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Experts Weigh in on the Fight to End Alzheimer’s

Photo: Courtesy of Simon Wijers

Experts explain the state of Alzheimer’s research today, including the most exciting innovations and biggest misconceptions surrounding the disease.

Robin Wolz-MD-Research-and-Development-IXICO

Robin Wolz, M.D.

SVP, Research and Development, IXICO

In your experience, what are the most impactful innovations made in Alzheimer’s research?

The ability to measure the progression of the disease through biomarkers and outcome assessments has been a key building block to understanding and eventually treating the disease. Recent developments in PET imaging ligands to measure amyloid and tau deposition in the brain have also enabled more effective testing of treatment hypotheses, and natural history studies like ADNI have helped validate and standardize these measures. Given recent negative clinical trials, there is clearly more work to be done, however we now have greater insight into the underlying mechanisms of Alzheimer’s disease.

Where do you see the future of Alzheimer’s research in the next five years?

Results from recent negative clinical trials have moved focus to treating patients earlier in the disease process. This includes

  • Pre-symptomatic stages, as currently being investigated in the EPAD and A4 studies.
  • Advancements in biomarker development have enabled improved patient selection in clinical trials to allow more targeted validation of treatment options.
  • Biosensor and mobile device technologies that offer more continuous and objective measures of daily living have the potential to more effectively measure patient outcomes; impacting the regulatory approval of new medicines and their subsequent use in the clinic.

What is a common misconception about Alzheimer’s disease?

A common misconception is to interchangeably think of AD and dementia. AD is the most common cause of dementia, but other diseases that also can lead to dementia. Currently, no drug treatments exist that slow AD progression. However, diet and other lifestyle choices have been shown to extend the period of independent living for AD sufferers. As such, a societal challenge is to avoid stigmatizing people with memory loss as “having dementia.” But to provide high-quality diagnosis as early as possible to enable access to effective interventions and care options.

Marc-E-Agronin-Miami-Jewish-Health-Systems

Marc E. Agronin, M.D.

Vice President, Behavioral Health and Clinical Research, Miami Jewish Health Systems

In your experience, what are the most impactful innovations made in Alzheimer’s research?

The most impactful innovation in Alzheimer’s research has been the discovery and increased use of biomarkers to increase diagnostic certainty. These biomarkers represent measurable physical evidence of the disease and include localized brain atrophy, metabolic loss and plaque build-up seen on different types of brain scans, and abnormal protein levels seen in spinal fluid. Put together, this biomarker evidence is helping to improve diagnosis and implement potential treatments at much earlier stages of disease.

Where do you see the future of Alzheimer’s research in the next five years?

In the next five years, we should know whether immunotherapy for Alzheimer’s disease really works when applied early. Our current model of Alzheimer’s has identified two toxic protein culprits — beta-amyloid and tau — as central causes of brain degeneration. We know that these proteins begin building up and damaging the brain years before symptoms begin. If immunotherapy using antibody infusions works well enough to significantly slow down or even stop the disease in its tracks, we will be closer to a potential cure.

What is a common misconception about Alzheimer’s disease?

Many people mix up and misunderstand the meanings of the terms “dementia” and “Alzheimer’s”. Dementia, now called major neurocognitive disorders, is a broad category that includes any form of brain damage that causes enduring cognitive impairment. Alzheimer’s disease is the most common form of dementia. It represents 60 to 70 percent of all cases after the age of 65. It is important for anyone with cognitive impairment to have a comprehensive evaluation with a dementia expert to determine not only whether they have dementia, but what type. It’s not always Alzheimer’s.

Emiliano-Santarnecchi-Department-of-Cognitive-Neurology-Beth-Israel-Deaconess-Medical-Center

Emiliano Santarnecchi, Ph.D.

Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Cognitive Neurology, Beth Israel Deaconess Medical Center

In your experience, what are the most impactful innovations made in Alzheimer’s research?

Emerging research has focused on the substantial changes in brain waves in Alzheimer’s disease. More specifically, brain waves known as “gamma oscillations” have been shown to be impaired in this population of patients and this may lead to cognitive impairment and accumulation of amyloid-beta and tau proteins in the brain. This discovery offers a potential new target for disease-modifying therapies based on non-invasive  electrical and magnetic brain stimulation. Additionally, the discovery that proteins begin to build-up well before cognitive symptom manifestation has led to the need for early-detection of the disease. New blood-based biomarkers, able to reliably estimate these protein levels in the brain, could soon replace expensive neuroimaging techniques. This will make large scale screening of Alzheimer’s in the general population more accessible.

Where do you see the future of Alzheimer’s research in the next 5 years?

Thanks to emerging technologies, the landscape of Alzheimer’s research and care is rapidly changing. While the need for cheaper, reliable diagnostic biomarkers will still guide research on Alzheimer’s, I foresee a shift from drug-based therapies toward the development of solutions based on a combination of cognitive training and non-invasive brain stimulation. Ideally these will be administered remotely at home, increasing therapeutic opportunities outside hospital settings and thus reaching a broader audience. Improved tools for early diagnosis will allow us to focus more on prevention or delay of cognitive deficits rather than rehabilitation, with more research on the preventative role of lifestyle, dietary and fitness habits.

What is a common misconception about Alzheimer’s disease?

That Alzheimer’s is an unpredictable, unstoppable disease. Studies have shown that remaining socially and mentally active may help build so-called “cognitive reserve”. This is the brain’s ability to make efficient use of brain resources to continue to carry out cognitive tasks, despite brain changes induced by protein accumulation in the brain. We now have a better understanding of where to look for early detection of pre-symptomatic signs. We also know that keeping a healthy body, for instance via aerobic exercise and mediterranean diet. Additionally, a stimulated mind early in life significantly helps with mitigating the impact of Alzheimer’s.

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