For over a decade, scientists have thought that if amyloid protein is the primary problem in dementia, the key to treatment must be drugs which reduce its production or stimulate its clearance from the brain. Initial efforts however, whilst they reduced the amount of protein, did little to improve clinical symptoms and outcomes.
Studies are ongoing to determine whether giving drugs very early in the condition (in people for example with evidence of amyloid in their brains but no symptoms of dementia) can halt or even prevent it. Let’s hope they yield positive results.
However, what if amyloid isn’t in fact causing the problem, but is simply associated with it? Cause and association are not the same thing, as I mention regularly when describing clinical trials. Around 25% of patients with amyloid in their brains at post mortem have no evidence of dementia when alive. In addition, around a third of patients with overt dementia have no evidence of amyloid on brain scans. This scenario is common in medicine. Biology is often not black and white, and this speaks to the importance of communicating information to patients in a way they can understand and interpret themselves.
Alternative hypotheses
In the 1990s, partly in response to conflicting evidence for amyloid, the theory emerged that blood supply to the brain was an important point that had until that point been overlooked. Stroke victims, who either have a bleed on the brain or an embolism are more likely to suffer dementia. Patients with diabetes have a 2-3x risk of developing dementia. Patients with metabolic syndrome are at increased risk. In the same way that a lack of blood and oxygen can cause a heart attack, might these factors affect the brain over many years?
The term now in common use is vascular dementia, and this makes up around one fifth of cases in Europe.
Inflammation also appears to play a role. In much the same way as cancer, and other chronic issues like heart failure, dementia patients have higher levels of inflammatory markers in their blood than controls. Might targeting inflammation therefore also play a role?
Gender differences
Alzheimers is nearly twice as common in women as in men. Women on average live longer, but this alone shouldn’t explain it. There is a school of thought that the menopause is a factor, but also how many children a woman has had, when she started menstruating, and oral contraceptive use may influence the risk.
On the flip side, Lewy body dementia and Parkinsons disease, which are related neuro-degenerative diseases, and twice as common in men as in women. Again, the exact reasons are unclear.
So whilst we wait to better treatments to be developed, what can the likes of you and I do? Next week I will go into dementia prevention, and present the evidence for what we can all do to reduce our risk.