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Reviewing Alzheimer’s Disease Treatments

In 1906 the German psychiatrist Alois Alzheimer introduced the disease which bears his name at a conference in Tübingen. In the century that has passed since this disease was recognized, there have been very few significant advances in diagnosis and treatment.

Very little is known about what causes Alzheimer's Disease (AD) and how the disease causes such drastic changes in the brain. Not knowing what is happening inside the brain of those afflicted with the disease makes finding good diagnostic and treatment options difficult.

One trial study of a new way to diagnose AD in the earliest stages shows the frustration this can cause in everyone dealing with the disease.

This researcher seems to have found a combination of biomarkers that will flag Alzheimer's before the symptoms begin to interfere with the memory and other "cognitive behaviors" that are lost in this disease.

The outcome looks promising, since all of the advanced AD patients in the study show the same chemical traces. There were also three people who did not have any symptoms of Alzheimer's in the study group. The researchers had this to say,

"Importantly, three of the participants had normal cognitive evaluations but had high PIB binding and low CSF amyloid- beta 1-42, suggesting the possibility that this combination of methods may be useful as "antecedent" biomarkers of AD, identifying the presence of AD amyloid pathology before the development of cognitive impairments. Alternatively, if these subjects never develop cognitive decline, it is possible that plaque number is not always a predictor of the disease."

Despite the frustration, there is good news in the study and treatment of Alzheimer's Disease. After decades of research, the medical profession is beginning to understand the processes involved with the progression of Alzheimer's. With that knowledge, therapies that target these processes and slow the progression of AD and, in some cases, even stop the damage from occurring are finally available.

In a review article published in the October 3, 2006 issue of the journal, Brain, several scientists involved in developing treatments for Alzheimer's disease share their knowledge about how the anatomy and processes of the brain are effected and what can be done to stop the symptoms from progressing. This review is a bit technical, but a very good overview of the treatment options available to Alzheimer's patients and the newer treatments that are being developed based on the latest research.

Hans-Wolfgang Klafki, Johannes Kornhuber and Jens Wiltfang from the Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg in Erlangen, Germany and Matthias Staufenbiel from the Novartis Institutes for Biomedical Research in Basel, Switzerland have put together an overview of "currently available drugs as well as novel therapeutic strategies, in particular those targeting amyloid and tau pathologies."

Amyloid pathologies are the processes that lead to the formation of amyloid plaques and tau pathologies result in the neurofibrillary degeneration found in brain cells of Alzheimer's patients.

The report presents a look at current treatments aimed at the symptoms of Alzheimer's Disease:

• Cholinergic deficit - In the 1970s and 1980s many studies pointed to the destruction of cholinergic neurons in the brains of Alzheimer's patients. The result of damage to these nerve cells was reduction in two enzymes, choline
acetyltransferase and AchE, that help the brain produce a chemical called Acetylcholine (ACh). ACh was the first neurotransmitter discovered by neuroscientists studying how brain cells work. Discovering that there were changes in this chemical process provided the first effective treatments for this disease.

Inhibition of brain cholinesterase activity - The drugs galantamine, donepezil and rivastigmine are all based on this research. These treatments have shown mixed results in slowing down the memory loss and other symptoms associated with Alzheimer's Disease. They are most effective in early Alzheimer's, which requires catching the symptoms when they first appear and accurately diagnosing the disease. The authors of this study wrote, "In a recent systematic review, however, the scientific basis for the recommendations of cholinesterase inhibitors for treatment of Alzheimer’s disease has been questioned."

• Glutamate-mediated neurotoxicity - Glutamate is another neurotransmitter, a chemical that helps the brain to process information. Several studies have reported that when neurons, the nerve cells in the brain, are exposed to too much glutamate they become overstimulated and are injured or die. This neurotoxicity or excitotoxicity is seen in Alzheimer's disease. NMDA-receptor antagonists are drugs that protect the neurons against this. Several drugs have been introduced that performed this function, but they interfered with normal brain activity as well. Memantine (Namenda®) has been successful at preventing the overstimulation while still allowing the barin cells to function.

• Combination therapy - The drugs used to correct cholinergic deficits and glutamate neurotoxicity seem to be compatible with each other. It makes sense that combining these two therapies might produce better control of Alzheimer's symptoms than using either one as a "monotherapy." The results of one study published in 2004 seem to support this. The authors report that a "...statistically significant benefit of the combination therapy as compared with the monotherapy was observed with regard to measures of cognitive function, activities of daily living, behaviour and clinical global status."

The newer therapies discussed in depth by the researchers are mechanism-based therapeutic approaches targeting b-amyloid and tau pathologies. The sections on therapeutic strategies targeting b-amyloid; modulation of Ab production; inhibition of AB-aggregation; and AB immunotherapy provide a basic understanding of where this research is leading in terms of preventing the loss of function associated with plaques and other changes in the cells of the brain in Alzheimer's Disease.

Therapeutic strategies targeting tau hyperphosphorylation & neurofibrillary degeneration include inhibition of tau kinases; Prolyl-isomerase Pin1; activation of phosphatases; and inhibition of tau aggregation. The authors add a discussion of other novel approaches showing promise in treating Alzheimer's disease.

In summary they find, "At present, however, there is no treatment available that can stop the progressive deterioration of cognitive functions in the Alzheimer’s disease patients. The development of novel drugs with strong disease-modifying properties therefore represents one of the biggest unmet medical needs today."

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