Dementia Matters

Harnessing the Power of Autophagy to Treat Alzheimer’s Disease

The Puglielli lab at the University of Wisconsin School of Medicine and Public Health has found a way to manipulate autophagy — a process where cells clean out damaged materials — to rid the brain of toxic proteins like amyloid and tau. Researchers hope to use the power of this process to develop future treatments for Alzheimer’s disease and other diseases of aging. Luigi Puglielli joins the podcast to discuss his team’s research over the past 15 years, why the scientific process can take years to turn ideas into possible treatments, and how he hopes this research can be used in the future.

Guest: Luigi Puglielli, MD, PhD, professor of medicine, University of Wisconsin School of Medicine and Public Health

Episode Topics

7:47 Tell us about how you manipulated this process of autophagy. Why is this discovery so important?

15:14 What role does acetyl-CoA play in the brain?

19:58 What does the future look like for this research?

Show Notes

Learn more about Luigi Puglielli, MD, PhD, and his work in his bio and on the Puglielli Lab website.

Read Dr. Puglielli’s recent paper “ATase inhibition rescues age-associated proteotoxicity of the secretory pathway,” published online on February 25, 2022 in “Communications Biology.”

Go with the (4D) Flow: Neuroimaging Technology Used to Study Overlap of Cerebrovascular Disease and Alzheimer’s

A recent study from Alzheimer’s disease researchers at the University of Wisconsin–Madison used neuroimaging technology called 4D Flow MRI to study the relationship between blood vessel disease and Alzheimer’s disease. Published in December 2021, the study found that people with Alzheimer’s disease symptoms had stiffer blood vessels in their brains, which could lead to inflammation and a buildup of Alzheimer’s biomarkers like amyloid and tau proteins. Lead researcher Leonardo Rivera-Rivera joins the podcast to discuss his findings, the developments made with new 4D Flow MRI scans, and how these developments could impact future Alzheimer’s disease research and clinical practices.

Guest: Leonardo Rivera-Rivera, PhD, neuroimaging scientist, Wisconsin Alzheimer’s Disease Research Center

Episode Topics

8:55 How does the 4D Flow MRI technology used in your study compare to MRIs used in clinics?

13:18 What did you look at in your study? What were your findings?

17:54 Did you see more pronounced findings in particular individuals with APOE4 or other chronic conditions like diabetes?

20:37 Why is this an important finding for Alzheimer’s disease research? Do you think 4D flow MRIs could be incorporated into clinical settings?

Show Notes

Read Leonardo Rivera-Rivera’s publication “Cerebrovascular stiffness and flow dynamics in the presence of amyloid and tau biomarkers,” published in the journal Alzheimer’s and Dementia: Diagnosis, Assessment & Disease Monitoring. 

Learn more about Leonardo Rivera-Rivera’s research at the Wisconsin Alzheimer’s Disease Research Center website.

Breaking Down Medicare’s Proposed Decision on Aducanumab and Monoclonal Antibody Treatments

On January 11, the Centers for Medicare and Medicaid Services (CMS) announced its much-anticipated coverage proposal for monoclonal antibody treatments that target amyloid for the treatment of Alzheimer’s disease. According to the proposed policy, this class of drugs, which includes aducanumab, also known by the brand name Aduhelm, would be covered for people with Medicare only if they are enrolled in qualifying clinical trials. Dr. Jason Karlawish joins the podcast to discuss the recent proposal, share his reaction to the decision, and tell us how this coverage policy could impact the development of other Alzheimer’s disease treatments in the future.

Guest: Jason Karlawish, MD, co-director, Penn Memory Center, professor of medicine, medical ethics and health policy, and neurology, University of Pennsylvania

Episode Topics

1:48 What’s the difference between the FDA and Centers for Medicare and Medicaid Services?

3:58 What is the purpose of sharing a proposal and allowing public comment after? Is it possible the proposal could change?

9:09 What are your key takeaways from the CMS proposal?

11:58 Who’s being charged the cost of the treatment if it is part of a clinical trial?

18:33 What does this decision, with its focus on research often occurring in major urban medical centers, mean for equity and access?

26:27 What is the future of Alzheimer’s disease research after the CMS decision?

Show Notes

Read the Center for Medicare and Medicaid Services’s press release about the proposed coverage policy, view submitted public comments about the decision, and submit your own comment.

Learn more about Dr. Jason Karlawish’s work and writing at his website.

Listen to our four-part episode series with Dr. Jason Karlawish about his book, The Problem of Alzheimer’s, on our website (episode 1, episode 2, episode 3, episode 4).

Nasal Vaccine for Alzheimer’s Disease Enters Clinical Trial

In November 2021, Brigham and Women’s Hospital in Boston launched the first human trial of a nasal vaccine for Alzheimer’s disease. Nearly 20 years of research went into developing the vaccine, which uses the immune system to clear Alzheimer’s disease-related proteins from the brain. Lead researcher Dr. Howard Weiner joins the podcast to discuss the science behind the vaccine and how it could introduce new ways of treating other neurodegenerative diseases in the future.

Guest: Howard Weiner, MD, professor of neurology, Harvard Medical School, co-director, Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital

Episode Topics

How does the vaccine work?

Why would a vaccine be a potentially better approach to treatment than a monoclonal antibody?

Do you think a vaccine could ever be used for prevention reasons instead of treatment?

Why a nasal vaccine versus into the muscle, like the COVID vaccine or flu vaccine?

Show Notes

Learn more about Brigham and Women’s Hospital’s nasal vaccine trial at their press release.

For those interested in participating in the study, you can call the Ann Romney Center for Neurologic Diseases at Brigham and Women's Hospital at 617-723-5588 or email protollinstudy@bwh.harvard.edu.

Watch Dr. Weiner’s film, What is Life?, The Movie, on YouTube.

Learn more about Dr. Weiner’s film, Abe and Phil’s Last Poker Game, on IMDb.

‘American Dementia’: Author Interview with Dr. Daniel George and Dr. Peter Whitehouse

Medical anthropologist and professor of humanities and public health sciences Daniel George, PhD, and professor of neurology and medicine Peter Whitehouse, MD, PhD, join the podcast to discuss their recent book, American Dementia: Brain Health in an Unhealthy Society. In it, they argue that 20th century policies focused on reducing inequality, increasing access to education and healthcare, and protecting the environment contributed to today’s declining dementia rates, but inequalities in the 21st century are reversing these trends. Discussing the pros and cons of current social and clinical approaches to Alzheimer’s disease, our guests challenge assumptions about dementia caregiving and show how we can work together to create a healthier society.

Guests: Daniel George, PhD, medical anthropologist, associate professor of humanities and public health sciences, Penn State College of Medicine, and Peter Whitehouse, MD, PhD, professor of neurology, Case Western University, professor of medicine, University of Toronto

Episode Topics

3:04 Why use the title American Dementia? What does that mean for you?

8:54 What do you think is wrong with our current societal, cultural and clinical approaches to Alzheimer’s disease?

16:10 What are the inequalities we’re facing in the 21st century compared to the 20th century? How are they affecting brain health?

19:04 How does climate change affect our cognition and brain health?

25:33 What would you want your reader to do next after finishing the book?

Show Notes

Read about American Dementia: Brain Health in an Unhealthy Society on Goodreads.

Listen to our episode about creative care with TimeSlips founder Anne Basting, who Dr. George mentions at 23:00, on our website, Spotify, Apple Podcasts, and more.

Find and follow Dementia Matters on Facebook, Twitter, or find us on our website.

New Research Shifts Thinking on Metabolism and Aging

There are many common beliefs about metabolism. Perhaps you’ve heard that a person’s metabolism slows around middle age, or that a woman’s metabolism is slower than a man’s. However widespread these beliefs are, recent research from the journal Science has found that these conceptions of metabolism are wrong. In a groundbreaking study, researchers have found that metabolism goes through four key phases over our lives, only beginning to slow around age 60. This, among other findings, are now changing how we think about human physiology and how we think about aging. Breaking down this new research and his perspective article on the findings, Dr. Rhoads describes our shifting understandings of metabolism and how it impacts chronic diseases like Alzheimer’s disease as we age.

Guest: Tim Rhoads, PhD, assistant scientist, Rozalyn Anderson laboratory, University of Wisconsin School of Medicine and Public Health

Episode Topics

2:30 - How is metabolism related to diseases of aging?

4:42 - What are the four distinct phases of metabolism and why are they important?

7:44 - What are other findings that change our understanding of metabolism?

12:00 - How does the decline in metabolism later in life affect chronic diseases like Alzheimer’s disease? Are there things we could do to prolong a high metabolism?

15:22 - How does caloric restriction affect the body and metabolism?

Show Notes

Read the perspective piece written by Dr. Rhoads and Dr. Rozalyn Anderson on the journal Science’s website.

Read the original research report, “Daily energy expenditure through the human life course,” by Pontzer et al. on the journal Science’s website.

Learn more about recent metabolism research in the article, “What We Think We Know About Metabolism May Be Wrong,” written for the New York Times.

Learn more about the Rozalyn Anderson Lab and their research at their website.

Aging Behind the Wheel: How Driving Behavior Can Identify Preclinical Alzheimer’s Disease

Dementia impacts a person’s ability to complete day-to-day activities like familiar tasks at work or at home. What if we could identify these changes in everyday behaviors early enough to identify preclinical Alzheimer’s disease? That’s what Dr. Sayeh Bayat, an assistant professor at the University of Calgary, looked to find out. Dr. Bayat is the lead author of a recent paper highlighting how driving behaviors such as braking, following the speed limit and the number of trips taken could predict preclinical Alzheimer’s disease. Dr. Bayat joined the podcast to share findings from the paper and discuss some of the ways engineering and machine learning can help us discover more about dementia and aging.

Guest: Sayeh Bayat, PhD, assistant professor, Department of Geomatics Engineering, University of Calgary

Episode Topics

1:05 - What led you to study this intersection of engineering and aging?

3:23 - What inspired you to study the topic of driving and aging?

5:30 - Who was involved in the study, and how long were these participants monitored?

7:01 - What did you find?

7:50 - Can you explain machine learning?

11:10 - Different health and life factors can impact driving. Is that something you’re looking to control for in future studies?

14:59 - How do you account for people who are just bad drivers without any cognitive change?

15:48 - What is the direction for your research in the future?

Show Notes

Learn more about Dr. Sayeh Bayat’s study in the New York Times article, “Seeking Early Signals of Dementia in Driving and Credit Scores” and in the BBC article, “How your driving might reveal early signs of Alzheimer’s”.

Find a free PDF of Dr. Bayat’s paper, “GPS driving: a digital biomarker for preclinical Alzheimer disease,” through the National Library of Medicine.

Global Challenges in Dementia Diagnosis: A Deep Dive into ADI’s World Alzheimer’s Report 2021

Alzheimer’s Disease International’s World Alzheimer’s Report 2021 recently found that 75% of people with dementia are undiagnosed, equating to 41 million people across the globe. The report, subtitled “Journey through the diagnosis of dementia,” also found clinician stigma is still a major barrier to diagnosis, and one in three believe nothing can be done about dementia. Dr. Serge Gauthier, co-author of the report, joins the podcast to discuss these findings, recommendations for improving dementia diagnoses, and more from the report.

Episode Topics

2:00 - How did you get into this field, and why did you choose to study dementia? 

3:04 - What was the methodology behind this research? What was that process like to collect this data?

5:47 - What are some of the key findings that you took away from the report?

7:59 - What did you discover about stigma while conducting this report? Why is that important to this discussion about diagnosis and subsequent care?

9:47 - How can people encourage their healthcare systems to have better diagnoses practices in place?

12:04 - What role do PET scans and blood-based biomarkers play in this effort for more diagnoses? Should everyone get these tests done?

13:56 - How do you think new therapies like Aducanumab are going to change how we view diagnosis?

16:33 - What are some of the key recommendations for government agencies from the report?

18:33 - Most agencies in the United States do not recommend screening for cognitive impairment without symptoms. Is that a mistake, and if so, how do we change those policies?

19:31 - What role do specialists, memory centers, and community agencies play in improving diagnosis? Should we have a primary care focus or should we train more specialists and organizations to help with diagnosis?

21:59 - Do you think there needs to be a change in how we use terms like dementia and major neurocognitive disorder? Should we adopt a universal terminology surrounding cognitive impairment, and do you think dementia should be retired due to the stigma it carries?

22:57 - What are some of the easiest things we can do to help our system diagnose people with dementia?

24:42 - What gives you hope that things will get better in the diagnosis and care of people with dementia?

Show Notes

The World Alzheimer Report 2021 includes over 50 essays from leading experts from around the world and is supported by findings from 3 key global surveys, which received responses from 1,111 clinicians, 2,325 people with dementia and carers, and over 100 national Alzheimer and dementia associations. Find more information about the 2021 World Alzheimer’s Report from Alzheimer’s Disease International on their website. A PDF of the report, “Journey through the diagnosis of dementia,” is also available on their website to read.

To learn more about Dr. Serge Gauthier, read his bio on the McGill University website.

Accessibility and Community: Bringing Alzheimer’s and Dementia Resources to the Latinx Community

UsAgainstAlzheimer’s newly-released tool, BrainGuide, may seem like a simple questionnaire, but the project highlights a growing movement to make Alzheimer’s disease research and resources accessible to a broader range of communities. Released in 2021, BrainGuide is a one-of-a-kind resource that provides information about Alzheimer’s disease in English and Spanish through online and telephone questionnaires. Dr. Maria Mona Pinzon, a physician-scientist at the University of Wisconsin School of Medicine and Public Health and a consultant on BrainGuide, joins the podcast to discuss the impacts this project has had on educating the Latinx community about Alzheimer’s disease. Discussing the barriers and risks that the Latinx community face surrounding brain health, the ways to connect with the community through research, and her experience working on BrainGuide, Dr. Pinzon highlights the importance and impacts of community-tailored research and resources. 

Guest: Maria Mona Pinzon, MD, MS, University of Wisconsin School of Medicine and Public Health

Episode Topics

1:17 - How did you get into this field of an aging population and people living with dementia?

6:12 - Is the idea of Alzheimer’s disease and dementia discussed within the Latinx community in general?

7:38 - Latinx individuals are 1.5 times more likely to develop dementia. Is there research that can explain this higher risk?

9:53 Tell us about this tool, the Spanish-Language BrainGuide, some of the resources it offers, and why it is important to make it available to Spanish speakers.

12:47 - What’s something you learned from this experience that surprised you?

14:14 - What are the barriers Latinx people face in learning about brain health, dementia, and getting involved in research?

18:25 - What strategies do you suggest to improve the connection between researchers and the Latinx community as well as recruitment into research?

20:06 - When thinking about education and raising awareness, what topics are most important right now for the Latinx community?

21:58 - What do you do in your personal life to keep your brain healthy? 

Show Notes

Learn more about the Spanish-Language BrainGuide, its questionnaire, and other resources on their website. To fill out the questionnaire, you can find it digitally on their website (mybrainguide.org) or complete it over the phone by calling or texting 855-272-4641.

Learn more about Dr. Mora Pinzon at her bio on the Wisconsin Alzheimer’s Institute website.

You Are What You Eat: Study of Diet and Brain Health Shows Cognitive Benefits from Cheese, Wine and Lamb

A recent study of nearly 1,800 participants from the UK Biobank found that three dietary elements — cheese, wine, and lamb — may improve long-term cognitive outcomes in aging adults. Dr. Auriel Willette, assistant professor of food science and human nutrition at Iowa State University, joins the podcast to discuss these new findings linking diet and cognitive changes. In November 2020, Willette published a study in the Journal of Alzheimer’s Disease titled “Genetic Factors of Alzheimer’s Disease Modulate How Diet is Associated with Long-Term Cognitive Trajectories: A UK Biobank Study,” where he and his team studied the effects of particular foods on a person’s brain health over time. As well as the findings surrounding cheese, wine, and lamb, they found that limiting salt intake was good for the brain, especially for those at risk for Alzheimer’s disease. Discussing the field of nutritional research, his prior work studying diet and brain health, and how these findings impact other recommended diets, Willette provides insight into how our current diets can impact our health and cognitive abilities later in life, allowing us to make better choices for the future.

Guest: Auriel Willette, PhD, associate professor of food science and human nutrition, Iowa State University.

Episode topics

1:34 - What sparked your interest in studying the effects of nutrition on the brain and on cognition?

4:41 - What prompted you to broaden your study to focus on overall diet and whole foods?

8:29 - Can you tell us about your prior research?

12:46 - Can you tell us a bit about the study and what you discovered?

19:48 - What do you think the mechanism is that allows cheese and alcohol to be beneficial for people’s brain health?

24:28 - How do you reconcile these findings, especially those surrounding cheese, with diets like the MIND diet?

28:38 - What dietary changes have you made in your own life that you might recommend for protecting your brain health?

Show Notes

Find out more about Dr. Willette by reading his bio from Iowa State University.

Learn more about Dr. Willette’s study at this article by Iowa State University.

Read the full study, “Genetic Factors of Alzheimer’s Disease Modulate How Diet is Associated with Long-Term Cognitive Trajectories: A UK Biobank Study.”

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