Alzheimer’s Disease: Early Diagnosis (Part VI)

Mental decline with aging is probably of a heterogeneous origin, manifesting itself as a symptom in many diseases as well as a normal process of aging. Any method that could identify the decline at an early stage, and pinpoint the pathology would allow for greater benefit in the treatment process. Since we appear to have some drug therapies (Aricept, Tacrine) which slow cognitive decline progression on Alzheimer’s disease, it follows that these therapies may prove more effective if used early on in the disease. Thus the search for early neuroanatomical and pathophysiological signs. At the same time, researchers will have to tease out those who have Alzheimer’s disease from other forms of cognitive decline on a more direct basis. A step in this direction appears to have been made by Dr. Scott A. Small, a neurologist at the Sergievsky Center and Columbia Presbyterian Medical Center, New York, who presented preliminary findings at the annual meeting of the American Academy of Neurology in Toronto.

Dr. Small and his group, using a functional magnetic resonance imaging device, found two distinct patterns within the hippocampus of the brain. Specifically, he studied the entorhinal cortex, finding that nondemeted but with minor cognitive impairment elderly showed functional changes associated with a clinical diagnosis of Alzheimer’s disease. Could this be the site of the first stages of the disease, still at a subclinical level? The object now is to follow these individuals over a period of time and see if they develop AD and distinguish between those that do and those that do not develop Alzheimer’s disease. The important part of this study is that each individual acts as his/her own control. A base line structural and functional image is established and changes are monitored over time and compared with base line.

Thus, Alzheimer’s disease would appear to typically start in the entorhinal cortex, spread to other parts of the hippocampus and than progress to the temporal cortex, parietal cortex, and frontal cortex. What the functional magnetic resonance imaging does is to provide a better look at smaller parts of the brain as they are being activated providing evidence of the progressive nature of this disease.

There is growing need of evidence that can distinguished Alzheimer’s disease from other dementias because drugs used to treat Alzheimer’s disease may not be effective in treating other dementias—even may worsen the condition. There is no gold standard for diagnosis of Alzheimer’s disease except on autopsy where an accumulation of neurofibrillary tangles and plaque density are found as a distinguishing marker of Alzheimer’s disease. It takes highly skilled professionals to make the diagnosis. It involves using neuropsychological testing and skillful clinical interviewing of the individual and family to establish the type of memory that is functionally impaired and extrapolating a diagnosis from this information.

In the early stages of Alzheimer’s disease both episodic and semantic memory are effected. Episodic memory involves recall of day's events, while semantic memory involves the ability to remember names, words or historical events. Further down the line, working memory (ability to briefly hold information and manipulate it before storing it more permanently) becomes vulnerable leading to difficulty doing checkbooks or driving safely. Concomitantly, visuospatial skills (sense of direction) deteriorate and the individual becomes disoriented. Interestingly, social behaviors are usually preserved in the early stages of the disease with agitation more significant in later stages of the disease. (Some recent studies are showing the effectiveness of anticonvulsant drugs i. e. carbamazepine, divalproex, neurontin etc., in controlling this symptom as opposed to Haldol, which appears to have a wider range of adverse side effects. Individual variations in these stages may occur and may be correlated to premorbid personality and the etiology of the disease i. e. early (familial) or late (sporadic) onset. (In the future parts of this series, more information about anticonvulsants will be presented as well as alternative therapies. In the meantime, check the other parts of this series for current pertinent information. )

Contrast Alzheimer’s disease with frontaltemporal dementias where memory, comprehension and sense of direction are spared, while planning, organizing, or contemplating and achieving a complex series of activities are impaired. Along with evidence of ritualistic compulsive behavior, social withdrawal, apathy and disinhibition and you begin to see how a good diagnostician can make the important diagnostic distinction on basis of indirect evidence. With functional magnetic resonance imaging, direct markers might be found which might make for more objective diagnosis and competent treatment regimens. Research in this area will not show fruition for about five years.

Other Articles on Alzheimer's Disease

Part I-Medication for Alzheimer's Disease
Part II-Clinical Studies of Alzheimer's Disease
Part III-Ginko Biloba and Alzheimer's
Part IV-Alternative Treatments for Alzheimer's Disease
Part V-Possible New Drugs for Alzheimer's Disease

July 15, 1999

Harold Rubin, MS, ABD, CRC, Guest Lecturer


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