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 Using SPECT to differentiate probable DLB from AD 
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Joined: Fri Aug 11, 2006 1:46 pm
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Location: SF Bay Area (Northern CA)
Post Using SPECT to differentiate probable DLB from AD
This just-published abstract is about using a special type of SPECT -- a (123)I-FP-CIT SPECT -- to differentiate between probable DLB and AD. "A mean value of 85.7% was achieved for overall diagnostic accuracy." Accuracy is measured by comparing the analysis of a SPECT scan reader with the clinical diagnosis. This isn't the best available measure of accuracy; it would be best if the SPECT scan analysis could be compared to the pathological diagnosis. Hopefully studies like this will start happening in LBD.
Robin


Lancet Neurology. 2007 Apr;6(4):305-13.

Sensitivity and specificity of dopamine transporter imaging with (123)I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study.

McKeith I, O'brien J, Walker Z, Tatsch K, Booij J, Darcourt J, Padovani A, Giubbini R, Bonuccelli U, Volterrani D, Holmes C, Kemp P, Tabet N, Meyer I, Reininger C; for the DLB Study Group.
Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK.

BACKGROUND: Dementia with Lewy bodies (DLB) needs to be distinguished from other types of dementia because of important differences in patient management and outcome. Current clinically based diagnostic criteria for DLB have limited accuracy. Severe nigrostriatal dopaminergic degeneration occurs in DLB, but not in Alzheimer's disease or most other dementia subtypes, offering a potential system for a biological diagnostic marker. The primary aim of this study was to investigate the sensitivity and specificity, in the ante-mortem differentiation of probable DLB from other causes of dementia, of single photon emission computed tomography (SPECT) brain imaging with the ligand (123)I-2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ((123)I-FP-CIT), which binds to the dopamine transporter (DAT) reuptake site. Diagnostic accuracy, positive and negative predictive values, and inter-reader agreement were the secondary endpoints and a subgroup of possible DLB patients was also included.

METHODS: We did a phase III study in which we used a (123)I-FP-CIT SPECT scan to assess 326 patients with clinical diagnoses of probable (n=94) or possible (n=57) DLB or non-DLB dementia (n=147) established by a consensus panel (in 28 patients no diagnosis could be made). Three readers, unaware of the clinical diagnosis, classified the images as normal or abnormal by visual inspection. The study had 90% power to detect the differences between our anticipated sensitivity (0.80) and specificity (0.85) targets and prespecified lower thresholds (sensitivity 0.65, specificity 0.73) using one-sided binomial tests with a significance level of alpha=0.025.

FINDINGS: Abnormal scans had a mean sensitivity of 77.7% for detecting clinical probable DLB, with specificity of 90.4% for excluding non-DLB dementia, which was predominantly due to Alzheimer's disease. A mean value of 85.7% was achieved for overall diagnostic accuracy, 82.4% for positive predictive value, and 87.5% for negative predictive value. Inter-reader agreement for rating scans as normal or abnormal was high (Cohen's kappa=0.87). The procedure was well tolerated with few adverse events.

INTERPRETATION: A revision of the International Consensus Criteria for DLB has recommended that low DAT uptake in the basal ganglia, as shown by SPECT or PET imaging, be a suggestive feature for diagnosis. Our findings confirm the high correlation between abnormal (low binding) DAT activity measured with (123)I-FP-CIT SPECT and a clinical diagnosis of probable DLB. The diagnostic accuracy is sufficiently high for this technique to be clinically useful in distinguishing DLB from Alzheimer's disease.


Sun Mar 18, 2007 6:41 pm
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Joined: Tue Feb 06, 2007 8:35 pm
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Location: Toronto, Canada
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Robin, since dopamine deficit figures predominantly in LBD (as compared to AD), why is the focus of treatment, for the most part, on acetylcholine deficit??? What am I missing here? I realize acetylcholine is an important neurotransmitter, more so for AD, no?

Are there any studies examining the effect of Ritalin (methylphenidate "MPH") administration on LBD sufferers? MPH is a dopamine reuptake inhibitor, which means that it increases the level of the dopamine neurotransmitter in the brain by partially blocking the transporters that remove it from the synapses. So, wouldn't it make sense to prescribe Ritalin for LBD sufferers? Is that being done??

My young son suffers from ADHD and several of my brothers were thought to be hyperactive in their youth. Now my mom has this diagnosis of "probable LBD." Ritalin SR (slow release) definitely helps improve my son's cognition. Wouldn't it help my mom more than Reminyl???

thx for your posts,
dale

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Dale
[My dear, Mom, Beatrice, (born in 1929) was diagnosed with LBD in Dec 2006. She passed away peacefully on July 12, 2013 at Embassy Hall, Shannex, Quispamsis, N.B.]


Sun Mar 18, 2007 8:14 pm
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Joined: Fri Aug 11, 2006 1:46 pm
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Location: SF Bay Area (Northern CA)
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Dale,

You pose interesting questions! I hope that someone more knowledgeable (Eric) will reply.

My attempt at an answer.... There is dopamine-targeted treatment too -- Sinemet in particular. Perhaps because both AD and LBD are dementias, MDs thought it was worth giving acetylcholinesterase inhibitors (AD drugs) to LBDers as well. Sometimes it's the MDs who "force" the drugs. Sometimes it's the patients or families who insist on the drugs -- they want to try something, anything. Some of the AChEase inhibitors do have positive benefits for LBDers. I don't know why.

I don't know the answer to the Ritalin question. You could do a search on pubmed of "Dementia Lewy Body Ritalin" and see what you get.

There is an MD in TX who is experimenting with Strattera (another ADHD drug) and PSP, the Atypical Parkinsonism disorder my father has. But someone in our local support group tried it and got off of it after day 3 due to increased falls. Let me know if you want me to dig up the name of the MD....if you'd want to contact the guy or have your MD contact him.

Robin


Mon Mar 19, 2007 12:58 am
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Joined: Tue Feb 06, 2007 8:35 pm
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Location: Toronto, Canada
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Hi Robin,

Was out all day and just noticed your reply post. Will discuss with my sister, who seems to be the primary caregiver for Mom right now. Initially it was my brother, but the doctor suggested that a designated sibling (we are five) be the one advising Mom, as Mom might get too confused with all of us coming from different angles. Mom actually calls me to run the medication by me and even sent me the info sheet that came with her Reminyl ER. She really trusts me to "tell her the truth" -- so, it's a bit of a tightrope walk right now, as the treatment is so idiosyncratic.

Will check out PubMed first, so that I have some literature on which to rely.

Thanks for your articles -- so succinct -- I could spend weeks on PubMed and still be going in circles. I would surmise that's the nature of the research.

We would at least like to try some melatonin to help her sleep. I did pass on the suggestion to ask her doctor about Klonopin (as Eric has mentioned). The hallucinations have not diminished, in fact, have gotten worse upon waking.

thx!

_________________
Dale
[My dear, Mom, Beatrice, (born in 1929) was diagnosed with LBD in Dec 2006. She passed away peacefully on July 12, 2013 at Embassy Hall, Shannex, Quispamsis, N.B.]


Mon Mar 19, 2007 10:48 pm
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Joined: Mon Feb 05, 2007 3:43 am
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Location: Seattle, WA
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Yes, yes, a thousand times yes...

I have Work Drama at the moment, so I can't give this the attention it so richly deserves, but psychostimulants (primarily Dexedrine and Provigil, but also Ritalin) are exceptionally useful in LBD - perhaps moreso than the atypical antipsychotics. After seeing the instant improvement in Cal on stimulants, I'm a total believer.

Knowing that the plural of "anecdote" is not "evidence", however, I would refer you to the Boeve article at:

http://www.lewybodydementia.org/Boevelink.php

There's information on stimulants about page 17 or so.

Eric

_________________
Cal is not the real name of a real 84 year old with DLB. I don't speak for LBDA, nor do I have clever initials behind my name, so information is provided without warranty. Caveat everybody. I blog at http://PragmaticCaregiver.blogspot.com


Tue Mar 20, 2007 12:22 am
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Location: Toronto, Canada
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Got it -- thanks, Eric.

Will also try the 5-HTP and L-tyrosine (if Mom will take it is another story).

Good luck with your Work Drama. Remember the sports psyc "peak performance" studies wherein there is an optimum level of effort that correlates with peak performance -- more is not necessarily better; i.e., the discovery of the benzene ring!!

Get some sleep!

all the best,
dale

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Dale
[My dear, Mom, Beatrice, (born in 1929) was diagnosed with LBD in Dec 2006. She passed away peacefully on July 12, 2013 at Embassy Hall, Shannex, Quispamsis, N.B.]


Tue Mar 20, 2007 12:41 am
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Joined: Mon Feb 05, 2007 3:43 am
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Location: Seattle, WA
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*chuckle* Hrm, maybe *I* should try the psychostimulants. Actually, I don't really burn the midnight oil day after day after day - I pretty much require seven solid hours on a daily basis, and I'm lucky that my work situation lets me accommodate that. I don't even touch caffeine anymore. I just have to devote a couple of weeks to getting this New New Thing cranked out.

To give you an idea... here's a link to capsule sizes:

http://www.torpac.com/capsule_size_chart.htm

The 5-HTP is a #3 or 4, the L-Tyrosine is a tablet a bit wider than a 000. We use half an L-Tyrosine so it's pretty swallowable. The 5-HTP could be emptied and the l-tyrosine crushed for mixing into applesauce or pudding/ice cream if that's an issue. Neither has an objectionable taste or odor.

Getting back to the topic - we were considering SPECT early on, but one of the major problems with SPECT is that he would have to wash out for *days* on the stimulants, which is the piece of the puzzle that has had the most visible effect on his quality of life. Thus, we're continuing to treat empirically, like the vast majority of other LBD patients.

Eric

_________________
Cal is not the real name of a real 84 year old with DLB. I don't speak for LBDA, nor do I have clever initials behind my name, so information is provided without warranty. Caveat everybody. I blog at http://PragmaticCaregiver.blogspot.com


Tue Mar 20, 2007 1:39 pm
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Joined: Wed Feb 21, 2007 11:39 am
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Location: Lucca, Italy
Post Cerebral SPECT
Hi, Here in Italy my husband had a Cerebral SPECT using 123-I-Ioflupano which pretty much confirmed his Parkinsonism. He may have another one with a different medium. It took 6 hours in isolation, poor guy. Irene

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Irene in Italy


Wed Mar 21, 2007 5:37 pm
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Eric, thanks for marking your scouting trail through the woods -- appreciate all your valuable research info. I know several people who "cure" other neurological disorders (e.g. MS) with a strictly modified diet and nutritional supplementation.

Mom has never been one to eat properly. Her idea of a decent meal is a hydrogenated peanut butter sandwich on white bread with a bowl of Campbell's condensed soup -- no milk, no fruit, no other vegies, except for the odd potato, carrots and cob of corn in summertime. She was dehydrated on admission to hospital; otherwise her routine blood tests were pretty much normal with a relatively low B-12 and low potassium.

Your Cal is in good hands. Wish my mom would cooperate and take nutritional supplements, meds and better food. She's starting to comply, (will eat yogurt now) but not nearly well enough according to family. My nutritionally savvy SIL is trying her best. Mom lives on the east coast in NB and loves her own home. She's pretty good during the day, except for those torturous hallucinations at night and on waking. Hope she gets the Klonopin at next MD appt. and that we can start her on 5-HTP and L-Tyrosine -- maybe mix them in a shake like the Learning Factors powdered mix for shakes???

just rambling ...

thx,
:)

_________________
Dale
[My dear, Mom, Beatrice, (born in 1929) was diagnosed with LBD in Dec 2006. She passed away peacefully on July 12, 2013 at Embassy Hall, Shannex, Quispamsis, N.B.]


Wed Mar 21, 2007 11:15 pm
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