Alzheimer’s disease vs. vascular dementia – Alzheimer’s disease and vascular dementia are the two most common forms of dementia. For some people, they can even overlap, resulting in mixed dementia. But what is the difference between the two? And how can you have both types of dementia at the same time?
Let’s find out.
Alzheimer’s disease is named after Alois Alzheimer (see my article on him here), a German neurologist/psychiatrist who described the disease for the first time in 1906/1907, based on his examination of Mrs Auguste Deter in 1901. Now, many people before Alois Alzheimer described similar cases to Mrs Deter, but his description made a critical difference in that he linked her clinical symptoms to the changes in her brain. The changes he observed in the brain are still the ‘gold standard’ for a definite Alzheimer’s disease today, so his work has clearly stood the test of time.
What are then the brain changes in Alzheimer’s disease?
The key changes in the brain of people with Alzheimer’s disease are the accumulation of two proteins – amyloid and tau. Amyloid and tau are both important proteins for the healthy functions of our brain. However, during Alzheimer’s disease, both proteins go awry. We know scientifically quite a lot about how amyloid and tau go awry, what is not known yet is why they go awry. So for now, we have to simply accept this.
How do amyloid and tau go awry?
The key process is the accumulation of amyloid and tau in and around the nerve cells of the brain.
For amyloid, the process involves how it is recycled in the brain, once it has completed its normal function. When the recycling process of amyloid goes awry it can produce one particular form of amyloid, which is called beta-amyloid. The beta-amyloid is ejected from the nerve cells where it is waiting to be transported away and recycled. However, when we age there is a higher chance that an increasing amount of beta-amyloid accumulates outside of the nerve cell. Once beta-amyloid accumulates it starts sticking together with other beta-amyloid molecules forming sheets of beta-amyloid, called amyloid oligomers (amyloid oligomers are nothing else than multiple amyloid proteins sticking together). If a lot of those amyloid oligomers accumulate they can form amyloid plaques. Amyloid players are nothing else than a random accumulation of amyloid oligomers stuck together. Both amyloid oligomers and plaques are dense, sticky structures, which cannot be that easily recycled anymore – like in life, cleaning up a sticky mess is a nightmare. That would be not per see a problem, however, the problem is once these beta-amyloid oligomers and plaques form, they become toxic to the nerve cell and eventually the nerve cell dies.
For tau, the process is quite similar to amyloid, even though tau has different functions in the healthy brain. Tau gets changed into a stickier form by too much phosphate being around in the nerve cell. We do not know yet why there is too much phosphate in the nerve cell. The phosphate starts sticking to tau, causing it to be full of phosphate (in scientific speak tau becomes ‘hyperphosphorylated’, meaning full of tau). This hyperphosphorylated tau cannot perform its healthy brain functions anymore and starts to stick together inside and outside of the nerve cells. Sticky tau forms fibrils – called tau fibrils, which are similar to amyloid oligomers. Again, similar to amyloid, the tau fibrils are starting to stick together and accumulate, and if enough accumulate become toxic to the nerve cells.
Now, for Alzheimer’s disease to develop one needs to have both beta-amyloid and hyperphosphorylated tau accumulating in the same brain region. Once they start accumulating in the same region, the whole process seems to accelerate and an increasing amount of nerve cell gets affected by beta-amyloid and hyperphosphorylated tau. In turn, this causes symptoms since those nerve cells cannot perform anymore their brain functions properly. For most people with Alzheimer’s disease, the accumulation of beta-amyloid and hyperphosphorylated tau occurs in a region of the brain called the medial temporal lobe, which lies on each side of our brain just behind our temples. The medial temporal lobe is particularly important for our memory and spatial navigation/orientation and hence, most people with Alzheimer’s disease develop memory and orientation problems as the first symptom. However, for other forms of Alzheimer’s disease, the proteins can accumulate in other brain regions causing other symptoms, such as vision, movement, speech or behavioural problems. In essence, the symptoms people will have depends on where beta-amyloid and hyperphosphorylated tau accumulate, as this accumulation affects the nerve cells in that brain region.
The final important aspect to understand with the proteins in Alzheimer’s disease is that they seem to ‘infect’ other brain regions once the accumulation process gets started. It is yet unclear why they seem to ‘infect’ neighbouring nerve cells (see also my blog entry on whether dementia is ‘infectious’), however, the consequence of this propagation is that the disease spreads through the brain affecting an increasing number of brain regions and causing further symptoms.
What is then the difference to vascular dementia?
Vascular dementia is not caused by proteins accumulations, as in Alzheimer’s disease, but instead is caused by damage to the blood vessels in the brain. The terms ‘vascular’ comes from the Latin word, ‘vas’ meaning vessel. In this context, our blood arteries and veins are referred to as the ‘vessels’ of our blood. Many people will be already aware of diseases caused by changes to our blood vessels in the brain, such as stroke and indeed the blood vessel changes in vascular dementia are very similar to stroke – the key difference is in the scale of those blood vessel changes.
There are two main types of strokes, ischemic and haemorrhagic stroke. Despite these complex medical terms, they are actually very simple to understand via a plumbing analogy. In essence, our blood vessels are like pipes carrying our blood to different parts of the body. Now, if a pipe gets blocked for some reason, nothing will arrive at the other side of the blockage. For our blood vessels, this means that no blood and therefore no oxygen or glucose (sugar) will arrive in the brain region beyond the blockage. That is the situation with an ischemic stroke, which is simply a blockage (mostly caused either by blood or cholesterol clots) of the blood vessels in the brain. For a haemorrhagic stroke, the situation is slightly different, instead of the blood vessels becoming blocked, they have a leak. Again, similar to a pipe if it is leaky less or no flow will arrive on the other side of that leak and the same applies to the brain where the brain region after the leak do not get sufficient oxygen and glucose. The lack of oxygen and glucose of those nerve cells affects after an ischemic or haemorrhagic stroke causes the nerve cells eventually to die. Now, these are the basic concepts for stroke and they also apply to vascular dementia.
So, what is the difference between stroke and vascular dementia?
The difference, as I mentioned before, is mainly in the scale of the blockages or leakages of the blood vessels in the brain. For stroke, major blood vessels get either blocked or leak, causing large areas of the brain to be affected and symptoms to occur as soon as the stroke occurs (for example, changes in speech and movement). Now, some stroke survivors can also develop vascular dementia subsequently, however, the more common scenario is that for vascular dementia, the smaller blood vessels in the brain get affected by blockages or leakages. Such strokes in smaller blood vessels are also referred to as ‘mini-strokes’ or ‘silent strokes’. The reason why they are referred to as ‘silent’ is that such mini-strokes occur often do not causing any visible symptoms in the person having them. The reason is that the brain region affected by the mini-stroke is so small that the brain can compensate the lost function of that region.
That those mini-strokes are silent makes them actually more dangerous than the major strokes. For the major strokes, we notice instantly symptoms and therefore the stroke can be treated. However, for mini/silent strokes nothing is noticed on the ‘outside’. This means that we can have multiple mini/silent strokes over time without us or anyone else noticing that such a mini/silent stroke has occurred in our brain. The problem is that once too many mini-strokes have occurred in our brain, we can actually develop symptoms, which is then often the ‘onset’ of vascular dementia. Our brain cannot simply cope anymore with those mini-strokes and we develop symptoms.
So, the key difference to understand between Alzheimer’s disease and Vascular dementia is that Alzheimer’s disease is caused by the accumulation of proteins, whereas vascular dementia is caused by the accumulation of mini-strokes.
How about the symptoms in vascular dementia?
This is another key difference to Alzheimer’s disease, in that for vascular dementia the symptoms will depend on where the mini-strokes are occurring. For the majority of Alzheimer’s disease people, protein accumulation happens in the medial temporal lobe of the brain causing the typical memory and orientation symptoms. But for vascular dementia, the symptoms can be far more variable as it depends on which brain regions are affected by the mini-strokes. Most people with vascular dementia will have pretty intact memory as it is rare for the medial temporal lobe to get affected by strokes. Instead, many of them show a slowing down of responses and decision making, which can appear very subtle. The other common symptoms are related to behavioural changes, in particular becoming more irritable or even aggressive, as the brain regions responsible for our behaviour are more often affected by strokes. Still, it makes it much harder to spot the symptoms as they can be subtle and ‘diffuse’.
We can see now that the range and severity of symptoms in vascular dementia can vary enormously between people. For example, someone who might have a major stroke and then develop dementia would be deemed to have vascular dementia, similar to someone who mini-strokes and very subtle cognitive changes. Because of this large variability in presentation, there is currently a shift in terminology occurring for vascular dementia. Many scientists and clinicians prefer now to use the term ‘Vascular Cognitive Impairment – VCI’, instead of vascular dementia as the vascular cognitive impairment can range from very subtle to quite severe cognitive changes caused by vascular changes in the brain. I just mention this, in case you come across the term vascular cognitive impairment, which is just a re-naming of vascular dementia.
What is the difference then to mixed dementia?
The term mixed dementia is also somewhat of a misnomer. It gives the impression that mixed dementia is a mix of all dementias as if they are all ‘smooshed’ together. Nothing can be further from the truth. Instead, mixed dementia is the condition when a person has both Alzheimer’s disease and vascular dementia.
That’s a bit strange, how can one have both types of dementia?
If we think about it a bit, it makes sense that we can potentially have both Alzheimer’s disease and vascular dementia since both types of dementia are caused by quite different disease processes. We know that Alzheimer’s disease is caused by proteins accumulations in the brain while vascular dementia is caused by blockages/leakages of the blood vessels in the brain. So, the two factors causing each dementia (protein vs. mini-stroke accumulation) are independent from each other, or to say it in fancy science language, they are ‘orthogonal’ to each other. This means that they can occur both at the same time in the same person. For example, we could have someone who has proteins accumulating in their brain and has blockages/leakages of their small blood vessels. Such a person would get a diagnosis of mixed dementia.
Now, for many years scientists and clinicians thought that mixed dementia would be quite a rare occurrence, since what are the chances of having both pathological processes in one’s brain. However, more recently there has been a re-think in this direction as it is more commonly recognised that older people, in general, have some levels of vascular changes in their brain. Similar to the rest of our body, our brain blood vessels are more susceptible to breakage or leakage, just because we have lived longer. This means that on brain scans we can often see brain vascular changes in older people’s brains, just because they are older and had more a chance of accumulating such breakage/leakage of blood vessels.
If such an older person is then also developing Alzheimer type symptoms, indicating that proteins are accumulating in their brain, do they have Alzheimer’s disease, vascular dementia or mixed dementia?
One could argue for each of the three, depending on how much emphasis we want to put on the protein or vascular changes. This realisation has resulted in a re-think of mixed dementia diagnostics, in that most people are now assumed to have mixed dementia since brain vascular changes are so common during ageing and only a minority of people have ‘pure’ vascular dementia. Finally, the age of diagnosis might play also a significant role in which diagnosis people receive. If we have someone in their 60’s who has a lot of brain vascular changes and some memory changes would we diagnose them with vascular dementia or Alzheimer’s disease? By contrast, if we have someone in their 90’s who has similar changes would we diagnose them with vascular dementia or Alzheimer’s disease? Many clinicians would lean to giving a diagnosis of vascular dementia to the person in their 60’s since brain vascular changes are rarer at this age, whereas they would tend more to Alzheimer’s disease or mixed dementia to the person in their 90’s since brain vascular changes are very common at that age. But it should become obvious that this is not a straightforward decision.
Is this not just an ‘academic’ question, you might rightly ask?
Actually, it is quite an important question, which will determine the treatment of the person. Importantly, people who have a mixed dementia diagnosis are – in most countries, including the UK and US – eligible for Alzheimer’s disease medication. However, someone with vascular dementia will not be eligible for Alzheimer’s disease medication. So, there is a big difference between having a vascular and mixed dementia diagnosis, even though the difference can be often not as clear cut and also depends on our age.
Still, not all is lost for vascular dementia. Quite the contrary, we actually know much more about treating and even preventing vascular disease changes. Not only is their medication but also lifestyle factors, such as physical activity and diet can make a significant difference in the health of our brain blood vessels. It is, therefore, worth keeping a healthy lifestyle and follow public health guidelines, as well as getting regular check-ups on blood pressure and cholesterol levels, which can affect our brain blood vessel health.
In summary, Alzheimer’s disease is caused by two proteins (amyloid and tau) accumulation, which eventually lead to nerve cells dying and symptoms emerging. By contrast, vascular dementia is caused by the breakage or leakage of blood vessels in the brain, which also leads to nerve cells dying and symptoms emerging. If large blood vessels are affected then this causes a stroke, which can lead to post-stroke dementia. However, more common is that smaller blood vessels break or leak leading to mini/silent strokes. The accumulation of mini/silent strokes leads then to symptoms in the long term. Finally, mixed dementia is when a person has both Alzheimer’s disease and vascular dementia changes in their brain. However, the distinction of whether someone has Alzheimer’s disease, vascular dementia or mixed dementia is often not straightforward, since brain vascular changes and memory problems can occur during ageing. One needs to carefully delineate therefore the factors contributing to the symptoms, as it will inform how we can treat the symptoms.
Just remember: Alzheimer’s disease is caused by the accumulation of proteins in the brain, vascular dementia is caused by the accumulation of blood vessel changes in the brain.
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