A leading expert answers GP questions about the early signs of dementia.
Professor Michael Saling presents an approach to the assessment of memory complaints to help GPs differentiate true early dementia from the worried well.
Early referral to a neuropsychologist is important to the patient and the family, as obtaining the correct diagnosis is critical. This is part one of this series.
Practice points
- People who are anxious, stressed or generally feeling unwell give quite a strident complaint and they draw your attention to their memory issue, sometimes repeatedly, quite obviously and prominently.
- When errors of capture are the predominant feature of the complaint, that’s very likely to be related to depression, stress or anxiety.
- Letter-based tasks don’t change in early Alzheimer’s disease despite the fact that they are difficult. Easier language-based tasks, the semantically based task, drops quite considerably.
- Early-onset dementia is approximately the late 40s, but more likely within the 50, or maybe even 60 years of age or so. That would also raise the question of an atypical onset.
- The atypical onsets of dementia are displayed in a language form. This begins with a focal language condition that we call “logopenic aphasia” and it presents as very slow halting language in which they clearly are dysnomic; they are missing out on names of things and their sentences are quite simplified.
- The other variant that is not uncommon is the posterior cortical variance, which takes the form of visual spatial disturbances. This is closely related to Alzheimer’s disease pathology.
- Lewy body dementia usually has about a 12-to-36-month history of Parkinsonism before the features of dementia set in and well-formed animate hallucinations and fluctuating cognitions occur.
- Rapid eye movement (REM) sleep behavioural disorder is a very big feature of diffuse Lewy body dementia.
Professor Michael Saling (MS)
My name is Michael Saling and I am a professor of neuropsychology at Melbourne University. I am also a clinical neuropsychologist based at the Austin Hospital, Melbourne. I have directed the department and been running a cognitive disorders clinic for quite a number of years. I have recently retired and am continuing as a professorial Fellow.
Patients with early-stage dementia are actually quite a big component of my clinical life and in many cases they have quite complex and unusual dementias. The differential diagnosis is one of the main things we are engaged in that can assist others.
Dr David Lim (DL)
This is a very common issue in general practice. Patients come in and say, “Doctor, I think I’m losing some of my memory!” or a family member comes in and says “I’m a bit worried about my father…” How do we know when these complaints are actually significant?
MS:
Certain subjective and presenting features are important. I think one of the most important is the length of the history of memory concerns. Generally speaking, with the worried well, the history is quite short; just a matter of weeks would be most unlikely to be a person who’s developing a dementia.
Generally speaking, we don’t see individuals who are in the earliest stages of a developing dementia. The patient, or somebody in the family, has usually first noticed the symptoms at least six to 12 months, or longer, before they come to you. The symptoms are of very gradual onset, and very often, they are put down to just ageing.
Another very important difference is the manner in which the symptoms are delivered. The complaint is rather muted in people developing Alzheimer’s disease, even at a very early stage. There is very cautious concern that possibly their memory is not as good as it used to be, but this is also accompanied by what we’ve come to call a “dismissive attitude”. As one gentleman said to me, “I’m not so bad, you should see the others at the bowling club!”. There’s very often a tendency to dismiss the severity of the issue, a very cautious complaint. This is opposed to people who are anxious or stressed or generally feeling unwell; you can get quite a strident complaint and they draw your attention to their memory issue, sometimes repeatedly, quite obviously and prominently. These patients talk a lot about their own memory complaint and when you get to ask about the last time they noticed a memory failure, they will give you quite a well-contextualised account. “You know, it was last Friday. I was in my shed … I was looking for my hammer…!”
People who are developing Alzheimer’s disease don’t contextualise their memory failures. At a very early stage, usually the patient presents on their own, the family hasn’t noticed anything. When the family begins to notice things, the situation is becoming a little bit more serious.
There are some useful screening tasks. The mini-mental state examination (MMSE) is very insensitive at the early stages, but the drawing test is sometimes quite useful if it shows a very particular feature we call the “minute hand effect”, when you ask them to set the time on their hand-drawn clock face at ten minutes past eleven. They put one hand against the 11 and the other hand against the ten. We’ve actually shown that they’re losing their concept of the dual meaning of numbers around the clock’s minutes and hours.
If you are not seeing that very obvious, strident kind of complaint discussed before, it may be worth referring the patients. Clinical neuropsychologists would do very detailed memory testing of associated features such as language. We now have some very evidence-based neurocognitive markers of an Alzheimer’s process and these can surface at a pretty early stage. One of them is the difference between generating words on an executive basis, as compared with semantic basis.
Essentially, what was once easy becomes harder, and what is usually difficult shows no change. That difference has now surfaced as a very important marker. In recent papers on this finding it has also been very closely tied to neuro-biomarkers.
DL:
Could you give an example of “what was easy becomes harder and what’s difficult shows no change”?
MS:
Certainly. We have a word generation task in which we ask the patient to give us as many words they can think of that begin with a particular letter. This is not a natural language task, because we don’t store words like a dictionary does. So that requires quite a lot of executive function and it’s quite a difficult task.
The second task is to generate as many words as they can that fit into a particular category, such as animals; for example, name as many animals as you can in 60 seconds. That is generally a much easier task because it’s a natural language task. The first task, the letter-based task, doesn’t change in early Alzheimer’s disease despite the fact that it’s difficult. However, the easier task, the language-based task, the semantically based task, drops quite considerably.
That gap translates as atrophy in the entorhinal cortex, it corresponds to 18F-FDG [a marker for tissue uptake of glucose] positron emission tomography (PET) markers and it actually translates to the distribution of early stage tauopathy [the deposition of abnormal tau protein in the brain causing neurodegenerative disorders]. It is a fascinating thing.
We can establish whether there’s a strong likelihood of an Alzheimer’s process, for example, by the typical clinical presentation. There is another thing that I might mention by way of presentation. The patient arrives with a significant other and their routine social interaction (e.g., weather, hobbies, sport) is normal, but when you discuss less-routine issues, the patient drops into the background and the significant other steps into the conversation. You find yourself talking to significant other while the patient has withdrawn. If you address something to them, they’ll often defer to the significant other for the answer. That is a feature of late-stage, mild cognitive impairment, a very-early-stage Alzheimer’s disease. This is something we’ve seen multiple times over the years. The Americans are call it the “head-turning sign”, which I think is unfortunate!
It is quite a characteristic presenting feature of some sort of early dementia. The other thing to bear in mind is, of course, that the patient is neurologically normal. They come across that way; there is no personality change, but there may be a degree of depression and, of course, the memory concern.
DL:
Which brings up the next point. How am I to understand, if you like, memory loss in a patient with significant depression?
MS:
It is possible to have both memory loss and depression. However, I would have to say that anxiety, depression, stress and just the general feeling of being unwell for any medical reason whatsoever may relate to the cause of the memory complaint.
There’s quite a bit of the stress around the memory complaint in all of those cases. Depressed patients keep bringing the memory issue to your attention. They don’t let you move away from it easily and they account for everything that’s going wrong. The complaint of a memory issue can sometimes be overgeneralised and will take in too many systems to be credible; for example, “I’ve forgotten how to tie my shoe laces!” or “I can’t switch on the kettle when I make tea…”, perhaps, “I’ve forgotten how to spell!”. All of those things have nothing to do with Alzheimer’s disease or other dementias.
The other common thing you’ll hear from that group is what we call “errors of capture”; for example, I walk into a room and I have forgotten what I wanted to do there. When errors of capture are the predominant feature of the complaint, that’s very likely to be related to depression, stress or anxiety.
DL:
These are two things that might be of great value to us. Certainly the drawing tests and asking a few questions about executive function, words and grouping as many animals or plants together as possible. This may give us an idea that we are dealing with something significant.
MS:
We do more than that in the form of assessment, but asking the patient to list things under a single letter, and then a single category, will give a sense of whether they are having more difficulty with the category than with the letter-based generation. You certainly can get a feel for cognitive impairment and the formal testing really discloses that if this is present.
DL:
So we’ve seen the patient, we may have an idea of whether or not we are less concerned about the symptoms being true dementia versus stress with the tools that you’ve given us.
What about age? Do we worry about people who are young? Are there particularly younger onset cases that we should be concerned about and do they present the same way?
MS:
That’s a wonderful question.
There is, of course, an autosomal dominant genetic form, which appears at a remarkably early age, (e.g., the 30s), but it is extremely rare. So for most practical purposes, early onset is approximately the late 40s, but more likely within the 50s, or maybe even 60 years of age or so. That would also raise the question of an atypical onset.
The atypical onsets that we commonly encounter are displayed in a language form. The condition begins with a focal language condition that we call “logopenic aphasia” and it presents as very slow halting language in which they clearly are dysnomic; they are missing out on names of things and their sentences are quite simplified. This is the slightly more advanced picture you get that. Anybody who triggers concern of an early-onset word-finding difficulties is worth referring, because this might be the logopenic variant.
The other variant that is not uncommon is the posterior cortical variance, which takes the form of visual spatial disturbances. That can be quite basic and quite profound. If a patient gives any suggestion of not quite being able to recognise things clearly, or not being able to see things clearly despite normal ophthalmology, should trigger suspicion of posterior cortical atrophy. This is very closely tied to Alzheimer’s pathology.
There are other pathologies, such as Creutzfeldt-Jakob disease (CJD), but this is very uncommon. Most cases of dementia (80% of them) have Alzheimer’s disease.
There is another variant that is a little bit of a misnomer and has now been downgraded; the so-called frontal variant, where they tend to present with changed behaviour. The family will tell you about that; they are not quite the same person they used to be. They present with disorganisation in their life rather than a memory problem. This can be a form of Alzheimer’s disease, but we now know that there is no pathology in the frontal lobes to explain it.
The idea of the frontal variant is now being downgraded. However, if somebody is very muddled and disorganised in life, it’s worth referring them anyway, because it can be an atypical onset of Alzheimer’s disease. The language variance and the visuospatial variance are probably the two most common atypical variants and they do begin early in the disease.
DL:
What about people who have been reported as getting lost … and those who keep very loudly telling us that somebody is coming into the house to steal their money?
MS:
That is a paranoid presentation. It is really when there is Alzheimer’s disease, this is quite an advanced feature, but this could also be somebody who’s developing a diffuse Lewy body dementia.
When there are neuropsychiatric features at an early stage, there can be well-formed animates, visual hallucinations. These are often very extremely well formed, very compelling, or there can be a feeling constantly feeding that somebody’s standing behind the person. There is a paranoia associated with that, but generally those patients will have presented with Parkinsonism. It has usually been about a 12-to-36-month history of Parkinsonism before the features of dementia set in. When they do set in, well-formed animate hallucinations and fluctuating cognitions (i.e. the patient’s cognition reduces and then comes back again) occur.
When you hear a story of rapid eye movement (REM) sleep behavioural disorder, that’s a very big feature of diffuse Lewy body dementia.
DL:
Which REM sleep behavioural disorders are you speaking about, in particular? The patients who throw their hands around and beat up their sleeping partner and break their sleep lamps, or what sort of disorders?
MS:
Well, it can include those patients. Yes, certainly it can include those. Sometimes it’s a bit more elaborate than that; they will actually get up and act out something. We had one case when his wife woke up in the middle of the night with a pillow over her head … she was fighting vigorously and she thought she was going to pass out and suddenly the pillow lifted and she’s greeted by the smiling face of her husband who was, uh, asleep. That was one of the more dramatic forms of the condition. However, thrashing around, shouting out or punching a partner would be suspicious.
To be continued in part two.
We would like to thank Professor Saling very much for his expertise and time.
This was first published on Healthed. To listen to the full episode, click here.
