alone."

Interestingly, the occurrence of Alzheimer's disease-like pathology in individuals with head trauma increases with age (if the injury was due to a fall, the incidence is even higher). Individuals who die within hours or days of traumatic brain injury already have plaque-like deposits containing b-amyloid upon brain autopsy. One proposed mechanism to account for these deposits is overproduction of the precursor to b-amyloid - namely, b-amyloid precursor protein, or b-APP. A similar sequence is thought to explain the development of senile plaques in families who are genetically predisposed to b-amyloid overproduction (although such families account for a tiny fraction of Alzheimer's disease cases). For these and other reasons, head trauma and the pathogenesis of Alzheimer's disease are thought to be somehow related.

Most recently it has been shown that the more severe the head injury, the greater the likelihood of developing Alzheimer's disease, at least among military veterans (Neurology, October 24th, 2000). This study used a large sample of retrospective data based on 1,776 individuals with and without head injury. The main finding was that "moderate" and "severe" forms of traumatic brain injury- involving unconsciousness of more than 30 minutes or, more than 24 hours, respectively - significantly increased the incidence of Alzheimer's disease. A growing body of animal research also suggests that traumatic brain injury can produce one or more of the lesions used to diagnose Alzheimer's disease.

Does this necessarily mean that head injury can cause Alzheimer's disease? Unfortunately, the evidence is still unclear. Most cases of Alzheimer's disease cannot be attributed to any specific event or events in the past, including head trauma. In fact, while plaques and tangles themselves are used to diagnose the disorder neuropathologically, neither lesion is actually known to produce Alzheimer's disease-related dementia.

Head trauma is viewed by many as another potential contributing factor in this disorder, one that may act in concert with other agents such as genetic predisposition, environment, lifestyle, etc. The role of head trauma as a risk factor for Alzheimer's Disease is likely to receive continued research attention for the next several years.

* Dr. Scott is a member of the Board of Director's and the Scientific Advisory Board of the Midlands Chapter (formerly the Omaha and Eastern Nebraska, also serving southwestern Iowa chapter) of the Alzheimer's Association. He is an assistant professor in the Department of Physical Therapy at Creighton University.

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