In 1901, Auguste Deter became the first person to be diagnosed with Alzheimer’s disease by the psychiatrist Alois Alzheimer. So where are we in the fight against dementia 118 years later?
We know that that excessive build-up of certain proteins in the brain (tau and amyloid) is seen in Alzheimer’s disease; the commonest cause of dementia. However, clinical trials such as the phase 3 Engage and Emerge which employed a monoclonal antibody against amyloid (aducanumab) in Alzheimer’s patients failed to reach its primary end-point, the slowing of cognitive decline. So far we have medications called cholinesterase inhibitors which have been shown to slow the rate progression of symptoms but do not modify the course of the disease. We also have medications that alleviate behavioural and psychological symptoms of dementia but they do not promote disease reversal. The challenges in identifying a treatment for dementia may also reflect uncertainties about the diagnostic categories we use. For example, just this year scientists identified a new sub-type of dementia called “Limbic-predominant Age-related TDP-43 Encephalopathy” or LATE which mimics Alzheimer’s dementia, predominately in the oldest old individuals. If we do not know exactly what we are treating, we are likely to have less success.
Alternative approaches to treating dementia are now being explored in a variety of areas. At present there are trials looking at: reducing brain inflammation in ageing and using fish oils and aspirin to reduce the risk of dementia; treating a rare early onset genetic form of Alzheimer’s disease before symptoms manifest; and genetic modification as target for treating a familial variant of frontotemporal dementia.
Another innovative approach is exploring whether established drugs used in treating other diseases could be trialled in dementia treatment – so-called “drug repurposing.” For example, the LACI2 trial at the University of Edinburgh is looking at the use of two medications used to treat heart disease (isosorbide mononitrate and clizostazol) in patients with evidence of small vessel disease in their brains to see if this prevents progression to dementia. Similarly, a drug which is used to treat type 2 diabetes (liraglutide) is now being trialled in the treatment of Alzheimer’s dementia. The RADAR study investigates the potential use of a blood pressure medication (losartan) to treat Alzheimer’s dementia. These are a few new approaches, some of which may lead to exciting findings. Furthermore, a combination of drugs may be more effective than a single one.
Whilst continuing to explore novel treatments for dementia we should also focus on reducing risk and preventing dementia symptoms developing in the first place. But above all, we should not forget the friends, families and carers of people with dementia and the need for coordinated and structured holistic care.
Dr Sahan Benedict Mendis
Alzheimer Scotland Clinical Research Fellow, University of Edinburgh and honorary Specialty Registrar in General Adult Psychiatry