Memory problems

We’re going to look at memory disorders in Alzheimer’s disease. We’ll start with Alzheimer’s own description of the disease that bears his name from when he met Auguste D. at the beginning of the 20th century, and you’ll see that the initial observation was quite a moving document. Alzheimer monitored this patient for a few years until she died.  

He reported the clinical observations that he had described in previous years with great precision. He explains that there are cognitive disorders, memory disorders – we’ll go over those again later – temporal and spatial disorientation, behavioural disorders, and psychiatric disorders involving agitation, paranoid ideas and auditory hallucinations. And he relates all this to the brain lesions he has observed in the patient’s cortex: amyloid lesions and tau lesions.  You should understand that Alzheimer’s disease is a clinicopathologic combination. It is a syndromic framework with brain lesions. So getting to the crux of the matter, let’s look at this syndromic framework in memory disorders. 

We have learnt a lot since Alois Alzheimer’s description, particularly about the natural history of the disease. The damage begins in a small area of the brain called the hippocampus.  This area is very, very important with regards to memory. We’ll look at it in more detail later because the hippocampus is like a gateway for memories. It starts with lesions in the hippocampus which, as you see in the centre here, gradually develop towards the anterior regions of the brain, the frontal regions.  Later, they invade the entire cerebral cortex in what we call the association areas. 

There are two main phases in Alzheimer’s disease. An initial phase – limited to the hippocampus – which is characterised by a progressive amnestic syndrome. There is an inaugural syndrome with inaugural memory disorders linked to this early damage to the hippocampal formations.  This is what I called the prodromal phase of Alzheimer’s disease. Then secondarily, as lesions spread over the entire cortex, judgement disorders and apathy appear, with a kind of reduction in behaviour, language disorders, a lack of words, disorders of programmed gestures (known as apraxia), being unable to recognise faces and objects, behavioural disorders, we have already covered that.   

All this impacts the patient’s autonomy, this loss of autonomy translates as what we call dementia, and we’ll talk about that again later. Now let’s focus on this early phase, the prodromal phase, where there is a relatively isolated amnestic syndrome that characterises Alzheimer's disease. Memory disorders are obviously relatively commonplace after a certain age. For example, I had a woman who came to see me for a consultation because she said she was no longer able to count in her head. She would forget what she was doing, she often entered a room without knowing what she was looking for. She told me about what happened when she arranged to meet her daughter: “I told her I was on my way, then I didn’t go. When she called me back, I had completely forgotten the appointment and the reason for it. I have no recollection of a document I wrote. I can’t remember what I did the day before. I can’t remember if I replied to a letter. 

On a journey close to my home, I forget where I’m going. I sometimes make aberrant spelling mistakes.” You might think that this poor woman has severe amnestic syndrome. Well ultimately, the paradox was that she had no memory problems during the tests, no objective memory deficit. 

That means there can be memory issues without an actual memory deficit. And that’s why what we’re dealing with is so difficult. As doctors, we see people complaining about their memories from a certain age. 

Of these, some will have objective memory disorders. That means we have to do tests to make proper analyses. Memory issues are actually a poor indicator. Look at this graph with two lines: the top one represents patients with depression. They have depression, but they have practically no memory disorders, they have an MMS of 29 out of 30, which means that actually have no cognitive disorder. They have quite severe depression and as you see, they are very high with regards to their complaint. They have a very high complaint level, ranging from 100 to 160. You can see when you follow the line, it’s very high. So they don’t have a deficit during testing, but they have a very high complaint level. 

They are depressed. And below that the line is almost completely flat, they are patients suffering from Alzheimer’s disease. You see they have quite severe cognitive problems since they have an MMS of 20 out of 30, that means they have significant memory problems, but they don’t complain. 

There is a sort of paradox that I talked about a few years ago. The more someone complains about their memory, the less risk they have of developing Alzheimer’s disease. It’s oversimplified, but it means that complaining about memory issues is not necessarily a useful indicator for memory function. 

Why? Because memory complaints, which are a very common syndrome and not correlated with test scores, as I said, are actually the expression of an attention disorder. Because a person can be depressed, have anxiety disorders, because there is professional stress, burn-out, because of certain medications which can influence our ability to concentrate, because of sleep disturbances, or simply because of ageing.  

We can have attention disorders that disrupt how our memory works for all these reasons, and we’ll see why later. However, it can also – that’s why the issue is complicated – it can also signal the onset of the condition. In my experience, what is the most evocative is a complaint that is often expressed by the people around the patient. 

Because, as I showed you, patients who have an amnestic syndrome in the case of Alzheimer’s disease do not usually complain much about their memory. What is telling is that they tend to repeat themselves or ask the same question several times from one minute to the next, which shows that while the question was probably important because they asked it, and they heard the answer, they did not remember the answer to an important question. 

It means that there really is a memory input deficit. On the one hand there are attention disorders about things that are solicited in everyday life for mundane things. A person constantly forgets where they put their glasses, keys or newspaper, because they are not paying attention to them. And on the other hand, the fact that they might forget something important, and that is probably a worrying sign. 

The important thing for us doctors is that we must differentiate between attention disorders and memory disorders. And to understand the difference, you have to understand what happens when you are dealing with information. On the left here you have a piece of information, it might be visual, something you’ve read, or something you’ve heard, a story, or so on.  What happens when we try to repeat this information a few minutes later? 

The information has to go through three different boxes. Input first, then storage, then recollection. We’ll analyse each of these boxes. Input first. For a person to remember the information, they have to be attentive to it. The perceptual system must capture the auditory information, the temporal or visual cortex, the occipital cortex. 

So the information must be input properly. The person needs to be attentive. If I give you a list of words and you’re thinking about something else, you won’t input the words into your memory and you won’t be able to recollect the words. The input will be disrupted if the person is tired, depressed, or simply if they have a slight attention disorder caused by ageing.  Once the information is input, it is sent to the hippocampus, which is like a tollbooth on the memory highway. The information must pass through the tollbooth, through the doorway to the brain bank. 

That is storage. When you have a disease in the hippocampus, as in Alzheimer’s disease, the information that has been input won’t enter the brain, it won’t be stored. So the person won’t be able to commit it to memory, it won’t ever reach the brain bank. Third scenario, the information has been entered correctly,  it is stored properly, but it is difficult to find. That’s what we call the tip-of-the-tongue syndrome “I know that I know, it will come back to me, that’s always how it is” And that’s when recollection strategies need to be put in place. 

The person has to look for the information stored in the bank so that they can recollect it. As doctors, our job is to distinguish between a problem of input, storage or recollection? Fatigue, depression and so on. Or is it a storage disorder, that means it’s linked to a disease of the hippocampus, in the case of Alzheimer’s disease.  How do we do that in practice? To study episodic memory, we simply ask about recent personal events: what did the person do the day before?  What did they do on previous days? 

We’ll measure the person’s ability to remember recent information, which will give us insight into how the hippocampus is working. We also ask them about temporal and spatial orientation, we do memory tests, word recollection. There is the very useful five-word test which has been developed.You should understand that memory complaints are common after a certain age, but they do not necessarily mean that there is an objective memory disorder. We need to run tests, and those tests will allow us to distinguish between the various issues.