Category Archives: LBD

This email is about DLB (dementia with Lewy bodies) genetics.  The headline is:  “These calculations put DLB’s genetic component at 31 percent, close to that of PD and half that of AD.”  If I understand this correctly, this means that 31 percent of DLB cases can be explained by genetics.  Two of these genetics research papers utilized brain tissue of DLB donors where we assisted with the brain donations!

A week ago, Brain Support Network handled four brain donations in 24 hours.  (We often see this in early January and late December.)  One of the cases was of a gentleman with a Parkinson’s Disease.  His sister suspects DLB.  Almost exactly two years ago, we handled the brain donation of their brother, also with a clinical Parkinson’s diagnosis.  In the brother’s case, DLB was confirmed through brain donation.  It seems that something genetic may be going on in this family.  So, the sister and I thought we’d ask the brain bank to run a genetics test for the alpha-synuclein gene on both brothers.  I went to the web to see what the latest was about that alpha-synuclein gene so I could correctly present the case to the brain bank.

I found an update on fascinating DLB genetics research published in November 2015, and presented at the International Dementia with Lewy Body Conference in December 2015.  Let me point out that this research is only possible through brain donation.  Many of the DLB brain donations we’ve helped with over the last several years have contributed to two of these research papers!  (Bras paper and Murray paper)

Here’s an excerpt of the update:

“Jose Bras of University College London, U.K., reminded the audience that late-onset Alzheimer’s and Parkinson’s were not considered genetic diseases until recently. By now some 30 genes are known to be involved in each of them, and their overall heritability is estimated at 60 and 28 percent, respectively. At the level of GWAS, the known common genetic risk factors for AD and PD do not overlap. Yet there is DLB, a clinical hybrid of the two…”

“To date, scientists have implicated four genes in DLB. They are:
* APOE…
* SNCA (encoding the α-synuclein protein)…
* A locus on chromosome 2 in a large family…
* GBA, variants of which drive up a person’s risk of developing DLB…”

Note that these four genes are not specific to DLB.  They are implicated in either Alzheimer’s (AD) or Parkinson’s (PD).

“Bras and collaborators in Europe, Australia, and across North America have thus far pooled 1,400 cases confirmed by neuropathology to have had DLB. This is still a far cry from the nearly 100,000 people whose samples are available for AD/PD GWAS, but it’s a first step toward a comprehensive look at the genetic signature of DLB, Bras said.”

“Samples of this size support heritability estimates. These calculations put DLB’s genetic component at 31 percent, close to that of PD and half that of AD, Bras told the audience. They also enable estimates of the genetic overlap among AD, DLB, and PD–diseases already known to overlap at the clinical and the neuropathological level. Genetically speaking, DLB correlates strongly with AD, though much of that is due to ApoE. Subtracting ApoE leaves DLB equally correlated to AD and PD, Bras reported.”

“Cyrus Zabetian of the University of Washington, Seattle, presented a comparison of candidate genes in a smaller sample of 348 neuropathologically confirmed DLB cases and 102 PDD cases from seven centers in the United States. Finding broadly similar results, this study suggested that ApoE4 is more common in DLB, the disease that is arguably closer to AD, than in PDD, the disease nearer to PD. ‘If you carry ApoE4, it pushes you toward an earlier presentation of dementia, hence you are more likely to be classified as having DLB. GBA mutations, on the other hand, push you toward alpha-synucleinopathy, so you are more likely to be classified as having PDD,’ Zabetian said.”

“Another hint that ApoE4 puts its finger firmly on the AD end of the DLB scale came from a study relating ApoE genotype to neuropathology in large series of people who had had a diagnosis of DLB during life. Melissa Murray from the Mayo Clinic in Jacksonville, Florida, reported that while ApoE4 carriers tended to have worse alpha-synuclein pathology than non-carriers, that link was due to the presence of amyloid pathology. About 90 percent of patients with DLB have AD pathology, as well. In AD research, ApoE4 is increasingly seen as an indicator that amyloid is present in the brain with age, and several presentations in Fort Lauderdale, including Murray’s, pointed in the same direction for DLB.”

“‘In the clinic, by and large DLB is not an inherited disorder,’ agreed Ian McKeith of Newcastle University, U.K.”

Here’s a link to the research update:  www.alzforum.org/news/conference-coverage/genetics-dlb-setting-fill-mostly-empty-canvas

If you reach different conclusions than I have, please let me know!

Robin

Probably many group members will know of Pat Snyder. She wrote a terrific book called “Treasures in the Darkness,” that circulates within our Lewy Body Dementia support group. Her book is focused on early-stage LBD. I often share the flyer about her book to those dealing with a new diagnosis.

Recently, the Huffington Post interviewed Pat Snyder. Her husband, John, died in early November–eight years after he was diagnosed. Pat believes that treatment, which started after visiting doctor #12, extended the period of mild symptoms. The stories relayed in this article are similar to what we hear at support group meetings.

This is one of the few articles published after the Robin Williams story re-emerged that I’m happy to read. (Your opinion may differ.)

See: www.huffingtonpost.com/entry/lewy-body-dementia-caregiving_563d4dd2e4b0411d30713906

Healthy Living
Huffington Post
What It’s Like To Love Somebody With Lewy Body Dementia
Inside the disease that contributed to Robin Williams’ death.
by Anna Almendrala, Senior Editor, Huffington Post
Posted 11/10/2015 02:47 pm ET | Updated Nov 17, 2015

Robin

This article in The Guardian (US edition) is about Kathleen Anduze, who lives in upstate New York and has a diagnosis of dementia with Lewy bodies. As the article says, everyone’s course with DLB is individual. So while Kathleen bemoans the loss of her imagination, others with DLB may not detect that loss.

The Brain Support Network group member that forwarded this article on to me was somewhat reluctant to do so. LBD seems to be lots more in the news now because of the statement by Robin Williams’s widow that he committed suicide not due to depression but due to DLB symptoms. But, the group member believes that the latest stories about LBD seem to have a sensationalist quality to them. Judge for yourself….

See: http://www.theguardian.com/society/2015/nov/17/dementia-lewy-bodies-disease-kathleen-anduze-robin-williams

Dementia
Losing her mind and watching it go: the slow suffering of Lewy body disease

“It is the second most common form of dementia and yet little is known about the disease that led to the death of Robin Williams. Rose Hackman tells the story of the Anduze family, and how Lewy body disease has forever changed their lives.”

by Rose Hackman
The Guardian
Tuesday 17 November 2015 08.00 EST

Robin

Medscape Medical News offers an email summary of medical journal articles. In yesterday’s email, they offered a summary of a new three-minute test to diagnose Lewy Body Dementia. The test is developed by Dr. Jim Galvin, an LBD expert. I’ve copied the summary below, plus a link to the journal article that describes the test.

I need to read the full medical journal article but the last one I read along these lines (that focused on fluctuating cognition) didn’t truly differentiate those with Lewy Body Dementia, Alzheimer’s, or Parkinson’s. We know from brain donation that lots of people don’t have “pure” LBD; they have LBD and AD. So I’m not sure how helpful such a three-minute test is. (Note that I’ve helped one of Dr. Galvin’s patients with brain donation. Dr. Galvin diagnosed the gentleman as having LBD; autopsy showed not a single Lewy body in the brain.)

Here are four key points from the summary:

• LBD includes both dementia with Lewy bodies (DLB) and Parkinson’s disease dementia. The new test, called the Lewy body composite risk score (LBCRS), was derived from clinical features in autopsy-verified cases of healthy controls, Alzheimer’s disease (AD), DLB, and PD with and without dementia.

  Robin’s note: The autopsy-verified cases of AD, DLB, PD, and healthy controls were described in a study in 2006. In that study, “Features that predicted Lewy bodies at autopsy included extrapyramidal signs, cognitive fluctuations, hallucinations, and sleep disturbances.” Only 20 DLB brain donors were included in that study. That’s not a very big number.

• Such a test might speed up a diagnosis of DLB and spare families a lot of strain and patients possible harm. An earlier study showed that these patients “had to see multiple doctors over multiple visits and 50% of the time they got a wrong diagnosis that eventually had to be corrected,” said Dr Galvin.
• (Dr. Galvin) added that half of the wrong diagnoses weren’t harmful, but the other half could have been. For example, some patients were diagnosed with a psychiatric disorder, such as schizophrenia “even though they were in their 70s and 80s,” and were put on the antipsychotic haloperidol, which is “potentially harmful and possibly fatal in this population,” he said. Some patients were never given a diagnosis at all, even after seeing multiple doctors. “People were wondering what was going on and nobody was there to help them,” said Dr Galvin.
• But would [a correct diagnosis of Robin Williams] have saved his life? “While Lewy body dementia itself doesn’t increase the risk for suicide, if you have someone who is not correctly diagnosed or isn’t completely diagnosed and they don’t know what’s going on, they can make decisions that can be harmful to themselves,” said Dr Galvin.

See: www.medscape.com/viewarticle/854577  (You need to be a registered user for access. I believe registration is free.)

Medscape Medical News > Neurology
Three-Minute Test for Lewy Body Dementia
Pauline Anderson
November 16, 2015

Robin