P1vital
CNS Experimental Medicine : COGNITION AND DEMENTIA
Background
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.
Arena Virtual Maze Model
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Using
virtual reality researchers at the Institute of Psychiatry
led by Prof Robin Morris and Prof Michael Brammer have developed
a human analogue of the frequently used preclinical test of
hippocampal dependent spatial working memory, the Morris Water
Maze.
The ‘Arena Task’ has convincingly demonstrated
bilateral hippocampal activation in humans, using functional
Magnetic Resonance Imaging (fMRI) (Parslow et al., 2001).
More recently it has been shown that in this task healthy
elderly male subjects, average age 72 years, perform significantly
less well and have reduced hippocampal activation compared
to healthy young males (average age 26 years). Currently,
the effects of scopolamine on performance and hippocampal
activation in healthy young males are being assessed.
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For more information on the
Arena Virtual Maze model or to discuss cognition & dementia
studies contact Info@p1vital.com
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