P1vital CNS Experimental Medicine : COGNITION AND DEMENTIA OVERVIEW

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Dementia is a descriptive term for a collection of symptoms that can be caused by a number of disorders that affect the brain. Patients with dementia have significantly impaired intellectual functioning that interferes with normal activities and relationships. They also lose their ability to solve problems and maintain emotional control, and may experience personality changes and behavioral problems, such as agitation, delusions, and hallucinations. While memory loss is a common symptom of dementia, memory loss by itself does not imply that a patient has dementia. A diagnosis of dementia is made only if two or more brain functions - such as memory and language skills -- are significantly impaired without loss of consciousness. Some of the diseases that can cause symptoms of dementia are Alzheimer’s disease (AD), vascular dementia, Lewy body dementia, frontotemporal dementia, Huntington’s disease, and Creutzfeldt-Jakob disease. AD is the most common cause of dementia and affects 4 million US citizens. It is a progressive, neurodegenerative disorder with a time course that can vary from 5 to 20 years and is characterized in the brain by amyloid plaques and neurofibrillary tangles composed of misplaced proteins. Age is the most important risk factor for AD; the number of people with the disease doubles every 5 years beyond the age of 65. As the life expectancy of the population increases the number of people affected by AD will continue to grow unless a cure or effective prevention is discovered. Symptoms of AD include memory loss, language deterioration, impaired ability to mentally manipulate visual information, poor judgment, confusion, restlessness and mood swings. Eventually AD destroys cognition, personality and the ability to function.

There is no cure for AD and no way to slow the progression of the disease. For some patients in the early or middle stages of AD, cholinergic drugs such as tacrine, donepezil, rivastigmine and galantamine may alleviate some cognitive symptoms for a limited period of time. The NMDA antagonist memantine was recently approved for use in the US and a number of European countries. It has been proposed that combining memantine with cholinergic drugs may be more effective than any single therapy. Nevertheless, these current drug therapies have significant limitations with troublesome side-effects including nausea, diarrhoea and vomiting. Most importantly, the current drugs have little or no effect on disease progression. Thus, there is an urgent need for a well tolerated drug treatment that can slow or halt disease progression. As registration trials require large numbers of patients and lengthy treatment periods there is considerable potential for Experimental Medicine studies to select the best compound(s) for late stage trials.