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 Diagnostic accuracy for pure DLB and DLB+AD 
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Joined: Fri Aug 11, 2006 1:46 pm
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Location: SF Bay Area (Northern CA)
Post Diagnostic accuracy for pure DLB and DLB+AD
Wonderful research out of the University of Kentucky, though the findings of 32% diagnostic accuracy for "pure DLB" and 12% diagnostic accuracy for mixed AD/DLB are quite pathetic.

The researchers find the diagnostic criteria for DLB to be lacking and state that it seems that the rate of misdiagnosis is increasing despite the revised diagnostic criteria!

The authors note that another "obstacle to clinical–pathological correlation in any ND is the prevalent, powerful, but unpredictable impact of cerebrovascular disease (CVD), both clinically and pathologically." In the brain donation cases I've been involved in, vascular dementia is a frequent confirmed diagnosis in many cases of supposed DLB.

I've copied the abstract below.

If anyone has a statistics background, could you let me know if you'd be willing to review the article and provide some analysis of it? (I have acquired a full copy of the article.) In particular, it would be interesting to figure out if any of the supplemental files indicate which of the 31 Alzheimer's Disease Centers have the highest accuracy rates for DLB diagnosis.

Robin


Journal of Neurology. 2009 Oct 1. [Epub ahead of print]

Low sensitivity in clinical diagnoses of dementia with Lewy bodies.

Nelson PT, Jicha GA, Kryscio RJ, Abner EL, Schmitt FA, Cooper G, Xu LO, Smith CD, Markesbery WR.
Division of Neuropathology, Department of Pathology, University of Kentucky Medical Center and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY.

The success of future neurodegenerative disease (ND) therapies depends partly on accurate antemortem diagnoses. Relatively few prior studies have been performed on large, multicenter-derived datasets to test the accuracy of final clinical ND diagnoses in relation to definitive neuropathological findings.

Data were analyzed from the University of Kentucky Alzheimer's Disease Center autopsy series and from the National Alzheimer's Coordinating Center (NACC) registry. NACC data are derived from 31 different academic medical centers, each with strong clinical expertise and infrastructure pertaining to NDs. The final clinical diagnoses were compared systematically with subsequent neuropathology diagnoses.

Among subjects meeting final inclusion criteria (N = 2,861 for NACC Registry data), the strength of the associations between clinical diagnoses and subsequent ND diagnoses was only moderate.

This was particularly true in the case of dementia with Lewy bodies (DLB): the sensitivity of clinical diagnoses was quite low (32.1% for pure DLB and 12.1% for Alzheimer's disease (AD + DLB) although specificity was over 95%.

AD clinical diagnoses were more accurate (85.0% sensitivity and 51.1% specificity).

The accuracy of clinical DLB diagnoses became somewhat lower over the past decade, due apparently to increased "over-calling" the diagnosis in patients with severe cognitive impairment. Furthermore, using visual hallucinations, extrapyramidal signs, and/or fluctuating cognition as part of the clinical criteria for DLB diagnosis was of minimal utility in a group (N = 237) with high prevalence of severe dementia. Our data suggest that further work is needed to refine our ability to identify specific aging-related brain disease mechanisms, especially in DLB.

PubMed ID#: 19795154 (see pubmed.gov for this abstract only, available for free)



Here are a few definitions:

"Sensitivity: the percentage of cases with a particular pathological diagnosis that had been clinically diagnosed correctly as having that diagnosis prior to death"

"Specificity: the percentage of cases without a particular pathological diagnosis that had been clinically diagnosed correctly as not having that diagnosis prior to death"


Sun Oct 04, 2009 9:26 pm
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Joined: Fri Dec 31, 2010 3:07 pm
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Location: Minnesota
Post Re: Diagnostic accuracy for pure DLB and DLB+AD
This is really interesting. Thanks for sharing it, Robin.

I'm having a hard time understanding the difference between sensitivity and specificity.

I'm really surprised at the results, especially since these come from the centers most qualified (I would think) to diagnose dementias correctly.

When I asked Dr. Boeve how certain he was that Coy really has LBD, he said that he is virtually certain. In all the cases in the study they have had only one example with documented RBD that the autopsy did not confirm LBD. Apparently when that factor is present along with other LBD symptoms that greatly increases the likelihood of Lewy bodies being present in the brain.

I wonder what percent of all diagnosed cases become brain donors? And I wonder if there is any reason that the donors would be different from the entire population? I can't think of one, except perhaps there might be a higher instance of wanting an autopsy when the diagnosis was uncertain or not accepted by the family. From what you've seen, do you think the donor population is likely to be representative of the dementia population at large?

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


Sun Jan 16, 2011 9:29 pm
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Joined: Fri Aug 11, 2006 1:46 pm
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Location: SF Bay Area (Northern CA)
Post Re: Diagnostic accuracy for pure DLB and DLB+AD
Maybe Dr. Boeve said documented RBD *plus* MCI or dementia is always Lewy Body Dementia. Documented RBD occurs in at least three neurodegenerative disorders.

It's interesting to me that RBD is only a suggestive symptom.


Mon Jan 17, 2011 2:20 am
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Joined: Fri Dec 31, 2010 3:07 pm
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Location: Minnesota
Post Re: Diagnostic accuracy for pure DLB and DLB+AD
Oh yes, Robin, I didn't mean that RBD by itself was what lead to the diagnosis, or that RBD is always associated with LBD. But the diagnosis made of LDB based on other factors (at least in this study) had a very high accuracy rate when a history of RBD was also present. No RBD? A less accurate diagnosis rate. Of course, many people who have sleep disorders do not seek treatment for them, and there is only after-the-fact speculation as to what they might have had before the LBD diagnosis.

And I also think it interesting that RBD is only a suggestive factor. Considering that this disease was only identified as a distinct condition in 1996, the research is in early stages. I was amazed that the first extracts Dr. Boeve gave me to read were based on 14 brain donors! As the research base grows there are bound to be many changes to conclusions and guidelines. As this University of Kentucky study demonstrates, science still doesn't have a good handle on diagnostic criteria. No doubt that will improve, too, as research continues, and especially as it has more cases to analyze.

I am very pleased that Coy has authorized his brain tissue to be used by both the Sleep Disorder clinic research, and the Mayo Clinic's dementia research. It gives him great satisfaction to know that he can make this contribution.

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


Mon Jan 17, 2011 2:54 am
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Joined: Wed Oct 28, 2009 11:53 am
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Location: Ocala, FL
Post Re: Diagnostic accuracy for pure DLB and DLB+AD
This article led me to reading more on the subject and I was struck by the fact that unless Dale's previous behavior is 'documented,' the autopsy wouldn't produce much information usable for research. Dale's long history of sleep walking is not documented anywhere. Neither are the major episodes of night time delusional behavior which led me to find another neurologist in 2009.

All this 'non-documentation' may be why our current neurologist will not identify Dale's condition positively.

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Leone Carroll (75); wife of Dale (75) who passed away March 23, 2011


Mon Jan 17, 2011 9:21 am
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Joined: Fri Dec 31, 2010 3:07 pm
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Location: Minnesota
Post Re: Diagnostic accuracy for pure DLB and DLB+AD
I don't think that any neurologist will identify LBD "positively" without brain tissue. Coy's official diagnosis is "probable LDB". In his case the doctor (a researcher) has high confidence in the diagnosis, in part because of the prior RBD (and current symptoms, of course). But we won't have a "positive" diagnosis until after death.

Without documentation, Dale's prior sleep history as reported by you would still be part of his records. It would not be as precise and thorough as someone who was treated for it, but it is still data that gets considered.

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


Mon Jan 17, 2011 11:19 am
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Post Re: Diagnostic accuracy for pure DLB and DLB+AD
JeanneG -

I am grateful to your husband for planning on donating his brain to Mayo Rochester!

Do you mind checking to see if the 14-brain study is posted to the LBDA Forum? If not, please post the abstract. Unfortunately we've seen very little on autopsy-confirmed DLB but Mayo is certainly leading the way in the US. Dr. Boeve believes Mayo Rochester's diagnostic acuracy percentage is higher than this large Alzheimer center study but, with nothing published, it's anecdotal evidence at this time.

Robin


Mon Jan 17, 2011 12:33 pm
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Joined: Fri Dec 31, 2010 3:07 pm
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Location: Minnesota
Post Re: Diagnostic accuracy for pure DLB and DLB+AD
Right, it is anecdotal, and he did not present it as anything more than that. He was just explaining to me why he was so confident in Coy's diagnosis, in spite of the fact that the disease is progressing extremely slowly in Coy's case.

The study Coy is enrolled in is ongoing. I don't know at what milestones they will publish results, but they are surely amassing all kinds of interesting statistics that will be published eventually.

I'll see if I can find those articles Boeve gave me 7 years ago. I've remodeled my office recently, and while things are better organized now, it is not always easy to retrieve older materials.

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


Mon Jan 17, 2011 12:45 pm
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