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 "Pure Alzheimer's" Rarely Seen Upon Brain Donation 
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Joined: Fri Aug 11, 2006 1:46 pm
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Location: SF Bay Area (Northern CA)
Post "Pure Alzheimer's" Rarely Seen Upon Brain Donation
Someone in our local support group, who knows my great interest in brain donation and diagnostic accuracy of the disorders in our local group, sent me this abstract published at the recent American Academy of Neurology meeting.

This is a study of patients who were enrolled in Alzheimer's clinical trials at the University of British Columbia over a nine year period. Unfortunately only 16 of the 47 patients who have died donated their brains (34%). We see much higher participation in brain donation in our local support group (about 50%)!

Of the 16 who donated their brains, only 5 had pure Alzheimer's. "Pure Alzheimer's" means they had Alzheimer's and no other pathology. So fewer than one-third of the patients had pure AD! Yet they were all participating in clinical trials for those with AD. There is a strong suspicion in the AD research community that one reason so many of the experimental AD medications have been failing in clinical trials is that the patients don't have AD or have something in addition to AD. This abstract proves that this suspicion is correct.

Nearly two-thirds of the 16 had multiple pathologies -- AD plus vascular problems, or AD plus Lewy body disease. We aren't given the exact breakdown between those two.

Indeed, in our local support group, we rarely see "pure Dementia with Lewy Bodies" upon brain donation. Usually it's DLB plus AD and plus vascular problems. In many cases, not a single Lewy body is found, the patient actually had AD plus vascular problems.

I've copied the citation below. (I don't think permission is given to post the full abstract as I can't find it on PubMed.) Whether this "meeting abstract" will go on to be published remains to be seen. But this seems to be an important paper for the AD community that there will probably be some pressure for the authors to publish the full paper.

A huge effort is underway to find biomarkers to help more accurately diagnose AD patients who are participating in clinical trials. I'm unclear how any of the new imaging technologies can sort out those people who have multiple pathologies, however. Does anyone else know? Maybe an individual would have to receive both a PiB PET and a DAT SPECT, but even that would be suggestive of diagnoses.

Robin



Neurology April 24, 2012; 78(Meeting Abstracts 1): S04.006

S04 Aging and Dementia: Therapeutic Interventions

Frequency and Presentation of Multiple Pathology in Patients Enrolled in Alzheimer Clinical Trials (S04.006)

Bing Wei Wang, Ellen Lu, Ian R. A. Mackenzie, Michele Assaly, Claudia Jacova, Philip Lee, B. Lynn Beattie and Ging-Yuek Hsiung

All are: Medicine University of British Columbia Vancouver BC Canada. Except Mackenzie, who is: Pathology University of British Columbia Vancouver BC Canada


Mon Jun 11, 2012 7:38 pm
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Joined: Fri Dec 31, 2010 3:07 pm
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Location: Minnesota
Post Re: "Pure Alzheimer's" Rarely Seen Upon Brain Donation
Thanks for sharing this, Robin.

Wouldn't it be great to have some diagnostic techniques that determine this brain has slight evidence of pathology A and even stronger evidence of pathology B (and there fore needs this kind of treatment)?

I heard a talk by a highly regarded local doctor, given to family and professional caregiver. "DLB is not hard to diagnose at all. I call it a bus-stop diagnosis. I can sit for 20 minutes with a patient who only has DLB and tell you at the end of that time that that is what he has. Unfortunately almost no one has only DLB."

Do you happen to know if brains from persons who had not exhibited signs of dementia before death often show signs of dementia?

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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 Jun 11, 2012 9:26 pm
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Joined: Wed Dec 30, 2009 1:46 pm
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Location: WA
Post Re: "Pure Alzheimer's" Rarely Seen Upon Brain Donation
Yes, it would be interesting to know how many 'control' brains also showed pathology.

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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.


Mon Jun 11, 2012 9:35 pm
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Joined: Fri Jan 15, 2010 9:33 pm
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Location: Vermont
Post Re: "Pure Alzheimer's" Rarely Seen Upon Brain Donation
I just wish there were a way to definitively diagnose these dementia illnesses early! I hope there is a lot of research being done on that as well. Interesting article Robin, thanks. Lynn

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Lynn, daughter of 89 year old dad dx with possiblity of LBD, CBD, PSP, FTD, ALS, Vascular Dementia, AD, etc., died Nov. 30, 2010 after living in ALF for 18 months.


Tue Jun 12, 2012 10:38 am
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Joined: Fri Aug 11, 2006 1:46 pm
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Location: SF Bay Area (Northern CA)
Post Re: "Pure Alzheimer's" Rarely Seen Upon Brain Donation
"Do you happen to know if brains from persons who had not exhibited signs of dementia before death often show signs of dementia?"

One of the things we've learned from the famous "nun study" (where a high percentage of nuns donated their brains for research) is that many, many nuns had Alzheimer's pathology in the brain but showed no signs of dementia. These were nuns who were not depressed during midlife, who had strong writing skills at the age of 19, had regular social interaction even late in life, and continued to use their cognitive skills late in life.


Tue Jun 12, 2012 12:16 pm
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Location: Vermont
Post Re: "Pure Alzheimer's" Rarely Seen Upon Brain Donation
did you mean "19" or "91"?

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Lynn, daughter of 89 year old dad dx with possiblity of LBD, CBD, PSP, FTD, ALS, Vascular Dementia, AD, etc., died Nov. 30, 2010 after living in ALF for 18 months.


Tue Jun 12, 2012 12:20 pm
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Location: SF Bay Area (Northern CA)
Post Re: "Pure Alzheimer's" Rarely Seen Upon Brain Donation
19.


Tue Jun 12, 2012 1:18 pm
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Joined: Thu Apr 21, 2011 9:07 pm
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Post Re: "Pure Alzheimer's" Rarely Seen Upon Brain Donation
We see very much the same pattern in our post-mortems here - many brains have more than one form of pathology. Also, many people who appear cognitively normal do in fact have some anomalies on post-mortem (plaques and tangles, Lewy bodies, micro-infarcts, etc.)

Our group at Rush has published a number of papers from the Religious Orders Study and the Memory and Aging Project, and they also have found at least some pathology in many people who were cognitively normal. They also found that people in clinic-based studies tend to have a little more AD pathology than those in community-based studies (Schneider et al., J Alzheimer's Disease, 2010). In the community cohort folks (n=188) with no cognitive impairment, they found about 40% had pathologic diagnosis of AD ("intermediate" for the most part by Reagan criteria), about 40% had some infarcts (equally split between microscopic and macroscopic) and about 12% had Lewy bodies. About 46% had only one type of pathology and another 8.5% had mixed pathologies, and the rest (around 45%) didn't have anything notable. So a little over half of the clinically normal people did have something noticeable on post-mortem. The mean age at death was almost 90 so these are really old folks!

The proportions with problems go up if you look at people who had mild cognitive impairment or dementia prior to death. The MCI folks had 53% with one pathology and 19% with two or more (mostly AD stuff, but 12% or so with LBD, of the total.) The dementia group found pretty much everyone having something, about equally split between one pathology (again mostly AD) and two or more. Interestingly, this was also true in the 16 who were clinically diagnosed with something other than AD. They still had pathology problems, and again, a lot of it looked like plaques and tangles.

Laurel

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Laurel - mother (97) diagnosed April, 2011, with LBD; died May, 2014.


Tue Jun 12, 2012 8:57 pm
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