Latest / Dementia Researcher Vodcast / Relay Podcast - Lewy Body Dementias PIA

Transcript

Relay Podcast - Lewy Body Dementias PIA · Dementia Researcher Vodcast

• 0:00
  (upbeat music)
• 0:02
  - [Voice Over] Hello, and welcome to season seven
• 0:04
  of the Dementia Researcher ISTAART Relay podcast.
• 0:08
  In this series, members of the ISTAART's
• 0:11
  professional interest areas interview each other
• 0:13
  about their PIAs and the hot topics in their fields.
• 0:18
  Each guest then becomes the next episode's host,
• 0:21
  passing the conversation along
• 0:22
  from one researcher to the next.
• 0:25
  We're releasing one episode a day
• 0:27
  in the run-up to the Alzheimer's Association
• 0:30
  International Conference, this year in London and online,
• 0:34
  showcasing the work of the ISTAART PIAs.
• 0:37
  Thank you for listening.
• 0:39
  (upbeat music)
• 0:45
  - Hi, and thanks for tuning in.
• 0:47
  I'm Patrick Lao, and I'm an assistant professor
• 0:49
  at Columbia University, and I work on the Down syndrome
• 0:51
  associated Alzheimer's disease professional interest area.
• 0:54
  I'm the current programme chair and the incoming vice chair.
• 0:58
  So today I'm excited to be talking with Joe
• 1:00
  from the Lewy body dementia professional interest area.
• 1:04
  So hi, Joe.
• 1:05
  Could we start with you introducing yourself?
• 1:07
  - Sure.
• 1:08
  My name is Joe Kane.
• 1:09
  I'm a geriatric psychiatrist and a researcher
• 1:12
  from Queen's University, Belfast in Northern Ireland.
• 1:15
  And I am the chair of the PIA.
• 1:18
  I will be handing over the reins
• 1:23
  to your incoming chair, Federico Rodriguez-Porcel
• 1:27
  at AAIC this summer.
• 1:29
  So it's been really exciting.
• 1:31
  It's been really fun, but it's time to hand it over.
• 1:34
  - That's great.
• 1:35
  So before we talk about your work with the PIA,
• 1:37
  could you tell us about your own work?
• 1:40
  - Sure.
• 1:41
  I've been working in Lewy body dementia
• 1:43
  for about 10 years.
• 1:46
  And one of the things about working in this disease area
• 1:50
  is that you really do get to experience the whole breadth
• 1:53
  of the topics that make up Lewy body dementia.
• 1:56
  And you get to bring all those strands together.
• 2:00
  So I started off with a very clinical angle.
• 2:04
  I worked on a programme called Diamond Lewy,
• 2:08
  which was a kind of multi-step programme
• 2:12
  to look at how Lewy body dementia was diagnosed
• 2:15
  and treated within the UK National Health Service.
• 2:20
  That was my introduction to Lewy body dementia.
• 2:22
  And one of the things we did
• 2:24
  was we did a large epidemiological study
• 2:27
  of clinical diagnosis of LBD.
• 2:31
  Even though we see pathological evidence
• 2:35
  in about 20 to 30% of brains of people with dementia,
• 2:41
  really it's diagnosed in what we find was around about 5%.
• 2:45
  So we then kind of set out to try and see
• 2:49
  what we could do about that.
• 2:51
  We did, amongst other things,
• 2:54
  we developed a consensus around how to best diagnose
• 2:57
  and treat Lewy body dementia.
• 3:00
  And we did a cluster-randomized trial
• 3:02
  where we introduced these toolkits,
• 3:05
  these consensus advice pieces in the different services
• 3:09
  and saw if they helped people.
• 3:12
  And we did find that there were some improvements
• 3:14
  in people's lives there.
• 3:15
  And then I complemented that
• 3:16
  with a bit of work with biomarkers.
• 3:18
  I used a scan, a cardiac scan,
• 3:23
  called MIPG, and we used that to differentiate
• 3:27
  Lewy body dementia from Alzheimer's disease.
• 3:30
  And that was pretty cool, that was pretty exciting.
• 3:32
  And it's something I've continued on as well,
• 3:35
  some of that type of work.
• 3:37
  And then once I returned to Belfast
• 3:39
  and returned to clinical work,
• 3:43
  I found myself doing a lot of clinical trials.
• 3:46
  And that's what I've been doing a lot of locally,
• 3:49
  as well as doing a bit of biomarker work
• 3:51
  and as well as doing the work with the PA.
• 3:53
  So I'm a local lead for a few different trials
• 3:57
  in Lewy body dementia.
• 3:59
  I recruit patients from my clinic
• 4:01
  and both organise and collect the data.
• 4:05
  And it's really great because I get to see
• 4:09
  where research sits in the life cycle
• 4:12
  of someone coming into a service,
• 4:14
  understanding their diagnosis,
• 4:17
  maybe doing a bit of patient public information work
• 4:21
  with us or advisory work with us,
• 4:23
  and then maybe coming into a trial.
• 4:25
  So it's great for me because it's also clinically aligned.
• 4:30
  And although I can do, try to work with scientists
• 4:36
  that really help develop my understanding in other areas,
• 4:39
  I really find that the patient and their care partners
• 4:42
  are at the middle of what I try to do.
• 4:45
  And what we see when we go to conferences like this,
• 4:49
  like AIC, is that we benefit from people
• 4:53
  with loads of different expertise
• 4:54
  that maybe they brought from the likes
• 4:56
  of the Alzheimer's world,
• 4:58
  but maybe they've brought from completely different places.
• 5:01
  We work closely with them to try and develop new projects
• 5:05
  and new angles on this.
• 5:07
  So it's a really exciting field to be in.
• 5:09
  I've been very fortunate to work on it
• 5:12
  over the last 10 years
• 5:14
  and I'm really excited to see how things develop
• 5:16
  in the future.
• 5:18
  - Yeah, that's great.
• 5:19
  That's an incredible range of different types of studies,
• 5:22
  doing clinical to clinical work,
• 5:25
  to clinical trials and epidemiological studies.
• 5:28
  So when you mentioned that there was about 30% of brains,
• 5:31
  or was it 30% of individuals diagnosed
• 5:34
  with Lewy body dementia,
• 5:35
  but only 5% of them had a pathology at autopsy?
• 5:40
  - So when we do autopsy studies
• 5:42
  of people with dementia,
• 5:44
  we find good going Lewy body pathology
• 5:47
  in about 30% of those brains.
• 5:49
  Now, in a good percentage of those brains,
• 5:52
  there's also a good amount of Alzheimer's pathology there.
• 5:56
  And we know that Alzheimer's pathology
• 5:58
  interacts with Lewy body pathology
• 6:01
  and in different ways
• 6:03
  that we're only just really starting to understand.
• 6:06
  But it's such a big jump
• 6:08
  from that huge proportion of people
• 6:09
  who have that pathology
• 6:12
  to the clinic whereby,
• 6:15
  5% in a Lewy body dementia research clinic.
• 6:19
  You know, in other services,
• 6:23
  you know, there are some services
• 6:24
  that might not see people with Lewy body dementia
• 6:28
  for months at a time.
• 6:30
  And our argument has always been
• 6:32
  that a big part of that is,
• 6:34
  yes, starting to co-morbid pathology
• 6:36
  and how it influences the expression of that pathology,
• 6:39
  but also the fact that there are symptoms there
• 6:44
  that not everybody is accustomed to looking for.
• 6:48
  And, you know, these are symptoms
• 6:49
  like REM sleep behaviour disorder,
• 6:51
  in which someone acts out their dreams.
• 6:53
  And we keep telling people
• 6:55
  that if they're not comfortable
• 6:57
  asking about these symptoms,
• 6:59
  you won't detect it.
• 7:00
  And if you don't detect the symptoms,
• 7:01
  you're not gonna make the diagnosis.
• 7:03
  So we feel that even though the pathology
• 7:06
  is a big part of it,
• 7:07
  we feel that the detection
• 7:09
  is also a really significant part of it.
• 7:12
  So we need to approach it from both angles, really.
• 7:15
  - And you mentioned that the guidelines that you published,
• 7:18
  they helped, the clinical guidelines that you published
• 7:22
  really helped sort of fix that gap.
• 7:26
  - Yeah, I mean, it's great
• 7:29
  when there's a huge body of evidence
• 7:31
  on which you can draw in a clinic
• 7:34
  and when you can rely on really good
• 7:37
  randomised control trial data and, you know,
• 7:39
  phase four studies.
• 7:41
  But the reality is for a lot of the less common dementias
• 7:46
  and for lots of different conditions in general,
• 7:49
  you're relying on different study designs.
• 7:52
  You're relying on a little bit of expert opinion.
• 7:56
  You're relying on some anecdotal data as well.
• 7:59
  So that was where that came about, how that came about.
• 8:03
  Rather than just do a systematic review
• 8:05
  and dredge the really, really good quality,
• 8:10
  robust data there, we were able to go out
• 8:13
  into our Lewy body dementia community.
• 8:16
  We were able to gain consensus through this process
• 8:19
  that we call a Delphi, where everyone or a good proportion
• 8:22
  of people needs to agree with a certain statement
• 8:26
  before it gets accepted into the guidelines.
• 8:29
  And whilst it's not perfect by any means,
• 8:32
  and even just today, I shared those guidelines
• 8:36
  with colleagues that were approaching me
• 8:38
  and asking me for advice.
• 8:40
  So yes, you can throw somebody
• 8:42
  a really good journal article
• 8:44
  which tells you about this or tells you about that,
• 8:47
  but to be able to say to somebody,
• 8:49
  here are consensus guidelines on how you should diagnose
• 8:52
  and treat this condition, it's just so invaluable
• 8:55
  for busy clinical staff.
• 8:58
  So that's been really rewarding,
• 8:59
  and we're actually in the process of updating those.
• 9:03
  - Oh, that's great.
• 9:04
  Yeah, and I think that's where biomarkers
• 9:06
  can really come in handy if the clinical diagnosis
• 9:09
  is tricky.
• 9:10
  So you mentioned using cardiac scans to differentiate
• 9:13
  between Lewy body disease and Alzheimer's disease.
• 9:16
  Could you tell me more about that?
• 9:19
  - Sure, one of the things that has always struck us
• 9:22
  about Lewy body dementia is that we see
• 9:25
  in the patient's symptoms evidence of pathology,
• 9:29
  not just in the brain, but throughout the body.
• 9:32
  A large proportion of people with Parkinson's disease
• 9:35
  and a large proportion of people
• 9:36
  with Lewy body dementia will not necessarily describe
• 9:40
  cognitive problems as their first problem.
• 9:43
  And what you see is a lot of constipation.
• 9:46
  You see a lot of autonomic dysfunction.
• 9:49
  And there is some good autopsy data to suggest
• 9:51
  that in a fair proportion of people
• 9:54
  with Parkinson's disease and other Lewy body diseases,
• 9:58
  that there is some degree of spread
• 10:00
  from lower down in the peripheral nervous system
• 10:03
  up in eventually to the central nervous system.
• 10:07
  So the idea behind the cardiac scans
• 10:09
  is that we leverage that fundamental difference
• 10:13
  between Lewy body dementia and Alzheimer's disease
• 10:15
  and try to identify pathology
• 10:19
  in the peripheral nervous system.
• 10:20
  And theoretically as well,
• 10:22
  doing that at a very early stage.
• 10:25
  And the cool thing about this scan is that,
• 10:29
  you know, in Japan, for example,
• 10:31
  nearly everybody suspected of having Lewy body dementia
• 10:34
  gets this as one of their first scans.
• 10:37
  So there's really good data out there.
• 10:40
  And what we did back in my PhD work
• 10:43
  was we compared this cardiac scan,
• 10:46
  which demonstrates adrenergic dysfunction.
• 10:51
  Due to Lewy body pathology.
• 10:53
  And we compared that with the other famous biomarker
• 10:57
  we have, which is the dopamine DAT scan.
• 11:00
  So which does look at the dopamine uptake in the striatum.
• 11:04
  And we find that even though it was very good biomarker
• 11:08
  in the UK population,
• 11:11
  wasn't quite as effective as the DAT scan.
• 11:15
  But there's been a lot that has changed
• 11:16
  in the Lewy body dementia sphere since then.
• 11:20
  And that we're now looking at disease
• 11:22
  earlier and earlier and earlier.
• 11:24
  What we are starting to think of is these cardiac scans
• 11:28
  and these DAT scans, dopamine scans,
• 11:31
  as being complementary rather than head-to-head biomarkers.
• 11:37
  And we also think that, you know,
• 11:39
  certain phenotypes may demonstrate
• 11:44
  that the biomarker may be more effective
• 11:47
  in certain phenotypes.
• 11:48
  So it's still very much there.
• 11:50
  It's still part of our diagnostic criteria.
• 11:52
  It's something that we're learning a bit more about,
• 11:54
  but it's always been a cool angle.
• 11:57
  I find that not only researchers and clinicians,
• 12:02
  but patients really buy into that
• 12:04
  because they, as soon as they hear that
• 12:09
  constipation is a symptom or urinary incontinence
• 12:12
  or heat or cold intolerance is a symptom,
• 12:19
  they will inevitably say, "Oh yeah, I had that.
• 12:21
  "I've had that for a few years."
• 12:22
  And it's crazy once you start going
• 12:24
  and systematically asking people about their bowels
• 12:27
  or systematically asking them about their sense of smell.
• 12:31
  There's a huge proportion of older people
• 12:33
  that are affected by that.
• 12:35
  While they're not necessarily the best means
• 12:39
  of discriminating Lewy body dementia
• 12:41
  from Alzheimer's disease,
• 12:42
  it does show us that there's different
• 12:44
  pathological processes,
• 12:46
  and we need to somehow leverage those.
• 12:49
  - Yeah, I've heard about some alphabetically in biomarkers,
• 12:52
  maybe some PET tracers at an early development,
• 12:54
  as well as the seed amplification assay.
• 12:57
  And that seems to only work in CSF right now,
• 12:59
  but not necessarily plasma.
• 13:02
  How would those change the field?
• 13:05
  - Well, the seed amplification assays
• 13:07
  have really sparked so much interest in the field.
• 13:11
  They have been really useful in CSF, and
• 13:18
  the USDLB Consortium and some of our colleagues
• 13:23
  in the likes of Newcastle-upon-Tyne and Amsterdam,
• 13:27
  they've really lent into the CSF analysis.
• 13:31
  But what's also interesting is that you can use
• 13:33
  the seed amplification assays on other tissues.
• 13:37
  My understanding is that in blood it's quite difficult
• 13:40
  because it's quite easy to get false positives
• 13:44
  because of the clumping together.
• 13:46
  But what a lot of my colleagues in the States
• 13:49
  have been using, and something that we're really looking
• 13:52
  forward to talking about on our PA day,
• 13:55
  is the use of skin biopsy.
• 13:57
  So with a very small punch biopsy in the skin,
• 14:01
  we can put them into these seed amplification assays.
• 14:04
  For those that don't understand,
• 14:05
  it's basically a mechanism of growing
• 14:08
  the alpha-signed eukaryotic fibrils
• 14:10
  until they're detectable.
• 14:13
  And even in very, very small quantities in the skin,
• 14:16
  they can be grown and detected,
• 14:18
  and they can indicate that there's evidence
• 14:20
  of this pathology.
• 14:21
  And you're right, although there is promising data
• 14:25
  around markers that we can use in neuroimaging,
• 14:29
  those aren't scalable yet, they have their issues.
• 14:32
  The idea of a skin biomarker or a CSF biomarker
• 14:38
  is just so much more seemingly within reach
• 14:42
  to clinical practise, and it's something we're finding out
• 14:46
  more and more data about.
• 14:49
  And until we get that really good PET tracer
• 14:52
  that's really stable and really scalable,
• 14:56
  I think we're gonna continue looking into this evidence
• 15:00
  of pathology through places like the skin,
• 15:03
  but also CSF and elsewhere.
• 15:06
  - And you mentioned with clinical trials,
• 15:10
  what are the targets for those?
• 15:12
  - And there's different targets for them.
• 15:15
  They're not necessarily the places
• 15:17
  where you expect to look for.
• 15:19
  So one of the trials that we're looking at
• 15:23
  led by University College London
• 15:26
  is called the TOPHAT trial.
• 15:27
  So it's using ondansetron, which is a very widespread use
• 15:32
  as a anti-sickness, anti-emetic drug
• 15:36
  in cancer and oncology practise in particular.
• 15:39
  Although we have long thought of the Lewy body dementia
• 15:44
  as a disruption of dopaminergic systems,
• 15:49
  and then later on, cholinergic systems,
• 15:52
  and the likes of the use of ondansetron,
• 15:55
  it's actually serotonergic.
• 15:58
  So it's looking at the upstream effects
• 16:01
  of the dopamine degradation
• 16:05
  that causes hallucinations that we see
• 16:07
  in Parkinson's disease and Lewy body dementia.
• 16:10
  So in some of the other studies,
• 16:11
  they're looking at different targets as well.
• 16:14
  And it's a really exciting time
• 16:16
  in Lewy body dementia research
• 16:18
  because these targets are emerging
• 16:20
  and because they are quite diverse.
• 16:23
  And that's before we even get to that idea
• 16:26
  that we hope is coming later on down the line
• 16:27
  of somehow modifying that Alzheimer's pathology
• 16:31
  in people with Lewy body pathology.
• 16:34
  So range of targets, all it takes is one of them to work
• 16:39
  for it to transform the field,
• 16:41
  but there's certainly plenty in the pipeline
• 16:44
  and plenty of cause for optimism as a consequence.
• 16:48
  - Yeah, that's great to hear,
• 16:49
  especially because you mentioned
• 16:50
  the different clinical subtypes
• 16:52
  and so there might be different strategies
• 16:54
  for different groups.
• 16:56
  - It's no secret in Parkinson's in particular,
• 17:02
  there's different clinical phenotypes
• 17:04
  represent very different symptom groups,
• 17:07
  prognoses and different responses to medication.
• 17:12
  We're fairly confident it's gonna be the same
• 17:13
  in Lewy body dementia,
• 17:14
  but we need the big sample sizes
• 17:16
  and the big studies to do that.
• 17:18
  - Great, so thinking more broadly,
• 17:20
  are there any emerging topics at the field
• 17:23
  that you wanna highlight?
• 17:25
  - Sure, I mean, the real thing that's on everyone's lips
• 17:29
  from my perspective is the trials
• 17:32
  and because so many of us are working in clinics,
• 17:35
  we're working closely with participants,
• 17:38
  working closely with advocacy groups and charities
• 17:44
  and it just totally transforms the conversation
• 17:48
  when you can talk about interventional trials
• 17:52
  and not just observational ones.
• 17:55
  Obviously, we've still got a lot to learn
• 17:57
  from observational trials,
• 17:58
  but it really transforms the dynamic in the clinic
• 18:01
  when you talk about,
• 18:03
  there are new treatments on that,
• 18:04
  that might be on the horizon,
• 18:06
  do you want to be a part of that?
• 18:09
  The thing is with the trials becoming more and more
• 18:11
  of an issue is that they really made us reflect
• 18:14
  on the trial environment and their trial design.
• 18:19
  One of the things that PEA has done really well
• 18:21
  has been to examine trial design.
• 18:26
  So we've always relied very heavily on things
• 18:30
  like outcome measures for things like Parkinson's,
• 18:34
  for things like Alzheimer's disease.
• 18:37
  We use the likes of the CDR, for example,
• 18:39
  that are designed for Alzheimer's disease
• 18:41
  and don't always necessarily reflect the experience
• 18:46
  of the patient.
• 18:47
  And we were also conscious that some trials
• 18:50
  might be failing because their outcome measures
• 18:52
  aren't specific to Lewy body dementia.
• 18:55
  So it's really made us think very hard about trial design.
• 18:58
  It's made us think about how we leverage biomarkers
• 19:02
  in trial design,
• 19:04
  how we look towards the start
• 19:07
  of kind of stratified medicine process
• 19:09
  of maybe using some of the Alzheimer's biomarkers
• 19:12
  to work out when someone's got mixed pathology.
• 19:16
  And the other thing that we really identified
• 19:18
  as a very significant need has been a DLB
• 19:22
  or Lewy body dementia specific rating scale.
• 19:25
  And that's what we've been working on
• 19:28
  over the past few years.
• 19:29
  I'll be presenting at AAIC some of our work with that.
• 19:34
  It's been really exciting because it's allowed us
• 19:36
  to engage the Lewy body dementia community.
• 19:39
  All of us working together on this one question
• 19:42
  with many kind of sub questions to it.
• 19:45
  And we've made really good progress
• 19:48
  but we do have some way to go.
• 19:49
  So that's been something which has really
• 19:52
  captured people's imagination in the field.
• 19:54
  And I think it's brought us together as a community.
• 19:58
  And we're hopeful that if we develop the right tool
• 20:03
  that it will actually catalyse trials
• 20:06
  and encourage some of these novel targets
• 20:10
  to be investigated.
• 20:11
  And for the regulatory authorities,
• 20:14
  people like the FDA, for example,
• 20:16
  to buy in to these treatments
• 20:18
  if they do appear to be effective.
• 20:21
  So obviously I'm biassed because it's something
• 20:23
  I've been working very heavily in
• 20:25
  but I do think that's generated a lot of interest.
• 20:30
  - Yeah, totally agree.
• 20:32
  When you can start talking about interventions
• 20:34
  to patients and participants,
• 20:36
  it really changes the entire conversation.
• 20:39
  So that's been really helpful to set the scene
• 20:41
  for what I wanna talk about next,
• 20:43
  which is the work of your PIA.
• 20:44
  So you mentioned a little bit
• 20:45
  of how you've been reevaluating
• 20:47
  the design of clinical trials.
• 20:49
  But are there some other examples
• 20:51
  of how the work of your PIA supports research?
• 20:54
  - Sure.
• 20:56
  Sorry, I'll just take a brief pause there
• 20:57
  'cause I don't have more on me to.
• 21:00
  Yeah, we in the PIA have had a quite diverse approach
• 21:05
  to our work groups.
• 21:08
  And we've got four different work groups
• 21:09
  and one of them is really heavily invested
• 21:12
  in trial design.
• 21:15
  We also have work groups on biomarkers,
• 21:18
  on developing research consortia,
• 21:20
  and also on prodromal Lewy body disease,
• 21:24
  which is, I suppose, analogous somewhat
• 21:27
  to mild cognitive impairment.
• 21:29
  And Alzheimer's disease.
• 21:31
  And one thing that these things,
• 21:33
  one thing that these working groups have all done
• 21:37
  is they've acted as a lightning rod
• 21:39
  for the international Lewy body community.
• 21:42
  And it has provided such a great vehicle
• 21:45
  and such great exposure.
• 21:46
  And it's allowed us to move beyond
• 21:49
  the three or four or five traditional giants
• 21:53
  in Lewy body dementia research,
• 21:56
  to diversify, to democratise our community,
• 22:00
  and to bring more and more people into the community.
• 22:03
  And we have had people that have started off
• 22:07
  doing some of these projects,
• 22:08
  like a publication for the trial methods group,
• 22:13
  for example.
• 22:14
  And in the case of my colleague, Dr. Rodriguez Purcell,
• 22:19
  he started off doing a systematic review on trial methods
• 22:25
  and now he's about to lead the PA.
• 22:27
  And then in other working groups,
• 22:30
  we've got really experienced colleagues
• 22:34
  working on biomarkers
• 22:35
  and really forwarding the conversation there.
• 22:38
  And again, what they've done really well
• 22:41
  is just energised the broader community.
• 22:44
  So where you previously looked at
• 22:46
  some of these great reviews,
• 22:48
  you had maybe four or five people
• 22:50
  from the same groups, same centres, contributing to them.
• 22:54
  And you look at some of our PA papers,
• 22:56
  and there's loads of authors from all over the world.
• 22:59
  And the people that have worked on these projects
• 23:02
  have stayed in Lewy body dementia,
• 23:04
  stayed in the PA,
• 23:06
  and they developed projects of their own.
• 23:09
  So the exposure and the ability to grow our network
• 23:14
  has been something quite different
• 23:16
  from anything we've been able to do
• 23:18
  in the Lewy body dementia community.
• 23:21
  - Yeah, I've always appreciated the ability
• 23:22
  to participate in working groups
• 23:25
  generated by the PAs.
• 23:26
  And exactly what you're saying,
• 23:28
  bringing groups together from all over the world,
• 23:31
  giving early career researchers
• 23:32
  a chance to sort of contribute
• 23:34
  and work with some of the giants in the field.
• 23:38
  You mentioned a prodromal working group,
• 23:40
  and I'm interested about that.
• 23:41
  How long is the disease force in the prodromal stage?
• 23:45
  - Great question, and the answer is we don't know.
• 23:48
  One of the things that we've been really lacking
• 23:51
  has been longitudinal Lewy body dementia data.
• 23:57
  And again, there's been a few well-resourced centres
• 23:59
  that have really got their act together
• 24:01
  and put really cool longitudinal projects in place.
• 24:06
  But the fact of the matter is
• 24:07
  that we don't fully understand conversion
• 24:12
  from prodromal disease to full-blown Lewy body dementia.
• 24:18
  We don't fully understand the role
• 24:22
  that the biomarkers have to play in that.
• 24:24
  We don't fully understand what things
• 24:26
  like Alzheimer's pathology has to play in that.
• 24:29
  And then the other big huge thing is that we believe
• 24:34
  that the prodromal phase of Lewy body dementia
• 24:37
  isn't just a cognitive one.
• 24:40
  And although we think of MCI in the context of AD
• 24:44
  to be very much driven by the cognitive symptoms,
• 24:48
  we also believe that there are significant groups
• 24:51
  of people out there ticking along
• 24:54
  without much in the way of cognitive symptoms.
• 24:56
  And the first evidence of their disease
• 24:59
  is psychiatric disease.
• 25:01
  So the first time somebody has to ask the question
• 25:05
  is this Lewy body dementia
• 25:07
  could be their first depressive symptom,
• 25:10
  could be that they get psychosis
• 25:12
  or new hallucinations.
• 25:15
  And then there's also another group
• 25:17
  whereby we think that people get delirium.
• 25:21
  We know that people with Lewy body dementia, for example,
• 25:23
  get delirium more frequently in the lead up to diagnosis
• 25:27
  than people with Alzheimer's disease.
• 25:30
  So we also don't know how that delirium onset
• 25:34
  prodromal disease then interacts
• 25:38
  with the full-blown dementia diagnosis.
• 25:42
  And it's a little easier
• 25:43
  and we've got a little bit more data.
• 25:45
  And in the PA, we've produced a couple of really nice
• 25:48
  systematic reviews on the conversion
• 25:52
  from mild cognitive impairment to dementia
• 25:56
  and the neuropsychological characteristics
• 26:00
  of those patients.
• 26:01
  But huge, huge gaps remain
• 26:03
  around the psychiatric and delirium prodromes.
• 26:07
  And that's something which is something
• 26:10
  we've got to really work on as a community
• 26:12
  and get the data and that's not that easy.
• 26:18
  - Yeah, and I think that really highlights the need
• 26:19
  for early intervention,
• 26:21
  if those are some of the earliest signs.
• 26:23
  Those are really impactful on patients' lives.
• 26:27
  - Yeah, I mean, different clinicians
• 26:29
  have different blind spots.
• 26:31
  And I'm a psychiatrist
• 26:33
  and if I see somebody with psychiatric symptoms,
• 26:36
  focus on the psychiatric symptoms
• 26:38
  and I'm maybe not always looking as closely
• 26:42
  as I could do about the likes of cognitive symptoms,
• 26:45
  even with disease progression.
• 26:47
  So we need to work out how this changes the behaviour
• 26:52
  of clinicians in different services
• 26:56
  with their different blind spots.
• 26:58
  And we've achieved so much in the realm
• 27:03
  of dream enactment behaviour, REM sleep behaviour disorder,
• 27:07
  kind of sleep physicians are now really, really good
• 27:10
  at identifying people at a high risk
• 27:12
  of the Lewy body dementia.
• 27:14
  And we could probably do better
• 27:16
  when it comes to psychiatrists,
• 27:19
  old age psychiatrists and neurologists and geriatricians,
• 27:23
  maybe asking a bit more systematically
• 27:25
  about some of these psychiatric symptoms
• 27:27
  and scrutinising for delirium a bit more closely.
• 27:30
  But we need the data, we need the studies
• 27:33
  and we can't really move forward until we've done those.
• 27:39
  - Yeah, and I think that's why these focus areas
• 27:41
  are so important, bringing together different scientists
• 27:44
  with different backgrounds to cover those blind spots.
• 27:47
  So what brought you to the PIA
• 27:49
  and how did you get first involved?
• 27:51
  - I didn't rack my brain about this
• 27:53
  because I've been involved in the PIA for many years now.
• 27:58
  And I first got involved with one of the PIA working groups
• 28:03
  just after the pandemic.
• 28:06
  And I had paused my research work.
• 28:08
  I had moved from Newcastle,
• 28:11
  which is one of those traditional giants
• 28:14
  and moved back to Belfast,
• 28:16
  didn't have the same and doesn't have the same pedigree
• 28:19
  for Lewy body dementia research.
• 28:21
  And I really wanted to carry on the work
• 28:23
  that I'd done in my PhD.
• 28:26
  And this call went out saying,
• 28:28
  do you wanna work on a paper about international consortia?
• 28:33
  I co-led that with Fabrizio D'Antonio
• 28:37
  and we worked really closely with Dag Arsland
• 28:41
  and Jim Nevins,
• 28:42
  who are some of the absolute giants in the field.
• 28:46
  And it was so much fun putting that together.
• 28:48
  It was hard work, but as part of that project,
• 28:51
  we basically had to reach out to all Lewy body consortia
• 28:55
  that were occurring throughout the world.
• 28:57
  And it really gave me an idea
• 28:58
  of what the network looked like
• 29:00
  and really put me in contact
• 29:02
  with people I would never have had contact with either.
• 29:06
  Shortly after that, I was asked to be communications chair.
• 29:09
  And at the time I was tweeting a lot
• 29:12
  and that worked really well
• 29:15
  with tweeting about some of my favourite subjects.
• 29:18
  And it was a really nice way and a really exciting time
• 29:21
  to get people that were interested
• 29:24
  in Lewy body dementia interacting.
• 29:26
  And we ended up going out for drinks at AIC
• 29:32
  and social media and getting out there
• 29:35
  has become a big, big part of who we are as a PA.
• 29:39
  Definitely not because of me,
• 29:41
  but because of my successors.
• 29:44
  And then it was shortly after that
• 29:46
  that I became vice chair and then chair.
• 29:49
  So it's been absolutely transformative for me
• 29:52
  as someone who,
• 29:55
  although I've been fortunate enough
• 29:56
  to work with some of the real luminaries in the field,
• 30:01
  I am a little bit isolated, it could be argued.
• 30:04
  And the PA just changes that,
• 30:07
  the PA just put me in the middle of these networks.
• 30:10
  And it gave me the opportunity
• 30:11
  to work on some really exciting grants,
• 30:14
  to collaborate with people
• 30:16
  I would never have collaborated with before.
• 30:18
  And sounds trite, but they're all my friends now.
• 30:25
  We go to AIC and we look for each other
• 30:28
  and we have fun together.
• 30:29
  And yeah, it's been such a privilege
• 30:33
  and such a boon for my career and for my life.
• 30:37
  So I'm very, very grateful.
• 30:39
  - Yeah, speaking of AIC,
• 30:41
  you mentioned you have one presentation.
• 30:43
  Does the PA have any other activities going on?
• 30:47
  - Yeah, we're really excited that this is maybe
• 30:50
  our biggest AIC for many, many years in the PA.
• 30:56
  We have lots of activities going on.
• 30:59
  We were in PA day after a brief hiatus last year.
• 31:03
  We're back to PA day
• 31:05
  and we're really happy with the programme we've got lined up.
• 31:09
  We've got a kind of a panel discussion
• 31:11
  that's gonna look at not only the data
• 31:13
  around the seed amplification assays,
• 31:17
  but also how they might start to influence
• 31:21
  our decisions in the clinic
• 31:22
  and how you might start figuring out clinical dilemmas
• 31:25
  using those biomarkers.
• 31:28
  We also, as part of that PA day,
• 31:30
  are really looking forward to awarding
• 31:32
  our first PA publication of the year award,
• 31:37
  which is an amazing paper.
• 31:39
  I'm not gonna let the cat out of the bag,
• 31:42
  but we're really excited
• 31:43
  that it's such a quality paper for our first award.
• 31:48
  Then straight up after that,
• 31:49
  we always really engage enthusiastically
• 31:51
  in the postdoc and student prizes.
• 31:56
  Probably one of my highlights of AIC every year
• 31:59
  is visiting the Lewy body posters
• 32:01
  and seeing the early career researchers
• 32:03
  and the great work that they're doing
• 32:06
  and sharing it far and wide.
• 32:08
  So there's that.
• 32:10
  And then I think we've got
• 32:11
  three featured research sessions.
• 32:14
  I'm in one of them.
• 32:16
  And one small part of a really exciting session
• 32:21
  that's going to talk about the integration
• 32:24
  of some of the new biological frameworks
• 32:27
  that have been developed in Lewy body disease
• 32:29
  and in Parkinson's disease
• 32:30
  and how it might relate to not only trials,
• 32:34
  but also practise and our cohorts as well.
• 32:39
  Then the last thing I'm really excited about attending
• 32:42
  is a clinical toolbox session,
• 32:46
  which I think is on the last day.
• 32:48
  As a clinician, you're looking every bit as much
• 32:51
  for some really good clinical presentations
• 32:55
  as much as breaking research.
• 32:57
  And our PM members, Bhavna Patel and Kate Wyman
• 33:02
  are gonna be sharing a really broad multidisciplinary look
• 33:06
  at how to manage some of the more troublesome symptoms
• 33:11
  in Lewy Body dementia.
• 33:13
  So I'm really looking forward to that.
• 33:15
  And I'm really looking forward to seeing everybody
• 33:17
  and being face-to-face.
• 33:20
  And I'm really looking forward to seeing
• 33:23
  what my colleague Federico has in store
• 33:25
  for the next few years of the PM.
• 33:28
  - Yeah, congrats.
• 33:29
  That sounds like a really productive programme at AAIC.
• 33:33
  And I'll have to stop by and check some of those out.
• 33:37
  - Please do, please do.
• 33:37
  You'd be very welcome.
• 33:40
  (upbeat music)
• 33:45
  - All right, well, thank you so much for your time.
• 33:47
  I think it's time to end today's podcast.
• 33:50
  Before we go, I do have a final question.
• 33:53
  So what advice do you have for someone
• 33:55
  who's just learning about ISTAART
• 33:57
  and how has it helped you being involved?
• 34:02
  - I think one of the things that ISTAART has helped with
• 34:07
  is to provide,
• 34:08
  we talk about providing a platform,
• 34:10
  but it's actually a bit of a pedestal.
• 34:12
  It kind of raises you up.
• 34:13
  It's really levelling and it really puts you
• 34:16
  at the same level of some amazingly talented
• 34:21
  and experienced people.
• 34:23
  So my advice is to take that opportunity with both hands.
• 34:29
  And what always surprised me earlier in my career
• 34:34
  is that when I went up,
• 34:38
  I'm usually quite nervous in doing so
• 34:40
  and kind of gingerly approaching really experienced,
• 34:44
  really important researcher in the field.
• 34:47
  How keen they were to speak
• 34:48
  with just about anybody on our topic.
• 34:52
  How keen they were to provide people with opportunities.
• 34:55
  And how keen they were to, especially with ISTAART,
• 35:00
  involve people as much as possible.
• 35:02
  So my advice would be, it's such a great opportunity.
• 35:06
  Use it, try and set your shyness to the side
• 35:10
  and ask that question
• 35:11
  because I guarantee it's not a stupid question.
• 35:14
  - Yeah, completely agree.
• 35:16
  So thank you, Joe, for taking time to join us today.
• 35:20
  - Thank you, Patrick.
• 35:21
  Really nice to speak with you.
• 35:21
  - So thank you for listening.
• 35:23
  You can find profiles of myself and my brilliant guest
• 35:26
  and information on how to become involved in ISTAART
• 35:29
  on our website.
• 35:31
  There's a link below in the show notes.
• 35:33
  So I've been Patrick Lao and you've been listening
• 35:35
  to the Relay podcast from Dementia Researcher
• 35:37
  and Alzheimer's Association.
• 35:39
  Hit subscribe on YouTube or in your favourite podcast app
• 35:41
  to ensure you don't miss an episode.
• 35:43
  Thank you.
• 35:44
  Goodbye.
• 35:47
  (upbeat music)
• 35:49
  - [Voice Over] You have been listening to the Relay podcast
• 35:52
  delivered as a collaboration
• 35:53
  between Dementia Researcher and ISTAART.
• 35:56
  This podcast is made at University College London
• 36:00
  with generous funding from the NIHR,
• 36:03
  Race Against Dementia, Alzheimer's Association,
• 36:07
  Alzheimer's Research UK, and the Alzheimer's Society.
• 36:11
  Please like and subscribe
• 36:12
  and share your thoughts in the comments.
• 36:16
  (upbeat music)