Dementia with Lewy Bodies (DLB)
by Clive Evers
Dementia with Lewy bodies (DLB) is a form of dementia that shares characteristics with both Alzheimer's and Parkinson's diseases. Lewy bodies(named after FH Lewy who discovered them in 1912) are tiny spherical protein deposits found in nerve cells. Their presence in the brain disrupt's the brain's normal functioning, interupting the action of important chemical messengers including acetylcholine and dopamine. Lewy bodies are also found in the brains of people with Parkinson's disease(PD), a progressive neurological disease that affects movement. Some people who are initially diagnosed with PD later go on to develop a dementia that closely resembles DLB.
Lewy body dementia, Lewy body variant of Alzheimer’s disease, diffuse Lewy body disease, cortical Lewy body disease, senile dementia of Lewy body type.
DLB often starts quite rapidly or acutely, with quite a fast decline in the first few months although later there may be some levelling off. DLB tends to progress faster than Alzheimer's disease and can last from 5- 7 years, although this will vary from person to person. People with DLB often experience memory loss, spatial disorientation and communication difficulties associated with Alzheimer's disease but also have some quite normal memory function. They may also develop the symptoms of Parkinson's disease, including slowness, muscle stiffness, trembling of the limbs, a tendency to shuffle when walking, loss of facial expression and changes in the strength and tone of voice. Characteristic symptoms of people with DLB include fluctuation of abilities on a daily and even hourly basis; fainting, falls or experiencing vague weaknesses of arms or legs; experiencing detailed and convincing visual hallucinations, often people or animals; falling asleep easily by day and having restless disturbed nights with confusion, nightmares and hallucinations. Additionally at least 50% of people with DLB are over sensitive to the side effects of neuroleptic drugs which may be prescribed for people with severe mental illness. Gradually progressive, symptoms gradually accumulate, average survival is 6 to 7 years. Age of onset 50 to 83, death 68 to 92, average survival from diagnosis 5 – 7 years.
Fluctuation of cognitive ability may cause problems, non-acceptance of disease, presence of hallucinations, probability of falls, safety of environment, possibility of falling asleep during the day.
Causes and risk factors
The cause of DLB remains unknown although there are overlaps with Alzheimer's and Parkinson's disease. Genetic research is looking at which genes may contribute to DLB but this is in its early stage. Some research has focused on the role of certain proteins and the damage caused to nerve cells especially ubiquitin and alpha-synuclein.
Rare causes of familial DLB have been reported.
DLB is thought to be the second or third most common cause of dementia accounting for 15% to 25% of cases of dementia which start after the age of 65 (Perry et al 1990 and Jellinger 1996). Male to female ratio is 1.5:1 but it is not clear if this represents increased male susceptibility to the disease or to reduced survival in men with DLB. Age at onset ranges from 50-83 years and 68-92 at death (Papka et al 1998).
Consensus guidlelines for the clinical and pathologic diagnosis of DLB have been published (McKeith et al, 1996).
The main requirement is progressive cognitive decline of sufficient magnitude to interfere with normal social or occupational function. Prominent or persistent memory impairment may not necessarily occur in the early stages but is usually evident with progression. Deficits on tests of attention and frontal-sub-cortical skills and visuospatial ability may be especially prominent.
The main diagnostic issue is to distinguish DLB from the commoner Alzheimer's disease. A common diagnostic error is to attribute the clinical features of DLB to cerebral vascular disease such as multi-infarct dementia or Binswanger's disease.
There are no specific diagnostic tests for DLB. CT and MRI imaging can assist in the process (Ince, P et al Copyright Brain Pathology 1998).
Care and treatment
For people with DLB neuroleptics may be particularly dangerous. This class of drugs induce Parkinson-like side effects, including rigidity and an inability to perform tasks or to communicate. Studies have shown that when prescribed for people with DLB it may cause sudden death. If a person with DLB must be prescribed a neuroleptic it should be done with the utmost care and under constant supervision with regular monitoring. In certain cases some people with DLB are able to tolerate such treatment so that their hallucinations are reduced. There is now some evidence to suggest that the more recently developed 'atypical' anti-psychotic dugs like olanzapine (Zyprexa), quetiapine (Seroquel) or respiridone (Risperdal), may be safe to use. It is still reasonable to try to simplify anti-parkinsonian medication as a first step, particularly withdrawing drugs of lower potency (and particular tendency to cause confusion) such as anti-cholinergics and selegeline; where possible dopamine agonists should also be withdrawn, leaving most patients on levodopa alone. (Ince, P et al Copyright Brain Pathology 1998) At present there is no cure for DLB. Recent research has suggested that the cholinesterase drugs used to treat Alzheimer's disease may also be useful in treating DLB, although they are not yet licensed for this use (Alzheimer Scotland-Action on Dementia 2002).
Ongoing research / Clinical trials
The 35% diagnostic sensitivity reported by Lopez et al supports their call for improvements in the clinical criteria for diagnosing DLB.
Contemporary theories emphasise impaired cellular function due to protein aggregation, disrupted synaptic connections and critical neurochemical changes including alterations in the muscarinic and nicotinic receptors.
This advance coupled with the recognition that parkin (Shimura et al, 2001) and torsin (Sharma et al, 2001) co-exist with a-synuclein in Lewy bodies will likely open new molecular and genetic approaches to future research.
Institute for Ageing and Health Wolfson Research Centre Prof. Ian McKeith Newcastle General Hospital Westgate Road Newcastle upon Tyne NE4 6BE United Kingdom firstname.lastname@example.org www.ncl.ac.uk/nnp/staff/profile/i.g.mckeith
The Lewy Body Dementia Association, Inc. www.lewybodydisease.org
Alzheimer Europe 145 Route de Thionville L- 2611 Luxembourg Tel: +352 / 29.79.70 Fax: +352 / 29.79.72 email@example.com www.alzheimer-europe.org
Alzheimer's Disease International 45-46 Lower Marsh London SE1 7RG United Kingdom Tel: +44 / 20 7620 3011 Fax: +44 / 20 7401 7351 firstname.lastname@example.org
- Diagnostic criteria (McKeith), Lancet paper on treatment
- Ince, P et al, Copyright Brain Pathology 1998
- Lopez et al, arch Neurol 2002:59;43-46
- McKeith, IG et al Neurology 1996 Nov.; 47(5) 1113-24
- McKeith, I. G., D. J. Burn, et al. (2003). Dementia with Lewy bodies. Semin Clin Neuropsychiatry 8(1): 46-57
- Shimura et al Science 2001; 293:263-269
- Sharma, N et al Am J Pathol 2001; 159: 339-344
Last Updated: vendredi 14 novembre 2014