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 Great review article on DLB and PDD (Mollenhauser) 
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Post Great review article on DLB and PDD (Mollenhauser)
This is a terrific review article by a German team, led by Dr. Brit Mollenhauser. The full article is available in English online.

Here are some of the most interesting points made in the article:

* Dementia with Lewy bodies (DLB)—"the occurrence of dementia before Parkinson's syndrome"—and Parkinson's disease dementia (PDD) "respond to treatment with cholinesterase inhibitors, and because of the serious side effects associated with administration of traditional neuroleptic drugs, it’s important to distinguish these from Alzheimer’s dementia."

* "The diagnostic evaluation and treatment of Lewy body dementia and Parkinson's disease dementia require notably higher resources per patient than in Alzheimer’s disease. The probable reason for this is the combination of cognitive and physical impairments in the former dementia types."

* "Neurologically, 25% to 50% of patients with dementia with Lewy bodies have symptoms of Parkinson’s disease at the onset of their illness."

* "Disorders of the autonomous nervous system are much more common in dementia with Lewy bodies than in Alzheimer’s disease. Often these lead to orthostatic dysregulations... Urinary incontinence is also more common in patients with dementia with Lewy bodies than in Alzheimer’s disease."

* "Patients with Lewy body dementia usually have slower EEG rhythms at baseline than patients with Alzheimer’s disease or Parkinson's disease dementia."

* "Attention needs to be paid to the reduced response of motor symptoms, especially akinesis, to levodopa in 40% of patients with Lewy body dementia."

* "Owing to the development of the dementia and the tendency to develop psychoses in dementia with Lewy bodies, monotherapy with levodopa is usually recommended."

* "The administration of anticholinergic drugs is contraindicated."

* "The question of how long treatment with ChEI should be continued is not unproblematic in view of the costs incurred and is currently the subject of critical discussion. In any case, the treatment should be controlled and evaluated 6 months after treatment initiation. Cessation of treatment with ChEI should be decided on an individual as well as clinical basis. In case of progressive dementia and an MMSE score of less than 10 in spite of ChEI, the treatment needs to be questioned because no license exists in this scenario in Germany. Caution is indicated in abrupt cessation of treatment with ChEI because this entails the risk of substantial cognitive deterioration."

* "It is in particular the productive-psychotic symptoms of dementia with Lewy bodies and Parkinson's disease dementia that place a heavy burden on relatives and carers; they are also responsible for a multitude of admissions to residential care homes, so that medication treatment is absolutely essential."

* "The raised sensitivity or intolerability of dementia with Lewy bodies vis-à-vis the typical antipsychotic drugs has been described repeatedly. By contrast, severe side effects in reaction to the atypical antipsychotic drug quetiapine (daily dosage 12.5–100 mg/d to a maximum of 200–300 mg/d) and clozapine (daily dosage 12.5–100 mg/d) have rarely been observed. Larger studies are lacking, and future studies should distinguish between dementia with Lewy bodies and Parkinson's disease dementia."

There are two handy summaries of the diagnostic criteria for DLB and PDD provided:

Box 1 - Clinical-diagnostic consensus criteria for dementia with Lewy bodies (DLB)

Box 2 - Summary of the clinical-diagnostic consensus criteria for Parkinson's disease dementia (PDD)

I've copied the link, citation, and abstract below.

Robin ... h&id=78599

Deutsch Aerzteblatt-International 2010; 107(39): 684-91
Mollenhauer, B; Förstl, H; Deuschl, G; Storch, A; Oertel, W; Trenkwalder, C
Lewy Body and Parkinsonian Dementia: Common, but Often Misdiagnosed Conditions

Background: Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are the two most common types of dementing neurodegenerative disease after Alzheimer’s disease (AD). Both of these conditions are often diagnosed late or not at all.

Methods: Selective literature review.

Results: The severe cholinergic and dopaminergic deficits that are present in both DLB and PDD produce not only motor manifestations, but also cognitive deficits, mainly in the executive and visual-constructive areas, as well as psychotic manifestations such as visual hallucinations, delusions, and agitation. The intensity of these manifestations can fluctuate markedly over the course of the day, particularly in DLB. Useful tests for differential diagnosis include magnetic resonance imaging and electroencephalography; in case of clinical uncertainty, nuclear medical procedures and cerebrospinal fluid analysis can be helpful as well. Neuropathological studies have revealed progressive alpha-synuclein aggregation in affected areas of the brain. In DLB, beta-amyloid abnormalities are often seen as well.

Conclusion: DLB should be included in the differential diagnosis of early dementia. If motor manifestations arise within one year (DLB), dopaminergic treatment should be initiated. On the other hand, patients with Parkinson's disease should undergo early screening for signs of dementia so that further diagnostic and therapeutic steps can be taken in timely fashion, as indicated. Cholinesterase inhibitors are useful for the treatment of cognitive deficits and experiential/behavioral disturbances in both DLB (off-label indication) and PDD (approved indication).

Sat Oct 16, 2010 11:09 pm

Joined: Wed Dec 30, 2009 1:46 pm
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Location: WA
Post Re: Great review article on DLB and PDD (Mollenhauser)
It is, indeed, interesting. I'm particularly interested in what their conclusions will be regarding continued use of AChEI in middle to late stage LBD. Thank you for keeping up with these things and sharing them, Robin.

Pat [68] married to Derek [84] for 38 years; husband dx PDD/LBD 2005, probably began 2002 or earlier; late stage and in a SNF as of January 2011. Hospitalized 11/2/2013 and discharged to home Hospice. Passed away at home on 11/9/2013.

Sat Oct 16, 2010 11:28 pm

Joined: Sat Jan 03, 2009 2:59 pm
Posts: 1978
Post Re: Great review article on DLB and PDD (Mollenhauser)
Yes I agree this is very interesting!

I picked up on the EEG results and at the time my husband had this with very low numbers I really didn't understand what it had to do with LBD !

Irene Selak

Tue Oct 19, 2010 10:47 am
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Location: SF Bay Area (Northern CA)
Post Re: Great review article on DLB and PDD (Mollenhauser)
This is a good article written for laypeople about the Mollenhauer review of DLB and PDD. (Sorry, but I added an S to his name in my post from 10/16.) The article mentions another review; I'll have to dig that up later.

From Medscape Medical News
Accurate Diagnosis of Dementia Type Crucial for Treatment, Future Interventions
by Deborah Brauser

October 27, 2010 — Clinical evaluations for specific type of dementing neurodegenerative disease are critically important, suggest 2 new literature reviews from German researchers.

In the first analysis, investigators write that correct diagnosis is crucial because treatment differs significantly between dementia with Lewy bodies (DLB), Parkinson disease dementia (PDD), and Alzheimer's disease (AD) dementia.

For patients with DLB, cognitive and/or psychiatric impairments are their first symptoms. For them, dopaminergic treatments should be given "if motor manifestations arise within 1 year," write Brit Mollenhauer, PD, Dr. med, from the Paracelsus-Elena Hospital in Kassel and the Georg-August University in Göttingen, Germany, and colleagues.

In PDD, memory impairment and cognitive deficits occur only after motor symptoms have fully developed and been present for at least 1 year. For these patients, the study authors write that early screening is needed so that "further diagnostic and therapeutic steps can be taken in timely fashion."

In addition, both DLB and PDD patients have been found to respond well to cholinesterase inhibitors for treating cognitive problems and behavioral disturbances. However, "because of the serious side effects associated with administration of traditional neuroleptic drugs, it’s important to distinguish" these dementia types from AD, add the study authors.

In the second review, the researchers note that new biomarkers can increase the probability of identifying AD at the predisease stage of mild cognitive impairment (MCI) to higher than 80%.

"Early detection of [AD] before the onset of dementia provides an opportunity to study potential approaches for secondary prevention, which are now an object of intense clinical research," write Gerhard W. Eschweiler, PD, Dr. med, from the Department of Psychiatry and Psychotherapy at the University of Tübingen and from the Geriatric Center at the University Hospital of Tubingen, Germany, and colleagues.

The 2 reviews were published in the October dementia theme issue of Deutsches Ärzteblatt International, the official journal of the German Medical Association.

Dementia Type Characteristics

"In Germany, 6.5% to 8.7% of the population older than 65 years and 30% of those older than 89 are affected by 1 of the different types of dementia," write Dr. Mollenhauer and colleagues.

DLB and PDD are the 2 most common dementia types, after AD. However, "both of these conditions are often diagnosed late or not at all," they add.

Highlights from their review show that patients with DLB:

* More often have disorders of the autonomous nervous system than patients with AD, which often lead to orthostatic dysregulations;

* More often have urinary incontinence than do those with AD;

* Often have slower electroencephalographic rhythms at baseline than do those with AD or PDD;

* 25% to 50% have symptoms of PDD at illness onset; and

* Often report colorful, sometimes complex hallucinations.

The investigators also found that both diagnosis and treatment of DLB and PDD require higher resources per patient than for AD. "The probable reason for this is the combination of cognitive and physical impairments in the former dementia types," they explain.

Although levodopa monotherapy is usually recommended for those with DLB, up to 40% of these patients develop a reduced treatment response for their motor symptoms. So "attention needs to be paid."

Cholinesterase inhibitors have also been found to be effective for treating cognitive deficits and neuropsychiatric symptoms in patients with DLB or PDD, but rivastigmine was the only drug licensed in Germany (as of 2009) for the treatment of PDD. No cholinesterase inhibitors are currently licensed for treating DLB — and their use in this way is off-label.

This, along with questions about treatment duration, has been the subject of lengthy country-wide debate. "In any case, the treatment should be controlled and evaluated 6 months after treatment initiation," write the study authors. Plus, "caution is indicated in abrupt cessation of treatment ... because this entails the risk of substantial cognitive deterioration."

In specifically treating the psychotic symptoms of dementia, past research has shown that DLB patients have increased sensitivity or intolerability to typical antipsychotics. However severe adverse effects "have rarely been observed" when patients with DLB were treated with the atypical antipsychotics quetiapine and clozapine.

The investigators write that large studies of these drugs that distinguish between treatment of DLB and PDD are now needed.

Diagnostic Tools, Biomarkers

AD "is characterized by a protracted preclinical phase [of up to 5 years] followed by the onset of slowly progressive dementia," write Dr. Eschweiler and colleagues in the second review, which evaluated studies between 2005 and 2009 from a selective MEDLINE search.

They report that classic diagnostic tools such, as the Mini-Mental State Examination (MMSE) and clock drawing tests, and newer techniques, such as the DemTect test, can all be simply used in a primary care setting to detect early manifestations of AD.

MMSE, which is used predominantly as a dementia exclusion test, was found to have 78% sensitivity, 88% specificity, a positive predictive value of 86%, and a negative predictive value of 96%. However, it cannot diagnose MCI.

Clock drawing tests have shown 90% sensitivity, 56% specificity, 84% positive predictive value, and 69% negative predictive value.

DemTect, which is commonly used in Germany but not much in other countries, showed 85% sensitivity for MCI and 83% sensitivity for AD.

Impaired odor identification tests were also found "to predict a decline in memory, both among healthy elderly persons and among patients with MCI," and a history of major depression doubled the risk of developing dementia.

In addition, the presence of [AD] was found even before the onset of dementia with a diminished concentration of Abeta-peptide (more than 85% sensitivity and specificity) and an increase of phospho-tau (more than 80% sensitivity and specificity) in cerebrospinal fluid.

Finally, new types of magnetic resonance imaging, single-photon emission computed tomography (SPECT), and positron emission tomography (PET) can help improve diagnostic assessments through higher-resolution imaging.

Future Interventions Need Reliable Diagnoses

In an accompanying editorial, Richard Mahlberg, PD, Dr. med, from the Institute of Psychogerontology at the Friedrich-Alexander-University of Erlangen-Nuremberg, Germany, writes that the 2 literature reviews address various problems that can arise in the 2 steps of a traditional diagnostic evaluation: confirming the presence of a dementia and then classifying it.

Recent developments "have followed a fundamentally different strategic path, owing to strong clinical interest in the premorbid and early stages of dementia that are known as [MCI]," writes Dr. Mahlberg, who was not involved with the studies.

"The evaluation now mainly addresses...the neurobiological and neurophysiological changes that are associated with the underlying dementing diseases and which are used as biological markers," he adds.

Regarding the use of impaired olfactory identification as a biomarker in the review by Dr. Eschweiler and colleagues, Dr. Mahlberg writes that "it has long been known" that this is a factor for patients with AD dementia and is easily tested, as are magnetic resonance scans.

However, a lumbar puncture, which is used to detect amyloid components and tau proteins, adds to patient stress and is not recommended under current guidelines. In addition, SPECT and PET can only be performed in specialized centers.

Overall, "the sensitivity and specificity of each of these techniques, considered individually, are no greater than those of the classic methods of diagnostic assessment; thus, the diagnostic yield improves only when all of their findings are considered together," writes Dr. Mahlberg.

Regarding the review by Dr. Mollenhauer and colleagues, Dr. Mahlberg writes that "marked differences in clinical manifestations that enable 1 type of dementing disease to be distinguished from another are evident only during the first third of the course of disease, if at all."

"The clinical manifestations that are relatively specific to various dementing diseases in their early stages, such as impairment of memory, language, or motor function, agitation, and hallucinations, can appear in any type of dementing disease at a later stage," he adds.

Still, correct diagnoses are extremely important for the development of disease-specific interventions, writes Dr. Mahlberg.

"Thus, clinical diagnosticians today must do their part to pave the way for better care of demented patients in the future," he concludes.

The study authors for both reviews report several financial relationships. A full list is included in the original articles. Dr. Mahlberg has disclosed no relevant financial relationships.

Dtsch Arztebl Int. 2010;107:675-676, 677-683, 684-691.

Thu Oct 28, 2010 8:42 pm
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