A newly identified form of dementia is surprisingly common

Symptoms of TDP-43 limbic-predominantly age-related encephalopathy (LATE) are comparable to those of Alzheimer’s disease, involving memory loss and problems with thinking and reasoning in older people.

A recent study indicates that the prevalence of brain changes caused by limbic-predominant TDP-43 age-related encephalopathy may be around 40% in older adults and up to 50% in affected individuals. Alzheimer’s sickness.

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, the researchers say. According to the results, the prevalence of TARD-related brain changes could be around 40% in the elderly and up to 50% in patients with Alzheimer’s disease.

“It’s a fundamental question about any disease or condition, ‘How often is it seen in people’s brains?’ and it’s deceptively difficult to answer that question,” said Pete Nelson, MD, Ph.D., neuropathologist and RC Durr Foundation Chair in Alzheimer’s Disease at the University of Kentucky.

Nelson and a large group of international scientists collaborated in 2019 to name this new type of limbic-predominant age-related encephalopathy TDP-43 (LATE).

13 existing community-based study cohorts and population-based study cohorts provided the data for this new survey. Over 6,000 brains of autopsy, genetic and clinical data were used in the research. The samples and data cover five separate countries on three continents. According to the results, LATE pathology was present in more than a third of the brains.

Memory loss and problems with thinking and reasoning are signs of LATE, the symptoms of which mimic Alzheimer’s disease. However, the researchers found that the brain affected by LATE differs from the Alzheimer’s disease brain in appearance, and treatments that may be helpful for one are likely ineffective for the other.

Ten National Institute of Health-funded Alzheimer’s disease research centers were represented, including the University of Kentucky, and operated as one large, cohesive team. This research also included two cohorts from the UK, as well as a total of three cohorts from Brazil, Austria and Finland.

“Not only is the size of this combined analysis important, but also the fact that those who participated in the studies leading to brain donation were drawn from longitudinal studies in study populations. For this reason, we can say more about the contribution of TARD to dementia in older populations. It’s quite different from most research that actually comes from individuals without that anchor,” said Carol Brayne, MD, a British academic and professor of public health medicine at the University of Cambridge. “Since older ages are when dementia is most common, LATE results 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 TARD and suggest that our findings will be relevant beyond any country or region of the world.

In addition to the University of Kentucky, other US Alzheimer’s disease research centers involved in this work include Northwestern University Medical Center, Rush University Medical Center, Mayo Clinic (MN and FL campuses), the Duke University, 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 volunteers for research,” said Nelson said, “To make progress, we need collaboration across institutions and across borders. NIH/NIA-funded Alzheimer’s disease research centers have leveraged their multidisciplinary resources and our esteemed international collaborators brought their own extraordinary expertise.

Although there have been previous reports of LATE from individual research centers and various groups, there has not been a previous study bringing together the results of many cohorts of community autopsies.

Nelson says that ultimately this study helps indicate that LATE is an extremely common contributor to the devastating clinical syndrome often referred to as Alzheimer’s disease or dementia. Reviewing the results, Nelson and the other researchers reported that LATE was even more common in brains with severe Alzheimer’s disease neuropathological change (ADNC) – more than half of severe ADNC cases also had Alzheimer’s disease. LATE.

With the world’s first clinical trial of LATE now underway at the University of Kentucky, and the focus on preventing LATE and Alzheimer’s disease, Nelson says basic information gained from studies like this are crucial. “It helps us formulate key questions like: ‘Who should be recruited into a research study? What should we be looking for? It may also help us better study ARD and Alzheimer’s disease when these two brain diseases are so often present in the same person.

Although progress is being made, there are still many knowledge gaps.

“We need more information in more diverse cohorts. People of African or Asian descent were relatively undersampled in this study. So far, it doesn’t appear that people of different ethnic backgrounds have a different risk of LATE, but more work is needed in this important area,” Nelson said.

The 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 the sole responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Reference: “Study indicates high prevalence of recently defined non-Alzheimer’s dementia,” June 14, 2022, University of Kentucky.

About Terry Gongora

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