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McKeith article on DLB and PDD
This article on DLB and PDD was written by Ian McKeith, MD, the lead author of the diagnostic criteria for DLB. Here's the abstract of the recently-published article:
Practical Neurology. 2007 Nov;7(6):374-82.
Dementia with Lewy bodies and Parkinson's disease with dementia: where two worlds collide.
Professor of Old Age Psychiatry, Wolfson Research Centre, Newcastle General Hospital, Newcastle upon Tyne, UK.
Parkinson's disease and dementia with Lewy bodies are two common presentations of a single, underlying disease process (Lewy body disease) which is thought to be related to dysregulation of the synaptic protein, alpha-synuclein. This article discusses the nature of the relations between Parkinson's disease and dementia with Lewy bodies, and what can be learned from them about the causes of dementia in patients with established Parkinson's disease. This is an area of clinical practice which is of increasing importance as greater numbers of ageing patients survive longer with good treatment of their motor symptoms. Precise use of terminology and a clear understanding of the biological substrates underlying symptom formation are particularly helpful to both clinicians and patients.
PubMed ID#: 18024777 (see pubmed.gov for the abstract only)
Thanks to Forum member Patty for sending me a scan of the article. I found it easy to understand. Some tidbits I gleaned from the paper:
* "(There) is no universally accepted pathological criteria" for PD.
* Up to 78% of those with PD will develop dementia.
* "The presence of the typical cognitive profile together with two out of three of these core features qualifies for a diagnosis of probable dementia with Lewy bodies which is more than 90% predictive of Lewy body pathology at autopsy." (There's no citation for this so perhaps it's McKeith's own diagnostic accuracy rate. This is a very high percentage.)
* "The Consensus group which met to delineate the dementia with Lewy bodies syndrome predominantly comprised dementia clinicians rather than movement disorder specialists..."
* "Other than age of onset, temporal course and possibly levodopa-responsiveness, no major differences between dementia with Lewy bodies and Parkinson's disease with dementia have been found..."
* 25% of those with DLB will never have parkinsonian symptoms.
Here are excerpts (including the tidbits from above): (see especially the paragraphs beginning with "So is the distinction...of any practical significance?" and "Most clinicians know from their clinical practice...")
There is a "seemingly endless debate which surrounds the classification of dementia with Lewy bodies and Parkinson's disease with dementia. My purpose here is to outline my own understanding of this matter, a subject which the reader may regard as either trivial or critical. I hope to persuade you that it is neither."
"(There) is no universally accepted pathological criteria" for PD.
"The recent recognition that dementia becomes increasingly prevalent in Parkinson's disease populations followed over the course of the disease, with reports of up to 78% period prevalence over eight years, has prompted renewed interest in generating more evidence-based criteria for Parkinson's disease with dementia."
"Dementia with Lewy bodies is now the preferred term for a series of diagnostic appellations... These included Lewy body variant of Alzheimer's disease, Lewy body dementia, senile dementia of Lewy body type, and cortical Lewy body disease. Dementia with Lewy bodies is...a clinically defined syndrome..."
"The presence of the typical cognitive profile together with two out of three of these core features qualifies for a diagnosis of probable dementia with Lewy bodies which is more than 90% predictive of Lewy body pathology at autopsy."
"Unfortunately, looking at this the other way round, many Lewy body pathology cases do not present in this 'typical' way -- indeed they often present with an insidious amnestic syndrome more suggestive of Alzheimer's disease. This probably reflects the fact that many such cases have substantial additional Alzheimer (neocortical tangle) pathology which colours the clinical picture."
"The Consensus group which met to delineate the dementia with Lewy bodies syndrome predominantly comprised dementia clinicians rather than movement disorder specialists..."
At the third (2005) meeting of the International Dementia with Lewy Bodies Consortium, the boundary issue between DLB and PDD was discussed again. The re-stated basic position is: "...This unitary approach to classification may be preferable for molecular and genetic studies and for developing therapeutics. Descriptive labels that include consideration of the temporal course are preferred for clinical, operational definitions. Dementia with Lewy bodies should be diagnosed when dementia occurs before or concurrently with parkinsonism, while Parkinson's disease with dementia should be used to describe dementia that occurs in the context of well-established Parkinson's disease. The appropriate term will depend on the clinical situation and generic terms such as Lewy body disease are often helpful. In research studies in which distinction is made between dementia with Lewy bodies and Parkinson's disease with dementia, the one-year rule between the onset of dementia and parkinsonism should be used. ... In other research settings, including pathological studies and clinical trials, both clinical phenotypes may be considered collectively under categories such as Lewy body disease or alpha-synucleinopathy."
"Other than age of onset, temporal course and possibly levodopa-responsiveness, no major differences between dementia with Lewy bodies and Parkinson's disease with dementia have been found..."
"There may be some minor pathological differences..." probably reflecting "disease severity and duration, and there is greater cortical beta-amyloid deposition in dementia with Lewy bodies..."
"So is the distinction...of any practical significance? ... For the patient, family and treating clinician, the diagnostic label generally carries considerable significance because it describes the primary problems (parkinsonism or dementia) and carries with it a particular set of expectations."
"Even in the clinic this unifying approach can be the easiest route -- telling a patient that he has Lewy body disease as the explanation for his myriad of symptoms is often more convincing than convoluted discussions about 'Parkinson's plus' or other complex diagnostic epithets. In terms of patient assessment and management, the issues posed by [DLB and PDD] are essentially the same..."
"Most clinicians know from their clinical practice that dopaminergic drugs cause worsening of hallucinations and confusion in an apparently dose-dependent manner. The research literature on the other hand finds hallucinating and non-hallucinating Parkinson's disease patients not to differ in their mean daily levodopa dose, and that high dose levodopa infusion does not produce hallucination in people with early stage Parkinson's disease. The answer to this conundrum appears to be that confusion and hallucinations are an integral part of Lewy body disease that can occur in the absence of dopaminergic treatment (as in dementia with Lewy bodies), and which seem more likely to occur when there is cognitive impairment and diffuse, cortical pathological involvement. Dopaminergic drugs do not therefore cause the psychiatric symptoms, rather they exacerbate them or bring them forward in time -- that is, they would have happened anyway but drug treatment precipitates them at an earlier time. This explains why drug-induced psychotic and confusional symptoms often fail to resolve completely on withdrawal of the offending drug and, even if they do, why they often recur within a fairly short space of time."
"The report of the third Consortium...concluded that 'the likelihood that the observed neuropathology explains the dementia with Lewy bodies clinical syndrome is directly related to the severity of Lewy-related pathology, and inversely related to the severity of concurrent Alzheimer-type pathology.' ... Memory deficits, hippocampal atrophy on brain CT/MRI and old age are likely predictors of Alzheimer pathology being the major determinant of dementia. Reduced occipital perfusion (PET or SPECT scanning), prominent attentional and visuo-perceptual impairments are suggestive of Lewy body disease itself being the main contributor."
"The progressive 'spread' of Lewy body pathology...proposed by Braak is compatible with the observation that dementia usually occurs late in the course of Parkinson's disease -- that is, after the motor features. It does not however account for dementia with Lewy body cases, which by definition start with 'cortical' features and 25% of whom will never show extrapyramidal signs."
"...the Braak staging system may need some extension to account for the full clinical variation of Lewy body disease. For example, Japanese scientists have reported three pathological subtypes of Lewy body disease: type 1, brainstem predominant; type 2, 'almost equal' for brainstem and cerebral cortex; and type 3 with a cerebral cortex-predominant pattern. This challenges the notion that Lewy body disease has to begin in subcortical regions and spread upwards."
There can "be no right or wrong about what one calls Parkinson's disease with dementia or dementia with Lewy bodies. It is a matter of opinion... However, patients and their families will expect us to be consistent in our approach and this is where the importance of this issue lies. ...any...health professionals who come into contact with what is an increasingly prevalent disease would do well to agree on the best way to describe it."
One reviewer to the article stated: "It may...be too early to conclude that there are no differences in clinical features between dementia with Lewy bodies and Parkinson's disease with dementia. ...large, prospective clinicopathological correlation studies are still necessary to validate and refine [the findings of the third Consortium report]."