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 Neuropathologic Criteria for DLB 
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Joined: Fri Aug 11, 2006 1:46 pm
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Location: SF Bay Area (Northern CA)
Post Neuropathologic Criteria for DLB
This post focuses on DLB (Dementia with Lewy Bodies). It says nothing about PDD (Parkinson's Disease Dementia).

I'm not sure how many of you will be interested in this article. It may be that only those who have donated the brains of their family members will be interested in this article. As I read a lot of neuropathology reports from the Mayo Clinic in Jacksonville, FL, this article is of interest to me. (Many of this article's authors are from Mayo Jax and others are from Mayo Rochester.) Many of the neuropathology reports I've read with the autopsy-confirmed diagnosis is "Lewy body disease" refer to this important article.

You might also be interested in this article if you follow the diagnostic accuracy of neurologists making the diagnosis of DLB. The Mayo clinicians in this small study of 43 patients diagnosed with DLB got the diagnosis right between 70% and 93% of the time, depending on how you define "accurately diagnosed."

The full article is available at no charge online at:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2745052/ --> HTML version
http://www.ncbi.nlm.nih.gov/pmc/article ... 131610.pdf --> PDF version

Highlights are:

* The Third Consortium on DLB (CDLB) pathological criteria "recommend that the neuropathologic diagnosis should be in the form of a probability statement related to the likelihood that the pathology would be associated with the DLB clinical syndrome and that the probability is positively correlated with the distribution of Lewy bodies and negatively correlated with the severity of Alzheimer-type pathological features. This recommendation was based upon prevailing evidence that the greater extent of Alzheimer-type pathology, the less likely the patient would have presented with the DLB clinical syndrome, even if widespread cortical Lewy bodies were present at autopsy."

* The clinical diagnoses of the study participants included 43 patients with probable DLB, 9 with possible DLB, and 24 with probable AD.

* Table 1A is worth looking at:
http://www.ncbi.nlm.nih.gov/pmc/article ... /table/T1/

It shows that all of the people with RBD and all of the people with fluctuating cognition had "probable DLB" diagnoses clinically. All of the people with visual hallucinations had either probable DLB or possible DLB diagnoses.

* The pathological diagnoses of the 76 study participants included "29 patients had high-likelihood, 17 had intermediate-likelihood, and 6 had low-likelihood DLB pathology. ... For the sake of discussion, cases that fell into the high- and intermediate-likelihood of DLB categories were considered to have the pathological diagnosis of DLB." So, 24 of the study participants did not have DLB pathology (76 minus 29 minus 17 minus 6).

* Table 2 is worth looking at:
http://www.ncbi.nlm.nih.gov/pmc/article ... /table/T2/

It shows that of "the 43 clinically probable DLB patients, 40 had intermediate- or high-likelihood DLB pathology. More than 80% of the cases with clinically probable DLB had diffuse cortical Lewy bodies."

So, in this small sample size of 43 clinically probable DLB, the diagnostic accuracy was 93% (40 out of 43) or 80%, depending on how you defined "accuracy."

* "One clinically probable DLB patient had PSP with concurrent Alzheimer-type pathology (Braak NFT Stage VI), but no Lewy bodies. This patient had 2 core clinical features as well as RBD. There were only 2 cases with low-likelihood DLB pathology; both had advanced Alzheimer-type pathology with limbic Lewy bodies."

* "Only 2 out of 9 clinically possible DLB cases had intermediate- or high-likelihood DLB pathology."

So, in this small sample size of 52 patients with clinically probable or possible DLB, 42 had intermediate- or high-likelihood DLB pathology, or 80%. I'm not sure we are told how many of the 52 patients had diffuse cortical Lewy bodies. Assuming none of the patients with clinically possible DLB had diffuse cortical Lewy bodies, then the diagnostic accuracy was just under 70% (36 out of 52).

There are at least two reasons why the diagnostic accuracy is higher in this study than we've seen in other studies. First, the Mayo clinicians are some of the best in the US at diagnosing DLB. Second, the sample size is very small.

* Table 3 is worth looking at:
http://www.ncbi.nlm.nih.gov/pmc/article ... /table/T3/

It shows that if a DLB patient had visual hallucinations within 3 years of symptom onset, there was a great likelihood that this patient had DLB.

"In this series, 2 clinically possible DLB cases had advanced Alzheimer pathology with Lewy bodies confined to amygdala. Visual hallucinations occurred in these patients at 5 and 7 years after the onset of dementia."

I've copied the abstract below.

Robin



Journal of Neuropathology and Experimental Neurology. 2008 Jul;67(7):649-56.

Validation of the neuropathologic criteria of the third consortium for dementia with Lewy bodies for prospectively diagnosed cases.

Fujishiro H, Ferman TJ, Boeve BF, Smith GE, Graff-Radford NR, Uitti RJ, Wszolek ZK, Knopman DS, Petersen RC, Parisi JE, Dickson DW.
Department of Pathology and Neuroscience, Mayo Clinic, Jacksonville, FL, USA.

Abstract
There is limited information on the validity of the pathologic criteria of the Third Consortium on Dementia with Lewy bodies (CDLB), and none are based on prospectively diagnosed cases.

In this study, the core clinical features of dementia with Lewy bodies (DLB) and the suggestive clinical feature of rapid eye movement sleep behavior disorder were assessed using a battery of standardized clinical instruments in 76 patients with the clinical diagnosis of either DLB or Alzheimer disease.

At autopsy, 29 patients had high-likelihood, 17 had intermediate-likelihood, and 6 had low-likelihood DLB pathology.

The frequency of core clinical features and the accuracy of the clinical diagnosis of probable DLB were significantly greater in high-likelihood than in low-likelihood cases. This is consistent with the concept that the DLB clinical syndrome is directly related to Lewy body pathology and inversely related to Alzheimer pathology.

Thus, the Third Consortium on DLB neuropathologic criteria scheme performed reasonably well and are useful for estimating the likelihood of the premortem DLB syndrome based on postmortem findings.

In view of differences in the frequency of clinically probable DLB in cases with Braak neurofibrillary tangle stages V (90%) and VI (20%) and diffuse cortical Lewy bodies, a possible modification of the scheme is to consider cases with neurofibrillary tangle stage VI to be low-likelihood DLB.

PubMed ID#: 18596548 (see pubmed.gov for this abstract and a link to the full article, available at no charge online)


Thu Jul 14, 2011 6:42 pm
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Post Re: Neuropathologic Criteria for DLB
Interesting.

So, if more clinicians applied the criteria as stringently as the Mayo research program does, the accuracy rate for diagnosis could be expected to climb?

_________________
Jeanne, 68 cared for husband Coy, 86. RBD for 30+ years; LDB since 2003, Coy at home, in early stage, until death in 2012


Thu Jul 14, 2011 7:30 pm
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Joined: Fri Aug 11, 2006 1:46 pm
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Post Re: Neuropathologic Criteria for DLB
I doubt it because the clinical criteria are very easy to follow.

This article is about applying the pathologic criteria. Apparently there can't be a "high likelihood" of having DLB if the person brain shows severe Alzheimer's pathology.


Fri Jul 15, 2011 11:38 am
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Post Re: Neuropathologic Criteria for DLB
Jeanne…I read the same thing you did….it seems the article stated that because it was done at Mayo and the way they do the clinical end….the results are possibly skewed the way you said…..so if other places look at criteria the same way Mayo does…..then….the pathology would be higher there too…at least that is what I think I read….

it seems this was about the pathology…interesting….because….one day….I will be one of those numbers….

_________________
Craig - Patient - Male - 56 years old - Lewy Bodies diagnosed on March 23, 2011 - cognitive disorder NOS dx 2007 - RBD REM dx 2007 issues for 20+ years - intention tremor 1974 - other issues many years


Fri Jul 15, 2011 12:13 pm
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Post Re: Neuropathologic Criteria for DLB
Depending on how you define "accurately diagnosed," the Mayo accuracy rate could be 70%, which is about the same as for Parkinson's Disease. Certainly not high enough for most drug companies and clinical trials.


Fri Jul 15, 2011 3:25 pm
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Post Re: Neuropathologic Criteria for DLB
Robin….this is all fascinating to me…for obvious reasons…(had to look up fascinating….yep it still is)

_________________
Craig - Patient - Male - 56 years old - Lewy Bodies diagnosed on March 23, 2011 - cognitive disorder NOS dx 2007 - RBD REM dx 2007 issues for 20+ years - intention tremor 1974 - other issues many years


Fri Jul 15, 2011 3:42 pm
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Joined: Tue Mar 29, 2011 3:02 pm
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Post Re: Neuropathologic Criteria for DLB
okay….here is what I was thinking….

for a living patient…..

in limbo….

looking for a diagnosis…..

an accurate diagnosis can be the kiss of death….

BUT…..even WORSE……

the absolute requirement by the medical community for an 'ACCURATE DIAGNOSIS' ……is WORSE than a kiss of death….

it is a slow strangulation….a tormenting….here take an antidepressant….kiss off….that for some lasts a lifetime…..

I am exploring the idea….that at least in the case of neuro diseases……

the search for an accurate diagnosis….and the defining of treatments to match may detrimental to only live patients….

what is more important?

what about meeting the needs of live patients?

what about just determining if the problem might be neuro….then proceeding in that direction?

the old centralization….decentralization conundrum…..

might it be better not to require an absolute answer….after all….there is a live person suffering in the mean time….and it is a MEAN time….

_________________
Craig - Patient - Male - 56 years old - Lewy Bodies diagnosed on March 23, 2011 - cognitive disorder NOS dx 2007 - RBD REM dx 2007 issues for 20+ years - intention tremor 1974 - other issues many years


Fri Jul 15, 2011 3:51 pm
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Joined: Wed Mar 02, 2011 1:04 pm
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Post Re: Neuropathologic Criteria for DLB
Amen to that Craig!

_________________
First symptoms in 2000 at 35 yrs old. LBD early onset dx 2-17-2011 at age 46.

' "I try not to worry about the future, but rather to "wonder"....and "wonder" is one step away from "awe" '......From a wise friend........


Fri Jul 22, 2011 3:22 pm
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Joined: Wed Dec 30, 2009 1:46 pm
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Post Re: Neuropathologic Criteria for DLB
Quote:
what about meeting the needs of live patients?
Craig, we caregivers have been asking that for years!

_________________
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.


Fri Jul 22, 2011 4:03 pm
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Post Re: Neuropathologic Criteria for DLB
Doctors are not supposed to do any harm. If there's no way to diagnose a patient accurately during life, then there's no way to test medications because you don't know really which disorder they are being tested on. What works for LBD can be harmful for FTD.


Fri Jul 22, 2011 4:43 pm
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Post Re: Neuropathologic Criteria for DLB
I understand doctors have to proceed carefully - but I have to agree with Craig about being pushed off for years on end -

I can say I was harmed by "take this anti-depressant nothing serious is wrong with you"....by many doctors for 11 years...that did harm me because if one of them had bothered to look carefully at the atrophy on my MRI from 2006 I might have been able to start some disease slowing/modifying medicines sooner than 2011.....At the very least it would have led to further investigation into possible neuro issues at that time -

but it took a car accident and head injury in 2009 to get anyone to notice the atrophy after that.....but I even got the "you are anxious and depressed" from Johns Hopkins in summer 2010 despite the MRIs - due to a doc who didn't take comprehensive history (and family history with a father with parkinson's and PDD) or do a thorough neuro exam and went on my MMSE score only....that did harm me because I have had the biggest cognitive decline in the last year - and aricept is helping me now -

but what if I could have started it sooner???.....Thank goodness for the neurologist I have now who is a cognitive and movement disorder specialist - Unfortunately I didn't get to her until Feb. 2011.....I took her all my 11 yrs of films, tests etc....she saw the atrophy on the 2006 films right away and was shocked it was missed by local docs and Johns Hopkins docs....she calls it "significant".....I am lucky because in my state we had no such specialist until she moved here from NY a year ago...I pray she doesn't leave....

Tonya

_________________
First symptoms in 2000 at 35 yrs old. LBD early onset dx 2-17-2011 at age 46.

' "I try not to worry about the future, but rather to "wonder"....and "wonder" is one step away from "awe" '......From a wise friend........


Fri Jul 22, 2011 6:05 pm
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Post Re: Neuropathologic Criteria for DLB
Tonya,
Have you posted elsewhere the name of your MD? Sounds like you've found a good one.
Robin


Fri Jul 22, 2011 11:33 pm
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