2.2.3 DEMENTIA WITH LEWY BODIES
Dementia with Lewy bodies (DLB) is a
common form of dementia in old age, accounting for 15-20% of cases in
hospital autopsy series (Weiner,
1999).
Pathology
Lewy bodies are neuronal inclusions
composed of abnormally phosphorylated neurofilament proteins aggregated
with ubiquitin and α-synuclein.
In Parkinson's disease, Lewy body formation and neuron loss in brain-stem
nuclei, particularly the substantia nigra, lead to movement disorder. In
DLB, significant Lewy body formation also occurs in paralimbic and
neocortical structures, and extensive depletion of acetylcholine
neurotransmission in neocortical areas occurs as a result of degeneration
in the brain-stem and basal forebrain cholinergic projection neurons. (Gómez-Tortosa
et al, 1999). Some Alzheimer-type changes are also present in the
majority of patients with DLB. Senile plaques, diffuse and neuritic, are
present in similar density and distribution as in AD, but the other
hallmark lesions of AD, neurofibrillary tangles, are relatively few (Weiner,
1999), as are biochemical measures of tau pathology.
Clinical Features
Dementia is usually, but not always,
the presenting feature — a minority of patients present with parkinsonism
alone, some with psychiatric disorder in the absence of dementia, and
others with orthostatic hypotension, falls or transient disturbances of
consciousness (Byrne
et al, 1989;
McKeith et al, 1992). Age at onset ranges from 50 to 83 years and
death usually occurs at 68 to 92 years. In contrast to AD, there is often
a relative preservation of short-term memory. Fluctuation in cognitive
performance and level of consciousness is the most characteristic feature
of DLB. It is usually evident on a day-to-day basis, and often apparent
within much shorter periods. About two-thirds of patients report visual
hallucinations, repeatedly seeing people and animals that appear to be
real but make no noise. Depressive symptoms are common and 40% of patients
have a major depressive episode. Up to 70% of patients have parkinsonism.
Recurrent falls and syncope occur in up to a third, presumably reflecting
autonomic nervous system involvement. Transient disturbances of
consciousness in which patients are found mute and unresponsive for
periods of several minutes may represent the extreme of fluctuation in
attention and arousal (McKeith, 2002).
Structural brain imaging in DLB
reveals generalised atrophy, although 40% of patients show preservation of
medial temporal lobe structures, unlike AD.
Management
There have been several reports that
patients who respond well to cholinesterase inhibitor (ChEI) treatments
are more likely to have DLB than AD at autopsy. Although further studies
are required, there is substantial evidence accumulating that ChEIs are
effective in some (although not all) DLB patients, and the class should be
considered as first-line pharmacological treatments for cognitive
dysfunction, apathy, psychosis and agitation in this disorder.
Managing psychosis is one of the most
difficult challenges in the care of patients with DLB. In DLB,
antipsychotic agents are preferably avoided or used only with great
caution, since severe neuroleptic sensitivity reactions can precipitate
irreversible Parkinsonism, further impair consciousness level, and induce
autonomic disturbances reminiscent of neuroleptic malignant syndrome. They
occur in 40-50% of neuroleptic-treated patients with DLB and are
associated with two- to three fold increased mortality. Acute D2 receptor
blockade is thought to mediate these effects, and despite some promising
initial reports, atypical and novel antipsychotic agents such as
risperidone and olanzapine seem to be about as likely to cause adverse
reactions as older, ‘typical’ drugs.
Other agents found effective in
management of DLB include levodopa for clinically significant motor
disability, and clonazepam for the sleep disturbances like vivid dreams
and loss of normal muscle atonia in rapid eye movement sleep (McKeith,
2002). |
