Ian G. McKeith Brit Mollenhauer Jim Galvin James B. Leverenz Walter J. Schulz-Schaeffer

On 15 June 2009, we hosted a Webinar discussion with slide presentations by Ian McKeith at Newcastle University, UK, James Leverenz at University of Washington, Seattle, James Galvin, Washington University, St. Louis, Brit Mollenhauer of Paracelsus-Elena Klinik, Kassel Germany, and Walter Schulz-Schaeffer of the University of Goettingen and audio provided via a telephone line.

Editor’s note: Nearly 400 caregivers and scientists logged on for this 80-minute event. In addition, the Alzforum received more than 100 caregiver questions. This discussion aimed primarily at increasing awareness of DLB among scientists and physicians and therefore focused on scientific research, but clearly there is a great unmet need among patients and caregivers to have their questions addressed. The Alzforum editors have collected comments received in advance of the discussion and during the live hour into a caregiver comment page and are asking the panelists to respond to these questions. Please visit the Lewy Body Dementia Association website to view the first installment of answers to some of the most frequently asked caregiver questions. View/Listen to the Webinar Click on this image to launch the recording.

Background Text
By Gabrielle Strobel

Dementia with Lewy bodies (DLB)—a disorder at the interface of AD and PD—competes with vascular dementia for second spot (after AD itself) on the list of most common causes of dementia among the elderly. If you just said “Huh!” to yourself, you are not alone. Most people wouldn’t know how frequent DLB is, judging by the vastly smaller amount of attention it receives across the board, from neurologists, psychiatrists, scientists, and funders. But this may be changing. Twenty years after DLB came to be recognized as a clinical and pathological category in its own right, a growing number of researchers from both the dementia and the movement disorder fields believe that AD and PD—formerly viewed as separate domains—are connected across a spectrum, and that DLB links the two. Investigators who formerly focused on one of the two established diseases at either end of the spectrum are now developing an active interest in this mixed disease. In DLB, patients suffer from various combinations of Alzheimer and Parkinson signs, which are compounded by frustrating fluctuations in symptoms, visual hallucinations, visuospatial impairments, and, in many cases, rapid decline. “DLB may provide a link between AD and PD that will help us understand both disorders better,” said Ian McKeith of Newcastle University, UK.

Since 1995, a series of targeted workshops have focused on DLB, and on its neighbor on the PD end of the spectrum (Parkinson disease dementia, aka PDD). The workshops have sharpened the clinico-pathological picture of these diseases to crisper definitions that are applicable in the clinic. Clinicians know now that DLB and PDD patients respond especially favorably to cholinesterase inhibitors as was predicted from their postmortem neurochemical pathology. This past March, the latest in this series of small meetings, held in the German city of Kassel, broke new ground by proposing working groups that are charged with hammering out a collaborative research agenda for both biomarker development and presymptomatic diagnosis. Another priority the scientists set is molecular pathogenesis research that aims to unravel how the three main proteins known to underlie this disease spectrum—amyloid-β, tau, and α-synuclein—conspire in various ways to drive an individual person’s disease. What’s more, a new player on the DLB/PDD/PD end of the spectrum recently burst on the scene in the form of glucocerebrosidase, an enzyme of lipid metabolism whose gene appears to underlie a significant number of cases, and whose modus operandi in disease urgently needs to be figured out.

The Alzforum this past week began an ongoing series of daily stories that summarize recent advances on this topic. They form the background material for this Webinar discussion. So that you can come armed with questions about the latest and greatest, consider reading the introduction about spectrum neurodegeneration, tau in Parkinson’s, dementia with Lewy bodies, oligomers in DLB, AD, brain imaging markers, fluid α-synuclein markers, fluid progranulin markers, Parkinson’s gene reshuffling, and GBA as DLB and PD gene.

Buoyed by such and other advances, the DLB/PDD scientists hope to disabuse the field at large, as well as physicians who see these patients, of the entrenched but quite possibly outdated notion that DLB is rare (they say it’s not), vague (ditto), of indeterminate relationship to AD and PD (ditto), and complex (yes, but tractable). Join us for slide presentations and subsequent discussion. Send in your questions and comments before the live hour by typing into the comment box below. During the live event on 15 June, type into the GoTo Webinar comment field on your screen and the moderator will pose questions to the panel.

	Comments on Live Discussion
	Comment by:  Phyllis Adams
	Submitted 8 June 2009  |  Permalink	Posted 9 June 2009
	Why do some people with LBD progress so rapidly and some progress so slowly, and why is it so difficult to diagnose? View all comments by Phyllis Adams
	Comment by:  Chris Greene
	Submitted 9 June 2009  |  Permalink	Posted 10 June 2009
	I thank you all so very much for what you are doing. We cannot cure this disease fast enough. Where are the clinical studies for this devastating disease? View all comments by Chris Greene
	Comment by:  Daisy Strasinger
	Submitted 8 June 2009  |  Permalink	Posted 10 June 2009
	Why is Dementia with Lewy bodies (DLB) so difficult to diagnose? My husband declined mentally over a number of years. He was under the care of a neurologist, and a number of good doctors for other health problems. Each one agreed he had dementia but not until 8 month before my husband died was he diagnosed with DLB. I later found out he had all the symptoms. Why did it take so long? Thank you in advance. View all comments by Daisy Strasinger
	Comment by:  Rhonda Hovater
	Submitted 8 June 2009  |  Permalink	Posted 10 June 2009
	In 2004 at the age of 68, my father, who was always active, athletic, and highly intelligent, started hallucinating after having quadruple bypass surgery. He never fully recovered from the surgery, but continued having detailed hallucinations, was unable to dial a phone, use the dishwasher, etc. He was diagnosed with dementia and started on Exelon, Namenda and Seroquel. These medications helped tremendously. After researching, I was sure he had DLB. 18 months ago, I took him to UCLA and he was then officially diagnosed with DLB. He is in a rapid decline now. He is bedridden, suffering from pressure sores, unable to communicate, doesn't open his eyes very often. He has lost a great amount of weight over the past 6 months, although he has a big appetite. Is it normal for a person with DLB to continue to lose weight, even when there are eating? Also, do you recommend that a person continues on with the medications to the end? Thank you for having this web forum. View all comments by Rhonda Hovater
	Comment by:  Karen Tinkham
	Submitted 10 June 2009  |  Permalink	Posted 10 June 2009
	My husband was a patient at Sun Health Research Institute in Sun City, Arizona. Charlie had a diagnosis of Lewy body dementia, but Dr. Marwan Sabbagh told us that the only way you know for sure is if an autopsy is done. We did that and found that my husband had not had LBD, after all. He had corticobasal dementia. It was most helpful for our family to know what Charlie suffered with for three years. I wish more physicians would encourage patients to be tissue donors and give their families peace of mind when they know for sure what their loved one had. View all comments by Karen Tinkham
	Comment by:  Pat Hackspacher
	Submitted 10 June 2009  |  Permalink	Posted 10 June 2009
	My husband was diagnosed at the age of 52 with Alzheimer disease and three years later with DLB. It's been a tough six years. He does a lot of spitting and no one can figure out why. At times he can go for days without spitting and other times he will spit every few minutes. He is currently on robinal to help dry up the secretions. This has helped to reduce the amount of secretion but not the frequency. Has anyone else had this issue and, if so, is there any help with it or is this just what we have to live with? Thank you for any information. View all comments by Pat Hackspacher
	Comment by:  Karen Ness
	Submitted 10 June 2009  |  Permalink	Posted 10 June 2009
	My father had Alzheimer's and my mom had dementia with Lewy bodies. How concerned should I and my siblings be of ending up with either one? View all comments by Karen Ness
	Comment by:  Lieve Vansteenkiste
	Submitted 12 June 2009  |  Permalink	Posted 12 June 2009
	I want to congratulate you for this excellent initiative. My husband was diagnosed mid-2006, at the age of 67, with probable DLB, mainly because of his visual hallucination symptoms and attention deficit. Only over the course of the next year did mild Parkinson’s symptoms, such as body stiffness, appear. Today, about three years out, he has severe Parkinson’s symptoms, including stooped posture, "frozen behavior," severe equilibrium problems, uncoordinated walking (almost Creutzfeldt–Jakob-like), but no noticeable tremor. I’d like to address this question primarily but not exclusively to Dr. Schulz-Schaeffer. Here is something that happens quite frequently: Although my husband has important cognitive loss and loss of speech, a sudden event, for example, loud shouting or a brisk movement, brings normal speech and attention momentarily back. It’s almost as if his brain got a boost by an electro-shock. My question: Is there any explanation, and how could this eventually be prolonged? I recall a press release in April 2007 announcing that...  Read more I want to congratulate you for this excellent initiative. My husband was diagnosed mid-2006, at the age of 67, with probable DLB, mainly because of his visual hallucination symptoms and attention deficit. Only over the course of the next year did mild Parkinson’s symptoms, such as body stiffness, appear. Today, about three years out, he has severe Parkinson’s symptoms, including stooped posture, "frozen behavior," severe equilibrium problems, uncoordinated walking (almost Creutzfeldt–Jakob-like), but no noticeable tremor. I’d like to address this question primarily but not exclusively to Dr. Schulz-Schaeffer. Here is something that happens quite frequently: Although my husband has important cognitive loss and loss of speech, a sudden event, for example, loud shouting or a brisk movement, brings normal speech and attention momentarily back. It’s almost as if his brain got a boost by an electro-shock. My question: Is there any explanation, and how could this eventually be prolonged? I recall a press release in April 2007 announcing that observations by your group offered a new understanding of the pathological processes behind neurodegenerative diseases such as DLB. Can your research explain my observation, and has it advanced since then? [Editor’s note: see Kramer and Schulz-Schaeffer et al., 2007.] Here are questions mostly for Dr. Mollenhauer, who recently organized the Clinicopathological Conference on Dementia, held in Kassel last March: What were the conclusions for treatment options in DLB and PDD? Which biomarkers are currently available? As far as I know, a new formula called "REMBER" that’s based on the protein tau has produced Phase 2 data. Can we expect a new drug? [Editor’s note: see ARF related conference story.] View all comments by Lieve Vansteenkiste
	Comment by:  Carol Shapiro
	Submitted 16 June 2009  |  Permalink	Posted 16 June 2009
	I found the Webinar to be very informative. I want to thank the Drs. for sharing their knowledge, and Gabrielle for asking important questions of the panel. One of the questions posed was should the ADNI Study include testing for α-synuclein protein to check for DLB. I would like to propose that testing for α-synuclein should also be added as a protocol for the DIAN (Dominantly Inherited Alzheimer Network) Study since 90 percent of eFAD victims will also develop that pathology (see ARF related news story). There is so much information that researchers can learn from studying non-symptomatic members of families where there is 100 percent penetrance of AD if the mutant PS1, PS2, or APP gene is present. All the more reason that the DIAN Study is so important and should be carried on for numerous years after the initial six-year study is complete. View all comments by Carol Shapiro
	Comment by:  Walter J. Schulz-Schaeffer
	Submitted 18 June 2009  |  Permalink	Posted 18 June 2009
	Schulz-Schaeffer Reply to Vansteenkiste Comment Indeed, our findings should be able to help explain the observations mentioned above. First of all, the observation that an particular ability that was believed to be lost reappears for a short period indicates that the cells responsible for the ability are still in place. Higher brain functions such as cognitive functions or speech require networks of nerve cells that communicate. In my opinion, the small aggregates do not immediately result in a loss of nerve cell communication; it is a progressively worsening process that results in loss of function when a critical threshold is reached. If the networks in principle still exist they may be stimulated to work for a short time. In the initial stages of the disease the partial loss of function may result in fluctuation of symptoms. In a more advanced stage short-time recurrence of function may occur. The findings of my working group provide good evidence that training is the best way to prolong deterioration of brain functions....  Read more Schulz-Schaeffer Reply to Vansteenkiste Comment Indeed, our findings should be able to help explain the observations mentioned above. First of all, the observation that an particular ability that was believed to be lost reappears for a short period indicates that the cells responsible for the ability are still in place. Higher brain functions such as cognitive functions or speech require networks of nerve cells that communicate. In my opinion, the small aggregates do not immediately result in a loss of nerve cell communication; it is a progressively worsening process that results in loss of function when a critical threshold is reached. If the networks in principle still exist they may be stimulated to work for a short time. In the initial stages of the disease the partial loss of function may result in fluctuation of symptoms. In a more advanced stage short-time recurrence of function may occur. The findings of my working group provide good evidence that training is the best way to prolong deterioration of brain functions. Electrophysiological experiments have shown that the use of synapses prevent the post-synapse from degeneration. In DLB, the problem seems to be the decrease of transmitter release from the pre-synapse, which leads to degeneration of the post-synapse. Training may be one way to slow down degeneration of the post-synapse. Since our last publication we have been working on the link between the presynaptic protein aggregation with postsynaptic degeneration, aspects of the spread of the disease, and aspects of the selective neuronal vulnerability. View all comments by Walter J. Schulz-Schaeffer
	Comment by:  Lieve Vansteenkiste
	Submitted 18 June 2009  |  Permalink	Posted 18 June 2009
	I understand from the comments of Prof. Schulz-Schaeffer that as long as the networks exist, they may be stimulated to work for a short time, suggesting that training is the best way to prolong brain functions. But in an advanced stage of the disease, such training isn't possible anymore, although short-time recurrence of function may occur. How could such recurrence then possibly be induced ? View all comments by Lieve Vansteenkiste
	Comment by:  Bill Worstell
	Submitted 17 June 2009  |  Permalink	Posted 18 June 2009
	Thank you for making this available to the researcher and caregiver communities -- the Alzforum is a tremendous resource for us all. Three years ago I lost my father to Parkinson's with dementia after many years of watching him and my mother (his primary caregiver) struggle with this disease. As a physicist working on developing PET instrumentation with potential application for differential diagnosis and earlier diagnosis, I am doubly interested in this live discussion. There were a number of presentations bearing on these subjects at the Society of Nuclear Medicine meeting that just concluded, and which coincided with the live discussion. A number of people attending that conference I'm sure would have added to your live attendance, and I'll thank you on their and my behalf for making the discussion available for us now that we've returned to our work. Dr. Chet Mathis received the Lassen prize from the Society of Nuclear Medicine at this year's meeting for his work creating the Pittsburgh Compound B PET amyloid imaging radiotracer. While, as has been noted here on the...  Read more Thank you for making this available to the researcher and caregiver communities -- the Alzforum is a tremendous resource for us all. Three years ago I lost my father to Parkinson's with dementia after many years of watching him and my mother (his primary caregiver) struggle with this disease. As a physicist working on developing PET instrumentation with potential application for differential diagnosis and earlier diagnosis, I am doubly interested in this live discussion. There were a number of presentations bearing on these subjects at the Society of Nuclear Medicine meeting that just concluded, and which coincided with the live discussion. A number of people attending that conference I'm sure would have added to your live attendance, and I'll thank you on their and my behalf for making the discussion available for us now that we've returned to our work. Dr. Chet Mathis received the Lassen prize from the Society of Nuclear Medicine at this year's meeting for his work creating the Pittsburgh Compound B PET amyloid imaging radiotracer. While, as has been noted here on the Alzforum, there is as yet no radiotracer on the horizon for alpha synuclein, there were presentations on a number of dopaminergic tracers both for PET and SPECT. In the talks and in the aisles, there was discussion of possible potential for future combinations of these methods in contributing information for diagnosis of mixed dementia. I and others are hopeful of being able to contribute to this, in concert with other biomarker methods and working with those who are developing the treatments which we all look forward to with such hope. View all comments by Bill Worstell
	Comment by:  Margaret Dabraccio
	Submitted 17 June 2009  |  Permalink	Posted 23 June 2009
	Found the Webinar very interesting. We have a dual Parkinson's/AD diagnosis. I strongly suspect Lewy body disease. The decline over spring has been so rapid we are struggling and a little overwhelmed at times. View all comments by Margaret Dabraccio
	Comment by:  Chirco Laurie
	Submitted 29 August 2009  |  Permalink	Posted 1 September 2009
	I would like to know how many younger people live with DLB. My husband was only 42 when his symptoms started. I always hear of elderly, not much about younger patients. Thank you for this discussion. No matter what the age, it is an awful disease for all of us. View all comments by Chirco Laurie
	Comment by:  Ian McKeith
	Submitted 2 September 2009  |  Permalink	Posted 2 September 2009
	Reply to Chirco Laurie There isn't any systematic information about age of onset of DLB, but the situation is probably similar to Alzheimer disease, i.e., that young onset does occur although is relatively uncommon. The sparse literature suggests that very early-onset Lewy body disease (a few cases begin as early as the twenties) is usually a combination of quite severe parkinsonism plus dementia; at older ages the clinical picture is much more variable. ApoE status or other genetic determinants may play a part in age of onset even in cases which have no obvious familial pattern. View all comments by Ian McKeith

	Submit a Comment on this Live Discussion
	Cast your vote and/or make a comment on this live discussion.  If you already are a member, please login. Not sure if you are a member? Search our member database. *First Name   *Last Name   Country or Territory: USA Canada Afghanistan Albania Algeria American Samoa Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory British Virgin Islands Brunei Bulgaria Burkina Faso Burma Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos Islands Colombia Comoros Congo Cook Islands Corte d'lvoire (formerly Ivory Coast) Costa Rica Croatia Cuba Cyprus Czech Republic Denmark Djibouti Dominica Dominican Republic East Timor Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands Faroe Islands Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Gambia Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guam Guatemala Guinea Guinea-Bissau Guyana Haiti Heard and McDonald Islands Honduras Hong Kong Hungary Iceland India Indonesia Iran Iraq Ireland Israel Italy Ivory Coast (now known as Corte d'lvoire) Jamaica Japan Jordan Kazakhstan Kenya Kiribati Korea, North Korea, South Kuwait Kyrgyzstan Laos Latvia Lebanon Lesotho Liberia Libya Liechtenstein Lithuania Luxembourg Macau Macedonia ( Former Yugoslav Republic of) Madagascar Malawi Malaysia Maldives Mali Malta Marshall Islands Martinique Mauritania Mauritius Mayotte Mexico Micronesia ( Federated States of) Moldova Monaco Mongolia Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands Netherlands Antilles New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island Northern Mariana Islands Norway Oman Pakistan Palau Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Island Poland Portugal Puerto Rico Qatar Reunion Romania Russia Rwanda S. Georgia and S. Sandwich Isls. Saint Kitts & Nevis Saint Lucia Saint Vincent and The Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Seychelles Sierra Leone Singapore Slovakia Slovenia Somalia South Africa Spain Sri Lanka St. Helena St. Pierre and Miquelon Sudan Suriname Svalbard and Jan Mayen Islands Swaziland Sweden Switzerland Syria Taiwan Tajikistan Tanzania Thailand Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu U.S. Minor Outlying Islands U.S.A. Uganda Ukraine United Arab Emirates United Kingdom Uruguay Uzbekistan Vanuatu Vatican City Venezuela Vietnam Virgin Islands Wallis and Futuna Islands Western Sahara Yemen Yugoslavia (Former) Zaire Zambia Zimbabwe *Login Email Address   *Password    Minimum of 8 characters *Confirm Password   Stay signed in?   Comment: (If coauthors exist for this comment, please enter their names and email addresses at the end of the comment.) References: *Enter the verification code you see in the picture below: This helps Alzforum prevent automated registrations. Terms and Conditions of Use: Printable Version By clicking on the 'I accept' below, you are agreeing to the Terms and Conditions of Use above.