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57 year old right handed man. Family history negative for neurological or cognitive disorder.
Birth and early development were unremarkable. He was schooled until the age of 15 and
trained as an electrician. He had always worked as an electrician, most recently in a printing
works. He has not worked for several months because of the difficulties with memory and
job performance.
Cognitive problems date back less than 9 months according to him and his brother in law. He
describes difficulties with remembering how to carry out tasks, like fixing printing machines.
He described an instance where he wired up a printing machine in the wrong way. Previously
he would be able to carry out jobs in the plant without any form of prompt, but recently has
had to write everything down. He has also developed a tendency to lose things, particularly
tools. There was no suggestion of particular problems with language function or praxis. He
became more hesitant in his manner according to his brother in law, without any more marked
behavioural changes. His mood had been low, and he had lost some weight. He would sleep
more during the day and sleep normally at night. There were no psychotic features.
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NEUROPSYCHOMETRY
WMS indices
Verbal memory XX
Visual memory XX
General memory XX
Attention/concentration XX
Delayed recall XX
2
Investigations
• EEG normal
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Discussion
1. This patient has an early organic dementia with symptomatic deficits in new
learning and anterograde memory.
2. Notice that the MMSE exam score is above the cut off score typically used to
identify cognitive disorder (24) whilst the Cambridge assessment yields a score that is
below the cut off used to predict cognitive disorder (84). The Cambridge assessment
incorporates additional tests of verbal fluency, new learning and delayed recall that
are useful in helping to pick up early dementia. The Cambridge assessment is
therefore more sensitive than the MMSE. Both MMSE and Cambridge assessment
have sensitivities of 96% but the sensitivity of the two tests is 52% and 82%
respectively (based on the cut offs above and a population of patients referred to the
Cognitive Clinic in Cambridge.
5. The NINCDS-ADRDA criteria are rather broad research criteria and also often
apply to other forms of dementia, especially Lewy Body dementia. In this case there
are no operational criteria to support that diagnosis. There are no features to suggest
the multi infarct form of vascular dementia although the distinction between vascular
dementia and AD can be very difficult clinically, radiological and pathologically.
6. In terms of imaging for early-onset dementia I think all patients should have at least
a CT scan, primarily to exclude a structural lesion such as frontal meningioma. In AD,
MRI research studies using volumetric analyses demonstrate hippocampal atrophy
followed by atrophy of other areas, but in early cases the MRI is often normal based
on a standard qualitative report. I do not think that SPECT is needed in most early-
onset cases of dementia and I reserve it for cases where 1) I am not sure if there is an
organic dementia or not and 2) when I want evidence as to whether the patient has a
frontotemporal dementia as opposed to one of the other types (when the distribution
of perfusion deficit is helpful).
7. The main use of the EEG in early-onset dementia is to provide supportive evidence
for the presence of an organic dementia, when slow wave changes will be present.
These are not specific, being present in most forms of dementia, and follow treatment
with a number of drugs. There is argument about whether the EEG can help
distinguish AD and other forms of dementia. I am not enthusiastic, especially in
clinical practice where you want single-subject inference rather than group
differences. The EEG can be normal in many cases of early-onset dementia. The
periodic complexes in CJD are specific, but often not present. Do not forget to tell the
EEG department if this is an issue as they will need to use disposable electrodes.
8. I do not think there is a role for routinely assessing mutations of Amyloid Precursor
Protein (APP), Presinilin (PrS), or ApoE ε4 in clinically probable early-onset
Alzheimers disease. I carry out occasional assays for APP and PrS if there is good
evidence for an autosomal dominant family history. In that case I only carry out the
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assessment after consultation with the genetics service who are able to counsel and
screen families after identification of index cases.
9. The definitive diagnosis of AD can only be made at autopsy. The hit rate using
current criteria during life is about the same as in idiopathic Parkinson’s disease,
about 80%.
Refs
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Case 2
58 year old right handed man. Family history negative for cognitive or other
neurological disorders. Premature birth with no clear index neurological event
otherwise. Degree in civil engineering and work as an engineer until just before
assessment. Previously fit and well and moderate alcohol drinker.
The main problem that his wife had noticed was the progressive difficulty with speech
with agrammatic non-fluent effortful output. No change in his behaviour noticed by
his wife. He did not describe any depression or biological features of depression. The
pattern was of clear-cut progressive deterioration in clear consciousness with no
diurnal or other variation. No accompanying neurological symptoms, hallucinosis or
psychotic features.
6
NEUROPSYCHOMETRY
WMS indices
Verbal memory 65
Visual memory <50
General memory <50
Attention/concentration <50
Delayed recall 51
7
Investigations
• CT and MRI showed diffuse atrophy affecting frontal temporal and parietal
lobes particularly
Coronal T1 weighted section through parietal cortex showing parietal and temporal atrophy (latter
more marked on left) and slight ventricular enlargement
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Discussion
1. This patient has a more aggressive organic dementia than case 1. He has a decrease
in VIQ and PIQ compared to his premorbid achievement and estimated premorbid IQ
(likely to be higher than the estimate because he has presented rather late with a
moderate dementia). The decreased performance compared to verbal index (even
despite the symptomatic and observed language deficit) is typical of Alzheimer’s
disease (AD) and a number of other types of dementia. The WMS shows striking
difficulties in memory and attention.
7. I do not carry out lumbar puncture on all patients presenting to the cognitive clinic,
but did so here because of the atypical features and rapid progression. This is mainly
to seek evidence for an inflammatory basis or vasculitis, and to allow 14-3-3 protein
testing in a small number of patients where there is a strong suspicion of CJD.
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Case 3
Transfer from one of the local hospitals two months after admission there. 59 year old
right handed man with no family history of cognitive or neurological disorder and no
index neurological event. He previously worked as an RAF flight sergeant. There was
a background of hypertension and a question about his previous alcohol intake. This
was recorded in the notes as being at a level of 70 or 80 units per week at one time but
this was not corroborated with his family.
He had a stroke two years before assessment when he was found to have a
haemorrhagic right frontal and temporal infarction from which he recovered well. He
had a single blackout of unclear cause one year before assessment shortly after return
from a trip to Goa, with no events after that to suggest generalised or partial seizures.
The current admission followed presentation to his local hospital in a confused state
after return from another trip to India. His money and credit cards had been stolen
and he had no recollection of the events whilst he was in India. He was disoriented
and had nystagmus on admission to the referring hospital.
During his admission to the referring hospital he had been agitated and restless and
exhibited repetitive motor behaviour such as pacing and repeatedly going to the toilet.
He had been disoriented in place, thinking that he was at his friend’s house and he
repeatedly tried to leave the ward. He needed to be prompted about meal times and
would forget that he had had a meal within one hour. His memory of events from one
day to the next was very poor. There were reports of auditory and visual
hallucinations and he expressed a number of abnormal beliefs including the belief that
he was still in the RAF. According to his care assistant his conscious level had not
shown any marked fluctuation over time over the last month and there had been little
change in his memory capacity.
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Investigations
• MRI showed changes consistent with the old right frontotemporal infarction
• EEG normal
• Lumbar puncture showed raised protein on two occasions two months apart
(0.98 g/L and 0.74 g/L). Sample as acellular and negative for oligoclonal
bands
• CXR normal
• serum B12, red cell folate, red cell transketolase levels not available prior to
receiving a month of B vitamin supplements
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Discussion
1. Detailed neuropsychometry is not really needed here, and has not been supplied.
The striking confabulation actually made formal neuropsychometry extremely
difficult.
3. In terms of recovery this is still possible in such cases after several months. In
studies by Victor a quarter recovered completely on thiamine, a half showed partial
recovery and the rest showed no recovery. Recovery can be delayed for months and
can take up to two years if it does occur.
Refs
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Case 4
Initial assessement: 49 year old fully right-hand dominant woman with normal birth
and early history and no index neurological event. Schooling to the age of 16 after
which she has worked as a librarian, shop assistant and housewife. Family history
negative for neurological disorder or vascular disease. Non-smoker and occasional
drinker.
Apart from a tendency to walk with a shuffling gait she had no other neurological
symptoms and she was systemically well.
Screening cognitive testing using the Cambridge schedule yielded a mini-mental state
examination score of 15 out of 30. She was disoriented with poor registration and
recall. New learning of a seven-item address was poor and she showed perseverative
errors, a tendency to mix items and phonemic paraphrasias. Language comprehension
and reading were good and her repetition for single words was normal but impaired
for phrases. Naming testing yielded a score of 7 out of 10 and her verbal fluency was
strikingly abnormal at zero. Her drawing was very poor.
Neurological examination revealed normal fields, fundi and eye movements. Lower
cranial nerve testing was normal. In the limbs she had normal tone with symmetrical
slightly depressed reflexes and bilateral downgoing plantar responses. There was no
finger nose dysmetria or gait ataxia. There were no primitive reflexes. She walked
with a shuffling gait which was not broad based with decreased arm swing. There
were no abnormal movements.
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NEUROPSYCHOMETRY
WMS indices
Verbal memory 65
Visual memory <50
General memory <50
Attention/concentration <50
Delayed recall 51
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Investigations
• MRI scan showed central and cortical atrophy with one or two small areas of
white matter signal change
• Screening blood tests normal and negative tandem repeat for Huntington
mutation.
• csf examination showed minor excess of protein in the CSF (0.58g/l), negative
14-3-3 protein and s100b.
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Discussion
1. This patient has a moderately severe dementia and meets operational criteria for
Dementia with Lewy Bodies (DLB). She exhibits fluctuation in conscious level,
hallucinosis, and extrapyramidal symptoms and signs. There is a particular sensitivity
to neuroleptic medication in this group and increased incidence of neuroleptic
malignant syndrome (not relevant here).
2. In terms of the neuropsychometry she shows poorer WMS-R indices than the VIQ
and PIQ as might be present in a patient with AD of comparable severity.
Comparisons of groups of subjects with AD and DLB show poorer attention and
working memory in the latter. They also show poorer visiospatial skills. It is
important to point out that these cognitive features are based on group studies and it is
very difficult to point out in any subject, on the basis of the psychology alone,
whether either diagnosis is more likely.
Refs
Calderon J, Perry RJ, Erzinclioglu SW, Berrios GE, Dening TR, Hodges JR.
Perception, attention and working memory are disproportionately impaired in
Dementia with Lewy bodies comapred with Alzheimers disease. J Neurol Neurosurg
Psychiatry 2001; 70: 157-164.
McKeith IG, Perry RH, Fairburn AF, Jabeen S, Perry EK. Operational criteria for
senile dementia of Lewy body type (SDLT). Psychol Med 1992; 22: 911-922.
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Case 5
86 year old right handed man with no family history of neurological or cognitive
disorder of which he was aware. No index neurological events or fits. He was
schooled until his teens at a secondary modern. He has had a variety of jobs including
managing a cinema and work as council planning department manager. He had a
history of several years of deterioration of walking and altered behaviour but he was
unaware of this when he was assessed in the cognitive clinic and he had no family to
corroborate the story. He has also had a history of possible TIAs. He volunteered no
vascular risk factors and was on aspirin when assessed.
The initial assessment was striking for him being disinhibited and showing echolalia
and perseveration.
Cognitive testing using the Cambridge Screen revealed him to be oriented to the year
and the season only with good registration but poor anterograde verbal memory (3/3
registration of three items but 0/3 1 minute recall even with cueing). There was
difficulty with strategy with new learning of a name and address, with the same score
based on different items over three attempts. Language comprehension was good,
repetition mildly impaired and naming also mildly impaired but he had a striking
deficit in verbal fluency with only two ‘p’ words in a minute and a tendency to
perserveration. Category fluency was also strikingly reduced with one neologism for
an animal he made up. Reading of regular and irregular words was normal but writing
strikingly impaired and his copying of figures was also mildly impaired.
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NEUROPSYCHOMETRY
He was rather difficult to assess. For example, he sang four lines from the song ‘love
and marriage’ when asked to explain the similarity between love and hate
Other tests:
Very poor peformance on Hayling and Brixton tests of executive functioning. The
Hayling test is a sentence completetion task requiring subjects to complete a sentence
with a nonsense ending (and suppress a sensible one) The Brixton test is a visiospatial
sequencing task with rule changes.
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Investigations
• MRI showed mild diffuse cortical atrophy, a left sided acoustic neuroma
without significant brainstem compression and a single infarction in the left
basal ganglia
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Discussion
1. This patient suffered from the most striking frontal lobe syndrome I have ever seen,
in combination with an asymmetrical extrapyramidal syndrome and stimulus sensitive
myoclonus. In addition to the frontal features there is some dyspraxia. The diagnosis
is corticobasal degeneration and there is really no differential here. The
extrapyramidal syndrome is often associated with alien limb (not present here), and
the helpful feature is the asymmetry of the extrapyramidal syndrome that is only a
striking feature in idiopathic Parkinson’s disease, dementia with Lewy bodies and
this. The acoustic neuroma and peripheral wasting are not associated features.
2. Studies of the associated cognitive features are few but it can present as something
that might be called ‘progressive apraxia’.
Ref
Watts RL, Mirra SS, Richardson EP. Corticobasal ganglionic degeneration. In:
Marsden CD and Fahn S, editors. Movement Disorders 3. Oxford: Butterworth-
Heinemann, 1994: 282-299.
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