On World Alzheimer Day 2021, the NeurologyLive team has compiled interviews with experts in the field of Alzheimer disease care to offer up a summary of the latest in treatment and the remaining challenges.
World Alzheimer Day, celebrated on September 21, brings together the larger community of patients, physicians, clinicians, industry, and advocacy organizations to raise awareness for Alzheimer disease (AD). This year, there is much for the community to be excited about, as June 2021 marked the first approval for the disease in almost 20 years and the first major breakthrough for therapeutic interventions with the FDA greenlighting of aducanumab (Aduhelm; Biogen/Eisai).
Although AD affects a large number of individuals globally, including more than 5.7 million Americans, and is well-known by the general population, it remains the sixth-leading cause of death in the United States. The complexity of this disease has presented a challenge for the medical community, and with the population expected to continue aging, AD care presents a major hurdle to overcome. At current rates, experts believe the number of Americans living with Alzheimer’s will quadruple to as many as 16 million by the year 2050.1
Swipe through the slideshow to see more of what experts in the field have to say about the current state of care in Alzheimer. Click here for more coverage of Alzheimer disease from NeurologyLive.
Although it has been previously documented that the frequency of AD dementia is higher in women, sex differences in the incidence of AD dementia are less than clear. To better understand the effects of gender and sex in AD, the National Institutes of Health (NIH) awarded a 4-year, $1.8-million grant to Jessica Caldwell, PhD, director, Women’s Alzheimer’s Movement Prevention Center, Cleveland Clinic. The grant marked the 1-year anniversary of the center’s opening, which was the first prevention center designed specifically for women.
Caldwell will use the grant to study how gender-linked stress exposure and estrogen may interact to impact memory, inflammation in the body, and brain activation and connectivity in women at risk for AD. She hopes that the findings will help to inform development of interventions targeting stress and inflammation to reduce AD risk.
In an interview with NeurologyLive, Caldwell discussed the details of the grant and how it will be utilized. She also provided insight on some of the biggest remaining questions regarding the impact of genetics and sex in AD risk and prevalence.
Discussing the recent controversial approval of aducanumab, Pierre N. Tariot, MD, director of Banner Alzheimer’s Institute, commented on the drug’s potential to “dominate the conversation” for the time being and the implications for research in the AD space. Specifically, the potential of biomarker outcomes and efficacy decisions being made earlier in drug development could shorten the length of trials in AD from spanning 6 years with 2000 patients, to 6 months with 100 patients, Tariot told NeurologyLive.
Additional emerging therapies such as antisense oligonucleotides and mRNA silencing techniques were also discussed, which will require new and different drug administration, Tariot said. His commentary coincides with his recent presentation at the 2021 Alzheimer’s Association International Conference, held July 26-30, where he and colleagues presented safety data on the use of pimavanserin in dementia-related psychosis.
At the 2021 Alzheimer’s Association International Conference (AAIC), July 26-30, research presented by Feixiong Cheng, PhD, identified sildenafil (Revatio) as a promising drug candidate for the prevention and treatment of AD. Using a developed endophenotype molecular network-based methodology, the investigators conducted 5 comparison analyses, which included other drugs such as diltiazem (Cardizem; Valeant), losartan (Cozaar; Merck), glimepiride (Amaryl; Hoechst) and metformin (Glucophage; Merck).
All told, the data showed a statistically significantly 69% reduced risk of AD for sildenafil users compared to matched non-sildenafil usage. In recent years, the AD research field has had an increase in the number of repurposed agents within the clinical pipeline. While there are several promising FDA-approved drugs in circulation, choosing the correct option to test in a clinical trial setting requires careful examination, according to Cheng.
In an interview with NeurologyLive, Cheng discussed what goes into deciding what drugs may be good candidates for AD, and which mechanistic actions researchers should key in on. He also stressed that being able to validate a given drug’s efficacy is crucial in understanding whether its right to spend time and resources on it.
There are several biomarker tests that are used for research on AD and related dementias. Changes in the brains of individuals with these disorders may begin many years before memory loss or other symptoms appear, and utilizing these biomarkers may help detect these changes and thus better identify people who may develop these diseases and may be eligible for treatment options.
Biomarkers such as neurofilament light chain, amyloid-beta, tau, and the radiotracer flurodeoxyglucose have all gained traction in recent years. While clinicians typically have agreed on several biomarkers that have clinical relevancy in AD, finding the gold standard biomarker—if one exists for AD—is still an ongoing process. The Critical Path for Alzheimer’s Disease (CPAD) consortium, an organization that promotes data-sharing among drug development stakeholders, has embarked on a new initiative since 2019 to acquire fluid and imaging biomarker-rich data sources that will hopefully assist in developing novel tools to quantify disease progression better.
Sudhir Sivakumaran, PhD, vice president, Neuroscience Program, and Executive Director, CPAD, and Klaus Romero, MD, MS, FCP, chief science officer, CPAD, recently sat down with NeurologyLive to discuss the thought of prioritizing specific biomarkers. The duo claimed that the consortium does not limit itself to a single biomarker focus, but rather any biomarker that correlates with disease progression and helps improve clinical trial efficiency.
Numerous studies have documented differences in dementia prevalence among racial and ethnic groups in the US. African Americans and Hispanics have been found to have a higher risk of dementia compared to Whites across studies despite differences in designs, sampling methods, and definitions of dementia. These differences may be a product of biological, behavioral, sociocultural, and environmental factors including socioeconomic determinants such as education, income, occupation, wealth, and access to health care.
Understanding and researching these differences may aid in the development of interventions, therapeutics, and public policy. A recently awarded 5-year, $13 million grant to James E. Galvin, MD, MPH, director, Comprehensive Center for Brain Health, University of Miami Miller School of Medicine, will be used to conduct a series of studies that aim to increase accuracy of early diagnosis, develop therapeutic targets, and improve health outcomes in patients with AD and related dementias With the grant, Galvin hopes to create a screening model that will follow a “healthy body, healthy mind,” approach to make the concept of mild cognitive impairment and ADRD screening more acceptable to diverse populations.
In an interview with NeurologyLive, Galvin detailed the projects entailed with the grant. He stressed that there are a number of factors, including higher blood pressure, that impact prevalence of dementia among individuals within rural and multicultural communities that need to be more-often identified.
The introduction of blood tests as a biomarker for AD has demonstrated immense potential for predicting the presence of amyloid-beta (Aß) plaque in the brain. Michael Weiner, MD, professor of radiology and biomedical imaging, medicine, psychiatry, and neurology, University of California–San Francisco, principal investigator, Alzheimer's Disease Neuroimaging Initiative, and director, Brain Health Registry, spoke with NeurologyLive about the recent advancements in blood testing, which he hopes will offer a more clinically- and cost-effective method to diagnose patients with AD.
Weiner’s commentary follows the publication of a systematic review, published earlier this year, which evaluated predictors of Aß for this patient population. In addition to plans to update the existing review to incorporate more recent research into blood biomarkers, Weiner also hopes research will move closer towards the prevention of AD, noting that finding a way to identify at-risk people who are otherwise healthy might allow clinicians to enact treatment before the onset of symptoms.2
Early detection of cognitive impairment due to neurodegenerative disease may be achieved with the Mobile Toolbox Battery (MTB), a mobile application, according to a study presented at the 2021 American Academy of Neurology (AAN) Annual Meeting, April 17-22.
Pila and colleagues developed the MTB to safely, remotely, and effectively collect data from assessments that measure executive function, language, memory, and processing speed in adults. The battery consists of several assessments such as the Flanker, Face-Name; Memory for Sequence; Picture Sequence Memory; and Vocabulary, Number Match, Spelling, and Dimensional Charge Card Sort tests.3
NeurologyLive spoke to senior author Richard Gershon, PhD, vice chair, research, Northwestern University Feinberg School of Medicine, to learn more about the potential of the MTB to screen hundreds of thousands of people for cognitive impairment or cognitive changes. He also discussed the potential of the MTB to be used to evaluate the effects of investigational treatments.
The use of telehealth over the course of the COVID-19 pandemic is something that Jessica Zwerling, MD, MS, believes will persist, particularly for patients with AD; however, some barriers do continue to generate difficulties for both patients and providers. A primary hinderance is the actual use of technology, which can be difficult for those in the AD population, who are often elderly and may not be as adept at navigating the virtual sphere.
In conversation with NeurologyLive, Zwerling, the director of the Montefiore Hudson Valley Center of Excellence for Alzheimer’s Disease and associate professor of neurology, Albert Einstein College of Medicine, commented on the navigation of these issues during the pandemic, as well as how experts continue to navigate them presently. Setting up proper camera angles within the home is of particular importance, ensuring that providers and social workers can evaluate the individual as a whole; often, additional insight can be drawn by observing patients in their living spaces. While transitional challenges remain, Zwerling further alluded to the fact that improved workflow during visits can be of assistance and adjusted so as to allow support staff to help.
The potential for blood-based biomarkers in AD diagnosis is an area of particular interest for Eric Reiman, MD, executive director of Banner Alzheimer’s Institute. Reiman spoke with NeurologyLive regarding the specific opportunities and promise blood testing may offer for AD, particularly to detect the presence or absence of amyloid plaque deposition.
Reiman discussed the potential of blood tests, noting his participation in a cross-sectional study, published in JAMA last year, which found plasma phospho-tau217 successful in discriminating AD from other neurodegenerative diseases.4 Access to blood tests, Reiman said, could be integral to advancing research efforts, among other goals within drug development and clinical care.