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Talk with an Alzheimer's Doc | Neurology Department | U of U School of Medicine
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data-drupal-selector="form-qg3oii1h2yhuxbu-udi1h1jqpu8y8gnmut1baay4ug4" type="hidden" name="form_build_id" value="form-qG3oIi1H2yHuxbu-udI1h1JqpU8y8GnMUt1baay4uG4" class="gls-margin" /> <input data-drupal-selector="edit-simple-gse-search-form" type="hidden" name="form_id" value="simple_gse_search_form" class="gls-margin" /> </form> </div> </div> </div> </div> </div> <div class="gls-navbar-item gse-search-link gls-navbar-right"> <a class="gls-navbar-toggle gls-text-primary" gls-toggle="target: #search-modal__navbar; animation: gls-animation-fade" href="#"> <span class="gls-icon gls-search-icon" gls-search-icon></span> <span class="gls-text-uppercase gls-margin-xsmall-left">Search</span> </a> </div> </div> </div> </div> </div> </div> </div> <div id="page--highlighted"> <div class="gls-container"> </div> </div> <div id="page"> <div id="page--wrapper" class="gls-grid" gls-grid> <main id="page--content" class="gls-width-1-1"> <a id="main-content" tabindex="-1"></a> <div id="region--content" class="region region-content"> <div data-drupal-messages-fallback class="hidden"></div> <div id="mainpagecontent" data-block-plugin-id="system_main_block" class="block block-system block-system-main-block"> <article class="gls-article"> <div> <div class="layout layout--uou--one--column gls-section gls-preserve-color gls-section-default gls-section-xsmall"> <div class="gls-container gls-container-xsmall"> <div data-block-plugin-id="field_block:node:story:created" class="block block-layout-builder block-field-blocknodestorycreated"> <span><time datetime="2024-05-29T12:53:29-06:00">May 29, 2024</time> </span> </div> <div data-block-plugin-id="field_block:node:story:body" class="block block-layout-builder block-field-blocknodestorybody"> <div class="gls-margin"><div class="text-container galileo-ap-content-editor"> <div> <div>For our latest session of <strong>Talks with Docs</strong>, cognitive neurologist Nicholas Frost, MD, PhD, joined department chair Stefan Pulst, MD, Dr med, to discuss recent advances in Alzheimer’s disease research.</div> <div> </div> <div>At the end of the session, we collected your leftover questions. Now they're all answered in the following article.</div> </div> </div> </div> </div> </div> </div> <div class="layout layout--onecol"> <div class="layout__region layout__region--content"> <div data-block-plugin-id="field_block:node:story:field_layout_canvas" class="block block-layout-builder block-field-blocknodestoryfield-layout-canvas"> <div class="gls-margin"> <div class="coh-container ssa-component coh-component ssa-component-instance-c32e72e8-097b-4950-bfdf-d0d6917119bd coh-component-instance-c32e72e8-097b-4950-bfdf-d0d6917119bd" data-lift-slot > <div class="coh-container gls-section gls-section-default default-size" style="padding-top: ; padding-bottom: ;" > <div class="coh-container gls-container default-width" > <div class="coh-container ssa-component coh-component ssa-component-instance-7eb7a69e-1596-44a7-8665-61fac901d6b2 coh-component-instance-7eb7a69e-1596-44a7-8665-61fac901d6b2 coh-heading-component" data-lift-slot > <div class="coh-inline-element gls-pre-heading gls-h4 gls-text-muted gls-margin-xsmall-bottom "></div> <h2 class="coh-heading gls-h3 gls-margin-medium-bottom" > <span class="coh-inline-element">Recap</span> </h2> </div> <div class="coh-container ssa-component coh-component ssa-component-instance-2c0c804d-afcb-471b-b4bc-acc8c93c7bda coh-component-instance-2c0c804d-afcb-471b-b4bc-acc8c93c7bda " data-lift-slot > <div class="coh-wysiwyg" > <p><strong>Talks with Docs</strong> is a series of webinars with our expert neurologists to explore how their research changes the future of treatments for brain diseases. This session, called “Talk with an Alzheimer’s Doc,” was hosted by Department Chair Stefan Pulst, MD, Dr Med, and featured cognitive neurologist Nicholas Frost, MD, PhD.</p> <p>Dr. Frost's laboratory focuses on understanding how disease states such as Alzheimer's disease alter the function of the brain. In his talk, he discussed recent advances in Alzheimer’s disease research, including breakthrough anti-amyloid therapies lecanemab and donanemab, which are revolutionizing dementia care and treatment. After this presentation, Dr. Pulst moderated a Q&A.</p> <p>If you missed this webinar or want to watch it again, please email <a href="mailto:Melissa.Lyons@hsc.utah.edu">Melissa.Lyons@hsc.utah.edu</a> for the recording. You can also find Dr. Frost’s presentation slides <a href="https://medicine.utah.edu/neurology/documents/talks-docs-may-2024-presentation-slides">here</a>.</p> <p>If your question during the session went unaddressed, don’t worry! We’ve gathered them all below with answers from Dr. Frost.</p> </div> </div> </div> </div> </div> <div class="coh-container ssa-component coh-component ssa-component-instance-f46b4dfa-19b7-4a87-a440-c75ed7db695a coh-component-instance-f46b4dfa-19b7-4a87-a440-c75ed7db695a" data-lift-slot > <div class="coh-container gls-section gls-section-muted default-size" style="padding-top: ; padding-bottom: ;" > <div class="coh-container gls-container default-width" > <div class="coh-container ssa-component coh-component ssa-component-instance-d528fc4c-fdfe-4c73-8398-f9ee0e24b469 coh-component-instance-d528fc4c-fdfe-4c73-8398-f9ee0e24b469 coh-heading-component" data-lift-slot > <div class="coh-inline-element gls-pre-heading gls-h4 gls-text-muted gls-margin-xsmall-bottom "></div> <h2 class="coh-heading gls-h3 gls-margin-medium-bottom" > <span class="coh-inline-element">Questions and Answers</span> </h2> </div> <div class="coh-container ssa-component coh-component ssa-component-instance-5a2d6121-68bf-4bea-980a-3dce7d660a19 coh-component-instance-5a2d6121-68bf-4bea-980a-3dce7d660a19 " data-lift-slot > <div class="coh-wysiwyg" > <p><strong>Q: If there is a strong family history of Alzheimer’s, would it be advantageous for someone in their 50s to have a blood test done? Can you specifically share the tests to request?</strong></p> <p>A: The apolipoprotein E gene (ApoE) is a strong genetic risk factor for Alzheimer’s disease and underlies predilection to develop Alzheimer’s disease in many families. However, it is important to remember that having one or two copies of the high-risk form of ApoE (ApoE4) does not guarantee that an individual will develop Alzheimer’s disease or dementia. Moreover, at this time there are no studies demonstrating that there is advantage to treating patients prior to onset of symptoms of Alzheimer’s disease. Thus, it is unclear at this point what the potential benefit of testing patients who do not yet have symptoms might be, and the possibility that knowing one has two copies of ApoE4 would lead to subtle symptoms being detected sooner (and therefore treated sooner) is balanced by the risk that it would lead to increased anxiety. <br><br>It may trigger a greater degree of concern in a patient who has mild symptoms that would permit identification and initiation of treatment earlier.</p> <p><strong>Q: I’m looking for recommendations for people who have a very large history of this in their family. Do you have any preventative suggestions for people with a heavy history?</strong></p> <p>A: My first very general recommendation is that people with a strong family history should adopt a healthy lifestyle with the goal of controlling modifiable risk factors for dementia. This means controlling cholesterol, obesity, blood pressure, and other vascular risk factors, and at the same time maintaining an active lifestyle with cardiovascular exercise, which actually increases the volume of the hippocampus. If you smoke, you should stop, and excessive alcohol is neurotoxic. And remember, social contact is good for brain health, and we should avoid social isolation, which means joining a club or spending time with family.</p> <p>The second point is that genetic testing is available for ApoE. However, at this point in time, no trials have been completed to prevent or treat patients who are asymptomatic. However, knowing that an individual is ApoE4/E4 may raise our level of suspicion if subtle symptoms start to crop up and trigger testing.</p> <p><strong>Q: I have had 5 strokes: 1 in my left ear, 1 in my vision center, and 3 in my basil arteries. My mother had Alzheimer’s disease (AD) when she died. I have had a birth defect in the basil artery. It is too small. My question is, will I develop AD? How soon should I get tested? I am 54. I had 4 strokes at 52; the ear stroke is old.</strong></p> <p>A: The first point I would like to make is that in terms of modifiable risk for dementia, vascular risk factors seem high on the list. Remember that Alzheimer’s disease is the most common but not the only cause of dementia, and vascular dementia can be caused by strokes. While I do not know the specific cause of your strokes, patients who have had strokes or been told they have had strokes should know that future strokes are largely preventable by managing vascular risk factors (i.e., blood pressure, diabetes, cholesterol, certain types of vascular lesions, etc). </p> <p>The second point I will make is that there are small strokes and large strokes and often, a single small stroke does not trigger specific symptoms in an individual, but when more and more accumulate, this can drive changes in cognition. Thus, even in patients who have had strokes already, it is useful to try to prevent further strokes.</p> <p><strong>Q: If a parent has been diagnosed with Alzheimer’s, what recommendations do you have for their children (60¬–65) to determine their risk to proactively develop the most appropriate strategy? Specifically, what kind of testing, etc.</strong></p> <p><strong>Also, if you do this testing, do you know if this is covered by insurance?</strong></p> <p>A: Every insurance is different, making this question difficult. Critically, not every patient who has Alzheimer’s disease will have a high-risk copy of ApoE, and not every patient with one or more copy of ApoE4 will develop Alzheimer’s disease or dementia. </p> <p><strong>Q: What are your thoughts on acid reflux medications that are taken for a long period of time increasing the risk of dementia by 33%?</strong></p> <p>A: The evidence on this is correlative and highly mixed, with the best studies usually showing no relationship. Notably, Proton Pump Inhibitors can drive B12 malabsorption and B12 deficiency, and so it is worth checking your B12 level if you are on a PPI for a long period of time.</p> <p><strong>Q: I am curious if there is an effort at increasing non-REM sleep in older adults (or just sleep efficiency) to clear more amyloid-beta by medication and/or neuromodulation?</strong></p> <p>A: Good sleep is critically important for cognition, and patients should maintain healthy sleep routines whether they have Alzheimer’s disease or not. We know, for example, that sleep deprivation drives the accumulation of Amyloid in the brain. Sleep can be disrupted in patients with Alzheimer’s disease due to loss of sleep promoting neurons in the hypothalamus, which can be ameliorated to some degree by habits that promote good sleep, such as exercising (and avoiding naps) during the day and going to bed at a set time; melatonin can help to set the clock and promote drowsiness/sleep if taken before bedtime.</p> <p><strong>Q: Are there any studies done with having mast cell activation syndrome (MCAS) and a link to Alzheimer’s?</strong></p> <p>A: There is related evidence that mast cells may be important in the pathogenesis of Alzheimer’s disease through their role in immunomodulation of microglial activation. For instance, one study (Lin et al, 2023) showed that mast cell depletion in mice modeling Alzheimer’s disease rescued deficits in certain types of learning. However, the relation between MCAS and Alzheimer’s disease has not been characterized to my knowledge.</p> <p><strong>Q: Does a high lipid level have an effect on ApoE?</strong></p> <p>A: ApoE is a key component of VLDL and HDL, which are both measured in blood when patients have their lipids measured. For that reason, lipid levels in the blood and ApoE will be related. ApoE4, in addition to raising risk of Alzheimer’s disease, is also related to cardiovascular disease risk. Interestingly, ApoE2, which is thought to protect against Alzheimer’s disease, raises risk of cardiovascular disease. ApoE2 increases atherogenic lipoprotein levels (it binds poorly to LDL receptors needed to clear the lipoproteins from blood), and ApoE4 increases LDL levels (it binds preferentially to triglyceride-rich, very low density lipoproteins, leading to downregulation of LDL receptors).</p> <p><strong>Q: We are recognizing association of macular degeneration with various forms of dementia and can now image B-amyloid and tau protein. How is this imaged on MRI?</strong></p> <p>A: Both amyloid and tau can be imaged using special PET scans with tracers targeted at amyloid and tau. MRI cannot directly visualize either protein but is useful for visualizing patterns of atrophy, which occur with neurodegenerative disease. MRI can also be used to rule out/evaluate for other conditions such as vascular conditions, stroke, hemorrhage, and tumors.</p> <p><strong>Q: I looked at a New England Journal of Medicine study about lecanemab (found </strong><a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2212948"><strong>here</strong></a><strong>). The differences in the dependent variables (DVs) were significant, but with the large sample and a repeated-measure design, the test of statistical significance would have been quite powerful. However, I didn’t see a test of strength-of-relationship measure. What were the obtained effect sizes in the study you were talking about (found </strong><a href="https://pubmed.ncbi.nlm.nih.gov/37459141/"><strong>here</strong></a><strong>)?</strong></p> <p>A: Great question: Both CLARITY (lecanemab) and TRAILBLAZER (donanemab) showed less decline in cognition in patients who received the drug than in placebo patients. These effects were statistically significant but were relatively small. This has led to discussion about what the clinically significant effect size should be – in other words, how much a drug should slow the progression of cognitive decline in order to be useful. This is extremely important, because, as you mention, we can achieve mathematically significant effects that are not significant to an individual on a drug. It is notable that in both studies, there was a statistically significant effect by six months, though in both cases the drugs continue to remove a substantial amount of amyloid over a much longer period. This leads to a broader question, which is how much amyloid has to be removed for the drugs to work, and if a greater degree of amyloid removal would result in a larger benefit over longer periods of time. A second question worth considering is whether certain patients or types of patients might respond better or worse to the medications. This is an area of active ongoing research.</p> <p><strong>Q: How do you explain that some super agers have amyloids in their brains?</strong></p> <p>The body makes amyloid throughout the lifespan of every individual. There is a stochastic random process by which amyloid misfolds, causing the generation of plaques in the brain, which accumulate decades prior to symptoms. This occurs in an age-related manner. If we were to delay this process by a certain number of years, we could also delay the onset of Alzheimer’s disease by the same amount of time. The takeaway is that all individuals are at risk for accumulating amyloid in their brain, but the later the age at which it accumulates, the less likely patients are to then develop Alzheimer’s disease. So, the super agers with amyloid in their brain have been relatively lucky and amyloid accumulated in their brain much later than in other individuals. But if they lived another 20 years, they would likely develop cognitive impairment.</p> <p><strong>Q: My husband has cerebral amyloid. Do the pills and things discussed during this Zoom meeting have any impact on cerebral amyloid? My husband is struggling with cognitive issues.</strong></p> <p>A: Unfortunately, much work has to be done to understand the best way to treat cerebral amyloid. The fundamental issue is that, similar to Alzheimer’s disease, beta amyloid build up in the brain, but in cerebral amyloid angiopathy, the amyloid is in the blood vessel walls rather than in the brain tissue. This raises the possibility of swelling and bleeding when we try to take amyloid out using monoclonal antibodies such as lecanemab. Currently we do not know if anti-amyloid therapy would be helpful in cerebral amyloid, and the fear is that these patients would be much more likely to develop intracerebral hemorrhage or other life-threatening side effects.</p> </div> </div> </div> </div> </div> <div class="coh-container ssa-component coh-component ssa-component-instance-95a29ee9-2275-43f2-8e38-60c229c706b4 coh-component-instance-95a29ee9-2275-43f2-8e38-60c229c706b4" data-lift-slot > <div class="coh-container gls-section gls-section-default default-size" style="padding-top: ; padding-bottom: ;" > <div class="coh-container gls-container default-width" > <div class="coh-container ssa-component coh-component ssa-component-instance-119274d5-cab0-436f-b9a6-8722dcea0c30 coh-component-instance-119274d5-cab0-436f-b9a6-8722dcea0c30" > <div class="coh-container gls-margin-medium-bottom" > <div class="coh-row coh-row-xl coh-row-visible-xl" data-coh-row-match-heights="{"xl":{"target":"none"}}"> <div class="coh-row-inner coh-ce-cpt_2_column_layout-17802b86"> <div class="coh-column coh-visible-ps coh-col-ps-12 coh-col-xl" > <div class="coh-container ssa-component coh-component ssa-component-instance-68b2500f-dd92-499e-b0b4-f92396913e1e coh-component-instance-68b2500f-dd92-499e-b0b4-f92396913e1e" data-lift-slot > <div class="coh-container gls-container gls-flex " > <figure class="coh-container gls-width-1-1 gls-width-2-3@m " > <div class="coh-container gls-inline" > <picture> <source srcset="/sites/g/files/zrelqx416/files/media/images/2024/Nicholas%20Frost%2C%20MD%2C%20PhD.jpg" media="(min-width: 2400px)" type="image/jpeg"> <source srcset="/sites/g/files/zrelqx416/files/media/images/2024/Nicholas%20Frost%2C%20MD%2C%20PhD.jpg" media="(min-width: 1599px) and (max-width: 2399px)" type="image/jpeg"> <source srcset="/sites/g/files/zrelqx416/files/media/images/2024/Nicholas%20Frost%2C%20MD%2C%20PhD.jpg" media="(min-width: 1199px) and (max-width: 1598px)" type="image/jpeg"> <source srcset="/sites/g/files/zrelqx416/files/media/images/2024/Nicholas%20Frost%2C%20MD%2C%20PhD.jpg" media="(min-width: 959px) and (max-width: 1198px)" type="image/jpeg"> <source srcset="/sites/g/files/zrelqx416/files/media/images/2024/Nicholas%20Frost%2C%20MD%2C%20PhD.jpg" media="(min-width: 639px) and (max-width: 958px)" type="image/jpeg"> <source srcset="/sites/g/files/zrelqx416/files/media/images/2024/Nicholas%20Frost%2C%20MD%2C%20PhD.jpg" media="(min-width: 0px) and (max-width: 638px)" type="image/jpeg"> <img class="coh-image coh-image-responsive-xl coh-image-responsive-lg coh-image-responsive-md coh-image-responsive-sm coh-image-responsive-ps coh-image-responsive-xs" gls-img data-src="public://media/images/2024/Nicholas Frost, MD, PhD.jpg" src="/sites/g/files/zrelqx416/files/media/images/2024/Nicholas%20Frost%2C%20MD%2C%20PhD.jpg" title alt="Headshot of Nicholas Frost, MD, PhD" /> </picture> </div> </figure> </div> </div> </div> <div class="coh-column coh-visible-ps coh-col-ps-12 coh-visible-xl coh-col-xl-8" > <div class="coh-container ssa-component coh-component ssa-component-instance-78fbfdeb-dc94-40ed-a258-d454a5616182 coh-component-instance-78fbfdeb-dc94-40ed-a258-d454a5616182 coh-heading-component" data-lift-slot > <div class="coh-inline-element gls-pre-heading gls-h4 gls-text-muted gls-margin-xsmall-bottom "></div> <h2 class="coh-heading gls-h3 gls-margin-medium-bottom" > <span class="coh-inline-element">About Dr. Frost</span> </h2> </div> <div class="coh-container ssa-component coh-component ssa-component-instance-d8541a87-d9a3-4db6-a970-9563914d6040 coh-component-instance-d8541a87-d9a3-4db6-a970-9563914d6040 " data-lift-slot > <div class="coh-wysiwyg" > <p><em>Dr. Frost is a board certified neurologist and neuroscientist. His clinical and research interests focus on understanding mechanisms that contribute to disorders of cognition, with an emphasis on neurodegenerative processes such as Alzheimer’s disease, frontotemporal dementia, and dementia with lewy bodies. In particular, he focuses on how neuronal loss in neurodegenerative disorders, or circuit abnormalities underlying neurodevelopmental disorders, alter how our brains represent information across distributed cortical networks.</em></p> <p><em>Dr. Frost received his medical degree and graduate research training from the University of Maryland School of Medicine. He then moved to San Francisco for further clinical training including an internship in internal medicine and residency in adult neurology at the University of California, San Francisco. Following residency he completed a research fellowship at UCSF focused on characterizing circuit-level endophenotypes underlying abnormal behavior in preclinical models of neurodevelopmental disorders. Clinically, he sees patients at the University of Utah with disorders of memory and cognition.</em></p> <p><em>View his faculty profile </em><a href="https://healthcare.utah.edu/find-a-doctor/nicholas-alonzo-frost"><em>here</em></a><em>.</em></p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="coh-container ssa-component coh-component ssa-component-instance-a0d20312-e790-4086-a661-70950cb6b238 coh-component-instance-a0d20312-e790-4086-a661-70950cb6b238" data-lift-slot > <div class="coh-container gls-section gls-section-default default-size" style="padding-top: ; padding-bottom: ;" > <div class="coh-container gls-container default-width" > <div class="coh-container ssa-component coh-component ssa-component-instance-1116e88e-3290-4a55-9674-b915419b7fd3 coh-component-instance-1116e88e-3290-4a55-9674-b915419b7fd3" data-lift-slot > <div class="coh-container gls-container gls-flex gls-flex-center" > <figure class="coh-container gls-width-1-1 gls-width-medium@m gls-margin-small-bottom " > <div class="coh-container gls-inline" > <picture> <source srcset="/sites/g/files/zrelqx416/files/media/images/2023/Want%20More%20NeurologyNews.png" media="(min-width: 2400px)" type="image/png"> <source srcset="/sites/g/files/zrelqx416/files/media/images/2023/Want%20More%20NeurologyNews.png" media="(min-width: 1599px) and (max-width: 2399px)" type="image/png"> <source srcset="/sites/g/files/zrelqx416/files/media/images/2023/Want%20More%20NeurologyNews.png" media="(min-width: 1199px) and (max-width: 1598px)" type="image/png"> <source srcset="/sites/g/files/zrelqx416/files/media/images/2023/Want%20More%20NeurologyNews.png" media="(min-width: 959px) and (max-width: 1198px)" type="image/png"> <source srcset="/sites/g/files/zrelqx416/files/media/images/2023/Want%20More%20NeurologyNews.png" media="(min-width: 639px) and (max-width: 958px)" type="image/png"> <source 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