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November 2022 ​Featured Interview


Although No Cure for Alzheimer's To Date,
​There is Hope on the Horizon
​

Interview with
Yuko Hara, Ph.D.
Director of the Alzheimer's Drug Discovery Foundation's Aging and Alzheimer's Prevention Team 

Picture
Photo Courtesy: Yuko Hara, Ph.D.

​​About Yuko:

Yuko Hara, Ph.D., is the director of the Alzheimer's Drug Discovery Foundation’s Aging and Alzheimer's Prevention team. In this capacity, she critically evaluates the scientific evidence behind therapies to promote brain health and/or prevent Alzheimer's disease. She also investigates potential risk factors as well as research proposals on prevention therapies. Yuko manages the content and updates for Cognitive Vitality, a program of the ADDF that provides a free resource on brain health that is evidence-based.
 
Yuko was previously an assistant professor in neuroscience at the Icahn School of Medicine at Mount Sinai, where she remains an adjunct faculty member. Her research focused on brain aging, specifically how estrogens and reproductive aging influence the aging brain’s synapses and mitochondria. She earned a doctorate in neurology and neuroscience at Weill Graduate School of Medical Sciences of Cornell University and a bachelor's degree in biology from Cornell University, with additional study at Keio University in Japan. She has authored numerous peer-reviewed publications, including articles in PNAS and Journal of Neuroscience.
​​
​
About Alzheimer's Drug Discovery Foundation (ADDF):

​The mission of the Alzheimer's Drug Discovery Foundation (ADDF) is to rapidly accelerate the discovery of drugs to prevent, treat and cure Alzheimer's disease.

​Founded in 1998 by co-chairmen Leonard A. and Ronald S. Lauder, the ADDF is the only charity solely focused on finding drugs for Alzheimer's. The foundation follows a venture philanthropy model, funding breakthrough research in academia and the biotech industry. Through the tremendous support of donors, the ADDF has awarded more than $209 million to fund over 690 Alzheimer's drug discovery programs, biomarker programs and clinical trials in 19 countries. Twenty percent of the drugs in clinical development for Alzheimer's disease received support from the ADDF.
Video Courtesy: Alzheimer's Drug Discovery Foundation

Karen Shan, co-associate editor, asked Yuko about the risk factors, treatment options, and recent clinical drug development for Alzheimer's disease.  
 
Please briefly explain Alzheimer’s disease as well as its risk factors and prevalence.
 
Alzheimer’s disease is a type of degenerative brain disease that leads to a loss of cognitive functions.

Increasing age is the biggest risk factor for Alzheimer’s disease, so people who are older are more susceptible to Alzheimer’s disease. After the age of 65, one’s risk for Alzheimer’s disease doubles about every five years.
 
How Alzheimer’s disease affects people depends on the stage of the disease. Early symptoms include difficulty remembering recent events, names or conversations. Later symptoms include impairment in communication, confusion, poor judgment, behavioral changes, and difficulty speaking.
Worldwide, there are 57 million people living with Alzheimer’s disease and other dementias.

​Can Alzheimer’s Disease be prevented?
 
The 2020 Lancet Commission on Dementia Prevention, Intervention and Care reported that 35% of dementia cases could be prevented by fully addressing 12 risk factors:

  • Early life: Not completing secondary education (8%)
  • Midlife: Hearing loss (9%), traumatic brain injury (3%), hypertension (2%), obesity (1%), excessive alcohol consumption (1%)
  • Late life: Smoking (5%), depression (4%), physical inactivity (3%), air pollution (2%), social isolation (2%), diabetes (1%)
 
Alzheimer’s is one of the most common causes of dementia (an umbrella term used for a group of symptoms including difficulties with memory, language, problem-solving, and other cognitive functions).
 
We recommend Seven Steps for Cognitive Vitality (see sidebar): eat a brain-healthy diet, get seven-to-eight hours of sleep each night, exercise, alleviate stress, be social, keep learning, and manage chronic diseases (e.g., high blood pressure, Type 2 Diabetes).​
Seven Steps to Brain Health
(ADDF’s Cognitive Vitality Brochure)
  1. Eat for Your Brain: Mediterranean, DASH, and MIND diets – fish, nuts, and vegetables rich in vitamins, nutritents, and omega-3 fatty acids. Limit red meat and processed foods.
  2. Get Enough Sleep: 7 to 8 hours recommended – establish a bedtime routine, maintain a regular sleep schedule, avoid over-use of sleeping pills and alcohol-induced sleep. Impaired sleep may increase your risk of Alzheimer’s by up to 55%. 
  3. Exercise: Recommendation by WHO: 150 minutes of moderate aerobic exercise per week (or 75 minutes of vigorous exercise per week) and at least two days of muscle strengthening activities. 
  4. Alleviate Stress: Prolonged stress can harm your brain, leading to fatigue, disturbed sleep, poor concentration, and memory lapses. Find the stress reduction technique that works for your lifestyle. 
  5. Be Social: Maintain and build social connections through hobbies, volunteering, and other group activities. Seek support for depression. 
  6. Keep Learning: Education at any age may protect against cognitive decline. Take a class or learn a second language. 
  7. Manage Chronic Illness: Hypertension, diabetes, and heart disease all present major risks to brain health. Diabetics can have up to 73% increased risk of dementia. 

​How is Alzheimer’s Disease treated? As I understand, there’s no cure for it yet, correct?
 
There is currently no cure for Alzheimer’s disease. In the United States, there are only six drugs approved by the FDA for the treatment of Alzheimer’s disease to date, and most of these only temporarily treat Alzheimer’s symptoms without changing the course of this debilitating disease. Aducanumab, which was approved by the FDA in 2021, does reduce beta-amyloid plaques in the brain, a hallmark of Alzheimer’s disease. However, aducanumab is not a cure, and it is undergoing post-approval clinical trials to determine whether there is clinical benefit in patients.
 
As with other diseases of aging, such as heart disease, cancer and hypertension, our success in fighting Alzheimer’s disease and related dementias will come from combination therapies, precision medicine and more focused prevention efforts. The ADDF is working to support and accelerate the development of novel drugs and prevention strategies that can stop Alzheimer’s in its tracks.
 
ADDF’s Statement on Topline Results of Phase 3 Trial of Amyloid-Clearing Drug Lecanemab: “The Alzheimer’s Drug Discovery Foundation (ADDF) is encouraged to see the positive data reported today by Eisai and Biogen for their amyloid-clearing monoclonal antibody lecanemab. According to the companies, lecanemab reduced cognitive decline by 27% compared to placebo and reduced amyloid levels in the brain in the phase 3 CLARITY AD clinical trial.”

What is the focus of research on Alzheimer’s Disease?
 
The ADDF is focused on the biology of aging as increasing age is the biggest risk factor for Alzheimer’s disease. Amyloid buildup is just one of many biological processes leading to the development and progression of Alzheimer’s. The ADDF funds a diverse research portfolio of drug targets and biomarkers that reflect the many biological pathways and systems involved in Alzheimer’s disease and other dementias, including inflammation, vascular dysfunction, misfolded proteins, metabolic dysfunction, and other mechanisms affected by aging that may contribute to this complex disease. Our portfolio also covers diverse biomarker modalities from neuroimaging to blood tests to digital apps.

​​What advances are being made in terms of treatment, diagnosis and prevention?
​There are many exciting advances being made in the prevention, diagnosis, and treatment of Alzheimer’s disease. As of early 2022, there were 143 therapeutics undergoing clinical trials for Alzheimer’s disease, of which 119 therapeutics were aimed at slowing the disease.
 
In addition to the diverse portfolio of Alzheimer’s drugs in development is the significant advancement in biomarkers that are necessary for early diagnosis and recruitment of the right patients for the right clinical trials. In 2020, the first blood test became available to help physicians with early detection and diagnosis of Alzheimer’s disease, which marked an important milestone. Before this test, Alzheimer’s disease could only be diagnosed with an expensive brain PET scan or an invasive spinal tap.
"In 2020, the first blood test became available to help physicians with early detection and diagnosis of Alzheimer’s disease, which marked an important milestone. Before this test, Alzheimer’s disease could only be diagnosed with an expensive brain PET scan or an invasive spinal tap."
                                                          ~ Yuko Hara, Ph.D.

In terms of prevention, the landmark Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) clinical trial, led by Dr. Miia Kivipelto, an ADDF board member, reported that a group of lifestyle changes improved cognitive function and memory in older people with APOE4, a genetic risk factor for Alzheimer’s disease. ADDF is supporting Kivipelto’s FINGER 2.0 clinical trial where the same lifestyle interventions are combined with a medication for diabetes to evaluate if the combination intervention has synergistic effects.

What does your role entail as director of the Aging and Alzheimer's Prevention program?
 
I direct the Aging and Alzheimer’s Prevention program at the ADDF. My team analyzes the scientific evidence of natural products, supplements, drugs, drugs-in-development, and non-pharmacological interventions as they relate to potential benefits for cognitive function and age-related diseases. I manage a portfolio of prevention research programs and seek additional projects to accelerate the discovery and development of effective prevention interventions. I also manage the content and updates for Cognitive Vitality* which provides information on various supplements and commonly prescribed drugs. We discuss the scientific evidence (or lack thereof) of efficacy and safety. The blog on Cognitive Vitality covers the latest scientific news on brain health. Our aim is to accelerate the discovery of drugs to prevent Alzheimer's disease and related dementias.
 
*Cognitive Vitality is developed and updated by ADDF’s Aging & Alzheimer’s Prevention program, whose mission is to evaluate, communicate, and accelerate the scientific evidence for proposed strategies to prevent brain aging, Alzheimer’s disease, and related dementias. Our team of neuroscientists evaluates and writes about the scientific evidence for and against the safety and efficacy of select food, drinks, vitamins, supplements and drugs. Our goal is to provide unbiased scientific information available to date to improve decision-making by patients, physicians and caregivers. 
 
Have you always had an interest in studying cognitive decline?
 
Prior to joining the ADDF, I was an assistant professor at the Icahn School of Medicine at Mount Sinai, where I examined the biological signatures of age-related cognitive decline as well as menopause-related cognitive symptoms. I was particularly interested in determining the biological characteristics that were associated with maintenance of cognitive functions into old age.
 
Where do you find sanctuary?
 
Home is my sanctuary. I also enjoy gardening and visiting botanic gardens.

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​NEWS...

March:
Women's History Month

Additional Themes:

Entrepreneurship
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Seeking Opportunity


Next newsletter goes out:
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March 15, 2023
Healing Through Joy & Movement​

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