Top scientists urge fast, affordable Alzheimer’s screening tools as cases surge amid health care shortages
Posted on January 29, 2025 at 11:46 am.
Advancement in the detection and treatment of Alzheimer’s and other neurodegenerative diseases means more people can preserve brain health for longer. But a crisis looms as an onslaught of people at risk for neurodegenerative diseases in the next 40 years is met with a shortage of health care providers. According to the U.S. Census Bureau, by 2060, there will be approximately 95 million people over the age of 65 and just 500,000 primary care providers.
A report published in the November/December 2024 issue of the Annals of Family Medicine outlines recommended guidelines from interdisciplinary geriatrics summits for an early cognitive impairment screening tool primary care providers can use in their practices. If impairment is detected, a multistep action plan was developed for further treatment.
The senior author of the report is Robin Hilsabeck, PhD, professor in the Department of Neurology, Joe R. and Teresa Lozano Long School of Medicine, division chief of the Clinical Neuropsychology Division and a faculty member with the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases. She said cognitive impairment is often missed in early or mild cases, but when the condition is caught early, there is a better chance to preserve brain function and quality of life.
“There are so many things we’ve learned in the past 20 years — interventions that can slow cognitive loss, new treatments, and there is a pipeline for new drug development,” Hilsabeck said.
Beginning in 2017, a series of summits hosted by the National Academy of Neuropsychology gathered stakeholders from a variety of disciplines to figure out what could be done to meet the cognitive health needs of this expanding population. Hilsabeck, a past president of the academy, said she was especially interested in developing better tools for primary care providers.
“From the very beginning I’ve had primary care providers ask me, ‘Who do I send to you?’ and ‘How do I do this?’ and I’ve been working with them to try to address this problem,” she said.
Primary point of contact
As one of the most visited health care providers, primary care physicians often know their patients well and can play a crucial role in detecting cognitive issues. However, it is estimated that up to 60% of cognitive impairment cases are not diagnosed. Risk-based assessments may be the answer, as they target people who are most at risk of developing neurodegenerative diseases.
During the National Academy of Neuropsychology summit in November 2022, participants considered the pros and cons of current dementia screening and cognitive assessment tools. These tools evaluate risk factors like age, body mass index, history of heart conditions, education and antidepressant use, along with orientation and word recall items. The summit noted some tools have not been tested for use by primary care providers.
Quick, easy screening tool
Top considerations for a cognitive impairment screening tool that could be used by primary care providers included one that is:
- Easy to understand and deliver.
- Takes less than 10 minutes to complete.
- Is acceptable to the individual.
- Is sensitive to even mild stages of cognitive impairment.
- Includes assessment of both memory and executive function.
“Some of the earliest signs are changes in behavior and mood, and we need a better way to investigate these things early on,” Hilsabeck said.
A risk-predictor tool for primary care providers would likely be a combination tool that compiles health data from electronic medical records with in-office language processing and memory assessments. After the assessment is completed, Hilsabeck said primary care providers, the patient and their families decide what treatment the primary care provider can deliver and what treatment should be conducted with a dementia specialist.
“Some primary care providers are more comfortable [providing dementia care] than others, so there is a huge effort to provide more education so primary care providers feel more empowered, more confident to do some of these things, because they absolutely can,” she said.
Just the beginning
The 2022 findings and subsequent report are just the starting point, and research teams are investigating potential solutions. With early detection, health care providers, patients and their families can create a plan for moving forward and retaining a significant quality of life.
While an ideal time for cognitive screening is during an annual wellness visit, less than 34% of adults regularly complete annual wellness checks and only 30% of primary care providers screen for cognitive impairment during these visits. When a cognitive screen is done, less than 35% of patients follow up with a dementia specialist.
Hilsabeck said people can be resistant to accepting a cognitive impairment diagnosis for a variety of reasons including fear of losing freedom, stigma and strong emotions surrounding the condition.
“Facing [dementia diagnosis] might mean big changes, and it is scary. There is just so much emotion wrapped up in it,” she said.
What comes next?
While overall dementia prevalence is increasing, extensive efforts to educate health care providers and individuals are leading to earlier detection and treatment for these conditions. Hilsabeck said real progress in fighting these diseases will take a trifecta of support from health care providers, the health care system and patients and their families. suggested future efforts should focus on:
- Increased education about Alzheimer’s disease.
- Education about the benefits of early detection.
- A plan for clinical trials of multistep protocols for neurodegenerative disease screening and treatment plans.
With an ever-increasing older population and continued shortage of health care workers, Hilsabeck said it is critical that work begins now to uncover fast yet accurate tools to identify people at risk for Alzheimer’s and other neurodegenerative diseases.
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Small steps, big difference
Simple lifestyle changes like increasing exercise, boosting socialization and keeping blood pressure down can have big benefits for brain health.
‘Micro-dosing’ exercise
Short bursts of activity, such as 10 minutes of walking, a quick stretching session or other low-impact activities can have tremendous health benefits, Hilsabeck said. Exercise improves blood flow to the brain, which triggers beneficial neurotransmitters and can lead to better mood, memory and cognitive function.
Prescription for connection
Recent studies show that isolation and loneliness can have devastating effects on the brain. Connecting with friends and family, participating in a group activity, joining a club or taking a class can all lead to improved immune function and cardiovascular and cognitive health.
Magic number: 120
The Systolic Blood Pressure Intervention Trial (SPRINT) was a major national study that highlighted the positive effect of lowering blood pressure on many body systems, including the brain. Scientists found that lowering systolic blood pressure (the top number) to 120 or less was beneficial for the cardiovascular, renal and central nervous systems. Among the study’s more than 5,000 participants, those with a systolic reading of 120 or lower were significantly less likely to develop cognitive impairment over the next five years.
Connecting minds in dementia research: UT Health San Antonio leads bioinformatics program for African scientists studying neurodegenerative diseases
Posted on January 22, 2025 at 7:30 am.
In the coming years, Africa is expected to sustain the greatest increase in Alzheimer’s and related dementia cases. Advancing the ability of African scientists to conduct research in these fields is critical for progress in understanding and treating these conditions.
A transformative training program crafted through a collaboration between the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at The University of Texas Health Sciences Center at San Antonio (UT Health San Antonio), which is also the home of the South Texas Alzheimer’s Disease Research Center and the Brain Research Africa Initiative aims to provide African researchers with the skills they need to gather, analyze and interpret biological data for neurodegenerative disease research.
The African Initiative for Bioinformatics Online Training in Neurodegenerative Diseases (AI-BOND) program emerged from a collaborative vision among UT Health San Antonio researchers and African biomedical leaders who recognized a need to address disparities in access to bioinformatics education in Africa and the growing urgency to address neurological health challenges globally. A report about the program was published in the October/December 2024 edition of Alzheimer’s & Dementia: Translational Research & Clinical Interventions.
The idea for the training program came after a series of conversations among researchers attending a dementia conference in Nairobi in 2022, said José E. Cavazos, MD, PhD, associate dean for research for the Joe R. and Teresa Lozano Long School of Medicine, professor in the departments of Cellular and Integrative Physiology and Neurology, and director of the South Texas Medical Scientist Training Program.
“The credit to crystalize and implement it falls squarely on the shoulders of Dr. Fongang. The impact of the successful implementation is shown by the great interest and quality of the applications for the round two of AI-BOND Scholars,” Cavazos said.
How AI-BOND began
Ongoing discussions over several years with scientists from around the globe highlighted the need to empower scientists from countries with smaller economies to develop and execute their own studies, said Sudha Seshadri, MD, DM, Robert R. Barker Distinguished University Professor of neurology and founding director of the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases. She said creating the capacity to expand research in low- and middle-income countries boosts scientific gains not only for these countries, but also for the entire world.
“No one type of human has a monopoly on creativity or intelligence, so we need to harness the energy and ideas of people all over the globe. To do that you need to build the infrastructure for people in lower- and middle-income countries to complete their own investigations,” Seshadri said, “There is a disproportionate amount of the science that is being done in countries with larger economies. We are missing out on the opportunity to learn from three-fourths of humanity.”
The overarching goal of AI-BOND is to build research capacity by fostering and nurturing the next generation of African scientists in biostatistics, bioinformatics and epidemiologic methods in neurodegenerative diseases, said founding volunteer faculty member Jayandra Jung Himali, PhD, William Castella Distinguished Chair for Alzheimer’s Disease Research, associate professor in the Department of Population Health Sciences, and adjunct associate professor of neurology and biostatistics at Boston University’s School of Medicine and of Public Health.
To reach this target, he said, a multidisciplinary team of mentors share knowledge through the free, comprehensive program, initiate innovative and adaptive research, encourage participants to disseminate findings through conference presentations and publications, foster international collaborations and garner grant funding.
“It is imperative to help develop human capital and future leaders in scientific communities capable of addressing the research needs of their own country to help benefit science and humanity at large,” Himali said.
About the program
From the launch of the first application process, enthusiasm for the AI-BOND program was evident. Beginning in September 2023, 173 individuals from 22 African countries applied for the free, six-month training. From that group, 41 students were chosen for the first cohort. Participants included graduate students, postdoctoral researchers and early-career scientists with a desire to focus their research on neurodegenerative diseases.
“If you want to really understand people living in a country, if you want to disseminate the research and understand what is going on, they should be the ones at the beginning and end of the research,” said AI-BOND program director Bernard Fongang, PhD, assistant professor in the departments of Biochemistry and Structural Biology and Population Health Sciences.
The initiative was made possible through the efforts of about a dozen UT Health San Antonio faculty members who volunteered to design the comprehensive virtual curriculum and lead twice-weekly sessions. The program’s 24-week course included modules on computer programming, biostatistics, bioinformatics, genetic epidemiology, neurodegenerative diseases and integrative multi-omics.
The program emphasized hands-on learning through access to real-world neurodegenerative disease datasets. Participants also applied bioinformatic tools to analyze genetic and proteomic data that they gathered, drawing meaningful insights to advance their own neurological research.
AI-BOND graduated its first cohort of 41 students in June 2024 with a stunning 100% completion rate. Fongang said graduates have gone on to present at conferences, write manuscripts and several are in the process of applying for grants.
What’s next for AI-BOND
Following the success of the first cohort, UT Health San Antonio volunteer faculty launched the next session of the AI-BOND program December 4, 2024. During this application period, 220 individuals from 24 African countries applied and 45 applicants from 16 countries were selected to form the second cohort of the AI-BOND training program. Students in this session will have access to a website (www.aibond.org) and mobile app features that provide recorded lectures and resource materials on demand.
AI-BOND leaders said they hope this program will continue and expand, but to do so will require more manpower, financial support and partnerships with other entities.
“Initiation of AI-BOND through the collaboration between the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at UT Health San Antonio, the South Texas Alzheimer’s Disease Research Center and Brain Research Africa Initiative was through the shared commitment to service at the core. To become sustainable and grow, we need to retain that ideal and extend our reach to the whole of Africa, identify appropriate partnerships, obtain funding and retain and expand the multidisciplinary team of experts,” Himali said.
As the second cohort begins, the AI-BOND program serves as a testament to the power of UT Health San Antonio-led initiatives in creating opportunities for scientific advancement worldwide.
Other AI-BOND faculty members from UT Health include Xueqiu Jian, PhD, Muralidharan Sargurupremraj, PhD, Habil Zare, PhD, as well as Yannick Wadop, PhD, Rebecca Bernal and Crystal D. Wiedner, PhD, a biostatistician working in a part-time capacity at the Glenn Biggs Institute.
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Fongang, B., Ayele, B. A., Wadop, Y. N., Epenge, E., Nkouonlack, C. D., Njamnshi, W. Y., Jian, X., Sargurupremraj, M., Djotsa, A. B. S. N., Seke Etet, P. F., Bernal, R., Atangana, A., Cavazos, J. E., Himali, J. J., Fonteh, A. N., Maestre, G., Njamnshi, A. K., & Seshadri, S. (2024). The African Initiative for Bioinformatics Online Training in Neurodegenerative Diseases (AI-BOND): Investing in the next generation of African neuroscientists. Alzheimer’s and Dementia: Translational Research and Clinical Interventions, 10(4), Article e70002. https://doi.org/10.1002/trc2.70002
Discovery sheds light on Alzheimer’s disease risk across genetic types
Posted on January 22, 2025 at 9:41 am.
Late-onset Alzheimer’s disease is a debilitating, progressive neurodegenerative disease that affects about 7 million Americans, a figure that is expected to nearly double by 2050, according to the Alzheimer’s Association. While there is no cure for the disease, early detection and treatment can preserve brain function for longer.
A study by researchers at The University of Texas Health Science Center at San Antonio (UT Health San Antonio), published in Springer Nature’s Molecular Neurodegeneration, discovered a specific protein-coding transcript that may contribute to Alzheimer’s disease risk across all genetic types of apolipoprotein E (APOE).
Understanding APOE and its variants
All humans have APOE protein in their genetic makeup, and the main forms, called alleles, are ε2, ε3 or ε4. Each person inherits two APOE alleles — one from each parent — resulting in one of six combinations. APOE ε3 is the most common and is seen as neutral, and APOE ε2 is believed to provide some protection against Alzheimer’s disease. Having one or two APOE ε4 alleles is linked to a higher risk of Alzheimer’s disease. However, the presence of APOE ε4 does not mean a person will develop Alzheimer’s disease, and this has led researchers to explore other genetic factors.
“Despite over three decades of dedicated research, the precise mechanism by which the APOE ε4 allele elevates the risk of Alzheimer’s disease and related dementias remains elusive. The complex regulation of APOE gene expression across various bodily systems, organs, tissues and cell types is believed to be pivotal in understanding its multifaceted role in chronic human conditions, including dementia,” said co-investigator Agustin Ruiz, MD, PhD, professor and director of the Biological Core Laboratory at the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases and the Pat V. Orme Endowed Chair in Alzheimer’s and Neurogenerative Diseases at UT Health San Antonio.
Liang Ma, PhD, awarded prestigious grant to advance Alzheimer’s research
This study was supported by a grant awarded to lead researcher Liang Ma, PhD, assistant professor with the Biggs Institute and the Joe R. and Teresa Lozano Long School of Medicine Department of Pharmacology. Out of 154 proposals from 34 centers, Ma was chosen to receive a New Investigator Award from the Alzheimer’s Association and the National Alzheimer’s Coordinating Center.
“I’m so fortunate to be one of only 13 researchers awarded this prestigious funding. This will allow me to move my Alzheimer’s research forward significantly. There are many Alzheimer’s centers, and I’m hopeful we can collaborate to pool our data and samples. By combining our resources, we can create a large, comprehensive dataset to uncover the best paths for advancing this critical work. With the right data and funding, we can make real progress in understanding and treating this devastating disease,” Ma said.
Insights from diverse brain studies
Recent large-scale genetic studies uncovered variants in the APOE region that may be linked to greater risk for Alzheimer’s disease. Still, the challenge remained to discover which APOE elements these variants affected in the brain.
Ma’s research team analyzed five datasets from more than 1,000 postmortem human brains of European and African ancestry. They focused on three regions of the brain, particularly the prefrontal cortex — a critical center for learning, memory and executive function. The inclusion of brains from diverse ancestries is critical, as Alzheimer’s disease prevalence, progression and risk factors may differ across populations. Studying multiple ancestries helps identify risk factors that are specific to certain groups or factors that may be universally applicable.
“We need brain data from other populations so we can compare it to data we have for Europeans. Hopefully in the future, we’ll be able to obtain data from Asian, Hispanic and other populations so we can get a more comprehensive understanding. But for now, we have a better understanding of some risk factors shared between African and European ancestries,” Ma said.
What are transcripts and single nucleotide polymorphisms?
Genes, such as APOE, produce messenger RNA, or mRNA, which act like an instruction book telling cells how to make proteins. Changes in mRNA, or how much is expressed, can influence disease risk. This study found that certain variants potentially cause changes to mRNA in the brain that increase the risk of developing Alzheimer’s disease.
An mRNA transcript is a nucleotide sequence formed during alternative splicing to create a protein. Variations in how RNA segments come together can affect how a protein is made or alter its function. The research team discovered that dysregulation of a certain APOE transcript (jxn1.2.2) in the prefrontal cortex was particularly associated with Alzheimer’s disease risk. This link correlated in both European and African brain samples regardless of APOE allele type (ε2, 3 or 4).
Single nucleotide polymorphisms appear normally in human DNA and are the most common genetic variation. They occur when there is a difference in one nucleotide — the most basic unit of DNA. Most of these variations are harmless, but some can affect how genes function. In the study, two single nucleotide polymorphisms (rs157580 and rs439401) are believed to be Alzheimer’s-causative genetic variants for impacting expression of APOE transcript jxn1.2.2 and their effects were consistent across European and African samples.
When compared with the genomic databases, these polymorphisms were associated with amyloid-beta and phosphorylated tau proteins — both significant biomarkers for Alzheimer’s disease. In people with Alzheimer’s disease, amyloid-beta proteins break down and clump together to form plaques between brain cells, while tau proteins become dysregulated, creating tangles that block the transport of nutrients and signals to neurons, ultimately causing their death.
“Fortunately, the data shows that the risk factor, gene expression changes and polymorphisms are consistent between European and African ancestries. This suggests these are common risk factors across both populations. That’s good news, because if we develop a drug, we can potentially use it to treat both populations,” Ma said.
Discovery opens new avenues for diagnosis, treatment
By expanding understanding of genetic risk factors beyond APOE ε4, research comes closer to identifying additional biomarkers and therapeutic targets for Alzheimer’s disease. The discovery of APOE transcript jxn1.2.2 and its association with Alzheimer’s risk across diverse populations provides a promising avenue for developing diagnostic tools for earlier detection and intervention. Understanding how these genetic elements influence disease progression may pave the way for innovative treatments that address underlying mechanisms, offering hope for more effective prevention and management of Alzheimer’s disease.
“This discovery not only enhances our comprehension of [APOE] function in the brain but also paves the way for novel research avenues into the underlying mechanisms of Alzheimer’s disease. Deciphering the physiological role of this transcript and its potential contribution to disease progression is a current challenge that holds promise for the development of innovative therapeutic strategies,” Ruiz said.
UT Health San Antonio-led study validates cerebral small vessel disease marker for wider use in dementia trials
Posted on November 21, 2024 at 9:40 am.
A new neuroimaging marker of cerebral small vessel disease is related to general cognition and may serve to identify persons at risk of dementia in future clinical trials, a landmark study has found.
The study led by researchers at The University of Texas Health Science Center at San Antonio (UT Health San Antonio) is especially relevant to South Texas and Hispanics, who have a higher dementia risk from vascular injury compared to non-Hispanic white persons.
Specifically, it found that the cerebral small vessel disease marker known as peak-width of skeletonized mean diffusivity (PSMD) could be used to efficiently process numerous brain images in multi-site dementia studies.
“Our biological validation work supports the pursuit of larger clinical validation studies positioning PSMD as a susceptibility/risk biomarker of small vessel disease contributing to cognitive impairment and dementia for use in clinical trials,” said Claudia Satizábal, PhD, associate professor at the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at UT Health San Antonio.
She is senior author of the study, titled, “Biological validation of peak-width of skeletonized mean diffusivity as a VCID biomarker: The MarkVCID Consortium,” published Nov. 21 in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
“This study is a direct result of a committed partnership between research participants from the community, patients, clinicians and researchers right here at the Glenn Biggs Institute, and the South Texas Alzheimer’s Disease Research Center, over the past seven years,” said Sudha Seshadri, MD, director of the Biggs Institute and another study author.
“Even during the COVID pandemic, study participants and researchers worked together, safely doing brain MRI scans and cognitive tests,” she said. “I congratulate Dr. Satizábal and the team of doctors, participants and scientists who worked with her on the validation of this important biomarker.”
Global burden of cognitive impairment
Increasingly, literature suggests that cerebrovascular pathology is present to varying degrees in most adults suffering from cognitive impairment, the study notes. Although the vascular contributions to cognitive impairment and dementia (VCID) are significant, it is difficult to determine the number of people impacted due to the frequent occurrence of VCID with other etiologies and comorbidities.
Advances in neuroimaging have identified a high prevalence of brain white matter damage in persons with VCID, leading to consensus that slow progressive changes in the brain related to cerebral small vessel disease (SVD) are a major mechanism involved in VCID.
Additionally, as life expectancy increases worldwide, the global burden of age-related cognitive impairment, including presumed vascular etiology, will rise. Therefore, the study authors believe that any intervention that alleviates the burden of VCID should be investigated.
“Despite the pressing need to develop VCID biomarkers, only a few can reliably detect and track SVD changes leading to VCID, and these have yet to be approved by regulatory agencies to be used in clinical trials,” said Alison Luckey, PhD, postdoctoral research fellow with the Biggs Institute and first author of the study.
Currently, the most used neuroimaging marker of SVD is white matter hyperintensities (WMH). However, the etiology of WMH remains undetermined and is further suggested to not only represent vascular lesions but also neurodegeneration.
Enter, PSMD
The new study notes that PSMD had shown excellent instrumental properties as a marker, meaning it showed reliability across users, sites and time points. So, the scientists set out to extend their work to perform a biological validation, defined as the association with clinically meaningful aspects of VCID, such as cognitive performance.
The UT Health San Antonio-led team studied a group of 396 participants from the MarkVCID consortium (https://markvcid.partners.org), founded from an initiative of the National Institute on Neurological Disorders and Stroke (NINDS) to identify, develop and validate fluid- and imaging-based biomarkers for the SVDs associated with VCID.
For their study, the scientists derived PSMD from diffusion tensor imaging (DTI) using an automated algorithm, and related it to a composite measure of general cognitive function using linear regression models adjusting for confounders.
From that, they observed that higher PSMD was associated with lower general cognition in MarkVCID, independent of age, sex, education and intracranial volume. The findings were replicated in three independent samples. Further, PSMD explained cognitive status above and beyond WMH, the more common cerebrovascular marker.
The researchers concluded that PSMD has ideal biomarker qualities for the clinical trial pipeline across the most common form of dementias, as it is non-invasive, fully automated, fast and has excellent reliability, repeatability and reproducibility.
Additional longitudinal validation studies assessing the use of PSMD as a surrogate of cerebral small vessel diseases are underway.
Other authors of the study are with the Boston Chobanian & Avidisian University School of Medicine; Boston University School of Public Health; National Institute on Aging of the National Institutes of Health; Harvard Medical School; University of New Mexico School of Medicine; University of New Mexico; University of Kentucky; University of California at San Francisco; and Johns Hopkins University School of Medicine.
Also, the University of Mississippi Medical Center; Icelandic Heart Association; University of Iceland School of Health Sciences; University of California at Davis; Massachusetts General Hospital; University of Southern California; The Mind Research Network; The University of Texas Health Science Center at Houston; Illinois Institute of Technology; and Rush University Medical Center.
UT Health San Antonio is a world-class research university, ranking at the top 5% among institutions globally for clinical medicine according to U.S. News & World Report. It is No. 12 in the world among universities for the impact of its discoveries – in normalized citation impact, which compares the number of citations its research receives per paper to the average for similar published work, a recognized core measure of research impact.
Biological validation of peak-width of skeletonized mean diffusivity as a VCID biomarker: The MarkVCID Consortium
Alison M. Luckey, Saptaparni Ghosh, Chen-Pin Wang, Alexa Beiser, Rebecca Bernal, Zhiguang Li, Djass Mbangdadji, Elyas Fadaee, Haykel Snoussi, Angel Gabriel Velarde Dediós, Hector A. Trevino, Monica Goss, Laura J. Hillmer, Christopher E. Bauer, Adam M. Staffaroni, Lara Stables, Marilyn Albert, Jayandra J. Himali, Thomas H. Mosley, Lars Forsberg, Vilmundur Guðnason, Baljeet Singh, Herpreet Singh, Kristin Schwab, Joel H. Kramer, Gary A. Rosenberg, Karl G. Helmer, Steven M. Greenberg, Mohamad Habes, Danny J.J. Wang, Brian T. Gold, Hanzhang Lu, Arvind Caprihan, Myriam Fornage, Lenore J. Launer, Konstantinos Arfanakis, Sudha Seshadri, Charles DeCarli, Pauline Maillard, Claudia L. Satizabal
First published: Nov. 21, 2024, Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association
Link to full study: https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.14345
