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Lewy Body Dementia
Can We Propose Rational Clinical Trials for Lewy Body Dementia?
a report by
Joseph Quinn, MD
Associate Professor of Neurology, Oregon Health and Sciences University, and
Director, Clinical Trials Program and Biomarker Core, Oregon Aging and Alzheimer’s Disease Center
A report on a recent consortium meeting on dementia with Lewy bodies DLB is made in the case of one core feature or one or more suggestive
(DLB) noted: “Virtually unrecognized 20 years ago, DLB could within this features. Features that are supportive but are not used in the diagnostic
decade be one of the best characterized and potentially treatable algorithm include repeated falls and syncope, transient unexplained loss of
neurodegenerative disorders of late life.”
1
Despite this level of optimism consciousness, severe autonomic dysfunction, hallucinations in other
regarding treatment, clinical trials for DLB are rare and the standard of modalities, systematized delusions, depression, relative preservation of
care is uncertain. For example, Clinicaltrials.gov lists no investigational medial temporal lobe structures on CT/magnetic resonance imaging (MRI)
drugs in clinical trials for DLB at present, and the American Academy of scan, generalized low uptake on SPECT/PET perfusion scan with reduced
Neurology (AAN) does not have a practice parameter dealing specifically occipital activity, abnormal (low uptake) metaiodobenzylguanidine (MIBG)
with Lewy body dementia. This situation is due in part to the fact that the myocardial scintigraphy, and prominent slow wave activity on
US Food and Drug Administration (FDA) has served notice that they will electroencephalography (EEG) with temporal lobe transient sharp waves.
not grant a drug indication for DLB because it is a heterogeneous Features that are considered as evidence against a diagnosis of DLB
syndrome with insufficiently sensitive and specific diagnostic criteria. The include the presence of cerebrovascular disease (focal neurological signs or
result has been a general inhibition of clinical trials for DLB, with some brain imaging), the presence of any other physical illness or brain disorder
effort to gain drug indications for more discrete types of dementia sufficient to account in part or in total for the clinical picture, or the
associated with Lewy bodies, such as Parkinson’s disease dementia (PDD). appearance of parkinsonism for the first time at a stage of severe
dementia. Among patients with DLB, there is considerable heterogeneity.
In this article, we will consider the clinical, neurochemical, and Some patients are recognizable from the time of clinical presentation with
pathological features of the various types of DLB, review therapeutic spontaneous parkinsonism and visual hallucinations; other patients
strategies based on these characteristics, and conclude with suggestions present looking like typical Alzheimer’s disease (AD), but develop Lewy
for developing a more potent therapeutic armamentarium for this body symptomatology over time.
challenging condition.
DLB has been distinguished from PDD not only by levodopa
The Spectrum of Lewy Body Dementia responsiveness of the motor symptoms (robust in PD; more modest in
According to the most recent consensus criteria,
2
a diagnosis of probable DLB), but also by the temporal relationship between dementia and motor
DLB requires the presence of dementia, in association with either two core dysfunction.
3
An arbitrary cut-off of one year between motor symptoms
features—fluctuating cognition with pronounced variations in attention and dementia has been established to distinguish the two entitites: if
and alertness, recurrent visual hallucinations, and spontaneous features of motor symptoms have been present for less than one year when
parkinsonism—or one core feature and one suggestive feature—including dementia becomes apparent, the diagnosis is DLB; if motor symptoms
rapid eye movement (REM) sleep behavior disorder, severe neuroleptic have been present for more than one year, the diagnosis is PDD. Despite
sensitivity, and low dopamine transporter uptake in basal ganglia this distinction and the use of two diagnostic terms, the cognitive profile
demonstrated by single photon emission computed tomography (SPECT) and brain pathology are similar in DLB and PDD. This is relevant because
or positron emission tomography (PET) imaging. A diagnosis of possible the diagnosis of PDD may be made with greater specificity than that of
DLB, leading the FDA to grant an indication for at least one drug
(rivastigmine) for the treatment of PDD. Based on the clinical and
Joseph Quinn, MD, is an Associate Professor of Neurology
at Oregon Health and Sciences University, Director of the
neuropathological similarities between PDD and DLB, some would
Clinical Trials Program and Biomarker Core of the Oregon interpret evidence of efficacy in PDD as supportive of efficacy in DLB. The
Aging and Alzheimer’s disease center, and Co-Director of
strategy of conducting clinical trials in PDD as an avenue to drug
the Portland VA Parkinson’s Disease Research, Education,
and Clinical Care Center (PADRECC). His research interests
development for DLB may be pursued with other therapeutic targets.
include clinical trials and biomarker studies in Alzheimer’s
disease and Parkinson’s disease. Dr Quinn completed his
Cognitive Profile of Dementia with Lewy Bodies and
medical degree at the University of Southern California
and a neurology residency and geriatric neurology fellowship at Oregon Health and
Parkinson’s Disease Dementia
Sciences University and the Portland VA Medical Center. In both DLB and PDD, the cognitive profile includes problems with
attention, executive functions, and visuospatial function. Much of the
quinnj@ohsu.edu
literature on the neuropsychology of DLB compares DLB versus AD,
12 © TOUCH BRIEFINGS 2008
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