Don Quixote - a short review for healthcare staff

(See also what the International Movie Database says about Don Quixote)

Please note: This article may spoil your spontaneous enjoyment of the film. A number of significant events are revealed, so if you want to watch the film without preconceptions, we advise you to read the article after watching the film.

Theme: Living with dementia
A story about a a misunderstood knight with a misunderstood dementing disease.

By Elisabet Londos, Reader, Head Doctor. Clinical workplace: Neuropsychiatric Clinic of the MAS University Clinic, Malmö. Academic workplace: Clinical Memory Research Unit, The Institution for Clinical Sciences, Malmö, Lund University

The character of Don Quixote in the eponymous film could be suffering from dementia with Lewy bodies. He is the right age, right sex, he has illusions/visual hallucinations, as well as the accompanying delusions. Occasionally, however, he also experiences moments of clarity, which illustrate his fluctuating cognition.

In the film, we see an older man who is said to have "slept and eaten too little and got too carried away reading chivalric novels". We get a clear insight, not only into what he experiences when he has illusions (the giants towering above him that emerge from windmills and wine skins), but also into how he experiences moments of joy with his beloved Dulcinea. For instance, when she throws him a flower during the joust and the flower vanishes in a puff of smoke when he catches it. A brief moment of double experience – reality and illusion simultaneously co-existing – like those so often described by patients, in particular, those in which they see figures which "vanish in a puff of smoke".

Our Lewy body patients do not, as it were, find themselves in such a difficult situation as Don Quixote, because, in the majority of cases, their environments do not enhance or multiply their illusions by setting up scenarios that follow in the wake of any "un-real" thoughts.

As Don Quixote moves through the world of chivalry and wizardry, his obvious response would be to explain away such mistaken perceptions with phrases, such as "It is just magic, they have transformed Dulcinea to an ordinary girl" etc.

The dream becomes a reality

The most remarkable thing, however, is that he seems to be lucid towards the end of his life, especially as he lies on his deathbed talking to Sancho. Perhaps it is the very fact that he is lying down that helps his brain to function? Blood pressure tends to fluctuate rather a lot in Lewy body patients, falling sharply in the standing position without returning to its normal level, as it does in other people. In our clinical findings, we have repeatedly observed that patients perform considerably better in cognitive tests when they are in a lying, rather than a sitting position!

Another symptom usually observed in patients with attentional fluctuations and fluctuations in the sleep-waking cycle is daytime fatigue. We do not see much of it in the film, apart from a few glimpses, but it does occur in logical situations, such as when Don Quixote is injured or at the end of his life.

In Cervantes' books we come across detailed descriptions of Don Quixote's symptoms of REM sleep disorder. This disorder is characterised, in particular, by the absence of automatic muscle relaxation during REM sleep, so that the body starts to enact the individual's dream, leading to such actions as getting out of bed, falling out of bed, shouting, fighting etc. We find many examples of this in the books. A scientific article has also been published on "Sleep and Sleep Disorders in Don Quixote" (ref. 1).

This aspect comes to the fore only once during the film, whereby "the dream becomes reality". The plot itself also tends to follow the same progression: nightmares lead to dream enactment which leads to illusions/visual hallucinations. However, there are individuals who experience REM sleep disorders for many years before experiencing other symptoms.

Neither films nor books depict Don Quixote as clearly suffering from Parkinson's disease. You might find an occasional brief reference to Don Quixote's body being "stiff", perhaps because of increased muscle rigidity? In the film, however, he is still quite mobile and exhibits no sign of slowing down, which is precisely the form that Parkinson's takes in Lewy body patients, in the majority of cases. Tremor is rare in dementia with Lewy bodies and should be excluded from a list of typical symptoms. What we do notice about Don Quixote in the film, however, is that he exhibits surprisingly few facial expressions. Could this be an unconscious symptom of Parkinsonian hypomimia?

In the depictions of Don Quixote in both film and book, we see that he meets the clinical criteria for dementia with Lewy bodies: two out of the three main criteria (visual hallucinations, fluctuations), as well as one supplementary criterion (REM disorder). Even the nature of his dementia, which is marked by relatively more frequent visuospatial difficulties than memory-related ones, may fit this profile.

My guess is that, 400 years ago, as he was writing the two books, Cervantes must have seen or known a person with the kind of symptoms he gave to the character of Don Quixote. The books provide a detailed description of REM sleep disorder, so it may be presumed that Cervantes's portrayal is not solely fictitious.
Another telling factor is his description of Don Quixote's fluctuating mental states.

The film does, in fact, use the word "demented" on one occasion, when Don Quixote is shown living in the past. But one does not get the impression that there is much wrong with his memory. In any case, it is not a major issue. Cervantes's books also provide many examples of the typical symptoms of dementia, especially Don Quixote's problem in understanding three-dimensionality, where he is shown struggling to determine the size and distance of objects. Likewise, Don Quixote has no concept of time

In the depictions of Don Quixote in both film and book, we see that he meets the clinical criteria for dementia with Lewy bodies.

 

Illustration by Ingrid Henell

Examples of how Don Quixote’s clinical picture fits the criteria for dementia with Lewy bodies:

"Den sinnrike junkern Don Quijote av la Mancha"
Translated into Swedish by E. D. V. Lidforss, 1925.
Albert Bonniers Tryckeri, Stockholm.

(English quotations taken from "The Adventures of Don Quixote" by Miguel de Cervantes Saavedra, translated by J. M. Cohen, Penguin Books, 1950)

The dementia picture

"He so buried himself in his books that he spent the nights reading from twilight till daybreak and the days from dawn till dark; and so from little sleep and much reading, his brain dried up and he lost his wits."

THREE EXAMPLES:
a. Lack of ability to determine distance
Don Quixote sees a bark by a river bank, believing it to be enchanted. He jumps into the river and lets himself be carried a short distance by the current: "But we must have already emerged and gone seven hundred or eight hundred leagues … or we have already crossed or shall shortly cross the equinoctial line … Sancho: 'I don’t believe a bit of it … for I can see with my own eyes that we have not moved five yards away from the bank, or shifted two yards from where the animals stand'"…

b. Temporal orientation
"'I cannot conceive', said he, "how your worship, in such a short time as that you have spent below, could see so many things, and ask and answer such a number of questions.' 'How long is it since I descended?', said the knight. 'Little more than an hour', replied the squire. 'That's impossible', resumed the knight, 'for night fell and morning dawned, and darkness and light succeeded each other three times; so that, by my reckoning, I must have remained three days in those sequestered shades, which are hidden from our view.'"

c. Relatively good memory
"… Don Quixote preserved them (the verses) in his memory, which was rather good"

Main symptoms

Complex visual hallucinations – has some insight – paranoid delusions

THREE EXAMPLES:
a. "The horrifying and preposterous adventure involving the windmills: Just then they came in sight of thirty or forty windmills that rise from that plain. And no sooner did Don Quixote see them that he said to his squire: 'Fortune is guiding our affairs better than we ourselves could have wished. Do you see over yonder, friend Sancho, thirty or forty hulking giants? I intend to do battle with them and slay them … Those you see over there, with their long arms. Some of them have arms well nigh two leagues in length.
Take care, sir,' cried Sancho. 'Those over there are not giants but windmills. Those things that seem to be their arms are sails which, when they are whirled around by the wind, turn the millstone.'
– 'It is clear,' replied Don Quixote, 'that you are not experienced in adventures. Those are giants …'"

b. "They now came in sight of some large water mills that stood in the middle of the river, and the instant Don Quixote saw them he cried out: 'Seest thou there, my friend? There stands the castle or fortress, where there is, no doubt, some knight in durance, or ill-used queen … or princess, in whose aid I am brought hither.'

Sancho: 'Don't you see that those are mills that stand in the river to grind corn?'

Hold thy peace, Sancho,' said Don Quixote, 'though they look like mills they are not so.'

The millers belonging to the mills, when they saw the boat coming down the river, and on the point of being sucked in by the draught of the wheels, ran out in haste, several of them, with long poles to stop it.

See what ruffians and villains come out against me' … and so saying he drew his sword and began making passes in the air at the millers.

c.  In one passage, Don Quixote is confronted by a duchess who claims that he has never seen Miss Dulcinea. "'She is only a fantastical mistress, begot and born in your imagination, which hath decked her with all the graces and perfection that fancy could conceive'

Much may be said on that subject', answered Don Quixote. 'God knows whether or not there is such a person as Dulcinea in the world, whether she is fantastical or not fantastical, for these things cannot be fully ascertained."

Don Quixote goes on to explain why he experiences reality the way he does (as regards Dulcinea): 'Now, since I myself neither am, nor, in all probability, can be enchanted, she is the person enchanted, offended, changed, perverted and transformed ...'

Don Quixote explains: 'All of that is nothing but the sheer cunning and trickery of those evil enchanters that persecute me.'

Insight – at various times, Don Quixote both recognises and fails to recognise that his visual hallucinations are not real:

Fluctuating cognition

FOUR EXAMPLES:
a. "Here they esteemed him as a man of sound understanding, and there he slipped in their opinion into the depths of madness, so that they could not determine what rank he should maintain between lunacy and sanity"

b. "They shrewdly noticed that their master in occasional moments demonstrated that he was in full possession of his reason"

c. "… but as he did not know him (Don Quixote), he thought him at times mad and at times wise; because everything that the knight had said was coherent, tasteful and well-expressed, whereas everything that he did unreasonable, rash and foolish"

d. "He is a madman, with frequent intervening moments of lucidity"

REM sleep disorder

More examples from the books:
Don Quixote engaged in bloody and terrifying combat with some skins of red wine, which he mistook for giants: "And the best of it was his eyes were not open, for he was fast asleep, and dreaming that he was doing battle with the giant … and believing he was laying on the giant, he had given so many sword cuts to the skins that the whole room was full of wine."

While I sat musing on this misfortune, I was, all of a sudden, overpowered by a most profound sleep”

DESCRIBES HIS EXPERIENCE OF REM SLEEP:
"While I sat musing on this misfortune, I was, all of a sudden, overpowered by a most profound sleep, and without dreaming of the matter, or knowing how, or wherefore, I awoke, and found myself in the midst of the most beautiful, charming and delightful meadow that nature could create, or the most fertile imagination conceive. I rubbed and wiped my eyes, so as to see that far from sleeping, I was broad awake … Then was my view regaled with a sumptuous palace or castle, with walls and battlements of clear, transparent crystal … The venerable Montesinos led me into the crystalline palace, where in a low hall, cool beyond conception, and lined with alabaster, stood a monument of marble … upon which I perceived a knight lying at full length … a man of real flash and bones … here he is kept enchanted by Merlin, that French enchanter …"

Diagnosis and treatment

By Dag Aarsland, The Norwegian Centre for Expertise in Movement Disorders, Stavanger
University Hospital, The University of Bergen, and King's College London

Diagnosis

Before a diagnosis can be made, the presence of dementia must be ascertained through application of dementia criteria and an objective test confirming impaired cognition, such as the MMT or the clock test. Curable diseases must be ruled out. These include, amongst others, hypothyroidism, hyperparathyroidism, hyperhomocysteinaemia, folic acid deficiency, hydrocephalus and brain tumour. To that end, a computed tomography (CT) scan and a blood test must be carried out (TSH, Ca, Alb, homocysteine).

The next stage involves identifying whether the condition in question is neurodegenerative, vascular or a combination thereof. CT results, in particular, are necessary in order to ascertain this.

The criteria for the different dementia conditions can then be applied. The applicable criteria for dementia with Lewy bodies are the consensus criteria from 2005, which describe the dementia picture, the main criteria and the supplementary criteria (ref. 2). The MMT profile may be used to substantiate the dementia picture.

Treatment

In dementia with Lewy bodies, treatment is based on any petrochemical deficiencies found in the patient, in particular, pronounced acetylcholine deficiency, dopamine and noradrenalin deficiency, but also changes in glutamatergic markers.

Currently, only one randomised, placebo-controlled study of cholinesterase inhibitors (rivastigmine) in dementia with Lewy bodies (McKeith et al 2002, ref. 3) is available. This study shows that the patients who received the study drug experienced less apathy and anxiety and fewer hallucinations and delusions than those who received the placebo. It also found improvements in attentional and certain memory functions. In addition, it showed that patients with hallucinations responded best to rivastigmine (McKeith et al 2004, ref. 4).

Following an evidence-based review in 2006, the American Academy of Neurology concluded that rivastigmine should be considered as a therapy in dementia with Lewy bodies (evidence level B) (ref. 5). Other treatment recommendations are based on established experience:

1. First-line treatment: cholinesterase inhibitors
2. Subsequently, subject to appearance of the worst symptoms:
   a. Parkinson’s disease – I-dopa (3-400 mg)
   b. Hallucinosis - quetiapin (Seroquel), clozapine (Leponex) low doses (6,25-25mg)
   c. Ortostatism - etilephrine (Effortil), midodrine (licensed preparation Gutron),
   d. sleep disorders/depression, mirtazapine, clozapine

Choosing the right drug is extremely important, because of hypersensitivity to neuroleptics, which have resulted in death in a number of cases which have been described (ref. 6). Where neuroleptics must be used, quetiapine or clozapine are recommended. There are three randomised control trial (RCT) studies of dementia with Lewy bodies: the above-mentioned rivastigmine study, a post-hoc analysis of olanzapine, which found a reduced incidence of delusions and hallucinations compared to placebo at 5 mg, but not at 15 mg (Cummings et al 2002, ref. 7) and, finally, a quetiapine study, which showed no effect on agitation or psychosis (Kurlan et al, ref. 8). However, this study was underpowered and the treatment involved vastly higher doses than would ever be prescribed for dementia with Lewy bodies! For this reason, we have no strong evidence that can help to determine the choice of neuroleptics. Perhaps, we could conclude that low doses of this drug are appropriate for patients!

Consensus criteria for dementia with Lewy bodies

(McKeith, Dickson et al. 2005, Ref 2)

1. Progressive decline of several cognitive functions of sufficient magnitude to interfere with normal social or occupational function.
2. Presence of at least two main criteria or one main and one supplementary criterion.

Main criteria

• Fluctuating cognition with pronounced variations in the sleep-waking cycle (typically expressed as daytime fatigue with >2 hours of sleep a day)
• Recurrent visual hallucinations which are typically complex and detailed (often accompanied by good insight)
• Spontaneous symptoms of parkinsonism (typically without tremor)

Supplementary criteria

• REM sleep disorder (whereby the patient enacts his or her dreams, which may occur a few years before the onset of dementia symptoms)
• Severe hypersensitivity to neuroleptics (applies to both typical and atypical neuroleptics)
• Low presynaptic dopamine receptor activity observed in basal ganglia during a dopamine transporter (DAT) scan (picture similar to Parkinson's disease)

Supporting symptoms or examination findings
(non-specific, i.e. they may also be associated with a number of other diseases, but are often present in dementia with Lewy bodies)

• Repeated falls and syncope
• Transient, unexplained loss of consciousness
• Autonomic dysfunction (may occur in the early stage of the disease)
• Abnormal MIBG myocardial scintigraphy (low uptake)
• Systematised delusions
• Hallucinations in other modalities
• Depression
• Relative preservation of medial temporal lobe structures on CT/MRI
• A generally low uptake SPECT/PET, reduced occipital activity

Prominent slow-wave activity in EEG with transient temporal sharp waves.

REM sleep disorder criteria

Bodily movement during REM sleep

including at least one of the following:

• Injurious/dangerous sleep behaviour
• Dream enactment
• Sleep behaviour with disturbance of sleep continuity

However, we need to take into account patients' dopamine deficiency and, therefore, the treatment will be similar to that applied to Parkinson's disease, if hallucinations are present.

Two RCT studies of memantine in dementia with Lewy bodies/Parkinson's disease accompanied by dementia are currently being carried out. One has been clinically initiated and is being conducted by our research groups in Malmö, London and Stavanger. Preliminary results are anticipated in February 2009.

Dementia with Lewy bodies should be treated by experienced doctors and those interested in treating dementing diseases. It is often difficult to treat, with many different drugs having to be balanced (acetylcholinesterase inhibitors, I-dopa, antidepressives, blood-pressure medicines etc.).

The onset age of dementia with Lewy bodies is approximately the same as that of Alzheimer's disease, which means that it is most common after the age of 65. Available studies suggest that the life span is significantly reduced in dementia with Lewy bodies, with survival from onset estimated at 5-7 years (ref. 10 and 11).

How common is dementia with Lewy bodies?

Given that the criteria for dementia with Lewy bodies were published as late as 1996 and revised in 2005, no classic epidemiological studies of this disease have yet been carried out. In the six studies that have been carried out, prevalence varies between 0 and 30.5% of demented subjects (ref. 9). In the study which recorded the highest prevalence levels, the criteria for dementia with Lewy bodies were not applied, because all the subjects enrolled had some form of Parkinson's disease. Another study showed a 21% prevalence (in this one, the highest median age was 83). The three studies with the lowest prevalence levels (0%, 1.7% and 2.8%) were all carried out by neurologists, so the author is doubtful as to whether or not these are of any relevance (it may be that cognitive symptoms in patients with Parkinson's disease were underestimated?).
Other reasons why dementia with Lewy bodies is under diagnosed could be that:

• The memory disorder is not prominent
• The patient's orientation ability is good, which may for a long time perpetuate the impression that the patient is not intellectually impaired
• Practical inability and visuospatial difficulties are often concealed by movement disorders and, thus, remain undetected
• The patient has a good insight into his or her visual hallucinations, but often avoids speaking about them
• The REM sleep disorder may have ceased long before the onset of other symptoms and its link to the disease may be overlooked

Dementia with Lewy bodies should be treated by experienced doctors and those interested in treating dementing diseases

Current research

Our Malmö-based research into dementia with Lewy bodies is concerned with:

• exploring the possibility of using simple diagnostic methods, which have already become part of established clinical practice, to increase the detection of DLB patients and make it more effective, i.e. making examinations more sensitive. Some of the examinations we use are MMT, AQT, the clock test, the cube test, orthostatic blood pressure control, EEG, the UPDRS movement rating scale
• ways of interpreting more advanced examination results, such as CSF and dopamine transport tests (DaTScan)
• health economics, which includes both cost estimation and resource utilisation, but also quality of life surveys
• drug scrutiny. We are conducting an RCT (randomised, placebo-controlled) study of memantine in dementia with Lewy bodies and Parkinson’s dementia, in conjunction with our research groups in London and Stavanger. The study has been clinically initiated and is due for completion in February 2009.

In addition, we have also engaged three research students, who are attached to projects researching dementia with Lewy bodies.

MARIA ANDERSSON, HOUSE OFFICER BASED IN VÄRNAMO:
Dementia with Lewy bodies is considered to be the second most common form of neurodegenerative dementia after Alzheimer's dementia. It is characterised by parkinsonism, visual hallucinations and fluctuating cognition. In addition to these main criteria, there are also a number of supplementary diagnostic criteria, such as autonomous dysfunction, which have not been as well researched. It is important to diagnose patients suffering from dementia with Lewy bodies correctly, because they respond well to cholinesterase inhibitors treatment, although they are rather susceptible to the side-effects linked to treatment with neuroleptics. That is another important factor, because DLB progression and prognosis differ from those of other dementing diseases.

The objective of my research: To investigate physiological factors and characteristics in patients with dementia with Lewy bodies, in order to detect patterns which could demarcate this group from patients with other dementing diseases. The long-term objective of this effort is to facilitate diagnosis of this patient group by using clinically established research methods and tests.

The studies carried out to date have shown that, in contrast to Alzheimer's patients, patients with dementia with Lewy bodies: (1) have a more pronounced orthostatic reaction and are orthostatic for a longer period of time, (2) have longer AQT reading times and (3) have an increased variability of slow EEG frequencies, which could be attributable to clinically observed sleep-waking cycle fluctuations.

Generally speaking, research into dementia with Lewy bodies will very soon reach the stage where we are be able to measure the levels of alpha-synuclein, the protein that makes up Lewy bodies, in the cerebrospinal fluid (CSF)

FREDRIK BOSTRÖM, HOUSE OFFICER BASED IN VÄRNAMO:
My research project is focused, on the one hand, on the impact of dementia with Lewy bodies on my patients' quality of life and DLB-related public expenditure and, on the other, on the pathogenesis of the disease, which involves the key method of analysing the levels of trace elements and protein in the cerebrospinal fluid (CSF).

We have conducted a comparison between 34 Lewy body patients and 34 Alzheimer's patients, with regard to quality of life and resource utilisation, which included an analysis, not only of community and medical care, but also of any unpaid care provided by the patients’ relatives. Our results show that patients with dementia with Lewy bodies have a significantly lower quality of life and require roughly twice as many resources as those with Alzheimer’s disease. In addition, our results point to differences in the ultimate outcomes of these two diseases and we will be able to use them in planning interventions, so as to reduce cost and alleviate suffering.

Trace elements are considered to play a key role in the development of degenerative dementing diseases. We have analysed trace element levels in the CSF of 29 Lewy body and 174 Alzheimer's patients, as well as that of 51 healthy voluntary control subjects, in order to ascertain whether or not trace elements play a specific role in the development of dementia with Lewy bodies. Our analyses have shown that the Lewy body patients had clearly increased magnesium and potassium levels in their CSF. Any changes could be used to diagnose dementia with Lewy bodies with a good degree of certainty and they constitute important pieces in the puzzle of understanding DLB's pathogenesis. In a follow-up longitudinal study, we are planning to study the impact of any deviating trace elements on survival and cognitive deterioration in the subjects enrolled in the above-mentioned study.

SEBASTIAN PALMQVIST, HOUSE OFFICER BASED IN MALMÖ:
With the increase in the number of people suffering from dementia, health centres and memory clinics are experiencing a great need for simple examination and follow-up methods which are ready to use now, rather than in five to ten years' time. For this reason, my research is focused on how to improve the interpretation and use of those tests currently in use. I have presented my findings in the form of simple, practical proposals which can be applied directly by clinics to improve examination and follow-up.

In another study which has already been completed, I have demonstrated that the simple cube copying test, which is used by many clinics, can be used to follow up the treatment of Alzheimer’s disease (AD). We did not know this previously. I have also shown that dementia with Lewy bodies (DLB), a common and under diagnosed dementing disease, can be identified and delimited from AD by applying simple interpretations of the MMT, the clock test and cube copying (sensitivity 93%, specificity 70%).

Generally speaking, research into dementia with Lewy bodies will very soon reach the stage where we are be able to measure the levels of alpha-synuclein, the protein that makes up Lewy bodies, in the cerebrospinal fluid (CSF). If this examination is included in clinical practice, it will mean a huge step forward for diagnostics.

We need to be able to assess alpha-synucleinopathy in conjunction with any symptoms of Alzheimer's pathology (plaques and tangles in the CSF, manifesting as beta-amyloid and tau protein), because, where they occur in combination, the patient's prognosis is worse and we, therefore, need to be more attentive and take more rapid action to provide help and care.

Dementia coupled with Parkinson's disease

Parkinson's disease (PD) is a neurological disease which is clinically defined as tremor at rest, rigidity, akinesia and postural instability, and pathologically as Lewy bodies and loss of dopaminergic neurons in substantia nigra (a midbrain structure). In the past decade, research has shown that a number of neuropsychiatric symptoms may occur in many patients with PD.

In terms of the neuropathology, degenerative changes have been found in many regions of the brain, both in the cortical and subcortical regions. The spread of Lewy body pathology through the brain follows a set pattern: the initial changes occur in the lower segment of the brainstem and then progress rostrally, involving serotonergic and adrenergic brainstem nuclei; only then do they affect the substantia nigra and the cholinergic nuclei, progressing further to the limbic structures, such as the amygdala and the hippocampus, and, finally, to the neocortical regions. It is, therefore, not surprising that the clinical picture includes, not only motor symptoms, but also disorders in many other systems, as well, such as autonomous, affective, cognitive and perceptual disorders and changes affecting the patient's ability to initiate action, the regulation of his/her sleep-waking cycle and attentiveness. The overlap between neurology and psychiatry in PD is more extensive and challenging than in any but a handful of other diseases, and studies investigating this overlap have helped increase the understanding of the correlation between brain and behaviour.

Cognitive failure and dementia coupled with Parkinson’s disease

In a third of all patients, a mild cognitive impairment is detected at the time of diagnosis. Typical impairments affect attentional, executive function and visuospatial ability, but memory impairment has also been observed, too. In contrast to Alzheimer’s disease, the most characteristic symptom of PD dementia is attentional disorder, which has been shown to be an important contributor to the impairment of practical and social functions.
Cross-sectional studies show that around one third of all patients with PD also suffer from dementia. The risk of dementia is 4-6 times higher in PD than in the general population and increases with the duration of the disease, age and severity of motor symptoms. Patients who exhibit relatively pronounced symptoms and do not respond well to levodopa, and whose symptoms are therefore deemed to be related to non-dopaminergic factors, such as postural instability or difficulties walking, are at particularly high risk of developing dementia. For this reason, the overall risk of dementia is very high, with up to 80% of patients developing dementia.

It can be difficult to diagnose dementia in patients with PD. In addition to the clinical interview with the patient and his/her family, it is also important to test his/her cognitive functions. MMSE is largely based on memory and language and is not that suitable as a tool for identifying initial cognitive failure in PD. Straightforward tests, such as the Stroop test, the verbal fluency test, the clock test and the trail-making test might be suitable, and so might cognitive screening methods, such as the Dementia Rating Scale. Visual hallucinations and apathy are typical neuropsychiatric symptoms which occur in patients with PD and dementia, and their presence should, therefore, warrant a thorough examination of the patient's cognitive functions. During MRI examinations, we have observed a more pronounced cortical atrophy in PD patients who have dementia than in those who do not, but this is still largely based on group data and MRIs will not be of any further help to us, as far as diagnosing dementia is concerned. However, an MRI should also be carried out on patients with dementia, in order to rule out any other possible causes of dementia in patients with PD, such as cerebrovascular illness. The recently published criteria for Parkinson's dementia (Emre et al, Mov Disord 2008) and recommendations for diagnostic procedures are now available to help us in arriving at a diagnosis of Parkinson's dementia (Dubois et al, Mov Disord 2008).

Many patients have a stable cognitive function for many years, while others exhibit a very fast progression

There are many similarities between PDD and DLB, both clinically and neuropathologically. According to the diagnostic criteria for DLB and PDD, patients who develop dementia after experiencing PD-related motor symptoms for more than a year should be classified as PDD, whereas patients who develop dementia before the onset of, or concurrently with, any motor symptoms should be classified as DLB. Despite the many similarities, there are findings which suggest that both clinical and biological differences exist regarding the onset of dementia. Patients who develop dementia early on have a more pronounced atrophy and more pronounced morphological changes, whereas patients who develop dementia during the later stages have a more pronounced cholinergic failure and less pronounced morphological changes.

Progression and treatment

Typically, cognitive failure progresses and develops in patient with PD just as fast as it does in patients with Alzheimer’s disease, but there is great variation between individuals. Many patients have a stable cognitive function for many years, while others exhibit a very fast progression. Great variation may also be observed in the time that elapses between the onset of motor symptoms and the development of dementia. Certain patients develop dementia within a few years of being diagnosed with PD, whereas others may not develop dementia until twenty or more years later. Older patients and patients with mild cognitive failure are significantly more at risk of developing dementia than patients whose cognitive function is intact.

Atrophy of cortical and subcortical structures has been found in patients with dementia and mild cognitive failure. In these cases, atrophy was probably caused by Lewy bodies, amyloid plaque and neurofibrillary tangles, symptoms of protein production, metabolism and/or processing such as alpha-synuclein, amyloid precursor protein (APP) and tau protein. In addition, it is thought that neurochemical changes are another factor which contributes to atrophy. Pronounced cholinergic disorders in the neocortex play a key role in this regard, because of atrophy of the cholinergic neuron in the nucleus basalis Meynert. Cholinergic failure is more pronounced in dementia patients with Parkinson’s disease than in those with Alzheimer's disease.

There is no treatment currently available to reverse the degenerative process of PD, nor any disease-modifying treatment. A naturalistic study has found that the glutamate antagonist amantadine reduces the risk of dementia, but because this was not a randomised, controlled study, this result should be interpreted with great caution. The cholinesterase inhibitor rivastigmine has proved to have a positive effect on dementia in PD, including on attention, in particular in patients with visual hallucinations. Treatment with rivastigmine should, therefore, be tested on all Parkinson's patients with dementia. Memantine’s potential to reverse the symptoms of dementia in demented Parkinson's patients has not been systematically examined yet, but such examinations are underway and it is hoped that they will provide an answer to this important question during the course of 2009. Dopaminergic anti-Parkinson's drugs may affect cognitive functions, but their effect is complex and varies, depending on the type and severity of PD. Their effect is moderate and also varies in relation to different cognitive functions. However, anticholergenic Parkinson’s drugs may cause cognitive functions to deteriorate and have also been shown to increase the incidence of Alzheimer's changes in the brain. This is why such drugs should not be administered to Parkinson’s patients with cognitive failure.

By E. Londos

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