Dementia has been a part of society for at least 1400 years. The word first appeared in recorded literature in around 600 AD in the book ‘The Etymologies’ by Saint Isidore, the archbishop of Seville. At the time the term was used to describe any kind of mental or neurological condition and it remained a very broad term until the end of the 19th century. Viewed by many as a normal part of aging, dementia was actually a really common reason for admittance into the horrific asylums of past centuries. Our understanding looked set to remain ignorant and naïve until the emergence of definitive data that dementia was a symptom of disease and not a normal part of life.
In 1906, Alois Alzheimer [1] identified the presence of “unusual” protein aggregates in the brain of a deceased patient who was suffering from dementia. These proteins would later be known as amyloid and tau, the two main hallmarks of Alzheimer’s disease. This sparked a new avenue of research that has gone on to definitively show that dementia is not part of normal life. It is pathological and nuanced. It can be cause by a wide variety of neurological diseases all with different mechanisms and requiring different approaches to research and treatment. Fast forward to today and we have made huge strides with the help of a few significant milestones along the way.
The 70s brought the discovery of reduced quantities of a neurotransmitter called acetylcholine in the brains of AD patients, sparking research into therapies to address this issue. Thanks to this, we developed the first round of treatments for AD. Drugs like donepezil (Aricept), rivastigmine (Exelon), and galantamine (Reminyl) which bost acetylcholine levels in the brain, providing patients with a temporary but still very valuable improvement in mental function and an increased quality of life for a set period of time.
The early 90s sparked a genetic revolution with identification of a genetic defect in familial Alzheimer’s. This discovery led to the development of the amyloid cascade hypothesis; the idea that amyloid is the initiator of AD, our biggest global cause of dementia. This led to a vast field of research into amyloid based therapies, two of which have been approved for clinical use (more on this later).
Between the early 90s and now, we also discovered that we could potentially diagnose diseases like AD from spinal fluid and we are working to utilised this as a tool for earlier diagnostics. Pair that with our discoveries around inflammation and AD and it sounds a bit like a success story. However, over 100 years passed since Alois Alzheimer’s without the development of any clinically approved drug that actually fights the root cause of AD.
That is… until now. In the last 2 years we have seen excitement around 2 new drugs to treat the build-up of toxic amyloid aggregates in the brains of dementia patients. Both drugs are a type of treatment called antibody therapy. The first to be approved (Aduhelm) proved somewhat controversial with many questioning if it actually works. However, more recently a drug called lecanemab came through trials with very positive results. It may be available as early next year and it is the first drug to universally be regarded as being capable of alleviating symptoms and slowing mental decline in AD. It will be covered more in a future blog from me but I genuinely think it is not coincidence that we have waited over 100 years for a drug to be approved and 2 have come along at once.
These developments are the result of billions of dollars and decades of laborious research. We have spent years planting seeds and we are finally seeing the fruits. I suspect these are to be the first of many in a flurry of exciting new treatments. Add 2022 to your list of key years in dementia research ARUK! There is a good chance this year sparks the start of a golden era of dementia research. We might finally be about to make a huge difference to millions of people across the globe and I think that is incredibly exciting!
Dr Sam Moxon
Author
Dr Sam Moxon [2] is a biomaterials scientist at the University of Manchester. His expertise falls on the interface between biology and engineering. His PhD focussed on regenerative medicine and he now works on trying to develop 3D bioprinting techniques with human stem cells, so that we better understand and treat degenerative diseases. Outside of the lab he hikes through the Lake District and is an expert on all things Disney.