Step Up for Dementia Research

What is dementia treatment research?

Current treatment for dementia is limited to improving the symptoms of dementia – how the disease affects people’s behaviour and functioning – rather than slowing or stopping the underlying pathology or causes of the disease itself. Whilst current treatments may produce short- and medium-term improvements in cognitive ability and functioning, the progressive nature of dementia means that cognition and functioning in day-to-day life will continue to decline with time.

Why is treatment research important?

Thanks to previous research efforts, improvements in cognitive ability in Alzheimer’s disease are possible with available medication.  Two classes of drugs are often used to improve cognitive function.  Donepezil and rivastigmine are examples of the class called cholinesterase inhibitors. These drugs increase the amount of the neurotransmitter acetylcholine in the brain. Normal cognitive function and memory are dependent on acetylcholine. In dementia, there is a loss of cells containing this neurotransmitter. Therefore, boosting levels with these drugs helps to restore function.

Another class of drugs work on a different neurotransmitter system – glutamate. An example is memantine. This drug may be prescribed if patients cannot tolerate cholinesterase inhibitors due to side effects. Memantine slows the rate of degeneration slightly in people experiencing the moderate to severe stages of Alzheimer’s.

Improving pharmaceutical treatments is only possible when people volunteer for clinical studies. Each new experimental drug requires multiple studies of different treatment protocols in order to progress through the rigorous multi-phase clinical trial process to market. For example, since 2003, over 200 dementia drugs have been trialled to date, none have cleared the clinical trial process and made it to market. However, research into treatments targeting the causes of Alzheimer’s disease continue, and there is reason for optimism (see section on cure).

What is required in order to conduct treatment research more effectively?

People with dementia, their carers, healthy controls and others volunteers are required for clinical drug trials to progress. Some clinical trials will aim to recruit people in the early or prodromal* stages of dementia, as some medication is more effective in this stage. Some trials aim to recruit people who do not yet have a diagnosis of dementia, but who have mild cognitive impairment (MCI) – about half of whom will go on to develop dementia. Other studies recruit people at later stages of dementia.

Historically, it has been challenging and expensive to recruit patients with dementia into clinical trials and research.  These challenges have acted as a bottleneck, slowing progress into trials. Having a large number of motivated, willing volunteers will accelerate the development of new treatments.

An example of treatment research

Effect of Citalopram on Agitation in Alzheimer Disease The CitAD Randomized Clinical Trial.  (Journal of the American Medical Association; Porsteinsson et al., 2014) 

This American study focused on treating agitation in people with dementia with the use of an antidepressant drug. Agitation includes emotional distress, excessive physical activity, aggression and irritability. Agitation is common in people with dementia and is related to lower quality of life for both patients and their carers.

The researchers recruited 186 people diagnosed with dementia who had agitation. Half of the participants were given placebo, and the other half received citalopram, an antidepressant drug, for 9 weeks. Both groups also received psychosocial support from a trained clinician.

The researchers found that the group of patients taking citalopram had significantly lower levels of agitation at follow up assessments. However, there were some side effects of this drug at higher doses. This study showed that antidepressant drugs delivered in combination with psychosocial support can effectively improve the treatment of agitation in people with dementia. This suggests a possible treatment alternative for agitation instead of antipsychotic drugs.

*Prodromal refers to people with deteriorating cognitive function, but below the threshold for Alzheimer’s diagnosis, and with a positive biomarker for amyloid.

 

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The University of Sydney

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