The symptoms of TDP-43 age-related encephalopathy (LATE) are comparable to those of Alzheimer’s disease, including memory loss and problems with thinking and reasoning in old age.
A recent study suggests that the prevalence of brain changes from limbic-dominant TDP-43 age-related encephalopathy may be approximately 40% in older people and up to 50% in people with Alzheimer’s disease
According to the researchers, the paper, soon to be published in Acta Neuropathologica, is the most comprehensive assessment of the incidence of a type of dementia identified in 2019 and now known as LATE. According to the findings, the prevalence of LATE-related brain changes may be around 40% in the elderly and up to 50% in Alzheimer’s patients.
“It’s a fundamental question for any disease or condition, ‘How often is it seen in people’s brains?’ and it’s a tricky challenge to answer that question,” said Pete Nelson, M.D., Ph.D., neuropathologist and president of the Foundation RC Durr on Alzheimer’s disease at the University of Kentucky.
Nelson and a broad group of international scientists collaborated in 2019 to name this new type of dementia limbic-predominant TDP-43 age-related encephalopathy (LATE).
13 existing community-based study cohorts and population-based study cohorts provided the data for this new investigation. The study used autopsy, genetic and clinical data on more than 6,000 brains. The samples and data span five different countries on three continents. According to the findings, LATE pathology was present in more than a third of the brains.
Memory loss and problems with thinking and reasoning are signs of LATE, whose symptoms mimic Alzheimer’s disease. However, the researchers found that LATE-affected brains differ from Alzheimer’s brains in appearance, and treatments that may be helpful in one are likely to be ineffective in the other.
Ten Alzheimer’s disease research centers funded by the National Institutes of Health, including the University of Kentucky, were represented and worked as a large cohesive team. This study also included two cohorts from the United Kingdom, as well as a total of three cohorts from Brazil, Austria and Finland.
“Not only is the size of this pooled analysis important, but also the fact that those who participated in the studies leading to brain donation were obtained from longitudinal studies in study populations. Therefore, we can say more about the contribution of LATE to dementia in older populations. It’s quite different from most research, which is essentially from individuals without that anchoring,” said Carol Brain, MD, a British academic and professor of public health medicine at the University of Cambridge. “Given that dementia is most prevalent in older age, the LATE findings are particularly important. Although there are many differences between the studies that are combined here—from design to methodologies—they all reveal the importance of LATE and suggest that our findings will be relevant beyond any single country or region of the world.
In addition to the University of Kentucky, other US Alzheimer’s research centers involved in this work include Northwestern University Medical Center, Rush University Medical Center, Mayo Clinic (both MN and FL campuses), Univ. Duke, University of California (Davis), University of California (Irvine), University of California (San Francisco), University of Washington, and Stanford University.
“The inclusion of so many high-quality cohorts from around the world is unprecedented. Each research center has its own set of biases and blind spots when it comes to recruiting research volunteers,” Nelson said. “To make progress, we need cooperation between institutions and across borders. The NIH/NIA-funded Alzheimer’s Research Centers used their multidisciplinary resources, and our esteemed international collaborators brought outstanding expertise of their own.”
Although there have been previous reports of LATE from individual research centers and from different groups, there has been no previous study pooling findings from multiple community-based autopsy cohorts.
Ultimately, Nelson says, this study helps indicate that LATE is an extremely common factor in the devastating clinical syndrome often called Alzheimer’s disease or dementia. While reviewing the findings, Nelson and the other researchers pointed out that LATE was even more common in brains with severe Alzheimer’s disease neuropathological change (ADNC)—over half of severe ADNC cases also had LATE.
With the world’s first clinical trial for LATE currently underway at the University of Kentucky, and attention focused on preventing LATE and Alzheimer’s, Nelson says the basic information gained through studies like this is critical. “This helps us formulate key questions such as: ‘Who should be involved in a research study?’ What should we be looking for?” It may also help guide us on how to better study LATE and Alzheimer’s disease when these two brain diseases are so often present in the same person.
Although progress has been made, there are still many gaps in knowledge.
“We need more information in more diverse cohorts. People of African or Asian heritage are relatively underrepresented in this study. So far, it does not appear that people of different ethnic backgrounds have a different risk of LATE, but further work is needed in this important area,” Nelson said.
Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under award number P30AG072946. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Reference: “Study shows high prevalence of newly defined dementia other than Alzheimer’s,” 14 Jun 2022, University of Kentucky.
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