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 Early Visuospatial Deficits Predict VH Later in DLB 
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Joined: Fri Aug 11, 2006 1:46 pm
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Post Early Visuospatial Deficits Predict VH Later in DLB
This is an interesting article as it's based upon the clinical records of 55 autopsy-confirmed DLB (Dementia with Lewy Bodies) cases and 55 autopsy-confirmed Alzheimer's cases at UCSD and the San Diego VA.

In looking back over the clinical records, researchers discovered that the "presence of early, severe deficits on neuropsychological tests of visuospatial skill" predicted the likelihood that patients with suspected DLB will have visual hallucinations. (The test is the WISC-R Block Design subtest.) The same test was not predictive with suspected Alzheimer's Disease cases.

Forty percent of those with the "severe visuospatial deficits" group with DLB had visual hallucinations at the beginning of the illness.

I've copied the abstract below.

Robin



American Journal of Geriatric Psychiatry. 2011 Oct 12. [Epub ahead of print]

Early Visuospatial Deficits Predict the Occurrence of Visual Hallucinations in Autopsy-Confirmed Dementia With Lewy Bodies.

Hamilton JM, Landy KM, Salmon DP, Hansen LA, Masliah E, Galasko D.
Departments of Neurosciences (JMH, JML, DPS, LAH, EM, DG) and Pathology (LAH, EM), University of California, San Diego, La Jolla; and Neurology Service (DG), Veterans Affairs San Diego Healthcare System, La Jolla, CA.

Abstract

OBJECTIVES:
The current study explored the value of visuospatial findings for predicting the occurrence of visual hallucinations (VH) in a sample of patients with dementia with Lewy bodies (DLB) compared with patients with Alzheimer disease (AD).

PARTICIPANTS/MEASUREMENTS:
Retrospective analysis of 55 autopsy-confirmed DLB and 55 demographically similar, autopsy-confirmed AD cases determined whether severe initial visuospatial deficits on the WISC-R Block Design subtest predicted the development of VH.

Visuospatial deficits were considered severe if Block Design z scores were 2.5 or more standard deviations below the mean of a well-characterized normal control group (severe visuospatial deficits [severe-VIS]; DLB: n = 35, AD: n = 26) and otherwise were considered mild (mild visuospatial deficits [mild-VIS]; DLB: n = 20, AD: n = 29).

RESULTS:
Forty percent of the severe-VIS DLB group had baseline VH compared with 0% of mild-VIS DLB patients. Only 8% of the severe-VIS and 3% mild-VIS AD patients had baseline VH.

During the follow-up period (mean = 5.0 years), an additional 61% of the severe-VIS but only 11% of the mild-VIS DLB patients developed VH. In that period, 38% of the severe-VIS and 20% of the mild-VIS AD patients developed VH.

After considering initial MMSE score and rate of decline, logistic regression analyses found that performance on Block Design significantly predicted the presence of VH in the DLB group but not the AD group.

CONCLUSIONS:
The presence of early, severe deficits on neuropsychological tests of visuospatial skill increases the likelihood that patients with suspected DLB will develop the prototypical DLB syndrome. The presence of such deficits may identify those DLB patients whose syndrome is driven by alpha-synuclein pathology rather than AD pathology and may inform treatment plans as well as future research.

[Robin's note: the preceding sentence is incomplete on PubMed.]

PubMed ID#: 21997600 (see pubmed.gov for this abstract only)


Sat Oct 15, 2011 7:33 pm
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Post Re: Early Visuospatial Deficits Predict VH Later in DLB
robin..
very interesting article. this is where my hubby goes for treatment.. the va hospital is located right across the street from ucsd.. and a lot of the docs are from there..
thanks for sharing~~

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sole CG for hubby.1st symptoms, 2000, at 55. Diag with AD at 62, LB at 64.. vietnam vet..100% ptsd disability,sprayed with agent orange, which doubled chances for dementia. ER visit 11-13,released to memory care..


Sun Oct 16, 2011 12:20 pm
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Post Re: Early Visuospatial Deficits Predict VH Later in DLB
Thanks for posting this, Robin - it's really interesting! You do such an awesome job of keeping up with this - I feel like I am always behind on my reading. Sigh.

I read the article and looked up a related reference by Chip Stebbins reporting some fMRI studies, in parkinson's patients, not LBD. One really interesting part is the specificity of the block design test results, the ones they call "early visuospatial deficits", as predictors of VH in DLB but not so much in AD, even in people of comparable age, dementia severity, and so on. The abstract is a little goofy in the results section - they report something as if it adds up to more than 100% (40% plus 61%) of the severe visuospatial deficits people developing hallucinations, but in fact they really mean 40% have them at baseline, and of the other 60% who did not have them at baseline, and had follow-up, 61% of that second group developed them. (Sorry to go all math-ish here but just in case someone else was wondering how they got that 101% of DLB people in the study overall had hallucinations, no, not so.)

Anyway the second thing that interested me was speculative, but consistent with Stebbins's paper. They were speculating on the mechanism for hallucinations, and one possibility is that processing of visual images in DLB becomes "top-down" rather than "bottom-up". That is, the usual way your brain figures out what you are seeing is to put all the little pieces together (shapes, lines, color, etc.) from the stream of information sent in from your retinal nerves, and use this to construct a sort of brain-picture, which takes place toward the back of the brain. But the fMRI suggests that in people with hallucinations, the processing may be shifted in part toward the front of the brain, and they surmise that maybe the brain is, to describe it picturesquely, guessing the answer based on something in its picture library, rather than doing its homework and organizing all the detailed information. It then convinces itself that the guess is the true answer. (Sort of a non-technical description, but maybe conveys the idea?)

Anyway this would also be consistent with how my mother's visual hallucinations seem to operate, including her responses on neuropsych testing. Her visual acuity is pretty good in that she can certainly see clearly the components of the picture, but something goes wrong after that, and she comes up with peculiar interpretations of what she "sees".

Maybe some hope for more precise ways of assessing specific brain damage. Doug Galasko, the senior (last) author, has a very strong interest in this area. I am an external advisor to their AD research group so will see what I learn next time I'm in San Diego.

Laurel

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


Mon Oct 17, 2011 8:55 pm
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Post Re: Early Visuospatial Deficits Predict VH Later in DLB
Laurel,

The 40% plus 61% part of the abstract was a poor way of putting things (why not just say how many total had VH?), but I do think it was accurately stated (as I was able to figure out what they meant).

What you've written about the speculation on the mechanism for hallucinations, and how this relates to your mother's case is fascinating!

One of the key differentiators in DLB and AD is that visual hallucinations *can* occur early on in DLB (but not always). If they occur in AD, it's late in the disease course. So, the question is -- how can you tell if a person has DLB or AD early on, when no visual hallucinations are present? In this research, the scores on visuospatial exams did not predict who had DLB or AD. Do the paper's authors suggest that this predictive ability was previously shown in other research?

I might've mentioned here that many of the brain donation cases I've been involved in where the person had a clinical DX of DLB but a path DX of something that was not Lewy body disease were cases where there was no VH. But, of course, it's not a required diagnostic symptom.

Robin


Mon Oct 17, 2011 9:59 pm
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Post Re: Early Visuospatial Deficits Predict VH Later in DLB
Hi Robin,
The paper cites at least one paper suggesting that, although presence of visuospatial problems is not necessarily a predictor of Lewy body pathology (because you can find such problems in other dementia subtypes), the absence of visuospatial functional impairment is a strong "negative predictor" in that if you don't have at least some impairment in this domain, you probably don't have Lewy bodies. (Tiraboschi et al, Brain 2006). I'm not too sure, though, how "early" this is, because their sample was 3-4 years from "onset" (defined clinically) although they did restrict to people in early stages according to DRS. The Tiraboschi study also just looked at some very simple visuospatial tests and they note in the discussion that the more sophisticated tests, like the ones used in the paper this year, may be more sensitive. It is also worth noting that when they say it predicts, they basically mean it's better than chance guessing, not that it has great diagnostic power.

Anyway it is all quite interesting, and the connection between visuospatial function and hallucinations seems to be something people are trying to look at more deeply. There are also some papers in the ophthalmology literature on this.

And yeah, I figured their percentages out, too, but the confusing way it was stated did make me want to get my red pen out. Electronically speaking.

Your notes on the other thread have reminded me to ask my mom if she has considered wanting autopsy. I could arrange it here pretty easily through Charlie's group but only if she and my dad are interested. Since she is not participating in any longitudinal follow-up, nor has she had imaging aside from the MRI, the usefulness for our research is probably limited. Mostly for personal information, if she and my dad wanted it. My guess is that she probably has a little of everything at this point.

Laurel

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


Tue Oct 18, 2011 9:11 pm
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Post Re: Early Visuospatial Deficits Predict VH Later in DLB
labeckett wrote:
Since she is not participating in any longitudinal follow-up, nor has she had imaging aside from the MRI, the usefulness for our research is probably limited. Laurel


Really? Is that true? Brains of persons diagnosed with lbd but who are not participating in a study are of limit value?

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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


Tue Oct 18, 2011 9:58 pm
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Post Re: Early Visuospatial Deficits Predict VH Later in DLB
Hi Jeanne,
I think whether post mortem would be of value for research depends very much on what the research group is doing. In our case, I know the work intimately, and for the kinds of questions we ask, we would want a longer-term follow-up. But this is quite specific to our center and the kinds of work we do. Other centers focus on different kinds of questions, and for them, a longitudinal perspective would not be required. I work pretty closely with our neuropathology core and know what they are doing and plan to do, and it probably wouldn't make sense for my mom, though I might ask our neuropathologist what he thinks, next meeting.

Best would be, as Robin advised in another place, to talk to folks early and arrange donation! It could also be that the local group has ties to other groups that may be able to use the information and tissue samples.

So I would just ask! Robin can probably put you in touch with the right folks in your area.

Laurel

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


Sat Oct 22, 2011 12:39 am
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Post Re: Early Visuospatial Deficits Predict VH Later in DLB
Regarding the findings: It certainly was true in my husband's case. Visuospatial deficits were one of his earliest symptoms and he had early and persistent hallucinations. Even now, with 50mg Seroquel three times a day he hallucinates much, if not most, of the time. It has never been terribly upsetting to him, just confusing.

_________________
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 22, 2011 2:14 pm
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Post Re: Early Visuospatial Deficits Predict VH Later in DLB
Laurel,

This is fascinating: "the absence of visuospatial functional impairment is a strong 'negative predictor' in that if you don't have at least some impairment in this domain, you probably don't have Lewy bodies." But then you say: "It is also worth noting that when they say it predicts, they basically mean it's better than chance guessing, not that it has great diagnostic power."

I guess that explains why "visual hallucinations" are not a required symptom in the diagnostic criteria.

Robin


Mon Nov 07, 2011 12:09 am
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Post Re: Early Visuospatial Deficits Predict VH Later in DLB
Jeanne,

Laurel is absolutely right that many medical research centers are only interested in the brain donations of the people that they've followed clinically and who have participated in years of research. Locally, UCSF is this way for some diagnoses, though not for all.

Many places will take any brain donated to them, regardless of how long or how recently the person has been seen there, and regardless of whether the person has participated in research.

From the family's and brain donor's perspective, the key is knowing what the brain bank (or medical research center) will do with the tissue after it's been autopsied. Does the organization actually publish research on that disorder and on a wide range of disorders? It's very sad to much such a precious donation and have the tissue sit in a freezer in perpetuity.

Robin


Mon Nov 07, 2011 12:19 am
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