Intended for healthcare professionals


Cerebral embolism and Alzheimer's disease

BMJ 2006; 332 doi: (Published 11 May 2006) Cite this as: BMJ 2006;332:1104

Are we misdiagnosing some of the cases of dementia?

Kivipelto and Solomon’s editorial (1) has raised a very important
point, are we over diagnosing Alzheimers and incorrectly treating some of
the dementia patients? At the moment there is no specific diagnostic test
available and the diagnosis of Alzheimer’s in life is purely on exclusion
of other causes and on the basis of a clinical picture including a long
preclinical phase with an insidious onset of dementia.

As they have pointed out that small and clinically silent emboli
occurring repeatedly over several months or years tend to cause slowly
progressive brain damage and cognitive deficits. In such cases there is a
chance of mislabelling the person as an Alzheimers’s patient and treating
only with acetylcholinesterase inhibitors and omitting the simple
treatment with Aspirin. In view of the fact that Purandare et al (2) have
found that there was not much difference in the occurrence of spontaneous
cerebral emboli in Alzheimers and vascular dementia patients i.e 32 versus
31- patients, it means that all the dementia patients irrespective of
label should receive blood thinning medications.

The importance of a correct diagnosis also becomes important as White
et al (3) found in the Honolulu-Asia Aging study that out of 56% patients
diagnosed with probable or possible Alzheimer’s disease during life time,
post mortem studies had confirmed only 19% of the cases showed neuritic
plaques and/or neurofibrillary tangles as the sole or dominant dementia
related lesion in the brain at autopsy. Their results therefore, suggested
that the clinical diagnosis of dementia made during life may fail to
reflect the pathogenic complexity of this condition in a very elderly
person. In this day and age of litigation, it is a worrying finding as
with media publicity, presence of pressure groups and pharmaceutical
companies aggressive campaigning, the stress is on acetylcholinesterase
inhibitors prescribing, rather than the correct diagnosis.

In November 2005 following discussion with EU regulatory agencies,
including the Medicines and Healthcare product regulatory Agency (MHRA)
Shire Pharmaceutical Ltd informed the medics that the final results of two
investigational clinical trials of two years duration with Reminyl in
individuals with mild cognitive impairment (MCI) had showed that the
mortality rate was significantly higher in the Reminyl group (1.4%) than
in the placebo group (0.3%) and that galantamine therapy failed to
demonstrate any benefits either in slowing cognitive decline or reducing
the clinical conversion to dementia (4). Bearing in mind that the word
Alzheimer’s is dreadful news for the carers and the advent of
acetlycholinesterase inhibitors is the last hope of dementia sufferers,
sometimes the pressure prescribing without sophisticated investigations is
a norm. I think that in view of White et al’s findings, and new safety
warnings about one of the anti dementia products, the relevant parties
need to think hard and work towards some new guidelines, rather than
dishing out the prescriptions to everybody who crosses through the doors
of memory clinics.


1) Kivipelto M and Solomon A. Cerebral embolism and Alzheimer's, BMJ
2006:332: 1104-15

(2) Purandare N, Burns A, Daly KJ, Hardicre J, Morris J, Macfarlane G,
McCollum C. Cerebral emboli as a potential cause of Alzheimer's disease
and vascular dementia: case-control study. BMJ 2006:332: 1119-22

(3) White L, Small BJ, Petrovitch H, Ross GW, Masaki K, Abbott RD, et al.
Recent clinical-pathologic research on the causes of dementia in late
life: update from the Honolulu-Asia aging study. J Geriatr Psychiatry
Neurol 2005;18: 224-7.

(4) Shire Pharmaceutical Ltd, Reminyl and Reminyl XL(Galantamine
Hydrobromide) important Safety information related to Final Clinical trial
Results in Mild Cognitive Impairment, Communication about the safety data,
dated 3rd.November, 2005

Competing interests:
The author works in a memory clinic, prescribes and monitors the effects of all three anti dementia medications available as per the NICE guidelines and has accepted hospitality and academic material gifts from all the three manufacturers, namely Shire, Novartis and Eisai.

Competing interests: No competing interests

22 May 2006
Dr.Zaffar Ul Hassan
STAFF GRADE Psychiatrist
Wakefield Memory Service,Fieldhead Hospital West Yorkshire WF1 3SP