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 Some MCI Patients Have Early LBD 
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Joined: Fri Aug 11, 2006 1:46 pm
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Location: SF Bay Area (Northern CA)
Post Some MCI Patients Have Early LBD
A lurker here forwarded this on to me because they know I'm a fan of Dr. Boeve, an LBD and sleep behavior expert at Mayo Rochester.

The Tangled Neuron is a website developed by a woman whose father has some form of dementia. I think the woman may've attended a Mild Cognitive Impairment (MCI) Symposium in Seattle in April '09, and heard Dr. Boeve speaking there about LBD and MCI. At the symposium, Dr. Boeve "presented an analysis of the symptoms of MCI patients at Mayo who were found at autopsy to have had Lewy body disease. In his experience, people with any type of MCI can develop Lewy body dementia. But it’s often patients with Non-Amnestic MCI (specifically those who have problems with attention, planning and organizing, and visuospatial functions) who are likely to have early Lewy body disease."

Again, you can see the importance of brain donation to this sort of research.

You can find the data Dr. Boeve presented at the symposium here:
http://www.tangledneuron.info/files/mci ... rfinal.pdf

And you can find an easy-to-understand description of Dr. Boeve's talk about LBD and MCI here:
http://www.tangledneuron.info/the_tangl ... d-mci.html

In that description, a sleep questionnaire developed by Dr. Boeve (and others at Mayo Rochester) is mentioned. The questionnaire is completed by the bed partner. It is helpful in diagnosing RBD (REM sleep behavior disorder). The questionnaire is available here:
http://www.mayoclinic.org/pdfs/MSQ-copyrightfinal.pdf

I've copied the full text below of the story about Dr. Boeve's presentation.

Robin



Mild Cognitive Impairment Symposium: Lewy Body Disease and MCI
from The Tangled Neuron (website)

Pathologists sometimes find Lewy bodies in the brains of people who had Mild Cognitive Impairment (more on this in a future report). But can a doctor make a diagnosis when the patient is still living?

So far, no blood, spinal fluid, imaging or other test can be used to diagnose Lewy body disease, although a more “normal” looking MRI and lack of amyloid on a PiB PET scan may indicate a patient is more likely to have Lewy body disease rather than Alzheimer’s or vascular dementia [see discussion of PiB in the Diagnosis report from the Symposium]. But a person’s medical history and symptoms may support a tentative diagnosis of Lewy body disease in someone with Mild Cognitive Impairment (MCI). At the Mild Cognitive Impairment Symposium, Brad Boeve, Professor of Neurology at the Mayo Clinic in Rochester, Minnesota, presented an analysis of the symptoms of MCI patients at Mayo who were found at autopsy to have had Lewy body disease.

In his experience, people with any type of MCI can develop Lewy body dementia. But it’s often patients with Non-Amnestic MCI (specifically those who have problems with attention, planning and organizing, and visuospatial functions) who are likely to have early Lewy body disease. These patients tend to perform well on language tests, but their performance on memory tests is highly variable [fluctuating cognition is a hallmark of Lewy body disease].

Another sign someone might have Lewy body disease is Rapid Eye Movement Sleep Behavior Disorder (RBD). In RBD, people (usually males age 20-50) act out their dreams. People with RBD may punch and kick in their sleep, and can sometimes hurt themselves or a spouse.

RBD may develop years or even decades earlier than any problems with memory and thinking. Dr. Boeve believes this indicates the alpha-synuclein pathology involved in Lewy body disease is already present in the brainstem, or lower part of the brain, where REM sleep is controlled.

RBD is also associated with other neurodegenerative diseases, but the association is strongest with those diseases involving alpha-synuclein pathology (including Lewy body disease and multiple system atrophy). In a group of 45 Mayo Clinic patients with RBD, only two were found to have non-alpha-synuclein pathology diseases. All Mayo patients studied who had both RBD and MCI had Lewy body disease at autopsy.

Dr. Boeve and his colleagues have developed a short questionnaire for spouses of patients to fill out, and have found it to be 97 percent accurate in detecting REM Sleep Behavior Disorder.

Other symptoms suggestive of early Lewy body disease are daytime sleepiness, constipation, loss of sense of smell and a large decrease in blood pressure when a person stands up.

What does it matter whether someone with MCI has a Lewy body disorder instead of another neurodegenerative disease, vascular dementia or other condition? “Identifying Lewy body disease as the underlying cause of mild cognitive impairment is important for several reasons,” explained Dr. Boeve in an email after the conference. “The symptoms that often evolve as the illness progresses are quite different from Alzheimer’s disease, and it is important to plan ahead in case some problems such as hallucinations or delusions occur. Plus, some patients experience significant improvement in their cognitive symptoms with acetylcholinesterase inhibitors. On the other hand, conventional neuroleptics such as haloperidol should never be used. Eventually when therapies that positively influence Lewy body disease pathophysiology are available, it will be critical to use them as early in the illness as possible, and MCI patients who have RBD would be particularly important to diagnose and treat.”


Note: “Identifying Mild Cognitive Impairment,” one of the supplemental films in HBO’s Alzheimer’s Project, features Dr. Ron Petersen interviewing a Mayo Clinic patient with both MCI and REM Sleep Behavior Disorder.


Sun Jul 12, 2009 1:02 am
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Joined: Fri Aug 11, 2006 1:46 pm
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Research related to this post from July was just published. These two sentences in the abstract are key:

"These findings indicate that among Lewy body disease cases that pass through a mild cognitive impairment stage, any cognitive pattern or mild cognitive subtype is possible, with the attention/executive and visuospatial domains most frequently impaired. "

"All cases with rapid eye movement sleep behaviour disorder and mild cognitive impairment were eventually shown to have autopsy-proven Lewy body disease, indicating that rapid eye movement sleep behaviour disorder plus mild cognitive impairment probably reflects brainstem and cerebral Lewy body disease."

Here's the very dense abstract:


Brain. 2009 Nov 4. [Epub ahead of print]

Mild cognitive impairment associated with limbic and neocortical lewy body disease: a clinicopathological study.

Molano J, Boeve B, Ferman T, Smith G, Parisi J, Dickson D, Knopman D, Graff-Radford N, Geda Y, Lucas J, Kantarci K, Shiung M, Jack C, Silber M, Pankratz VS, Petersen R.

Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN, and Jacksonville, FL.

There are little data on the relationship between Lewy body disease and mild cognitive impairment syndromes. The Mayo Clinic aging and dementia databases in Rochester, Minnesota, and Jacksonville, Florida were queried for cases who were diagnosed with mild cognitive impairment between 1 January 1996 and 30 April 2008, were prospectively followed and were subsequently found to have autopsy-proven Lewy body disease.

The presence of rapid eye movement sleep behaviour disorder was specifically assessed. Mild cognitive impairment subtypes were determined by clinical impression and neuropsychological profiles, based on prospective operational criteria. The diagnosis of clinically probable dementia with Lewy bodies was based on the 2005 McKeith criteria. Hippocampal volumes, rate of hippocampal atrophy, and proton magnetic resonance spectroscopy were assessed on available magnetic resonance imaging and spectroscopy scans.

Eight subjects were identified; six were male. Seven developed dementia with Lewy bodies prior to death; one died characterized as mild cognitive impairment. The number of cases and median age of onset (range) for specific features were: seven with rapid eye movement sleep behaviour disorder-60 years (27-91 years), eight with cognitive symptoms-69 years (62-89 years), eight with mild cognitive impairment-70.5 years (66-91 years), eight with parkinsonism symptoms-71 years (66-92 years), six with visual hallucinations-72 years (64-90 years), seven with dementia-75 years (67-92 years), six with fluctuations in cognition and/or arousal-76 years (68-92 years) and eight dead-76 years (71-94 years).

Rapid eye movement sleep behaviour disorder preceded cognitive symptom onset in six cases by a median of 10 years (2-47 years) and mild cognitive impairment diagnosis by a median of 12 years (3-48 years). The mild cognitive impairment subtypes represented include: two with single domain non-amnestic mild cognitive impairment, three with multi-domain non-amnestic mild cognitive impairment, and three with multi-domain amnestic mild cognitive impairment. The cognitive domains most frequently affected were attention and executive functioning, and visuospatial functioning. Hippocampal volumes and the rate of hippocampal atrophy were, on average, within the normal range in the three cases who underwent magnetic resonance imaging, and the choline/creatine ratio was elevated in the two cases who underwent proton magnetic resonance spectroscopy when they were diagnosed as mild cognitive impairment.

On autopsy, six had neocortical-predominant Lewy body disease and two had limbic-predominant Lewy body disease; only one had coexisting high-likelihood Alzheimer's disease. These findings indicate that among Lewy body disease cases that pass through a mild cognitive impairment stage, any cognitive pattern or mild cognitive subtype is possible, with the attention/executive and visuospatial domains most frequently impaired. Hippocampal volume and proton magnetic resonance spectroscopy data were consistent with recent data in dementia with Lewy bodies. All cases with rapid eye movement sleep behaviour disorder and mild cognitive impairment were eventually shown to have autopsy-proven Lewy body disease, indicating that rapid eye movement sleep behaviour disorder plus mild cognitive impairment probably reflects brainstem and cerebral Lewy body disease.

PubMed ID#: 19889717 (see pubmed.gov for the abstract only - available for free)


Sun Nov 08, 2009 12:46 pm
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