Q&A: Dr Emer MacSweeney

How would you define dementia?
The first thing to understand is that dementia is an umbrella term, not a specific condition. It refers to a number of cognitive symptoms, which can be caused by many different conditions: for example, Alzheimer’s disease, cerebrovascular disease, Parkinson’s disease, Lewy bodies disease, among others. For these conditions or diseases to sit under the umbrella term ‘dementia’, the degree of cognitive impairment must fulfil three key conditions: the symptoms must be in more than one domain—a domain being defined by the type of task it covers, such as calculation ability, speech and language, memory, planning ability, that kind of thing; the second is that the symptoms have to be progressive; the third is that the symptoms have to interfere with what we call ‘the activities of daily living’.

We hear a lot about dementia and the ageing population. Is dementia inevitable?
We know that as we grow older, the incidence of conditions that can progress to dementia increases, and as we’re living longer, the number of people dying with cognitive impairment or severe symptoms of dementia is certainly on the rise. If you develop features of cognitive impairment when you’re aged between 40 and 60, it is more likely that these symptoms are caused by stress, anxiety or possibly depression. As you get older, the statistical likelihood increases that the impairment is due to a condition such as Alzheimer’s, vascular disease or Parkinson’s disease—so to a certain extent, dementia is currently a statistical inevitability in an ageing population.

What will lead you to investigate for dementia?
This is extremely tricky, because signs of cognitive impairment are not very specific. It is important to identify, early, those causes of cognitive impairment that are reversible as opposed to progressive. Reversible causes require appropriate action to reverse symptoms, whereas progressive symptoms need to be managed as proactively as possible. When someone has very mild symptoms, it is often very difficult to distinguish between reversible and progressive conditions.

Things such as putting something down and not remembering where you left it, or walking up the stairs and forgetting what you had intended to do, are usually the result of a lack of concentration, or may be a feature of anxiety. But if a person has difficulty following a conversation because they can’t remember what was said earlier, unknowingly repeats themselves frequently to the same person within half an hour, or develops difficulties with calculations—we’re not talking higher maths here, but daily things like working out how much to give the shop assistant for a simple purchase— there is more likely to be cause for concern. A particularly significant marker is the inability to remember a recent event, despite being given hints or cues.

So, is it short-term memory that’s the real marker?
Usually we are particularly concerned when someone has problems with their short-term memory. On the whole, our older memories are the last ones to go—it is newer memories that dementia sufferers find most difficult.

How important is early diagnosis?
At the moment, there are no drugs on the market that can slow down the death of our cognitive brain cells. As brain cells cannot regenerate, once they are gone, they are gone. So, it is important that we diagnose issues before too much damage is done

How do you approach this?
Initially, a cognitive clinician undertakes a clinical assessment, including a discussion with the individual and frequently their partner, close family member or friend. The clinician will consider possible causes for cognitive impairment and arrange for specific tests to be performed to assist in confirming the diagnosis. These will usually include a blood screen for various metabolic, hormonal and other conditions. A more detailed neuropsychology assessment may also be required, plus brain imaging. The latter will invariably include an MRI brain scan, which can be analysed to provide volumetric data on the relative size of the different parts of the brain involved in memory and other cognitive activities. To confirm a diagnosis, more specific tests may be required. For example, the PET FDG scan looks at different levels of metabolic activity in the brain, a DAT scan may be used to diagnose Lewy body disease, and a PET amyloid scan has an extremely high sensitivity for the detection of amyloid protein: one of the hallmarks of Alzheimer’s disease.

Once a diagnosis has been identified, appropriate treatment can commence; this may be pharmacological, non-pharmacological or both.

What are some of the mechanisms through which the conditions mentioned can cause dementia?
One of the conditions that can lead to dementia is cerebrovascular disease, which is a disease of the small vessels in the brain. These vessels naturally narrow as they go out into the further reaches of the brain, but this disease causes them to narrow even further. Finally, you reach a point where the vessels are so narrow that not enough blood can pass through them to properly feed the area of the brain they serve; gradually the cells in those parts of the brain start to die.

Is this different from the way Alzheimer’s disease affects the brain?
Absolutely: Alzheimer’s works in a completely different way. Here we look for abnormal levels of amyloid and tau proteins in the brain.
It is believed that one of the early problems in Alzheimer’s is an increase in the production of a fragment of the amyloid protein called Aß (a-beta) amyloid. The brain does have a clearance system for this protein fragment, but the increase in production means the brain can’t clear the Aß efficiently. It accumulates in the brain, forming insoluble amyloid clumps or plaques which interfere with communication between brain cells. If any part of the brain cannot work properly it begins to atrophy, so as these plaques become more numerous the brain cells become less efficient and eventually die.

What about the tau proteins?
These are found inside the brain cells. The problem arises when the tau protein starts to change its configuration and causes the brain cells to become less efficient. The abnormal tau protein starts to replicate itself, eventually filling up the brain cell to the extent that the cell just bursts. Abnormal tau protein can cross from one brain cell to another, so the problem spreads, meaning that cognitive symptoms gradually become more complex, as well as more severe.

So dementia presents a complex picture…
Yes, it does. We still don’t really understand what triggers the abnormalities we have been talking about, and these are just two of the processes involved. There are several others, each of which presents a different challenge.

What advances have there been in recent years?
The big advances at the moment are twofold. Firstly, the advances in our diagnostic ability—not just in imaging through techniques like MRI and PET scans, but through the increased ability to measure biomarkers like the Aß amyloid and tau proteins. We are now able to detect these biomarkers when cognitive symptoms are very mild, and even before they are present at all. But as with all screening techniques, there is no great merit in being able to detect future risk of disease unless there is the possibility of a treatment which, if given early, will delay the onset of symptoms or slow the progression of existing mild symptoms.

Fortunately, the second area of progress is in developing new treatments. Final phase clinical trials are currently underway for several new drugs designed to reduce the level of amyloid and tau proteins in the brain. Re:Cognition Health has three centres in the UK where these large international clinical trials are taking place. Individuals who have cognitive symptoms are screened with sophisticated diagnostic tests to see if they are clinically eligible, and if so have the opportunity to gain early access to these new Alzheimer’s disease medications.

While most current studies are for those with mild to moderate symptoms, new studies are also starting for people aged 60 to 85 who have no cognitive symptoms but wish to find out if they are at significant risk, perhaps due to the experience of a family member suffering from Alzheimer’s disease. If they are found to have high levels of amyloid protein in their brain, they have the opportunity through a clinical trial to gain early access to a new medication to reduce further production of Aß amyloid protein. Initially, some people will receive a placebo, but eventually—assuming the study goes well—everyone will receive the active medication.

What is the difference between previous medications and the ones that are coming?
At the moment the only medications for people with Alzheimer’s are symptomatic medications. These are designed to help the dying cognitive brain cells work more effectively, or enable the unaffected cells to work super-efficiently to make up for the cells that have been lost. They do this by indirectly increasing the amount of neurotransmitters available to the cells. But these existing medications cannot slow down the process that is causing the brain cells to die in the first place.

The new drugs are designed to keep the dying brain cells alive—if you can do this, you can slow down the progression of the disease. The drugs do this by reducing the amount of amyloid and tau proteins in the brain.

We also have new symptomatic drugs in final phase clinical trials, designed to provide a more powerful boost to memory and other cognitive function.

As all these new drugs work in a different way to existing ones, in most instances an individual can continue to take their current medications while simultaneously accessing a new medication.

How long do you think it will be before they are generally available?
It will still be four to five years before the first of these drugs may be on the market. The great thing about these medications is that they work in a completely different way to the symptomatic medications we now have, so people on these medications will be able to carry on taking them when the new drugs are available. This will lead to a two-pronged approach, in which we have one set of medications working to keep dying cells alive and another for making the best of the cells that exist.

What do you like about this area of medicine?
I think the brain is where it’s at—and our cognitive health is incredibly important at every age. Early, accurate diagnosis is essential and also a significant challenge, as the onset of cognitive impairment is often very gradual and symptoms are very non-specific. The rate of new understanding of progressive cognitive conditions such as Alzheimer’s is matched by that of traumatic brain injury, the autism spectrum and many others. It’s a very exciting and interesting area to be working in.

For more information, visit ReCognition Health