Yale Psychiatry Grand Rounds: April 1, 2022

Transcript

• 00:00And welcome to the grand rounds
• 00:02that's sponsored by the Division of
• 00:04Women's Behavioral Health Research.
• 00:06The Department of Psychiatry.
• 00:08I am Carolyn Missouri.
• 00:09As the director of the division,
• 00:12it's a pleasure to welcome members
• 00:14of the Department of Psychiatry,
• 00:16some of whom we've said
• 00:17hello to this morning.
• 00:18Harvey, Heathers,
• 00:20and it's a pleasure to also welcome
• 00:23colleagues from other key departments,
• 00:25both across the medical school
• 00:26and across the university,
• 00:28as well as collaborators that we have in
• 00:29a variety of settings clinical settings.
• 00:32Search settings.
• 00:34The division is designed to bring
• 00:37together investigators who study the
• 00:39health of women and the influence
• 00:41of sex and gender on mental
• 00:44health and on the intersection.
• 00:46Of mental health with a wide
• 00:49variety of other disorders.
• 00:51We also have the opportunity to
• 00:53invite outstanding scientific
• 00:54leaders to speak with us about
• 00:57critical issues in the field.
• 00:58And so it's my privilege to introduce
• 01:01today's grand round speaker who is an
• 01:04outstanding and accomplished researcher.
• 01:06At a translational epidemiologist.
• 01:10She focuses on understanding the
• 01:12etiology and epidemiology of
• 01:14neurodegenerative and aging related
• 01:16diseases and sex specific differences
• 01:18as well as gender differences in the
• 01:21risk and progression of these diseases.
• 01:25In particular,
• 01:27Doctor Michelle Milky focuses
• 01:29on identifying biomarkers.
• 01:31For accelerated aging and for the diagnosis,
• 01:35prediction,
• 01:35and progression of Alzheimer's disease.
• 01:39And she does this really for the
• 01:41purpose of enhancing precision
• 01:42medicine initiatives and providing
• 01:44better care for both women and men.
• 01:47Previously,
• 01:48Doctor Milky was a professor at
• 01:50the Department of Quantitative
• 01:51Health Sciences in the division
• 01:53of Epidemiology and Professor
• 01:55of Neurology at the Mayo Clinic
• 01:57College of Medicine.
• 01:57Today,
• 01:58April 1 marks the start of her new position,
• 02:01which is at Wake Forest School of Medicine,
• 02:04where she is now the chair of the
• 02:07Department of Epidemiology and Prevention.
• 02:09As well as professor of Epidemiology,
• 02:11Gerontology and geriatric medicine,
• 02:14and neurology.
• 02:15So you can already tell there's a
• 02:19very significant interdisciplinary
• 02:21flavor to Michelle's work.
• 02:23Doctor Milky received her bachelor's
• 02:25degree in neuroscience from
• 02:27the University of Pittsburgh.
• 02:29She then went on to Johns Hopkins
• 02:31University to the Bloomberg School
• 02:33Public Health where she received her pH.
• 02:36D and she did a postdoctoral
• 02:38fellowship in the epidemiology of
• 02:40aging and then subsequently was
• 02:43awarded elidia against Gillespie
• 02:46Postdoctoral Fellowship in Psychiatry.
• 02:48Among her many achievements
• 02:50in leadership positions,
• 02:52she is currently,
• 02:53I'll just mention the current ways
• 02:55in which she is very involved in
• 02:58the broader scheme of understanding
• 03:00Alzheimer's disease.
• 03:01Doctor Melki is currently a member
• 03:03of the Alzheimer's Drug Discovery
• 03:05Foundation Scientific Review Board.
• 03:07The Alzheimer's Association
• 03:09International Society to advance
• 03:11Alzheimer's Research and treatment.
• 03:14The global Biomarker Standardization
• 03:16Consortium and the standardization
• 03:19of Alzheimer's blood biomarkers.
• 03:21She's also on the CDC's World Trade Center,
• 03:24Cognitive aging and impairment
• 03:27scientific working group.
• 03:28And finally, one other example.
• 03:31She's one of the members of the
• 03:33External Advisory Board for Brigham
• 03:35Harvard's NIH funded U 54 score,
• 03:39which studies neural processing of stress,
• 03:41which is strongly linked to
• 03:44health outcomes in aging women.
• 03:46She also served on many NIH as
• 03:48well as FDA and DoD review panels
• 03:50focusing on Alzheimer's disease.
• 03:52Research has done extensive mentoring in
• 03:54this area with a large number of students.
• 03:58And she has provided service on
• 04:00a variety of editorial board.
• 04:02She's a member of the editorial board
• 04:03of the journal, Neurology and senior
• 04:05editor of Alzheimer's and dementia,
• 04:08the Journal of Alzheimer's,
• 04:10the Alzheimer's Association.
• 04:12Consistently,
• 04:13she's been funded throughout her
• 04:15career with multiple oral ones.
• 04:17You owe one RF,
• 04:18one NIH grants on topics such as
• 04:20reproductive risk factors for
• 04:23Alzheimer's disease, dementia,
• 04:24and pathology, and sex.
• 04:26Specific effects of endocrine disruption
• 04:29on aging and Alzheimer's disease.
• 04:32Most notably to me, however,
• 04:34beyond her many achievements
• 04:36and contributions,
• 04:37is the quality of her work.
• 04:39As well as the strength of her
• 04:41commitment in informing our view
• 04:43on the influence of sex and gender
• 04:45on human health and behavior,
• 04:47we're thrilled to have doctor Milky
• 04:49here today to talk about sex and gender
• 04:53differences in Alzheimer's disease.
• 04:54Epidemiology, risk factors, genetics,
• 04:57brain structure and pathologies.
• 05:00And with that, I turn it over to you.
• 05:02Doctor milk.
• 05:04Well, thank you so much.
• 05:06Doctor Missouri really appreciate that.
• 05:09The wonderful opportunity to present
• 05:11with you to you today and again.
• 05:14I, I apologize. As you mentioned,
• 05:16it's my first day and so we're we're
• 05:18hiring out a lot of the kings.
• 05:20It is my background too loud.
• 05:23No, you're good. I'm good.
• 05:25OK, alright great so hopefully there won't
• 05:28be any more interruptions and and again,
• 05:31I apologize.
• 05:33So yes, I'm I'm really excited to
• 05:35talk with you today and and also
• 05:37talk after this as well.
• 05:39Focus today will be on sex and
• 05:41gender differences,
• 05:41but as Doctor Missouri had mentioned,
• 05:44I do do quite a bit with blood
• 05:46based biomarkers,
• 05:46which I'm not going to talk about today,
• 05:48but I'm happy to have a call
• 05:50with anybody to talk about
• 05:51those down the road as well.
• 05:58And these are my disclosures.
• 06:02So what I thought I would do today was
• 06:06to give more of a a general outline
• 06:08covering a variety of topics and ways
• 06:10in which we need to think about sex
• 06:12and gender differences in Alzheimer's
• 06:14disease and related dementias.
• 06:16From incidents to understanding of brain
• 06:20structure and neuropathology's genetics,
• 06:21as well as risk factors including
• 06:24both sex differences in the risk
• 06:26factors and sex specific risk factors.
• 06:28And as you, I'm sure all can understand.
• 06:32You know, once you start to
• 06:33dive deeper in this topic,
• 06:34you realize that there are a lot of areas,
• 06:36a lot of gaps, a lot of things that
• 06:38are not yet understood and, and I,
• 06:41I hope to put forward that the
• 06:44appreciation of that today and the
• 06:47need for much additional research.
• 06:50So the the first thing I'm going to start
• 06:52with is are women affected by a D more
• 06:55than men and or women are at greater risk?
• 06:59A lot of times we hear through the
• 07:02media as well as some of the top.
• 07:05Newspapers, New York Times,
• 07:07Washington Post.
• 07:08Variety of others that women are at greater
• 07:10risk and sometimes I've even heard that
• 07:13Alzheimer's disease is is a woman's disease.
• 07:16But I think when you start to look at
• 07:20the numbers and also how you define risk,
• 07:23this is a little bit questionable.
• 07:26So if we start to talk about
• 07:27the frequency of the disease,
• 07:28so that's the the count.
• 07:30The number of people with a diagnosis.
• 07:32It's absolutely true that more women can have
• 07:35a clinical diagnosis of Alzheimer's disease,
• 07:37and this graph here comes from the
• 07:40Alzheimer's Association awhile back,
• 07:42but it generally has maintained
• 07:45throughout the past ten years that
• 07:47about 2/3 of those with the diagnosis
• 07:50of Alzheimer's disease are women.
• 07:52However,
• 07:52when we think of frequency,
• 07:54essentially any aging related disease,
• 07:57there's more women than men at older ages.
• 08:00And so there's going to be more
• 08:02women than men with most chronic and
• 08:05conditions and aging related diseases.
• 08:09So what about when we think
• 08:11about the prevalence?
• 08:13So this is a graph that was published
• 08:17in The Lancet by the GBS 2016
• 08:20Dementia Consortium and I just want
• 08:23to highlight here that women are in
• 08:26blue and men are in red and this
• 08:29is looking at Alzheimer's disease
• 08:30as well as other related dementias.
• 08:33And there is a higher prevalence so the
• 08:35number of women for example with the
• 08:38disease divided by in a certain age
• 08:40group divided by the number of women.
• 08:43In that age group.
• 08:44So when we take that into account,
• 08:47there is slightly higher prevalence
• 08:49for women than men.
• 08:50However,
• 08:50there's a lot of overlap and and then
• 08:53it's not statistically significant.
• 08:57So then the next question then is,
• 09:00are women at greater risk?
• 09:01Do they have a greater incidence
• 09:03of developing Alzheimer's disease?
• 09:05And what's really interesting is that
• 09:08when you start to look at various
• 09:10countries and regions of the world,
• 09:12we start to see different answers.
• 09:15So if we look at the top of this.
• 09:19This is kind of covering this up
• 09:20it so I I think it's a stock home,
• 09:23the UK, Southwest France as well
• 09:26as the pooled eurodam data we we
• 09:29do see that there is a greater
• 09:31incidence for women compared to men,
• 09:33and this generally starts
• 09:35around the age of 85.
• 09:37However, when we look at some
• 09:39studies in the United States,
• 09:40including the Framingham Heart study as
• 09:42well as some early work that was done in the
• 09:45Rochester Epidemiology project in Rochester,
• 09:47MN, we don't see it a sex difference.
• 09:51Now, you'll probably notice right away
• 09:53that this paper was published in 2002,
• 09:56and there's been a lot of additional
• 09:58epidemiological studies in the past 20 years.
• 10:01I I'd like to show this because it
• 10:03does split it out by country and
• 10:06and show some of these differences.
• 10:09But for the vast majority
• 10:11of studies since 2002.
• 10:14Particularly in the US,
• 10:15we do not see sex differences in terms
• 10:18of the incidence of Alzheimer's disease,
• 10:21and these are just some of
• 10:23the studies listed down here.
• 10:25The only one that I'm aware of in
• 10:26the US is Cache County study of
• 10:28memory and aging in Cache County,
• 10:30Utah,
• 10:31which did identify a greater incidence
• 10:34for women after the age of 85.
• 10:37However,
• 10:37the 90 plus study recently in California
• 10:40had did not find that difference.
• 10:43When we look at systematic
• 10:45reviews and meta analysis,
• 10:47there was one that was funded by the
• 10:50Canadian government feast at all,
• 10:51which is a compilation of more
• 10:54than 20 different studies.
• 10:56The vast majority of them in
• 10:58North America and again for both
• 11:00the prevalence and incidence.
• 11:02They did find a trend for women,
• 11:04but it wasn't statistically
• 11:06significant and by statistically
• 11:08significant the P values were about .6,
• 11:11so it's it wasn't even that that
• 11:13it was necessarily close.
• 11:14But interestingly,
• 11:15roughly a year after this was funded,
• 11:18or this was published,
• 11:19there was another meta analysis
• 11:21completely of European studies.
• 11:23And again they did show that there
• 11:25was a higher incidence overall
• 11:27for women as compared to men.
• 11:32So what about trends overtime?
• 11:35Here we're showing the cognitive
• 11:36function and aging studies one and two.
• 11:39So the first incident wave was
• 11:41between 1989 and 19, roughly 92,
• 11:45and the 2nd incidence wave was
• 11:47between 20 or 2008 and 2011,
• 11:50and there's some some interesting
• 11:53findings in the United Kingdom.
• 11:56Man on the left and women on the right.
• 11:59And of course the first wave is in
• 12:01blue and the 2nd wave is in purple.
• 12:03And what we can see to start
• 12:04with was that the incidence was
• 12:06actually higher in men than women.
• 12:09During this first wave.
• 12:11However, interestingly,
• 12:12about 20 years later,
• 12:13during the second wave there was a
• 12:16a large decrease in the incidence
• 12:18of dementia for men and an
• 12:20increase or maintenance for women.
• 12:22And So what happened subsequently
• 12:24was that the incidence for women
• 12:26ended up being higher than men.
• 12:30Now when we look at the
• 12:33Framingham Heart study here again,
• 12:34we do find that the trends for
• 12:36dementia and this is all caused
• 12:38dementia have decreased overtime,
• 12:40but the decrease has been much sooner and
• 12:42much greater in women compared to men.
• 12:48So I I just showed you a lot of
• 12:50discrepancies, a lot of questions.
• 12:53For me. This is actually really exciting
• 12:56because as an epidemiologist it suggests
• 12:58that if we're seeing differences by
• 13:01countries or even by regions of countries.
• 13:04Potentially modifiable risk factors
• 13:07and possibilities to intervene,
• 13:09and so I get really excited about
• 13:11this and and thinking about what
• 13:13some of the causes might be,
• 13:15and whether there are some biases
• 13:17that may play a role in interpreting
• 13:20some of these results.
• 13:21So I mean, one thing we we do
• 13:24have to keep in mind is that from
• 13:26the studies that I did show that
• 13:28there was a sex difference in,
• 13:30particularly in Europe,
• 13:31it tends to be after the age of 80,
• 13:33and by that.
• 13:34Point in time nobody is going to have peer
• 13:37Alzheimer's disease dementia anymore.
• 13:40It's going to generally be mixed pathology,
• 13:42so you might have vascular dementia,
• 13:43Lewy bodies, Alzheimer's pathology,
• 13:46TDP 43 and and also general brain aging
• 13:50that are are being mixed together.
• 13:53That there is the possibility that there
• 13:56could be a differential diagnosis by sex,
• 13:59and this is something that I I will
• 14:01go into a little bit more depth later,
• 14:03but it does.
• 14:04It is something that worries me
• 14:05when we see all these headlines
• 14:07of women are at greater risk.
• 14:09Melissa Murray from Mayo Clinic,
• 14:11Jacksonville had published a paper
• 14:12where they looked in the Florida brain
• 14:15bank and about 3000 different brains.
• 14:17And they compared both the clinical
• 14:20diagnosis and the pathological diagnosis.
• 14:22And interestingly,
• 14:24they found for men generally
• 14:27between the ages of 60 and 70.
• 14:30There were men were more likely
• 14:33to have Alzheimer's pathology,
• 14:35but to have a different dementia
• 14:38diagnosis so they they weren't clinically
• 14:41diagnosed as Alzheimer's disease despite
• 14:43the theology and then at older ages,
• 14:45there were generally past the age of 80
• 14:48that tend to be is like over clinical
• 14:51diagnosis for women compared to men,
• 14:53and so women were a little bit more
• 14:56automatically determined to have
• 14:57Alzheimer's disease clinically,
• 14:58even though pathologically.
• 14:59That may have not been the case,
• 15:01or it was a very mixed apology.
• 15:05And then you know lastly,
• 15:07and I think a very important
• 15:09consideration here,
• 15:10as we're looking at these,
• 15:11is that these sex differences
• 15:13across the regions of the world
• 15:15is that there are many social,
• 15:17cultural,
• 15:17and historical events that have taken place.
• 15:21Certainly the women,
• 15:22for example in the United States,
• 15:24experience World War Two much
• 15:26differently than those in Europe
• 15:29did similarly to the Cold War.
• 15:30And I really like to discuss
• 15:33with Walter Rocha.
• 15:35Who's at mail clinic as well?
• 15:37His family grew up in Italy and hearing
• 15:39about kind of Faustus was regime and
• 15:42the effect and the the stress and
• 15:44and implications on that on disease.
• 15:46And certainly that plays a role
• 15:49for women and men right now that
• 15:51are at greatest risk of dementia
• 15:53and older age ranges.
• 15:55So a question is whether some
• 15:57of these European countries
• 15:58will see similar sex differences
• 16:00in future generation.
• 16:02And we also have to think about
• 16:03other countries and regions.
• 16:04There's a variety of countries.
• 16:05They're going through stressful situations.
• 16:09Wars, variety of other things as well.
• 16:13And in addition, there are one of
• 16:16the things we're thinking about.
• 16:18These country differences is that
• 16:20there are social cultural factors
• 16:22that the impact of gender that
• 16:24particularly affect risk and that
• 16:26differ across regions of the world,
• 16:29but that also differ, for example,
• 16:31within the United States.
• 16:32So we think about North versus
• 16:34South in terms of education.
• 16:38So as we're thinking about these
• 16:41gender differences historically.
• 16:42Women have had less access to
• 16:44education compared to men,
• 16:46and as I mentioned,
• 16:47this does vary by different or does
• 16:49differ by country as well as culture,
• 16:51but also region within the USI know
• 16:54some states women were able to get high
• 16:57school education sooner than other states.
• 16:59There was a nice study that was recently
• 17:02published in Lancet public health
• 17:04by Bloomberg ET al using two studies
• 17:06from England consisting of over 15,000
• 17:09participants born between 1930 and 1955
• 17:12who had over 19 years of follow-up,
• 17:16and they found that there have
• 17:18been significant trends in
• 17:20memory performance overtime.
• 17:22So historically,
• 17:24women tended to perform better
• 17:26on verbal memory,
• 17:27which is generally well known,
• 17:30but the performance was much
• 17:32better for those that were later
• 17:34born compared to earlier born.
• 17:36And the memory decline was actually
• 17:38faster in men versus women after
• 17:41considering these educational differences.
• 17:44So these results further suggest
• 17:46a role of education and secular
• 17:48changes in education in determining
• 17:50cognitive performance and women.
• 17:52And it, you know,
• 17:52as we think about in the United States,
• 17:54where now there are more women
• 17:56than men in four year colleges,
• 17:58it will be interesting to see how this
• 18:00might affect the sex differences in
• 18:02terms of the incidence of dementia,
• 18:04particularly Alzheimer's disease
• 18:05down the road.
• 18:09Another aspect that is is
• 18:11really important to consider,
• 18:12but until recently there have
• 18:14been a few studies on this.
• 18:17Is the effect of work and family
• 18:20experience on subsequent risk of dementia.
• 18:22And made it all and made a colleagues
• 18:25using the health Retirement Study examined
• 18:27the life course patterns of employment,
• 18:30marriage and childbearing between
• 18:32the ages of 16 and 50 years.
• 18:34And then memory decline after the age of 55.
• 18:38And overall what they found was that
• 18:40women who worked outside the home
• 18:43had less decline after the age of 55.
• 18:46Whether it's memory decline or
• 18:48or even global cognitive decline.
• 18:50Now this.
• 18:52It impact was regardless of whether
• 18:54women took time off to have their
• 18:56children and went back into IT workforce.
• 18:59Some women took up to 20 years off,
• 19:01went back and and still had benefits,
• 19:04and it was also regardless of marital status,
• 19:07so there there was some concern that
• 19:09those women who were single that were
• 19:11also raising families and working
• 19:12that would result in more stress and
• 19:15more negative impact on cognition.
• 19:16But that actually was not found
• 19:18to be the case.
• 19:19And so again,
• 19:20you know in terms of our
• 19:23culture and gender experiences,
• 19:25gender roles these are changing over
• 19:28time and the impact of those on
• 19:31cognitive decline and and risk of
• 19:33dementia still need to be examined further.
• 19:38So I I've given you, you know,
• 19:40obviously it's not a straight answer.
• 19:42Are women at greater risk than men?
• 19:44There does appear to be a lot of caveats.
• 19:48I have been asked multiple times
• 19:50that if women are not at greater risk
• 19:53of Alzheimer's disease than men,
• 19:55why do we have to look at
• 19:56sex and gender differences?
• 19:58And this you know particularly bothers
• 20:00me because you shouldn't have to have
• 20:03a greater prevalence or incidence in
• 20:05one sex forces another in order to
• 20:07look at sex and gender differences.
• 20:09I mean, if we take.
• 20:12We take cardiovascular disease,
• 20:14for example.
• 20:15Cardiovascular disease is the number
• 20:17one killer for both women and men,
• 20:19but we know that there are
• 20:21different risk factors.
• 20:22There are differences in terms
• 20:24of morbidity and mortality.
• 20:26There are differences in terms
• 20:28of heart attack symptoms.
• 20:30There are differences in terms
• 20:32of response to treatment,
• 20:33and so even if the prevalence
• 20:35and incidence is the same,
• 20:37there still are a lot of other factors
• 20:39that we need to think about in
• 20:40terms of sex and gender differences.
• 20:42Both for the incidence,
• 20:44prevalence and treatment of Alzheimer's
• 20:47disease and related dementias.
• 20:49So I'm next going to transition
• 20:51to talking about what some of
• 20:53these differences might be,
• 20:55and so one is potential sex differences
• 20:57in brain structure as well as
• 21:00different types of neural pathologies.
• 21:04So it is well known that men have a larger
• 21:06head size and through volume than women,
• 21:09and this has historically been put
• 21:11forth as women having a smaller brain.
• 21:14Therefore, they're more susceptible
• 21:16to Alzheimer's disease and other
• 21:18types of of dementia, but really,
• 21:21among cognitively normal individuals,
• 21:24men have greater age,
• 21:25associated brain volume decline
• 21:27as compared to women.
• 21:28There are also some differences in in
• 21:31Gray and white matter percentages such
• 21:33that women have a higher percentage
• 21:35of brain matter and men tend to have a
• 21:38higher higher percentage of white matter.
• 21:40However, how these differences contribute
• 21:42to susceptibility of dementia and
• 21:45dementia types are not yet clear.
• 21:50To further highlight some of these
• 21:52sex differences, I I'd like to show
• 21:54this particular study by Kotani ET al.
• 21:57Looking at language lateralization so that
• 22:00they brought in a group of men and women
• 22:04looking to understand whether language
• 22:07lateralization tended to be at strong,
• 22:11left, or bilateral, and in general,
• 22:14what they thought or what they
• 22:15found among all individuals.
• 22:17Was that about 2/3?
• 22:19Had a strong left lateral isation and then
• 22:22about 20% either had bilateral with left,
• 22:26predominant or bilateral symmetrical,
• 22:28both right and left lateralization.
• 22:31But what was interesting is when they met,
• 22:34then looked at sex differences so men
• 22:37are in blue and women are in pink.
• 22:40They found that men were primarily
• 22:42strong left lateral isation,
• 22:44whereas women were pretty much split equally
• 22:47between these three different groups.
• 22:49So again,
• 22:50how this might predispose women versus
• 22:52men to certain types of dementias,
• 22:55such as primary progressive
• 22:56aphasia is not understood yet,
• 22:58but could be a reason for some
• 23:00of these differences or risks.
• 23:04In terms of biomarkers of amyloid,
• 23:07there are really no consistent,
• 23:10consistently reported sex differences
• 23:12in amyloid pet CSF amyloid beta 42 or
• 23:16even blood amyloid beta 42 levels.
• 23:19However, there have recently been
• 23:21a couple studies that suggest,
• 23:23for a given CSF amyloid beta level,
• 23:27women have greater declines in memory
• 23:30and hippocampal volume that men do.
• 23:32It may also have a greater increase
• 23:35in CSFP tell now again the results
• 23:38are not consistent and I I can say
• 23:40within the Mayo Clinic study of Aging.
• 23:43We do not find that pattern either,
• 23:45but it could depend on the samples that
• 23:47are used and it's certainly something
• 23:49to consider because if that is the case,
• 23:52this could have an effect on cut points
• 23:54and there could be a need for sex
• 23:56specific cutpoints in terms of prognosis.
• 24:01Richard Buckley and and colleagues,
• 24:03as well as several other groups,
• 24:05have really been looking at sex
• 24:07differences in terms of Tau pathology.
• 24:09Of course, Tau, being associated
• 24:11with neurofibrillary tangles.
• 24:13The other homework pathology
• 24:15of Alzheimer's disease,
• 24:17and again here there are some
• 24:19conflicting results what?
• 24:21He has has suggested was that
• 24:23for a given level of amyloid
• 24:25women do have Tau in more Tau and
• 24:29some brain regions than men do,
• 24:31and these are highlighted up here in red
• 24:34such that female have greater levels.
• 24:37Now there's been another study
• 24:39that has not replicated this,
• 24:41and there's currently an
• 24:43ongoing meta analysis.
• 24:45Buckley is leading combining a
• 24:47variety of our studies and so
• 24:49hopefully by combining and increasing
• 24:51the sample size will be able to
• 24:53really understand whether there
• 24:54is a a sex difference or not.
• 24:59In addition, there are sex differences
• 25:02in cerebral vascular disease,
• 25:04and so this is a courtesy of my colleague
• 25:08Prashanti Burberry and has been published,
• 25:11and I, I believe neurology,
• 25:13but looking within our population,
• 25:15we find that women have a greater probability
• 25:18of having white matter intensities.
• 25:21Hyper intensities across ages
• 25:23and a greater number of white
• 25:25matter hyperintensities than men.
• 25:28Interestingly,
• 25:28when we look at subcortical infarcts,
• 25:31we don't see a sex difference.
• 25:33But when we look at cortical infarcts,
• 25:36there are more cortical infarcts
• 25:37among men than there are among women.
• 25:40Some further research that I haven't
• 25:42shown here is using DTI and assessing
• 25:46white matter integrity and we do
• 25:48see less white matter integrity
• 25:50or or more problems in that area,
• 25:52typically across the age for
• 25:54women as compared to men.
• 25:56But again it it does specifically
• 25:58depend on the region.
• 26:02So next time I'm going to discuss
• 26:04some of the genetic differences.
• 26:06And of course, we all know that Apple
• 26:09we for a Leo is the greatest risk
• 26:11factor for us or genetic risk factor
• 26:13for sporadic Alzheimer's disease.
• 26:15But interestingly, there are some
• 26:18sex differences in in terms of risk.
• 26:21So here, when the first papers
• 26:23that were published on this by
• 26:25far and colleagues up here,
• 26:27we have men and women with two E 4
• 26:29alleles and down here with one E 4 allele.
• 26:32And here in the diamonds we can see that
• 26:35women have a greater odds of having
• 26:37dementia with two E 4 Leos compared
• 26:40to men starting around the age of 60.
• 26:43And even for one E 4 allele,
• 26:46women have a greater odds of having
• 26:50Alzheimer's disease compared to men.
• 26:52Now there has been a lot more work
• 26:55on this and there you know further
• 26:57in terms of prognosis.
• 26:59So among cognitively normal individuals
• 27:01it's also found that women with an E4
• 27:04allele compared to men are at greater
• 27:06risk of developing mild cognitive
• 27:08impairment and also progressing from Mayo,
• 27:11cognitive impairment to dementia.
• 27:13Now of note,
• 27:14pretty much all of these studies has have
• 27:17been done on white Caucasian samples
• 27:19and the role of appellee in risk of dementia.
• 27:23Non African Americans and some Hispanics,
• 27:25depending on origin are appearing to
• 27:28be less so whether we would see similar
• 27:32sex differences and those racial and
• 27:34ethnic groups is not yet known.
• 27:39Most of the genetic work that has
• 27:41been done for Alzheimer's disease,
• 27:43if they look at sex differences,
• 27:46it's been primarily focused on Autozone's.
• 27:48There is very little work to date that
• 27:51have focused on the X or Y chromosomes,
• 27:53and obviously as you can see here,
• 27:55looking at some of the factors
• 27:58and genes on the X chromosome,
• 28:00there are several that affect the brain.
• 28:03There are also several that
• 28:04affect cardiovascular,
• 28:05endocrine and immunological
• 28:06function which themselves can.
• 28:08Also contribute to Alzheimer's disease
• 28:11and other types of of dementia,
• 28:13and so there.
• 28:14There's certainly a very important need to
• 28:17look at some of these X chromosome genes,
• 28:20and even more importantly,
• 28:22or maybe not more importantly,
• 28:24but to go beyond that,
• 28:26you know women are complex and in that way
• 28:29in terms of the role of X inactivation,
• 28:33where not all of the chromosomes will
• 28:36be inactivated for 1X versus the other.
• 28:40But many of them are,
• 28:41and it's that the randomization of
• 28:44the X chromosome that is inactivated.
• 28:48It is independent across a variety of
• 28:51of tissues as well as organs and cells.
• 28:55And so how this might play into
• 28:58susceptibility of developing
• 29:00cognitive impairment and dementia
• 29:02again is is not well understood and
• 29:05really has not been looked at yet.
• 29:08And just I'm going to put this out there.
• 29:10This is something that I I saw
• 29:12a few years back,
• 29:13which I've been really intrigued in and
• 29:15I've been encouraging my neuropathology
• 29:17colleagues to take a look at more.
• 29:19There was a this one,
• 29:21this study here that was done in mice
• 29:23looking at the laterality of X inactivation.
• 29:26And interestingly,
• 29:27the the red dots indicate paternal
• 29:30inheritance and the green dots
• 29:33indicate maternal inheritance
• 29:34and what was interesting,
• 29:36particularly about this figure,
• 29:37is, as you can see,
• 29:38is that there tend to be laterality
• 29:40in in terms of paternal and
• 29:43maternal her inheritance.
• 29:44And so whether this is a common aspect,
• 29:48whether this is unique and really
• 29:50how this might affect risk of
• 29:52cognitive decline and Alzheimer's
• 29:54disease is completely unknown.
• 29:56But something that absolutely
• 29:58needs to be investigated.
• 30:03Next thing or more lastly,
• 30:05I'll talk a little bit more about
• 30:07sex and gender differences in risk
• 30:09factors for Alzheimer's disease and
• 30:11before I dive into just talking
• 30:14about some of these differences,
• 30:16I do want to highlight that we're at a
• 30:19point where we need to move beyond just
• 30:21saying that there are sex differences
• 30:23or there are gender differences.
• 30:25But to understand what some
• 30:27of the overall impact is.
• 30:29So for example,
• 30:30there are four different ways that
• 30:33in terms of of frequency and effect,
• 30:35that there can be sex and gender differences.
• 30:38So one or risk factor could have the
• 30:40same frequency but a different effect.
• 30:43And an example of that is what I've
• 30:45just shown with the Apple E4 allele.
• 30:47The E4 allele.
• 30:48The frequency is exactly the
• 30:51same for men versus women,
• 30:53but it looks like women with the
• 30:55E 4 Leo may be at greater risk.
• 30:58You can also have a factor that has
• 31:01the effect, but a different frequency.
• 31:04So in terms of education.
• 31:07There's low education is similarly
• 31:09associated with risk of dementia
• 31:12for both men and women.
• 31:13However, as I mentioned,
• 31:15historically women have had less
• 31:17access to education and therefore
• 31:20there's more women that are
• 31:22affected by the risk factor.
• 31:24There can also be factors that have
• 31:27both different frequencies and effects,
• 31:29and one interesting example,
• 31:31there is brain trauma and there there's been,
• 31:34you know.
• 31:35Generally we think of TBI as being
• 31:38more prevalent among men than women,
• 31:40particularly at younger ages,
• 31:42although many of these studies do not
• 31:45take into account violence against women.
• 31:47But there is more research coming
• 31:49out of at least college athletics
• 31:51and soccer suggesting that women
• 31:53who sustained concussions actually
• 31:55have more long term effects on
• 31:57their brain than men do.
• 31:59And then lastly,
• 32:01there are those factors that
• 32:02are restricted to one sex.
• 32:04So such as pregnancy for ectomy for
• 32:07women and then such as prostate cancer.
• 32:13So we were interested in a while back.
• 32:15I'm trying to understand what some of
• 32:17the sex differences in risk factors were
• 32:20for the development of mild cognitive
• 32:22impairment in the Mayo Clinic study of 18,
• 32:24and this is among Olmsted County
• 32:26residents that were aged 70 and older,
• 32:29and so we looked at factors that
• 32:31were equally important for both
• 32:33women and men and then those factors
• 32:35that were unique for women or.
• 32:38And as I mentioned,
• 32:39what we saw solo education was a risk factor.
• 32:43Memory concerns stroke
• 32:45and atrial fibrillation.
• 32:47But really among women we found
• 32:50that midlife cardiovascular
• 32:52conditions had a greater risk for
• 32:55mild cognitive impairment in women
• 32:57compared to men and among men.
• 33:00Some Kitty risk factors were obesity,
• 33:04particularly with BMI greater
• 33:06than 30 and those.
• 33:08Of men that were never married
• 33:10or widowed or divorced.
• 33:14We subsequently start to look at this
• 33:17among earlier ages and I I I I do a lot
• 33:20of work with Women's Health and and.
• 33:23A passion of mine, but in Full disclosure,
• 33:26both my father in law and his
• 33:29father had Alzheimer's disease,
• 33:31and so I've also been very interested in
• 33:33trying to identify risk factors that might
• 33:36be more specific for men and in mid life.
• 33:39Of course, men have more cardiovascular
• 33:42risk factors than women,
• 33:44and so I had a a postdoc fellow man,
• 33:47Hugh, who then went on to examine, well,
• 33:51men have a higher prevalence of all these
• 33:54cardiovascular risk factors in midlife.
• 33:55Does that result in greater cognitive
• 33:58decline for them over that period of time?
• 34:02And as this shows, looking at the
• 34:04ages of 50 to 69 men had critters,
• 34:07factors of cardiovascular risk factors,
• 34:09hypertension, diabetes,
• 34:10dyslipidemia as well as congestive heart
• 34:14failure and coronary artery disease.
• 34:17But interestingly,
• 34:18we did not find a greater effect of these
• 34:23risk factors and conditions on men.
• 34:25We actually found that even though women
• 34:27were less likely to have these conditions,
• 34:29those women that did in midlife had
• 34:32more cognitive decline overtime.
• 34:34And I, I realized that this is is quite busy.
• 34:38Just to Orient you a little bit,
• 34:40the farther to the left indicates
• 34:42greater cognitive decline.
• 34:44Red is women and the blue green is.
• 34:48With men,
• 34:48we especially saw differences in terms of
• 34:52language such that women with hypertension,
• 34:55dyslipidemia,
• 34:56diabetes as well as coronary heart
• 34:59failure all had greater declines
• 35:01on language as well as some
• 35:03global cognition and attention.
• 35:08So in addition to looking at.
• 35:11At sex, differences in in factors.
• 35:14Of course there are also a lot of
• 35:16sex specific factors to consider,
• 35:18and so for females this will
• 35:20include pregnancy, whether it's
• 35:22hypertensive pregnancy disorders,
• 35:23number of pregnancies.
• 35:25Gestational diabetes can include menopause,
• 35:28so this could be early
• 35:30menopause due to pre menopause,
• 35:31bilateral for ectomy or ovarian
• 35:33insufficiency as well as the transition
• 35:36through menopause and also hormone use.
• 35:40So contraceptives which.
• 35:42Have varied in in dose of
• 35:44medications over the last 4050 years,
• 35:48menopausal hormone therapy and
• 35:50also breast cancer treatments and
• 35:52prevention manage medications.
• 35:54I I do want to know we have a paper
• 35:57that is is just going to be submitted
• 35:59now led by a postdoc fellow throughout
• 36:01car from our group looking at the
• 36:04effects of Raloxifene and tamoxifen
• 36:06on both cognition and brain structure
• 36:09and we did not find any differences.
• 36:12Or or really, any effect of those
• 36:15drugs on cognition in our group.
• 36:17For today's purposes I'm I'm not going
• 36:19to talk anymore about hormone use,
• 36:21but again,
• 36:22I'm happy to answer questions and
• 36:23and talk more about that later.
• 36:25I will focus more on work being
• 36:27done with pregnancy as well as
• 36:29some of our work with menopause.
• 36:34So historically, when you look
• 36:35in the literature and there have
• 36:37been more papers out recently,
• 36:39a greater number of pregnancies,
• 36:41with the exception of 1 paper have been
• 36:44associated with reduced risk of dementia.
• 36:46And so a question of course,
• 36:49is is what is the mechanism?
• 36:51And most often when
• 36:52discussing about pregnancies,
• 36:54the first thing that comes up is that
• 36:56during pregnancies women have higher
• 36:58estrogen levels and this must be,
• 36:59you know, one of the reasons for
• 37:02this reduced risk of dementia
• 37:04or other or Alzheimer's disease
• 37:06and other types of dementia.
• 37:08But really we need to move beyond.
• 37:11I mean, certainly hormones are important,
• 37:13but there are a lot of other factors
• 37:15that occur during pregnancy.
• 37:17That allow a woman to carry a baby,
• 37:19and so there are significant changes in
• 37:22inflammation in terms of blood volume.
• 37:24Vascular changes.
• 37:25There are also many stress related changes,
• 37:29and so it's really important going
• 37:32forward to understand some of these
• 37:34effects and how they change over
• 37:36the pregnancy period and how those
• 37:39changes might influence risk of
• 37:41cognitive impairment down the road.
• 37:42And in one case I I've worked
• 37:44quite a bit with Vesna Jarabeck,
• 37:46who is an Afro Logest at Mayo.
• 37:48And I I really like the way she
• 37:50looks at this in terms of pregnancy
• 37:52being a stress test and so there may
• 37:54be women that go in that develop
• 37:57hypertensive pregnancies that,
• 37:59because partly of this stress,
• 38:03that may have been predisposed,
• 38:05but otherwise would not have
• 38:07developed hypertension.
• 38:07This early and so in a way,
• 38:09it's it's a it can be seen as a
• 38:11positive because you can identify
• 38:13those women that are having these
• 38:15conditions under this stress as
• 38:16potentially greater risk down the road.
• 38:21We have shown, as well as others that
• 38:23hypertensive pregnancy disorders,
• 38:25both gestational hypertension.
• 38:26The eclampsia is associated with worse
• 38:29cognitive performance and low brain
• 38:31volume even in women in their 60s.
• 38:35One question that has come up though,
• 38:37is what the result or what
• 38:40the mechanism might be.
• 38:42Whether this is through vascular pathology,
• 38:45general brain aging or
• 38:47even Alzheimer's disease,
• 38:49and there have been a couple studies
• 38:51that have looked at the placentas
• 38:53of women who have had preeclampsia
• 38:55and they find amyloid plaques
• 38:57within the placentas and so that
• 38:59that kind of caused us to look at
• 39:01this a little bit further and say,
• 39:03well, you know is this?
• 39:04Indicative of maybe blacks
• 39:05going on in the brain?
• 39:06Or is there something there?
• 39:08Interestingly,
• 39:09we we are just finishing up these
• 39:11analysis now and we do not see
• 39:14associations between pre clamp C or
• 39:16gestational hypertension with amyloid
• 39:18pathology either amyloid or Tau pet.
• 39:21But we do with white matter hyper
• 39:23intensities and we also do looking
• 39:26at diffusion tensor imaging and
• 39:28white matter integrity and in
• 39:30several key regions as well.
• 39:32There is also a question about Nulliparity.
• 39:36Some studies suggest that women that
• 39:38are deliveries are at greater risk.
• 39:41Some studies suggest that they
• 39:43are at reduced risk in our data.
• 39:45We're finding that it it really depends
• 39:48on education and of course no parity
• 39:51can be due to inability to conceive,
• 39:53but then also many women that choose
• 39:56not to have children and so in.
• 39:59In our study there appeared to be a very.
• 40:02Significant education interaction such that.
• 40:07Who had a greater than a
• 40:09high school education?
• 40:10Who were nulliparous were not at
• 40:12any greater risk of developing
• 40:13cognitive impairment or dementia.
• 40:16But women who had less than a
• 40:17high school education were no.
• 40:19Liberals were at at greater risk,
• 40:21and so again it's it's much more
• 40:23complicated than just staying at
• 40:25whether somebody has children or not.
• 40:26Trying to understand maybe some
• 40:28of the reasons behind that and
• 40:30and some of the other societal
• 40:32and social factors at play.
• 40:36Menopause transition has has gained
• 40:38a lot of attention and I I think is
• 40:41is really important. There has been.
• 40:45Some announcements or or.
• 40:49Things that have come out suggesting
• 40:51that menopause may be a risk
• 40:52factor for Alzheimer's disease,
• 40:54and it's certainly true that there
• 40:56are many changes over the menopausal
• 40:58transition in terms of cardiovascular
• 41:00changes and fat redistribution.
• 41:03And it's still a bit unclear how
• 41:05these might affect subsequent
• 41:07cognitive decline down the road.
• 41:09There's of course a lot of reports during the
• 41:13menopausal transition of cognitive changes,
• 41:15but at least in Moscone,
• 41:17as as well as a lot of Pauline Mackey.
• 41:19Works suggest for the majority of women.
• 41:22This does tend to be temporary.
• 41:25What time I think it's important to think
• 41:28about menopause and the transitions,
• 41:30but I I don't like the idea of,
• 41:33say, menopause or risk factor
• 41:34for Alzheimer's disease or risk
• 41:36factor for other types of diseases,
• 41:38because all women go through menopause.
• 41:40But not all women develop
• 41:42Alzheimer's disease.
• 41:43And so again, I,
• 41:44I think this is a one of those advantages
• 41:46that we have with women similar to pregnancy,
• 41:49where you've got this biological and and
• 41:52emotional transition kind of distress.
• 41:55Past and someone when we'll do better
• 41:57over their transition than others will.
• 41:59And there might be clues during
• 42:01that transition,
• 42:01such as more severe hot flashes,
• 42:03more severe mood changes,
• 42:05other types of sleep abnormalities that
• 42:08someone might have more severe than others,
• 42:11but this then might indicate who
• 42:14may be at greater risk of certain
• 42:16diseases and those women that do
• 42:18have these more severe symptoms.
• 42:19Hopefully,
• 42:19if we can follow them up and treat them,
• 42:22then we can delay some of these diseases,
• 42:24so it is.
• 42:25It is also an exciting window
• 42:27of opportunity as well.
• 42:32Now Walter Rocca, my colleague,
• 42:35and and I and several others,
• 42:37have suggested that early
• 42:38menopause is associated with later
• 42:41cognitive impairment and dementia,
• 42:43and this is a paper that we
• 42:44recently published using data in
• 42:46the Mayo Clinic Study of Aging.
• 42:48So red is global cognitive decline
• 42:51among women who underwent bilateral
• 42:54reflect me less than the age of 40.
• 42:57Blue is 40 to 45 and orange is 46 to 49.
• 43:02And generally what we see is that
• 43:05for women who undergo bilateral for
• 43:07ectomy prior to natural menopause,
• 43:10less than the age of 45,
• 43:11they have about a two fold greater risk
• 43:14of having mild cognitive impairment.
• 43:16When we look at the less than 40 group we,
• 43:18it's actually about a threefold greater risk.
• 43:21And so you know, historically,
• 43:25women who were undergoing or had
• 43:27their uterus removed for fibroids
• 43:29or or for several other conditions,
• 43:31also had their ovaries taken out at the
• 43:34time because the general thought was that,
• 43:36well, you're not going
• 43:37through reproduction anymore.
• 43:38You don't need the ovaries and so if
• 43:40you take out the ovaries then there's
• 43:42no way you can develop ovarian cancer.
• 43:44But we're now finding that it's
• 43:47it's really critically important
• 43:48to keep these ovaries ovaries
• 43:50in particularly for women.
• 43:51That are not at great family risk,
• 43:54for example that have BRCA mutation
• 43:56mutations in their family or have
• 43:59strong family history and so it's
• 44:02it's really important going forward to
• 44:04highlight the need to keep ovaries in.
• 44:06Now.
• 44:06On a side note,
• 44:08interestingly to thinking about estrogen,
• 44:11we often come back to memory
• 44:14performance and in our studies both
• 44:16this study as well as a couple of
• 44:19other cohorts we're looking at,
• 44:20there really seems to be in effect.
• 44:22And attention as opposed to memory.
• 44:24And so again,
• 44:25this kind of gets at the question
• 44:28of if bilateral refractory is
• 44:30a risk factor for dementia.
• 44:32Is it through Alzheimer's pathways,
• 44:34vascular pathways or other
• 44:36aging related pathways?
• 44:37And that's something that again,
• 44:39we're trying to look at
• 44:40and understand right now.
• 44:44So I I talked a little bit about this work,
• 44:48but we do have a grant right now with Mayo
• 44:50Clinic study of Aging where we've tried to
• 44:53take more much more of a lifespan approach.
• 44:55So historically in the literature you might
• 44:57see a paper on hypertensive pregnancies.
• 45:00You might see a paper on bilateral fracta me.
• 45:02Maybe just on the number of pregnancies,
• 45:05but if you think about a 56 year
• 45:08old woman coming in and wine or
• 45:09no at risk of future disease,
• 45:11she is the accumulation of all the factors.
• 45:14That she went through and when we look at,
• 45:16for example, the Framingham risk score,
• 45:18we know that it does not.
• 45:19Is not as good in women as compared to men,
• 45:23and so our hope is that if we understand
• 45:26what some of these specific factors are
• 45:28and incorporate them into risk scores,
• 45:31particularly for cognitive impairment,
• 45:33that will be better than the
• 45:36current risk scores.
• 45:38Now it it has been very interesting.
• 45:40We have a a median medical
• 45:43records of about 45 years.
• 45:44It took us over four years to go through
• 45:47and abstract all the information from
• 45:49the medical records for the women.
• 45:52But we also realize the difficulty
• 45:54in terms of societal aspects.
• 45:56So for example,
• 45:57we found that tubal ligation attended to
• 46:00be protective for Alzheimer's disease,
• 46:02and we couldn't figure out what
• 46:04the reason for that was.
• 46:05Our concern was that with two ligation there,
• 46:07maybe.
• 46:07Manipulation of ovaries and
• 46:09that could be detrimental,
• 46:11but we found it to be protective.
• 46:13Well when we looked at it
• 46:15more and and what the.
• 46:17Medical practice was at the time
• 46:19at really women who had a lot of
• 46:21children were the only ones that
• 46:23were allowed to have tubal ligations
• 46:25in the 50s or 60s in Rochester,
• 46:27MN, and in fact actually if they
• 46:29had it at Saint Mary's Hospital,
• 46:31which was run by the Sisters
• 46:33of Saint Francis you're,
• 46:34you're never going to find tubal ligation or
• 46:37effective or prescription of contraceptives.
• 46:40If women were seen in that area,
• 46:43so again,
• 46:44there's a lot of societal aspects
• 46:46that have changed overtime that.
• 46:48We need to think about as
• 46:50we're looking at these factors.
• 46:52Before I go into my final slide,
• 46:55I I am often asked ahead of time.
• 46:57What about transgender men and women
• 46:59and and what are the effects of of
• 47:02hormones and and whatnot on on their
• 47:04risk of dementia down the road?
• 47:07And really,
• 47:08there's very little information
• 47:10out at this period at this time.
• 47:13One of the reasons when I I've
• 47:15talked to researchers historically,
• 47:17they've stated that you know hormone.
• 47:21Doses and things like that for
• 47:23transgender men or women have
• 47:25not been uniform overtime,
• 47:27and so trying to separate those doses
• 47:31and differences in hormone levels as
• 47:33well as all the stress that goes in.
• 47:36To get to the stage,
• 47:38maybe to have surgery or decide to
• 47:40become transgender really has a role
• 47:41and and it's not clear what those
• 47:43are yet. So there there's an absolute
• 47:45need to understand those factors,
• 47:47and I've been working with a group the
• 47:50diversity and disparities professional
• 47:51interest area on sex and gender differences,
• 47:54and have also been trying to put
• 47:56forward to think about sex and gender
• 47:58is not just being a binary construct,
• 48:01and so we certainly need to move
• 48:04forward there from a continuous aspect.
• 48:06And then also not just think about
• 48:08it from a US centric standpoint,
• 48:10because clearly these many cultures
• 48:13around the world are different.
• 48:14There are some that are more accepting
• 48:16some that are less accepting and
• 48:17it's going to be important to look
• 48:19at this from a global perspective.
• 48:24So in conclusion, as I first talked
• 48:26about in terms of the epidemiology,
• 48:28more women than men have a
• 48:31diagnosis of Alzheimer's disease.
• 48:32However, the prevalence and incidence
• 48:34is a little bit more equivocal and
• 48:37may depend on area of the country
• 48:39as well as area of the world.
• 48:42As a field I I do get concerned
• 48:44in terms of how we present this,
• 48:47because as an epidemiologist to and with
• 48:49the blood based biomarker work I do,
• 48:51I tend to think more from a primary
• 48:54care perspective and so if primary care
• 48:56providers who are the ones that are are
• 48:59going to see these dementia patients first.
• 49:01If they automatically think oh,
• 49:03a woman memory impairment,
• 49:05it's probably Alzheimer's disease may
• 49:08be losing out on some other factors
• 49:11or treatments that could potentially.
• 49:13Help sustain their their cognitive decline.
• 49:16Similarly,
• 49:16we don't want men to be misdiagnosed either.
• 49:21Overall,
• 49:21there still are two few studies that
• 49:24examine sex and gender differences,
• 49:26and the vast majority of studies
• 49:28still typically adjust for it instead,
• 49:30and so it's it's not.
• 49:32It would be difficult to do a
• 49:34meta analysis until we would have,
• 49:36for example, uniform reporting,
• 49:37and so it's possible that some of
• 49:39the papers that are being reported
• 49:41on with sex differences are that
• 49:42they just happen to find it,
• 49:44and many other papers they didn't
• 49:46look or or they they didn't see
• 49:49anything and so they didn't report it.
• 49:51So it really in need for whole
• 49:53studies to report whether there
• 49:55are sex or gender differences.
• 49:57And there's also a need for
• 49:58more diverse cohorts.
• 49:59As I mentioned,
• 50:00most of this work has been done on White,
• 50:03Caucasian,
• 50:04European background cohorts,
• 50:06and I've been working with Nila
• 50:08major wall at Rush University in
• 50:10the Chicago Healthy Aging project.
• 50:12Looking at pre menopausal bilateral
• 50:14reflect me on both white and black
• 50:17women and the average age of bilateral
• 50:19for ectomy for white women was 49.
• 50:22And the average age for black women was 40,
• 50:25and so there are some.
• 50:26You know,
• 50:27definite key differences that we need
• 50:30to consider by race ethnicity as well.
• 50:34As I mentioned,
• 50:35even if there the prevalence of the
• 50:38disease is the same for men and women,
• 50:40the mechanisms and factors can differ by sex,
• 50:43and so we we shouldn't have to
• 50:44say men are at greater risk.
• 50:46But women are at greater risk to really
• 50:48look at sex differences and hone in
• 50:51that we should be doing it regardless.
• 50:53As I mentioned there,
• 50:54there is a need to examine more of
• 50:57these sex and gender differences from
• 50:59a diversity and disparities culture
• 51:01and social determinants of health.
• 51:04And as Doctor Missouri had mentioned earlier,
• 51:08really important to look at these
• 51:10sex differences from a precision
• 51:11medicine standpoint.
• 51:12But I I also want to argue that it's
• 51:15also important to look at it from a
• 51:17socio cultural standpoint as well.
• 51:18Because as we look at some of these.
• 51:22Look at dementia around the
• 51:24world and some of these
• 51:25countries where women have
• 51:27significantly less education and
• 51:28their family roles are different.
• 51:30There are opportunities to change
• 51:33and lower their risk for more
• 51:35of a sociocultural perspective,
• 51:36so both precision medicine and
• 51:39social medicine is is important.
• 51:42So again, I'm I.
• 51:43I'm sorry I don't know
• 51:45what the time frame is.
• 51:46I hope I didn't go over too much,
• 51:48but I'm I'm very,
• 51:49very happy to be here and and have
• 51:51to answer questions I I don't
• 51:52have a Wake Forest email address,
• 51:54but you can get ahold of
• 51:56me by my Gmail account.
• 51:58Thank you.