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Breakdown of the mitochondrial "cargo system" drives neurodegeneration

At any given moment, every cell within the human body is diligently executing its specialized task. But just as cogs in a machine rely on a steady energy supply to fuel their movements, cells can only carry out their diverse functions if supplied with a constant influx of fuel. Miniature locomotives within cells, also known as the mitochondria, make this energy delivery possible.
These specialized compartments, or organelles, power every cellular activity from signaling to programmed cell death. But now, researchers are increasingly linking the malfunction of these locomotives to neurogenerative diseases like Alzheimer's disease and Parkinson's. This means that understanding mitochondrial dysfunction &mdash; and finding ways to mitigate it &mdash; holds promise for developing innovative therapies that can ultimately slow down the progression of neurodegenerative diseases. &nbsp;&nbsp;

<h2>A journey inside the mitochondria &nbsp;&nbsp;</h2>
Imagine mitochondria as compact, bean-shaped locomotives within a vast railway network. Each mitochondrion has an outer protective membrane and an inner membrane with intricate folds called cristae. Cristae divides the mitochondrion into smaller compartments, allowing it to churn out energy with remarkable efficiency. These cellular locomotives are also highly dynamic, constantly adjusting their structure and function through fission (division) and fusion (merging) to accommodate varying cargo loads that meet cells' energy demands. &nbsp;
Amidst this dynamic landscape, mitochondria produce adenosine triphosphate (ATP), the cell's primary energy currency, through a process called oxidative phosphorylation. It unfolds within the inner membrane of the mitochondria, where specialized chains of proteins break down glucose and fatty acids, releasing energy that is then used to synthesize ATP. This energy is then shuffled off to different parts of the cell to power activities like muscle contraction, cell communication, programmed cell death, and the production of essential molecules, such as proteins, DNA, and RNA. &nbsp;
<div class="wysiwyg-img-caption-wrapper" style="display: inline-flex; flex-direction: column;"><img src="https://wmnhealthpublicfiles.blob.core.windows.net/publicfiles/MediaLibrary/0c836abe_6d7f_4639_853d_ae4a8a222473_3d45f156c1.png" alt="Infographic about mitochondria function and dysfunction" width="800" height="587" />Infographic by Cat Lau. (References below.)</div>

<h2>What causes mitochondria to go awry &mdash; and what does that mean for brain function? &nbsp;</h2>
In brain cells, where energy demand is exceptionally high, mitochondria are vital for supporting neuronal function, enabling communication between brain cells, and producing chemicals essential for this communication.&nbsp;&nbsp;&nbsp;
When these organelles malfunction, neurons are left with reduced fuel to complete energy-intensive tasks like maintaining their health and transporting important substances along their axons. This energy deficit in the brain eventually causes problems with memory, learning, and overall cognitive function, signs and symptoms that arise as neurodegenerative diseases develop and progress.&nbsp;&nbsp;&nbsp;
<a href="https://www.sciencedirect.com/science/article/pii/S0925443916302927" target="_blank" rel="noopener">Mitochondrial dysfunction</a> can be caused by a variety of factors:&nbsp;&nbsp;&nbsp;
Genetic mutations: When genetic changes occur at the DNA in the cell's nucleus (nDNA) or in the DNA of the mitochondria themselves (mtDNA), they lead to defects in proteins critical for producing energy and transporting it to brain cells. These abnormalities disrupt communication between neurons by impairing synaptic transmission, the chemical event that allows neurons to send electrical signals to one another.&nbsp;&nbsp;&nbsp;
Environmental factors: Exposure to environmental toxins and pollutants can harm the mitochondrial outer membrane and ramp up the production of harmful molecules called reactive oxygen species (ROS) in the brain. These molecules are notorious for damaging brain cells by disrupting their ability to maintain a balanced internal environment and promoting inflammation and neuronal death.&nbsp;&nbsp;&nbsp;
Age-related changes: It's typical for mitochondria to accumulate damage over time. This decline in function means the organelles struggle to produce sufficient ATP, essential for keeping neurons alive and functioning. Age-related mitochondrial dysfunction can accelerate cognitive decline and render the brain more vulnerable to neurodegenerative diseases.&nbsp;&nbsp;&nbsp;
Mitochondrial dynamics dysregulation: This type of dysfunction occurs when processes such as mitochondria fission (division of one mitochondrion into smaller ones) and fusion (merging of multiple mitochondria into one) malfunction. This can lead to mitochondria becoming too small and weak to produce enough energy or forming larger mitochondria with disjointed halves that cannot function together.&nbsp;&nbsp;

<h2>Connecting mitochondrial dysfunction to neurodegenerative diseases<a href="http://Eugenia Trushina"></a></h2>
<a href="https://www.mayo.edu/research/faculty/trushina-eugenia-ph-d/bio-00027310" target="_blank" rel="noopener">Eugenia Trushina</a>, a professor of neurology at the Mayo Clinic in Rochester, Minnesota, has dedicated decades to studying mitochondrial dysfunction and its connections to neurodegenerative diseases. Her focus has finally begun to yield insights, with studies around the globe underscoring mitochondria's role in the onset and progression of conditions like Alzheimer's and Parkinson's disease.&nbsp;&nbsp;
<a href="http://Eugenia Trushina"></a>
<a href="http://Eugenia Trushina"></a>
In <a href="https://wmnhealth.org/blog/a-short-guide-to-alzheimers-disease-in-women/" target="_blank" rel="noopener">Alzheimer's disease</a>, the buildup of proteins&mdash;specifically amyloid-beta and tau&mdash;in the brain is a key characteristic of the condition. Studies have found that these amyloid-beta aggregates can disrupt mitochondrial function in neurons by causing them to break apart and impair their ability to produce sufficient ATP. On the other hand, an excess of tau protein impacts mitochondria's ability to transport energy within neurons. It also induces excessive fission and fusion of mitochondria, which exacerbates oxidative stress and ultimately leads to cell death.&nbsp;&nbsp;&nbsp;
<a href="http://Eugenia Trushina"></a>
<a href="http://Eugenia Trushina"></a>
Similarly, in <a href="https://wmnhealth.org/blog/what-is-parkinsons-disease/" target="_blank" rel="noopener">Parkinson's disease</a>, the <a href="https://wmnhealth.org/blog/the-protein-misfolding-problem-how-some-neurodegenerative-disorders-intersect/">aggregation of alpha-synuclein protein</a> and subsequent loss of dopamine-producing neurons in the brain's substantia nigra region are hallmark characteristics. Research indicates that these aggregated alpha-synuclein proteins directly interfere with mitochondrial function, disrupting energy production. Moreover, dysfunction in the mitochondrial quality control system contributes to the accumulation of damaged mitochondria in neurons, leading to their removal by the body.&nbsp;&nbsp;
<a href="http://Eugenia Trushina"></a>

<h2>What sex differences in mitochondrial function tell us about neurodegeneration</h2>
Fascinatingly, mitochondria have their own DNA, distinct from the DNA bound up in the nucleus of our cells. This DNA, also known as mitochondrial DNA or mtDNA, is inherited exclusively from the mother: During fertilization, the egg cell retains its mitochondria, while those from the sperm are left behind in the sperm tail. According to Trushina, this maternal inheritance pattern may be responsible for the notable differences in mitochondrial function between males and females.&nbsp;&nbsp;
"Mitochondria are adapted in the organism using the female hormonal landscape," she says. "Then, when a mother gives birth to a boy, these female mitochondria have to adapt to the male hormonal landscape, and that makes mitochondria work a little bit differently in males and females."&nbsp;&nbsp;
Indeed, studies have found variations in how mitochondria generate energy and activate cell death between males and females. These differences have big implications, particularly in brain injury or neurodegeneration, when the brain initiates a series of metabolic changes to improve cellular function and repair damaged tissues. While mitochondria mainly utilize fats to produce energy in females, these organelles rely on proteins in males. These fundamental differences in how cells obtain energy influence how well they survive following an injury.&nbsp;&nbsp;
"What it implies is that if energetic stress is the early event in any disease, like Alzheimer's, for example, males and females could respond very differently to [it]," Trushina adds. "Some mitochondria may be more adaptive and could be more robustly compensating for the disease."&nbsp;&nbsp;&nbsp;
Trushina's work has revealed that the female sex hormone, estrogen, may be underlying these sex differences in mitochondria function. While studying female mice undergoing menopause, the researchers found that glucose-dependent mitochondria start "cannibalizing" myelin lipids once estrogen levels decline. These lipids form a protective sheath around neurons, and their breakdown can lead to the degeneration of white matter in the brain. This process is a hallmark of conditions like Alzheimer's and multiple sclerosis, so the transition to menopause &mdash; and the subsequent changes in mitochondria metabolism &mdash; may be a factor increasing women's likelihood of developing neurodegenerative diseases.&nbsp;&nbsp;&nbsp;
<blockquote>
"Two decades ago, mitochondria were considered a nuisance, and I was among the very few hooked on them. Now, these organelles are turning out to be more important than we've ever realized &mdash; a gift that keeps giving."&nbsp;
</blockquote>
In a world where there are stark differences in how &mdash; and how many &mdash; men and women experience neurodegeneration, peering inside mitochondria could be the answer to transforming female brain health.&nbsp;&nbsp;&nbsp;
"Two decades ago, mitochondria were considered a nuisance, and I was among the very few hooked on them," says Trushina. "Now, these organelles are turning out to be more important than we've ever realized &mdash; a gift that keeps giving."&nbsp;

<h2>Infographic References</h2>
<ol>
<li><a href="https://www.genome.gov/genetics-glossary/Mitochondria" target="_blank" rel="noopener">Mitochondria.</a> The National Human Genome Research Institute. (Accessed February 22, 2024)</li>
<li><a href="https://biologywise.com/functions-of-mitochondrial-dna" target="_blank" rel="noopener">Functions of mitochondrial DNA.</a> Biologywise. (Accessed February 22, 2024)</li>
<li>Lindsey Shapiro,&nbsp;<a href="https://parkinsonsnewstoday.com/news/mitochondrial-dna-damage-linked-neurodegeneration/" target="_blank" rel="noopener">Mitochondrial DNA damage linked to spread of neurodegeneration.</a> Parkinson's News Today. (Accessed February 22, 2024)</li>
<li>Millichap LE, Damiani E, Tiano L, Hargreaves IP. <a href="https://www.mdpi.com/1422-0067/22/21/11444" target="_blank" rel="noopener">Targetable Pathways for Alleviating Mitochondrial Dysfunction in Neurodegeneration of Metabolic and Non-Metabolic Diseases.</a> Int J Mol Sci 22(21):11444 (2021).</li>
<li>Bustamante-Barrientos FA, Luque-Campos N, Araya, MJ et al. <a href="https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04493" target="_blank" rel="noopener">Mitochondrial dysfunction in neurodegenerative disorders: Potential therapeutic application of mitochondrial transfer to central nervous system-residing cells.</a> J Transl Med 21, 613 (2023).</li>
</ol>
<h2>Banner Image</h2>
Mitochondria are the powerhouses of the cells, generating the energy the cells need to do their tasks and to stay alive. Researchers have studied mitochondria for some time because when these cell organelles don't work as well as they should, several diseases develop. In this photograph of cow cells taken with a microscope, the mitochondria were stained in bright yellow to visualize them in the cell. The large blue dots are the cell nuclei and the gray web is the cytoskeleton of the cells.&nbsp;
Credit:&nbsp;Torsten Wittmann, University of California, San Francisco&nbsp;
<a href="https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04493-w#Fig2" target="_blank" data-saferedirecturl="https://www.google.com/url?q=https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04493-w%23Fig2&amp;source=gmail&amp;ust=1713626375602000&amp;usg=AOvVaw2mRw9e04l-3vtKiCsijg1h" rel="noopener"></a>

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Q&A: What’s the connection between hearing loss and dementia?

What&rsquo;s the key to lowering your risk of dementia? Brain health experts have identified 12 modifiable risk factors for dementia, ranging from smoking to social isolation and diabetes to depression. One of the leading modifiable risk factors is hearing loss, which ranked second only to education in a <a href="https://www.google.com/search?client=safari&amp;rls=en&amp;q=The+Lancet+Commission+on+Prevention%2C+Intervention%2C+and+Care+2020&amp;ie=UTF-8&amp;oe=UTF-8" target="_blank" rel="noopener">2020 report by The Lancet Commission: Dementia prevention, intervention, and care</a>.&nbsp;
Hearing loss affects about <a href="https://pubmed.ncbi.nlm.nih.gov/37505496/">two-thirds of Americans over 70</a>. Over the past decade, studies have shown that hearing loss doubles the risk of dementia. In people with severe hearing impairment, dementia risk increases five-fold. 
<blockquote>
Hearing loss doubles the risk of dementia. In people with severe hearing impairment, dementia risk increases five-fold. &nbsp;
</blockquote>
The global brain health community is mobilizing in response to these findings because hearing loss is often treatable. With hearing aids and other support, it may be possible to reduce the risk of dementia and prevent or slow cognitive decline.&nbsp;
But there are still many open questions about hearing impairment and dementia&mdash;not least, the biological mechanisms connecting the two. &nbsp;
<div class="wysiwyg-img-caption-wrapper" style="float: left; display: inline-flex; flex-direction: column;"><img style="float: left;" src="https://wmnhealthpublicfiles.blob.core.windows.net/publicfiles/MediaLibrary/73dcd637_db97_47ad_ba81_5a0fa3c40fd4_a1fd4a9d65.png" alt="Megan Fitzhugh" width="250" height="250" />Megan Fitzhugh, Ph.D.</div>
There is also the question of how sex differences come into play. 
&ldquo;The data on an association between hearing loss and dementia is pretty strong. If and how they differ by sex is very limited,&rdquo; says <a href="https://www.palab.ucsd.edu/our-team" target="_blank" rel="noopener">Megan Fitzhugh</a>, Ph.D., a postdoctoral scholar at the University of California, San Diego, who works with neuroscientist <a href="https://www.palab.ucsd.edu/our-team" target="_blank" rel="noopener">Judy Pa</a>, Ph.D. Fitzhugh and Pa study brain health and Alzheimer&rsquo;s disease, including the influence of biological sex. &nbsp;
In this Q&amp;A, Fitzhugh shares her research on hearing loss and dementia, including the critical need to understand why women appear to be at greater risk. <span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;
This interview has been edited for length and clarity.&nbsp;

<h2>wmnHealth: Hearing loss is widely accepted as an important modifiable risk factor for dementia. What&rsquo;s the evidence supporting this connection?&nbsp;</h2>
Megan Fitzhugh: The connection is largely based on association studies. These are studies that ask, if you have hearing loss, and if it&rsquo;s more progressed, are you more likely to have dementia or Alzheimer&rsquo;s? The mechanisms behind this association are still unknown and being explored. That's what I'm trying to dig into.<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;

<h2>What could be happening to the brain? What are some of the ideas about how hearing loss is linked to dementia?<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;</h2>
Fitzhugh: It isn't clear, but there are a few theories. One is that there's something common between hearing loss and Alzheimer's, such as <a href="https://wmnhealth.org/blog/an-often-missed-disease-in-women-increases-the-risk-of-dementia/">cardiovascular disease affecting the really small vessels</a> that go to the cochlea, as well as the ones that go to the brain. <span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;
There are two other theories that I'm leaning my hat into. One is that hearing loss is taking away resources that the brain usually uses to do tasks like communication or complex problem-solving. The other one is the idea that [hearing loss] has direct effects on the brain. It makes sense that reduced auditory input would impact auditory areas of the brain. But everything's really connected. One of the theories I have is that it is impacting memory areas of the brain. There's actually a lot of research done in rodents to support this. Specifically, in rodent models that have some sort of induced hearing loss or even hearing impairment from birth, neurons in the hippocampus, the brain&rsquo;s memory center, are degraded or their synapses are kind of screwy. Memory performance is equally reduced compared to those animals who are not in that hearing loss model.<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;
<div class="wysiwyg-img-caption-wrapper" style="display: inline-flex; flex-direction: column;"><img src="https://wmnhealthpublicfiles.blob.core.windows.net/publicfiles/MediaLibrary/d52968d3_cdb5_44cd_8a5a_2ccf8827ed07_38cdbaae20.png" alt="" width="800" height="587" />Infographic by Cat Lau. (References below.)</div>

<h2>So, you&rsquo;re saying that with hearing loss, your brain has to work harder to process sound, and to do that it may be borrowing resources that support other cognitive functions? Or, it could be that brain changes related to hearing loss spill over into other areas and affect how they work?<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;</h2>
Fitzhugh: Right. Either it's detracting from other cognitive functions, or it's affecting the brain regions involved in those other functions, such as the hippocampi. Between those two, I think that's why you're getting these declines in cognitive function with hearing loss, and that, overall, increases your risk for dementia.<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;

<h2>What about social isolation? Is there a relationship between hearing loss, social isolation, and dementia?<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;</h2>
Fitzhugh: Separate from hearing loss, social isolation is also a risk factor for dementia. Some people have proposed that hearing loss is acting through that mechanism. In other words, you have a hearing loss and become socially isolated, which in turn puts you at risk for dementia. I think that one&rsquo;s worth talking about as well.<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;

<h2>You recently published a paper looking at sex differences in hearing loss and dementia. What did you find&mdash;and were there any surprises?<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;</h2>
Fitzhugh: Our findings turned out to be super interesting and not in the direction that I expected.&nbsp;
We know that men tend to experience hearing loss earlier in life and it tends to be more severe, at least until the older ages when women seem to catch up. Since the men in the study had experienced hearing loss for a longer period, I expected that they would have an increased risk of dementia. We found that for milder levels of hearing loss, men and women were pretty equal. But at more severe levels, men were significantly different from chance, and women had an even greater increase of dementia risk.<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;
This follows a pattern scientists are seeing for other dementia risk factors: That women seem to be at this increased risk. One reason could be hormones. It&rsquo;s kind of an easy grab, but women have a lot of hormones and they fluctuate. Maybe something is going on there.<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;

<h2>Is there anything known about the effects of sex hormones like estrogen and testosterone on hearing? <span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;</h2>
Fitzhugh: There is a moderate-size literature on the effects of estrogen and hearing, mostly in animal models, but some in humans as well. Studies tend to show that estrogen is protective. For example, if you expose rodents to a bunch of white noise for a long period, the female animals tend to have less hearing damages compared to the males. 
I'm kicking around the idea that maybe the menopause shift&mdash;the sudden, drastic loss of estrogen with menopause&mdash;not only kickstarts hearing loss in women but also causes it to progress at a much more rapid rate than men. Maybe instead of having this lifelong decline in hearing from their 30s and on, as we see in men, it's more like 50s and on in women, and maybe that rapid decline is having a more detrimental effect on women's brains.<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;
There's even less data on the relationship between hearing and testosterone, but some studies suggest it might be mildly detrimental to hearing.<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;
I think we need to establish a baseline for how sex hormones impact hearing. Only then can we ask, do these hormone differences related to hearing relate to dementia?<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;

<h2>Research on hearing loss and dementia is still in its early days, but some organizations are already suggesting hearing aids can mitigate dementia risk.<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;</h2>
Fitzhugh: There is <a href="https://www.sciencedirect.com/science/article/abs/pii/S014067362301406X?dgcid=author" target="_blank" rel="noopener">one large randomized, controlled clinical trial</a> out of <a href="https://publichealth.jhu.edu/faculty/2634/frank-r-lin" target="_blank" rel="noopener">Dr. Frank Lin</a>'s group [at Johns Hopkins University] looking at whether hearing aids could reduce cognitive decline older adults. It had mixed results. Hearing aids didn&rsquo;t help everyone, but they did slow cognitive decline in a smaller group of participants who had a higher risk for cognitive decline. The results suggest that if you have other risk factors, or if you're at a particularly increased risk for dementia, hearing aids may be beneficial for preventing or at least slowing cognitive decline. <span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;

<h2>Did they find any differences between men and women?<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;</h2>
Fitzhugh: I don't think they looked at sex differences at the time. But I wouldn't be surprised if my work or future work by others eventually shows that we might want to target women specifically for hearing aids.&nbsp;
Unfortunately, one of my studies showed that older women were less likely to wear hearing aids. I don&rsquo;t know if that holds true in other cohorts. But it makes me wonder why. Is there some sort of social phobia? Or maybe women are just not being asked by their doctor if they if they have a hearing loss or if they're just struggling to understand conversation. Maybe there's a point of intervention there around getting more women to use hearing aids, and then hopefully that might prevent or delay their risk for cognitive decline. <span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;

<h2 style="font-weight: 400;">Infographic References</h2>
<ol>
<li>Livingston G, Huntley J, Sommerlad A, Ames D, Ballard C, Banerjee S, Brayne C, Burns A, Cohen-Mansfield J, Cooper C, Costafreda SG, Dias A, Fox N, Gitlin LN, Howard R, Kales HC, Kivim&auml;ki M, Larson EB, Ogunniyi A, Orgeta V, Ritchie K, Rockwood K, Sampson EL, Samus Q, Schneider LS, Selb&aelig;k G, Teri L, Mukadam N. <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30367-6/fulltext" target="_blank" rel="noopener">Dementia prevention, intervention, and care: 2020 report of the Lancet Commission.</a> Lancet. 2020 Aug 8;396(10248):413-446. doi: 10.1016/S0140-6736(20)30367-6. Epub 2020 Jul 30. Erratum in: Lancet. 2023 Sep 30;402(10408):1132.&nbsp;</li>
<li>Powell DS, Oh ES, Reed NS, Lin FR, Deal JA. <a href="https://www.frontiersin.org/articles/10.3389/fnagi.2021.769405/full" target="_blank" rel="noopener">Hearing Loss and Cognition: What We Know and Where We Need to Go.</a> Front Aging Neurosci. 2022 Feb 28;13:769405.</li>
<li>Fitzhugh MC, Pa J. <a href="https://pubmed.ncbi.nlm.nih.gov/38026760/" target="_blank" rel="noopener">Women with hearing loss show increased dementia risk and brain atrophy.</a> Alzheimers Dement (Amst). 2023 Nov 27;15(4):e12499.</li>
<li>Reavis KM, Bisgaard N, Canlon B, Dubno JR, Frisina RD, Hertzano R, Humes LE, Mick P, Phillips NA, Pichora-Fuller MK, Shuster B, Singh G. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10234332/" target="_blank" rel="noopener">Sex-Linked Biology and Gender-Related Research Is Essential to Advancing Hearing Health.</a> Ear Hear. 2023 Jan-Feb 01;44(1):10-27.</li>
</ol>
&nbsp;

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A guide to the different types of Alzheimer’s disease 

Alzheimer's disease (AD) was once perceived as a monolith. However, this progressive neurodegenerative disorder comes in various forms that kick off when abnormal protein deposits &mdash; beta-amyloid plaques and tau tangles &mdash; begin to buildup in the brain, killing off nerve cells and severing neural connections. In time, this neurodegeneration leads to dementia. &nbsp;
As the disease progresses, patients experience a range of symptoms from memory loss, confusion, and difficulty with communication to changes in mood and behavior. While the effects of look similar, a <a href="https://www.nature.com/articles/s43587-023-00550-7" target="_blank" rel="noopener">new study</a> by a team of Dutch researchers has found five different biological subtypes of the disease &mdash; each with a distinct molecular makeup and risk profile.
This new way of characterizing the disease based on different biological mechanisms that may be driving it &mdash; hyperplasticity, innate immune activation, RNA dysregulation, choroid plexus dysfunction, and blood-brain barrier dysfunction &mdash; is one of many efforts to redefine the disease and move beyond the categories researchers and clinicians have relied upon for decades.&nbsp;
<blockquote>
Potential molecular mechanisms of Alzheimer&rsquo;s&nbsp;
A <a href="https://www.nature.com/articles/s43587-023-00550-7" target="_blank" rel="noopener">recent study</a> suggests there may be five molecular mechanisms driving Alzheimer's disease. If the results can be replicated, they have implications for how the most common form of dementia is diagnosed and treated.&nbsp;
&nbsp;
Hyperplasticity &ndash; characterized by higher levels of brain cell growth and tau protein levels.&nbsp; 
Innate immune activation &ndash; characterized by an overactive innate immune system leading to greater brain atrophy and elevated tau levels.&nbsp; 
RNA dysregulation &ndash; characterized by the dyregulation of RNA, which impairs the brain&rsquo;s production of proteins. &nbsp;
Choroid plexus dysfunction &ndash; characterized by the disruption of the brain&rsquo;s blood vessels and extracellular matrix and slower brain cell growth, leading to brain atrophy.&nbsp; 
Blood-brain barrier dysfunction &ndash; characterized by a breakdown of the blood-brain-barrier, a protective membrane that lines the brain&rsquo;s blood vessels, leading to microbleeds and slower brain cell growth.&nbsp;
</blockquote>

As scientists get closer to uncovering the biological basis of the disease, the subtypes still used to describe the condition today are likely to shift. Until then, here are the major faces of AD:&nbsp;
<h2>Familial Alzheimer's Disease (FAD) &nbsp;</h2>
This rare form accounts for less than 5% of all AD cases and is characterized by its early onset and strong genetic component. Unlike other types of Alzheimer&rsquo;s that manifest around the age of 65, people with FAD begin to experience symptoms as early as in their 30s. Research suggests when a <a href="https://wmnhealth.org/blog/is-alzheimers-disease-genetic-and-should-you-get-tested/" target="_blank" rel="noopener">mutation in one of the three genes</a> &mdash; amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) &mdash; that regulate the production of amyloid beta protein is inherited, it is highly likely the individual will develop FAD. This type of AD tends to have a rapid progression, with women experiencing <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311541/" target="_blank" rel="noopener">more severe cognitive decline</a> than men.
Distinct signs and symptoms: People with Familial Alzheimer's Disease (FAD) may experience unusual symptoms like seizures, and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4548970/" target="_blank" rel="noopener">muscle stiffness and twitching</a>, which are not typical in other types of Alzheimer's.&nbsp;&nbsp;
Diagnosis: FAD is typically diagnosed through genetic testing to identify mutations in genes like APP, PSEN1, and PSEN2. Clinicians also conduct cognitive assessments and brain imaging to confirm symptoms and structural brain changes characteristic of the disease. Genetic counseling is recommended for individuals undergoing genetic testing for AD to understand &mdash; and cope &mdash; with results.
<div class="wysiwyg-img-caption-wrapper" style="display: inline-flex; flex-direction: column;"><img src="https://wmnhealthpublicfiles.blob.core.windows.net/publicfiles/MediaLibrary/1a012360_ca81_4502_a2a0_45a3547d7d40_f76d0dc0b8.jpeg" alt="An" width="800" height="587" />Infographic by Cat Lau. (References below.)</div>

<h2>Sporadic Alzheimer's Disease &nbsp;</h2>
This is the most common form of AD, accounting for the majority of Alzheimer&rsquo;s cases globally. Symptoms of sporadic Alzheimer&rsquo;s typically become noticeable around the age of 65, and the disease progression is generally slow but relentless. While both men and women are affected by this subtype, the condition is significantly more prevalent in women. The exact causes of sporadic AD are unclear, but studies suggest it&rsquo;s a combination of <a href="https://wmnhealth.org/blog/is-alzheimers-disease-genetic-and-should-you-get-tested/" target="_blank" rel="noopener">genetic</a>, environmental, and lifestyle factors.
Distinct signs and symptoms: Many individuals with sporadic AD initially experience mild cognitive impairment, where memory loss and other cognitive difficulties are noticeable but not severe enough to interfere significantly with daily functioning.&nbsp;
Diagnosis: Sporadic AD is diagnosed through a careful review of medical history, memory and thinking tests, and brain scans like an MRI. While genetic testing may also be conducted, it isn&rsquo;t common as sporadic AD isn't caused by specific genetic mutation. Instead, diagnosis relies on identifying typical AD symptoms like memory problems and changes in thinking. &nbsp;
Suspected cases of AD are then corroborated with PET scans, a cerebrospinal fluid (CSF) analysis, or MRI scan. A PET scan is an imaging test that searches for proteins such as amyloid-beta and tau in the brain. CSF analysis involves examining a sample of fluid that surrounds the brain and spinal cord, known as cerebrospinal fluid. This fluid analysis can indicate the presence of elevated levels of proteins associated with Alzheimer's disease. An MRI can be used to looks for signs of neurodegeneration or neuronal injury and dysfunction.<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:259}">&nbsp;
<blockquote>
The ATN System<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:259}">&nbsp;
&nbsp;
In 2018, researchers from the U.S. National Institute of Aging Alzheimer's Association Research Framework released a <a href="https://www.alz.org/research/for_researchers/diagnostic-criteria-guidelines?_gl=1*uxmlzh*_ga*ODI2NTQ5MDA2LjE3MTI2OTEyMzk.*_ga_9JTEWVX24V*MTcxMjY5MTIzOC4xLjAuMTcxMjY5MTIzOC42MC4wLjA." target="_blank" rel="noopener">biological definition of Alzheimer disease</a> for research purposes. It marked a shift from defining the disease based on stages (preclinical, mild cognitive impairment (MCI), and dementia), to biological changes in the brain that can be detected using fluid and imaging <a href="https://wmnhealth.org/blog/from-clues-to-cures-why-biomarkers-are-essential-to-progress-on-neurodegenerative-diseases/" target="_blank" rel="noopener">biomarkers</a>.<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:259}">&nbsp; 
&ldquo;A&rdquo; stands for beta amyloid measured by PET scan or cerebrospinal fluid (CSF). <span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:259}">&nbsp;
&ldquo;T&rdquo; stands for tau pathology measured by CSF or PET. <span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:259}">&nbsp;
&ldquo;N&rdquo; stands for neurodegeneration or neuronal injury and dysfunction measured by MRI or CSF.<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:259}">&nbsp;
</blockquote>

<h2>Early-Onset Alzheimer's Disease (EOAD)</h2>
This is another rare subtype of AD that affects individuals younger than 65 years old, with symptoms typically appearing between the ages of 30 and 60. While EOAD and Familial Alzheimer's Disease (FAD) may look similar, their progression differs &mdash; FAD advances more rapidly, causing faster cognitive decline and functional impairment. &nbsp;
EOAD, much like FAD, is also linked to mutations in genes controlling amyloid beta protein production. However, their inheritance patterns vary &mdash; EOAD can occur sporadically without a clear family history, while FAD follows an autosomal dominant pattern. This means that if an individual has a family history of FAD, there's a 50% chance they'll inherit the mutation and develop the disease.
Diagnosis: When diagnosing EOAD, clinicians consider a broader range of environmental and lifestyle factors alongside genetic testing, although genetic factors are typically less emphasized.&nbsp;&nbsp;

<h2>Late-Onset Alzheimer's Disease (LOAD)</h2>
Late-Onset Alzheimer's Disease (LOAD) is the most prevalent form of Alzheimer's, commonly affecting individuals aged 65 and older. Symptoms of LOAD progress gradually, with patients experiencing a slow decline in cognitive abilities over the course of several years.&nbsp;
While both LOAD and sporadic AD have genetic components, LOAD is notably influenced by the presence of the <a href="https://wmnhealth.org/blog/is-alzheimers-disease-genetic-and-should-you-get-tested/" target="_blank" rel="noopener">APOE &epsilon;4 allele</a>, which plays a role in the metabolism of fats and cholesterol in the body. In contrast, sporadic AD is linked to a complex interplay of genetic, environmental, and lifestyle factors, with less emphasis on specific genetic mutations.&nbsp;
Diagnosis: LOAD is diagnosed similarly to sporadic AD, but clinicians typically place more emphasis on age-related risk factors and the APOE &epsilon;4 allele.&nbsp;&nbsp;

<h2>The path to Alzheimer&rsquo;s treatments&nbsp;</h2>
Understanding the many faces of Alzheimer&rsquo;s disease is essential for patients and their families to plan for what lies ahead, but it's also key for driving innovation in clinical research. By grouping patients based on their specific subtype during clinical trials, researchers can test treatments more precisely. This approach could bring us closer to developing drugs that can actually change how the disease progresses and, eventually, tailoring treatments to each individual. It&rsquo;s trying to solve a puzzle &ndash; the more we understand about each piece, the closer we get to finding a solution.

<h2>Infographic References</h2>
<ol>
<li><a href="https://www.alz.org/media/documents/alzheimers-facts-and-figures.pdf" target="_blank" rel="noopener">2023 Alzheimer's Facts and Figures: Special Report</a>, Alzheimer's Association (Accessed June 20, 2023).&nbsp;</li>
<li>Castro-Aldrete L, Moser MV, Putignano G, Ferretti MT, Schumacher Dimech A and Santuccione Chadha A (2023) <a href="https://www.frontiersin.org/articles/10.3389/fnagi.2023.1105620/full%20" target="_blank" rel="noopener">Sex and gender considerations in Alzheimer&rsquo;s disease: The Women&rsquo;s Brain Project contribution</a>. Front. Aging Neurosci. 15:1105620.</li>
</ol>

pexels-cottonbro-studio-4661287.jpg

Closing the Gap: Sex-specific biomarkers for Alzheimer's disease

Jessica Caldwell, Director of the <a href="https://womenpreventalz.org/">Women&rsquo;s Alzheimer&rsquo;s Movement Prevention Center</a> at the Cleveland Clinic, has said it before and she&rsquo;ll say it again: &ldquo;At its core, Alzheimer&rsquo;s is a women&rsquo;s health issue.&rdquo;
What&rsquo;s behind her assertion? About two-thirds of people living with Alzheimer&rsquo;s, the most common form of dementia, are female. And while females are generally diagnosed with the condition later than males, they tend to face a steeper cognitive decline.&nbsp;
&ldquo;To address it,&rdquo; according to Caldwell, &ldquo;we must understand how biological sex contributes to the underpinnings of this disease.&rdquo;
Scientists are beginning to pinpoint biological changes that are sex-specific and may account for why the disease plays out differently in women. For example, researchers at the Cleveland Clinic have <a href="https://pubmed.ncbi.nlm.nih.gov/35523454/">found</a> evidence that the immune system may play a bigger role in Alzheimer&rsquo;s disease in females than males. Specifically, they pinpointed a set of proteins that are present at much higher levels in the blood of females with Alzheimer&rsquo;s compared with males. The proteins are all involved in the immune response, and could serve as a biological signature, or <a href="https://wmnhealth.org/blog/from-clues-to-cures-why-biomarkers-are-essential-to-progress-on-neurodegenerative-diseases/" target="_blank" rel="noopener">biomarker</a>, of the disease in women.
<blockquote>
Sex-specific biomarkers are biological indicators or measurable characteristics that differ between males and females. Examples may include hormone levels (such as estrogen), gene expression patterns, metabolites, or specific proteins that are more prevalent or active in one sex compared to the other.
</blockquote>
Today, scientists worldwide are searching for and validating biomarkers of neurodegenerative diseases in the skin, blood, cerebrospinal fluid (CSF), eyes, brain and elsewhere. While these discoveries are promising, there&rsquo;s an urgent need for sex-specific biomarkers that will ensure Alzheimer&rsquo;s can be accurately diagnosed and effectively treated in women as well as men. After all, if the biological mechanisms driving the disease are different in females and males, the biomarkers may be, too.&nbsp;

<h2>What are biomarkers&mdash;and why are they important?</h2>
Biomarkers are ways to measure and monitor disease. For neurodegenerative diseases, the most common biomarker categories are blood, CSF, and imaging. For example, if a physician suspects a person has Alzheimer&rsquo;s disease, they may corroborate their diagnosis by looking for the accumulation of protein fragments known as beta-amyloid and tau in the blood, CSF, or brain.&nbsp;
Biomarkers hold the key to detecting Alzheimer&rsquo;s early, when it is possible to intervene and slow the inevitable cognitive decline as the disease progresses. Biomarkers are also critical to developing effective treatments because they help researchers identify the biological mechanisms driving the disease in a given individual and monitor whether a treatment is having an impact on those mechanisms.
<div class="wysiwyg-img-caption-wrapper" style="display: inline-flex; flex-direction: column;"><img src="https://wmnhealthpublicfiles.blob.core.windows.net/publicfiles/MediaLibrary/c105d3ff_77ee_4103_b64c_b363b9754118_19b3573d07.png" alt="/" width="800" height="633" />Infographic by Cat Lau. (References below.)</div>
&nbsp;

<h2>How is Alzheimer&rsquo;s disease different in women?</h2>
The hallmark of Alzheimer&rsquo;s disease is the buildup of amyloid beta and tau protein fragments in the brain. While these two proteins accumulate in the brains of males and females, studies suggest tau is a particularly important component of the disease in females, who tend to accumulate more abnormal tau than males. Researchers <a href="https://bsd.biomedcentral.com/articles/10.1186/s13293-020-00310-x)">suspect</a> tau may be part of the reason Alzheimer&rsquo;s is more prevalent in women and progresses faster.&nbsp;
However, there are <a href="https://www.sciencedirect.com/science/article/pii/S0006322321010982">other molecular mechanisms at play</a> that affect females differently, including dysfunctional immune activity and altered metabolism. These mechanisms may magnify the effects of other disease-causing processes and accelerate cognitive decline.&nbsp;
Immune activation: The brain&rsquo;s of people with Alzheimer&rsquo;s show signs of chronic inflammation. This may be caused by the activation of non-neuronal cells like microglia that normally clear waste and debris, including amyloid beta. However, research suggest microglia malfunction in Alzheimer&rsquo;s and contribute to brain inflammation, which causes further damage to neurons.&nbsp;
Altered cellular metabolism: The brain, more than other organs, has high energy needs, requiring a healthy supply of glucose and oxygen. However, in people with Alzheimer&rsquo;s, research shows a decrease in glucose and energy production.&nbsp;&nbsp;
A recent <a href="https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.13546">study</a> found that interactions between the immune system and cell metabolisms may increase the risk of Alzheimer&rsquo;s and its severity in women.&nbsp;

<h2>The search for sex-specific biomarkers for Alzheimer&rsquo;s</h2>
Scientists like the Cleveland Clinic&rsquo;s <a href="https://www.lerner.ccf.org/genomic-medicine/bekris/">Lynn Bekris</a> are looking for sex-specific biomarkers that could transform care for women with the disease. Bekris is leading a <a href="https://consultqd.clevelandclinic.org/blood-based-biomarkers-for-alzheimers-disease-in-women-podcast">new study</a> funded by the Women&rsquo;s Alzheimer&rsquo;s Movement (WAM), which aims to determine if there are biomarkers that are highly sensitive and specific to women or men. The study builds on Bekris&rsquo; work <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9117433/">suggesting</a> inflammatory factors play a role in the early stages of Alzheimer&rsquo;s disease, especially in women.
Other researchers have also found sex-specific differences in Alzheimer&rsquo;s, including in the immune response to the disease. For example, a study led by <a href="https://portal.research.lu.se/en/persons/claudia-cicognola">Claudia Cicognola</a> of Lund University in Sweden <a href="https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.055153">showed</a> an increase in biomarkers of microglial activation and inflammation in samples of CSF. Microglia are non-neuronal cells that protect neurons from damage and clear cellular debris and other substances from the brain. But they are also involved in the immune response and, when activated, may contribute to brain inflammation.
<a href="https://neurosciences.ucsd.edu/research/labs/banks/people.html">Sarah Banks</a> and <a href="https://profiles.ucsd.edu/erin.sundermann">Erin Sundermann</a>, both professors at the University of California, San Diego, are also studying sex-specific biomarkers as part of research programs dedicated to understanding why Alzheimer&rsquo;s rates are higher in women. They have a particular interest in immune function and neuroinflammation. Women tend to show a more robust immune response than men, which is helpful to stave off infection. But chronic inflammation in the nervous system may enhance the risk of Alzheimer&rsquo;s and its progression. Banks and Sundermann&rsquo;s research <a href="https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/dad2.12284">suggests</a> that women are more vulnerable to the negative effects of neuroinflammation and that tau plays a role in mediating these effects. The researchers are <a href="https://www.nature.com/articles/s41380-022-01675-8">building on this work</a> to identify sex-specific biomarkers that can be used to diagnose women in primary care and to strengthen the search for effective Alzheimer&rsquo;s treatments.

<h2>Infographic References</h2>
<ol>
<li><a href="https://womenshealth.obgyn.msu.edu/blog/sex-differences-biomarkers-impact-clinical-testing" target="_blank" rel="noopener">Sex differences in biomarkers impact clinical testing</a>, Women's Health Research Institute (accessed January 23, 2024) &nbsp;</li>
<li>Dubois, B., von Arnim, C.A.F., Burnie, N. et al. <a href="https://alzres.biomedcentral.com/articles/10.1186/s13195-023-01314-6" target="_blank" rel="noopener">Biomarkers in Alzheimer&rsquo;s disease: role in early and differential diagnosis and recognition of atypical variants.</a> Alz Res Therapy 15, 175 (2023).</li>
<li>Klyucherev, T.O., Olszewski, P., Shalimova, A.A. et al. <a href="https://translationalneurodegeneration.biomedcentral.com/articles/10.1186/s40035-022-00296-z" target="_blank" rel="noopener">Advances in the development of new biomarkers for Alzheimer&rsquo;s disease.</a> Transl Neurodegener 11, 25 (2022).&nbsp;</li>
</ol>

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What is Lewy body dementia (LBD) —and why should women care about it?

Lewy body dementia (LBD) is a term that might not be as familiar as Alzheimer's, but it is a condition that deserves just as much attention. This neurodegenerative disorder affects thinking, memory, movement, and can significantly alter behavior and mood.&nbsp;&nbsp;
But it is difficult to diagnose&mdash;often confirmed only by autopsy after a person&rsquo;s death. That was the case for comedian Robin Williams, who died by suicide in 2014. Williams had been diagnosed with Parkinson&rsquo;s a few months before his death. <a href="https://www.neurology.org/doi/10.1212/WNL.0000000000003162">According to his wife</a>, he initially struggled with seemingly unrelated symptoms that would come and go, including sleeplessness, a poor sense of smell, and a slight tremor in his left hand. Over 10 months, he developed extreme anxiety, paranoia, delusions, problems with memory, continuous tremor and a shuffling gait.<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;
The prevalence of Lewy body dementia appears to be higher in men than women, but not all studies agree on that. What's clearer is that the condition is often misdiagnosed or undiagnosed in women because women don&rsquo;t always display the disorder&rsquo;s core symptoms. Recent research also suggests that the disease might have a unique impact on women.&nbsp;
By understanding the symptoms, diagnosis, and treatment of LBD, as well as the sex- and gender-specific aspects of the disease, we can better support those affected by this challenging condition and their families.&nbsp;
<blockquote>
This article covers:&nbsp; 
<ul>
<li><a href="#LBD-what">What is Lewy body dementia (LBD)?</a>&nbsp;</li>
<li><a href="#LBD-differ">How does LBD differ from Alzheimer&rsquo;s and Parkinson&rsquo;s?</a>&nbsp;</li>
<li><a href="#LBD-symptoms">What are the key symptoms of LBD?</a><span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;</li>
<li><a href="#LBD-sex-differences">Do the symptoms of Lewy body dementia differ between men and women?</a>&nbsp;</li>
<li><a href="#LBD-diagnosis">How is Lewy body dementia diagnosed and treated?</a><span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;</li>
<li><a href="#LBD-sex-gender">What are the sex and gender differences in LBD?</a>&nbsp;</li>
<li><a href="#LBD-risk-factors">What are the risk factors for LBD, and can it be prevented?</a><span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;</li>
<li><a href="#LBD-research">What&rsquo;s happening in LBD research?</a><span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;</li>
<li><span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}"><a href="#LBD-support">LBD support networks and resources</a>&nbsp;</li>
</ul>
</blockquote>
&nbsp;

<h2><a id="LBD-what"></a>What is Lewy body dementia (LBD)?&nbsp;</h2>
There are many causes of dementia, just like there are many causes of a cough or high blood pressure. Alzheimer&rsquo;s is the most common cause, followed by Lewy body dementia.&nbsp;&nbsp;
Lewy body dementia is characterized by the presence of abnormal protein deposits, known as Lewy bodies, in the brain. These deposits cause brain cells to degenerate and die, leading to a decline in cognitive, physical, and emotional functions. The symptoms of LBD can be challenging to diagnose because they overlap with those of other more well-known diseases like Alzheimer's and Parkinson's.&nbsp;
<blockquote>
Lewy body diseases&nbsp;
&nbsp;
Lewy bodies can be seen under the microscope within nerve cells. They consist of deposits of abnormally folded alpha-synuclein, the protein that also builds up in the brains of people with Parkinson&rsquo;s. As a result, both Parkinson&rsquo;s and Lewy body dementia are considered &ldquo;Lewy body diseases.&rdquo; Lewy bodies disrupt chemical signaling in the brain, altering the neuronal pathways that depend on those signals.&nbsp;&nbsp;
</blockquote>
<div class="wysiwyg-img-caption-wrapper" style="display: inline-flex; flex-direction: column;"><img style="display: block; margin-left: auto; margin-right: auto;" src="https://wmnhealthpublicfiles.blob.core.windows.net/publicfiles/MediaLibrary/8f9040d8_5932_42ea_af6b_03d5a060c954_535ac2b433.png" alt="/" width="800" height="1423" />Infographic by Cat Lau. (References below.)</div>

<h2><a id="LBD-differ"></a>How does Lewy body dementia differ from Alzheimer&rsquo;s and Parkinson&rsquo;s?&nbsp;</h2>
Lewy body dementia shares features with Alzheimer&rsquo;s and Parkinson&rsquo;s, but there are also key differences. For example, people living with Alzheimer&rsquo;s and Lewy body dementia experience cognitive impairment. However, in Alzheimer&rsquo;s, people are most likely to have memory issues. In Lewy body dementia, people tend to struggle with executive functions like attention and decision-making, as well as visuospatial processing. In Parkinson&rsquo;s disease, cognitive impairment tends to occur much later than in Lewy body dementia, where it is usually the defining characteristic. Essentially, a person is diagnosed with Parkinson&rsquo;s or Lewy body disease, depending on which symptoms present first.&nbsp;
<div class="wysiwyg-img-caption-wrapper" style="display: inline-flex; flex-direction: column;"><img src="https://wmnhealthpublicfiles.blob.core.windows.net/publicfiles/MediaLibrary/Dementia_Newsletter_v1_652eaa68cd.jpg" alt="/" width="800" height="587" />Infographic by Cat Lau.</div>

<h2><a id="LBD-symptoms"></a>What are the key symptoms of Lewy body dementia?</h2>
The symptoms of Lewy body dementia are diverse and can vary significantly from person to person. However, some common symptoms include cognitive fluctuations, visual hallucinations, and Parkinsonian movement problems. Cognitive fluctuations can manifest as variations in attention and alertness, while visual hallucinations can be vivid and detailed. Parkinsonian symptoms might include stiffness and difficulty with movement.&nbsp;&nbsp;
Other symptoms can include sleep disturbances, including Rapid eye movement behavior disorder (RBD), behavioral and mood changes, and autonomic dysfunction, which affects the automatic functions of the body, such as blood pressure and digestion.&nbsp;
<blockquote>
Rapid eye movement (REM) sleep behavioral disorder&nbsp;
&nbsp;
Rapid eye movement (REM) sleep is the stage when we&rsquo;re dreaming. It is characterized by quick eye movement, relaxed muscles, irregular breathing, elevated heart rate, and increased brain activity. In REM sleep behavioral disorder (RBD), people don&rsquo;t experience the paralysis normally associated with REM sleep. Instead, they act out their dreams and may shout, punch, kick, or flail in their sleep. RBD has a variety of causes, including Lewy body dementia, sleep apnea, and medications. If you or a loved one develops RBD, you should talk to your doctor about it.&nbsp;&nbsp;
</blockquote>

<h2><a id="LBD-sex-differences"></a>Do the symptoms of Lewy body dementia differ between men and women?&nbsp;</h2>
The symptoms of Lewy body dementia are generally milder in women than in men. However, women display fewer of the common symptoms associated with the disease, such as Parkinsonian movement problems. As a result, they tend to be diagnosed later than men, and therefore have more advanced symptoms at the time of diagnosis. Researchers are just beginning to investigate the sex and gender differences associated with Lewy body dementia, including how symptoms vary and how the disease progresses.<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;

<h2><a id="LBD-diagnosis"></a>How is Lewy body dementia diagnosed and treated?<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;</h2>
Diagnosing LBD can be complex because so many of its symptoms overlap with other conditions, especially Parkinson's and Alzheimer's. Furthermore, there is no single test for the disease. Diagnosis often requires a comprehensive evaluation that includes medical history, physical and neurological examinations, and sometimes brain imaging tests, which help doctors determine which brain structures are involved. <span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;
There is no cure for LBD, therefore treatment focuses on managing symptoms. This can include medication to help with movement problems or mood disorders, as well as non-pharmacological approaches like physical therapy and cognitive exercises.&nbsp;
<blockquote>
Biomarkers for Lewy body dementia
&nbsp;
The search is on for <a href="https://wmnhealth.org/blog/from-clues-to-cures-why-biomarkers-are-essential-to-progress-on-neurodegenerative-diseases/" target="_blank" rel="noopener">biomarkers</a>&mdash;objective measurements of the body in health or disease&mdash;that can help doctors diagnose Lewy body dementia more quickly and accurately. Biomarkers for LBD could help detect the condition early and, by distinguishing it from Alzheimer's and Parkinson's, lead to more effective treatment and care. Scientists are currently evaluating potential protein biomarkers in the blood or in the cerebrospinal fluid that surrounds the brain and spinal cord. Another category is imaging biomarkers, which use technologies like MRI and EEG during sleep, to visualize structural and functional changes in the nervous system. Skin biopsies, which can be tested for the presence of abnormal alpha-synuclein deposits, also show promise for detecting Parkinson's and Lewy body dementia long before symptoms appear.&nbsp;
</blockquote>
<div class="wysiwyg-img-caption-wrapper" style="display: inline-flex; flex-direction: column;"><img src="https://wmnhealthpublicfiles.blob.core.windows.net/publicfiles/MediaLibrary/c105d3ff_77ee_4103_b64c_b363b9754118_19b3573d07.png" alt="/" width="800" height="633" />Infographic by Cat Lau. (References below.)</div>

<h2><a id="LBD-sex-gender"></a>What are the sex and gender differences in LBD?&nbsp;</h2>
Studies on sex and gender differences in Lewy body dementia are still few and far between. However, they have indicated that females with LBD might experience a faster progression of the disease compared to men. This could be due to biological differences, such as hormonal changes, or social factors, like differences in caregiving roles. Additionally, females might have different responses to medications used to treat LBD, necessitating a sex-sensitive approach to treatment.&nbsp;

<h2><a id="LBD-risk-factors"></a>What are the risk factors for Lewy body dementia, and can it be prevented?<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;</h2>
The main risk factor for Lewy body dementia is age, just as it is for Alzheimer&rsquo;s. Other known risk factors include: Parkinson's disease and REM sleep behavior disorder. There is not a clear genetic basis for Lewy body dementia, but having a family member with this condition does slightly increase a person's risk.<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;
While the exact causes of Lewy body dementia are not fully understood, research suggests that lifestyle factors might play a role in reducing the risk of developing LBD. <a href="https://news.wjct.org/show/whats-health-got-to-do-with-it/2024-02-17/wjct-med-show-brain-conditions">According</a> to Dr. Philip Tipton, a neurologist at the Mayo Clinic in Jacksonville, Florida, the following lifestyle modifications may help prevent Lewy body dementia as well as other neurodegenerative diseases:<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;
<ul>
<li>Cognitive exercise &ndash; focus on challenging yourself to learn a new skill.<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;</li>
<li>Social exercise &ndash; regular engagement with others.<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;</li>
<li>Aerobic exercise &ndash; getting your heart rate up.&nbsp;</li>
</ul>

<h2><a id="LBD-research"></a>What&rsquo;s happening in Lewy body research?&nbsp;<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;</h2>
Researchers are exploring new treatment options, diagnostic tools, and potential risk factors for Lewy body dementia. A variety of clinical studies are underway to test the effectiveness of new medications and interventions. Participating in research studies can provide access to cutting-edge treatments and contribute to the collective knowledge about Lewy body dementia, <a href="https://wmnhealth.org/blog/the-dementia-hardly-anyone-talks-about/" target="_blank" rel="noopener">including sex and gender differences</a>. <span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:279}">&nbsp;

<h2><a id="LBD-support"></a>LBD support networks and resources&nbsp;</h2>
Living with Lewy body dementia can be challenging, not only for the individuals diagnosed with the condition but also for their families and caregivers. Support networks and resources play a vital role in providing information, emotional support, and practical assistance to those affected by LBD.&nbsp;
Local and national organizations such as the <a href="https://www.lbda.org/">Lewy Body Dementia Association</a>&nbsp; States and <a href="https://www.canadianlbdinfo.ca/">Canadian Lewy Body Dementia Information</a> often offer helplines, support groups, educational materials, and research opportunities. These resources can help individuals navigate the complexities of LBD, access specialized care, and connect with others who understand their experiences.&nbsp;
<ul>
<li data-leveltext="" data-font="Symbol" data-listid="3" data-list-defn-props="{&quot;335552541&quot;:1,&quot;335559685&quot;:720,&quot;335559991&quot;:360,&quot;469769226&quot;:&quot;Symbol&quot;,&quot;469769242&quot;:[8226],&quot;469777803&quot;:&quot;left&quot;,&quot;469777804&quot;:&quot;&quot;,&quot;469777815&quot;:&quot;hybridMultilevel&quot;}" aria-setsize="-1" data-aria-posinset="1" data-aria-level="1"><a href="https://www.lbda.org/">Lewy Body Dementia Association</a> (USA)</li>
<li data-leveltext="" data-font="Symbol" data-listid="3" data-list-defn-props="{&quot;335552541&quot;:1,&quot;335559685&quot;:720,&quot;335559991&quot;:360,&quot;469769226&quot;:&quot;Symbol&quot;,&quot;469769242&quot;:[8226],&quot;469777803&quot;:&quot;left&quot;,&quot;469777804&quot;:&quot;&quot;,&quot;469777815&quot;:&quot;hybridMultilevel&quot;}" aria-setsize="-1" data-aria-posinset="1" data-aria-level="1"><a href="https://www.canadianlbdinfo.ca/">Canadian Lewy Body Dementia Information</a>&nbsp;</li>
<li data-leveltext="" data-font="Symbol" data-listid="3" data-list-defn-props="{&quot;335552541&quot;:1,&quot;335559685&quot;:720,&quot;335559991&quot;:360,&quot;469769226&quot;:&quot;Symbol&quot;,&quot;469769242&quot;:[8226],&quot;469777803&quot;:&quot;left&quot;,&quot;469777804&quot;:&quot;&quot;,&quot;469777815&quot;:&quot;hybridMultilevel&quot;}" aria-setsize="-1" data-aria-posinset="1" data-aria-level="1"><a href="https://www.lewybodydementia.ca/lewy-body-dementia-phases-and-stages/">Lewy Body Dementia Canada</a>&nbsp;</li>
<li data-leveltext="" data-font="Symbol" data-listid="3" data-list-defn-props="{&quot;335552541&quot;:1,&quot;335559685&quot;:720,&quot;335559991&quot;:360,&quot;469769226&quot;:&quot;Symbol&quot;,&quot;469769242&quot;:[8226],&quot;469777803&quot;:&quot;left&quot;,&quot;469777804&quot;:&quot;&quot;,&quot;469777815&quot;:&quot;hybridMultilevel&quot;}" aria-setsize="-1" data-aria-posinset="1" data-aria-level="1"><a href="https://www.lewybody.org/">The Lewy Body Society</a> (United Kingdom)</li>
<li data-leveltext="" data-font="Symbol" data-listid="3" data-list-defn-props="{&quot;335552541&quot;:1,&quot;335559685&quot;:720,&quot;335559991&quot;:360,&quot;469769226&quot;:&quot;Symbol&quot;,&quot;469769242&quot;:[8226],&quot;469777803&quot;:&quot;left&quot;,&quot;469777804&quot;:&quot;&quot;,&quot;469777815&quot;:&quot;hybridMultilevel&quot;}" aria-setsize="-1" data-aria-posinset="1" data-aria-level="1"><a href="https://www.ninds.nih.gov/health-information/disorders/lewy-body-dementia">National Institute of Neurological Disorders and Stroke: Lewy Body Dementia</a></li>
</ul>
&nbsp;

<h2>Infographic References</h2>
Lewy body dementia
<ol>
<li><a href="https://www.nia.nih.gov/health/lewy-body-dementia/what-lewy-body-dementia-causes-symptoms-and-treatments" target="_blank" rel="noopener">What Is Lewy Body Dementia? Causes, Symptoms, and Treatments</a>, The National Institute on Aging. (Accessed March 20, 2024)</li>
<li><a href="https://www.lbda.org/diagnosis-and-prognosis/" target="_blank" rel="noopener">Diagnosis and Prognosis: How is LBD diagnosed?</a> Lewy body Dementia Association (Accessed March 20, 2024)</li>
<li>Bayram, E., Reho, P., Litvan, I. et al. <a href="https://www.nature.com/articles/s41531-024-00649-7" target="_blank" rel="noopener">Genetic analysis of the X chromosome in people with Lewy body dementia nominates new risk loci.</a> npj Parkinsons Dis. 10, 39 (2024).&nbsp;</li>
<li><a href="https://www.lbda.org/symptoms/" target="_blank" rel="noopener">Symptoms</a>, Lewy body Dementia Association (Accessed March 20, 2024)</li>
<li><a href="https://www.lbda.org/treatment-options/" target="_blank" rel="noopener">Treatment Options</a>, Lewy body Dementia Association (Accessed March 20, 2024)</li>
</ol>
What are biomarkers?
<ol>
<li><a href="https://womenshealth.obgyn.msu.edu/blog/sex-differences-biomarkers-impact-clinical-testing" target="_blank" rel="noopener">Sex differences in biomarkers impact clinical testing</a>, Women's Health Research Institute (accessed January 23, 2024) &nbsp;</li>
<li>Dubois, B., von Arnim, C.A.F., Burnie, N. et al. <a href="https://alzres.biomedcentral.com/articles/10.1186/s13195-023-01314-6" target="_blank" rel="noopener">Biomarkers in Alzheimer&rsquo;s disease: role in early and differential diagnosis and recognition of atypical variants.</a> Alz Res Therapy 15, 175 (2023).</li>
<li>Klyucherev, T.O., Olszewski, P., Shalimova, A.A. et al. <a href="https://translationalneurodegeneration.biomedcentral.com/articles/10.1186/s40035-022-00296-z" target="_blank" rel="noopener">Advances in the development of new biomarkers for Alzheimer&rsquo;s disease.</a> Transl Neurodegener 11, 25 (2022).&nbsp;</li>
</ol>

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Q&A: The dementia hardly anyone talks about

Lewy body dementia (LBD) is a surprisingly common and deeply impactful neurodegenerative disease. Yet, everywhere from the laboratory to the clinic, it is overshadowed by&nbsp;Alzheimer's disease&mdash;a more common cause of dementia. As a result, urgent questions about LBD remain unanswered, including what causes the disease, who's most at risk, and how to treat it. <span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:300,&quot;335559739&quot;:300,&quot;335559740&quot;:279}">&nbsp;
While LBD affects both men and women, emerging research suggests that there may be distinct differences in how the disease manifests and progresses in females. Yet, what factors contribute to those differences is still unknown. <span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:300,&quot;335559739&quot;:300,&quot;335559740&quot;:279}">&nbsp;
<div class="wysiwyg-img-caption-wrapper" style="float: left; display: inline-flex; flex-direction: column;"><img style="float: left;" src="https://wmnhealthpublicfiles.blob.core.windows.net/publicfiles/MediaLibrary/90165f3c_29e6_4b8f_afbd_30fcab545dbf_97e5999a95.jpeg" alt="/" width="225" height="225" />Ece Bayram, M.D., Ph.D.</div>
LBD is characterized by the accumulation of <a href="https://wmnhealth.org/blog/the-protein-misfolding-problem-how-some-neurodegenerative-disorders-intersect/" target="_blank" rel="noopener">abnormal protein deposits</a>, known as Lewy bodies, in the brain. These deposits disrupt normal brain function, leading to a range of changes in thinking, behavior, movement, and sleep that set it apart from Alzheimer&rsquo;s and other neurodegenerative diseases, including visual hallucinations.<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:300,&quot;335559739&quot;:300,&quot;335559740&quot;:279}">&nbsp;
This Q&amp;A with LBD expert&nbsp;<a href="https://profiles.ucsd.edu/ece.bayram" target="_blank" rel="noopener">Ece Bayram, M.D., Ph.D.</a>, Assistant Project Scientist&nbsp;in the Department of Neuroscience at the University of California, San Diego, explores the ways in which the dementia affects females, both biologically and socially, and the remaining gaps in our understanding. <span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559685&quot;:0,&quot;335559737&quot;:0,&quot;335559738&quot;:300,&quot;335559739&quot;:300,&quot;335559740&quot;:279}">&nbsp;
This interview has been edited for length and clarity.<span class="EOP SCXW174568120 BCX4" data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;
<h2>wmnHealth: What led you to study Lewy body dementia, including potential sex and gender differences?<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;</h2>
Ece Bayram:&nbsp;I've been working on movement disorders since my PhD days and really like the Parkinsonian community. And I realized there's absolutely nothing on Lewy body dementia.&hellip; No one knows about it. No one talks about it. Alzheimer's tends to get the spotlight, as it should, but other dementias deserve the spotlight, too.&nbsp;<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;
I started working on sex differences in Parkinson's first because one of my mentors was interested in it. Then, I realized there's not much known about sex and gender differences in Lewy body dementia. It's striking because it's such a common type of dementia. Plus, you see sex differences in Alzheimer's; you see them in Parkinson's. Lewy body dementia is this type of dementia that stands at the crossroads of those two diseases, so there's likely going to be some sex differences there, too.<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;
From our <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8530264/" target="_blank" rel="noopener">first paper</a> on Lewy body dementia, it was so striking, so marked how things look so different for females and males. And once I started focusing on this topic more, I started seeing the cracks in the field.&nbsp;<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;

<h2>wmnHealth: Based on current data, males are more likely to be diagnosed with Lewy body dementia than females. But not all studies have found a big difference, correct?<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;</h2>
Bayram:&nbsp;Yes, especially in Asian countries. For some reason, movement disorders look so different in Eastern versus Western populations. That sex difference is very prominent in the Western population when it comes to the prevalence of Lewy body pathology and disease, but it's not as marked in Eastern populations.&nbsp;<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;
I suspect once the awareness increases, it's going to be kind of like Parkinson's: The prevalence for women and men is not going to be as wildly different as before. I think we need to increase awareness about Lewy body dementia and the fact that women aren't getting represented in research.&nbsp;<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;

<h2>wmnHealth: How does Lewy body dementia affect the daily lives of women? Are there unique challenges they face?<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;</h2>
Bayram:&nbsp;We really don't know. But I would assume so because in Parkinson's, we know that even when men and women have the exact same disease&mdash;the exact same symptoms, disease severity, etc.&mdash;the impact on their daily lives may differ. It has to do a lot with gender norms and roles. Based on that, you can easily assume that Lewy body dementia is going to impact women's lives very differently, too.&nbsp;<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;
<div class="wysiwyg-img-caption-wrapper" style="display: inline-flex; flex-direction: column;"><img src="https://wmnhealthpublicfiles.blob.core.windows.net/publicfiles/MediaLibrary/8f9040d8_5932_42ea_af6b_03d5a060c954_535ac2b433.png" alt="Infographic about Lewy body dementia" width="800" height="1422" />Infographic by Cat Lau. (References below)</div>

<h2>wmnHealth: What's happening in the brains of people with Lewy body dementia?<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;</h2>
Bayram:&nbsp;Lewy body dementia is defined by someone having dementia and, when you cut open their brain, Lewy body pathology,&nbsp;in which clumps of proteins called Lewy bodies build up. But Lewy body pathology loves companions. There are many other pathologies that we see alongside Lewy bodies, but I'll touch on Alzheimer's. So, for people with Lewy body pathology, you usually also get the build-up of abnormal tau proteins, which form tangles inside neurons and are one of the hallmarks of Alzheimer's disease. When Alzheimer's tags along with Lewy body dementia, it loves taking center stage. When that happens, especially for women, Alzheimer's really rules the dementia profile.<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;
We don't see Alzheimer's co-pathology as often in males. But the Lewy body pathology just acts naughtier. It causes dementia more for men. It causes Parkinsonism more for men. That's the typical phenotype more for men&mdash;the slowness, the shakiness, the stiffness.&nbsp;<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;

<h2>wmnHealth: And in females?<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;</h2>
Bayram:&nbsp;What's most striking is that females don't look like males. When you look at their brains, they don't have the same pathology, including the degree of build-up of Lewy bodies and tau tangles. So, females may have a bit of resilience to the disease. That's true when you look at brains and also in imaging studies. These sex differences are consistent.&nbsp;<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;

<h2>wmnHealth: What about the symptoms? If the pathology differs by sex, do the symptoms, too?<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;</h2>
Bayram:&nbsp;Behavioral issues&nbsp;such as visual and auditory hallucinations and depression&nbsp;may be more common for women, whereas motor issues may be more common for men. However, those symptomatic differences may reflect how we diagnose the disease rather than "true" sex differences. For example, much of my research uses pathologically defined cohorts, which means we've confirmed the presence of Lewy bodies in the brain after death. And in those cohorts, I found that women weren't as likely as men to have hallucinations. However, in clinically defined cohorts, which rely on the existing diagnostic criteria, women are more likely to have visual hallucinations.<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;
<blockquote>
<h2>Common symptoms of Lewy body dementia</h2>
<ul>
<li>Dementia, especially changes in&nbsp;memory, decision making, problem solving, planning, and abstract or analytical thinking.</li>
<li>Cognitive fluctuations, such as unpredictable changes in concentration, alertness or attention.</li>
<li>Parkinson&rsquo;s-like symptoms including slowness of movement, rigidity or stiffness, shuffling gait, tremors, and balance problems.</li>
<li>Behavioral changes including hallucinations, delusions or changes in mood.</li>
<li>Sleep disorders&nbsp;include REM sleep behavior disorder (RBD), excessive daytime sleepiness, temporary loss of consciousness with difficulties wakening, insomnia, and restless leg syndrome.</li>
<li>Autonomic symptoms,&nbsp;including problems with temperature and blood pressure regulation, as well as constipation, urinary incontinence, and sexual dysfunction.&nbsp;</li>
</ul>
Source: <a href="https://www.lbda.org/symptoms/" target="_blank" rel="noopener">Lewy Body Dementia Association</a>
</blockquote>

<h2>wmnHealth: I'm glad you brought up diagnosis because women with Lewy body dementia are often misdiagnosed or diagnosed much later than men. Are the current diagnostic criteria failing women?<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;</h2>
Bayram:&nbsp;If women are dealing with more misdiagnosis, more delayed diagnosis, that means the diagnostic criteria are not serving them. So we've got to figure out how the disease actually shows up for women so we can create criteria that better serve them.&nbsp;<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;
The problem is that most of the available data in Lewy body research comes from males. If you're primarily looking at men and saying that this is how they present with Lewy body dementia. Of course, the diagnostic criteria are not going to apply to women. Women aren't represented. So, the things we know right now that drive the treatment plans and the treatment studies, too, come from a problematic sample. There are a lot of voices that get unheard.<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;

<h2>wmnHealth: The boundaries of these neurodegenerative diseases are so blurry. Is there a need for biomarkers&mdash;objective ways of measuring the signs of disease&mdash;that can help clinicians correctly diagnose Lewy body dementia and also distinguish it from Alzheimer's or Parkinson's?<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;</h2>
Bayram:&nbsp;Absolutely. In fact, Lewy body dementia is so heterogeneous, even in men, that we are likely missing a huge part of the story. There are some exciting advances in biomarkers, and if we can increase their use, I think we're gonna get better at diagnosing people and also avoiding misdiagnosis. But there has to be combined use of Alzheimer's and Lewy body biomarkers because Alzheimer's so often co-occurs with Lewy body dementia. You cannot exclude Lewy body dementia once you have a positive Alzheimer's test.<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;

<h2>wmnHealth: What are you working on now?<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;</h2>
Bayram:&nbsp;Right now, I'm focusing on risk factors: Are there different genetic factors driving these sex differences? Are there different environmental factors or reproductive health-related factors driving these differences?&nbsp;<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;
I'm conducting a <a href="https://www.lbda.org/environmental-and-reproductive-health-risk-for-lewy-body-dementia-lbd-toros/" target="_blank" rel="noopener">survey study</a>, sponsored by the Lewy Body Dementia Association, on environmental, occupational, and reproductive health. We're recruiting 50 males and 50 females for a one-time survey that can be filled out online or over the phone. The survey is completely anonymous.&nbsp;<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;
<blockquote>
Study: <a href="https://www.lbda.org/environmental-and-reproductive-health-risk-for-lewy-body-dementia-lbd-toros/" target="_blank" rel="noopener">Environmental and Reproductive Health Risk for LBD (LBD &ndash; TOROS)</a>
&nbsp;
<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">Dr. Bayram is leading the LBD-TOROS study, named after the Toros Mountains near her hometown in Turkey. She is seeking to understand how biological, environmental, occupational, and socioeconomic factors impact the risk of LBD and whether and how the impact risk differs between women and men. Participants who meet the eligibility criteria are welcome.
</blockquote>

<h2>wmnHealth: What are some of the risk factors you're interested in?<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;</h2>
Bayram:&nbsp;In general, people may be exposed to different environmental and occupational factors during their lifetimes based on their gender. Hormones and reproductive health factors look different based on people's sex. Caffeine, alcohol, smoking, history of anxiety, and depression may relate to Lewy body dementia and can differ across sexes and genders. Even when exposed to the same factors, female and male brains may not react the same way. For instance, genetic risk factors like GBA mutations may not increase the Lewy body dementia risk for females despite increasing the risk for males. Reproductive health and environmental history can alter the level of risk in this way, with differences between females and males.&nbsp;<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;
The influence of reproductive health is interesting because, until the ages of 70 to 75, men are more likely to get Lewy body dementia than women. But after the age of 70, 75, there seems to be more of a balance. Women start catching up. Personally, I think that has to do with reproductive health factors like menopause. Of course, women are not going through menopause at 70, but there may be long-lasting effects.&nbsp;<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;

<h2>wmnHealth: Are you suggesting women may be buffered against neurodegenerative diseases such as Lewy body dementia for the first 50 years or so, then slowly catch up to men after menopause?<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;</h2>
Bayram:&nbsp;It's a hypothesis and one that has important implications for women taking hormone therapies, including people identifying as gender minorities. Environmental factors are also going to differ a lot once for people who identify as a sexual or gender minority, and I want to bring that out because there's nothing that community when it comes to Lewy body dementia. Yet the disease doesn't discriminate.<span data-ccp-props="{&quot;134233117&quot;:false,&quot;134233118&quot;:false,&quot;201341983&quot;:0,&quot;335551550&quot;:0,&quot;335551620&quot;:0,&quot;335559738&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:279}">&nbsp;

<h2>Infographic References</h2>
<ol>
<li><a href="https://www.nia.nih.gov/health/lewy-body-dementia/what-lewy-body-dementia-causes-symptoms-and-treatments" target="_blank" rel="noopener">What Is Lewy Body Dementia? Causes, Symptoms, and Treatments</a>, The National Institute on Aging. (Accessed March 20, 2024)</li>
<li><a href="https://www.lbda.org/diagnosis-and-prognosis/" target="_blank" rel="noopener">Diagnosis and Prognosis: How is LBD diagnosed?</a> Lewy body Dementia Association (Accessed March 20, 2024)</li>
<li>Bayram, E., Reho, P., Litvan, I. et al. <a href="https://www.nature.com/articles/s41531-024-00649-7" target="_blank" rel="noopener">Genetic analysis of the X chromosome in people with Lewy body dementia nominates new risk loci.</a> npj Parkinsons Dis. 10, 39 (2024).&nbsp;</li>
<li><a href="https://www.lbda.org/symptoms/" target="_blank" rel="noopener">Symptoms</a>, Lewy body Dementia Association (Accessed March 20, 2024)</li>
<li><a href="https://www.lbda.org/treatment-options/" target="_blank" rel="noopener">Treatment Options</a>, Lewy body Dementia Association (Accessed March 20, 2024)</li>
</ol>
<a href="https://www.nia.nih.gov/health/lewy-body-dementia/what-lewy-body-dementia-causes-symptoms-and-treatments" target="_blank" data-saferedirecturl="https://www.google.com/url?q=https://www.nia.nih.gov/health/lewy-body-dementia/what-lewy-body-dementia-causes-symptoms-and-treatments&amp;source=gmail&amp;ust=1711640827219000&amp;usg=AOvVaw3Ajtn2AbCPA2qHZxGPA7DW" rel="noopener"></a>

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