A new form of dementia that “mimics” the symptoms of Alzheimer’s and is thought to affect about one in five elderly people has been recognised in a major scientific report.
The international review concluded that a substantial fraction of patients aged over 80 who were assumed to have Alzheimer’s are suffering from a different brain disorder known as LATE. The under-recognised disease is likely to have a public health impact comparable to Alzheimer’s, the authors said.
Symptoms for the two diseases, including memory problems, cognitive decline and mood disorders, are very similar, but LATE progresses more slowly. Crucially, LATE is caused by problems with an entirely different brain protein and will probably require different drugs to treat it in the future.
Nina Silverberg, a director of the US National Institute on Aging and co-chair of the review, said: “Recent research and clinical trials in Alzheimer’s disease have taught us not all of the people we thought had Alzheimer’s have it.”
Robert Howard, a professor of old age psychiatry at University College London, described the work as “probably the most important paper” on dementia in the last five years.
“Those of us who work in dementia have long been puzzled by our patients who have all the symptoms of Alzheimer’s disease, but whose brains do not contain the pathological features of the condition,” he said, adding that another mystery was why some of the oldest patients did not progress as rapidly as would be expected with Alzheimer’s disease.
“We now know that these puzzling patients are probably suffering from LATE and not Alzheimer’s disease and that LATE may be ‘mimicking’ Alzheimer’s in about 20% of cases,” he said.
While the underlying biology of Alzheimer’s is still not fully understood, one telltale sign is the presence of sticky proteins called amyloid plaques that form clumps in the brains of patients, causing neurons to die and resulting in irreversible brain damage. However, autopsies of trial participants have revealed a subset of patients without these changes. In about 20% of all patients over 80, scientists found buildups of a different protein, called TDP-43, which they believe is the culprit in LATE.
The findings are unlikely to change the way dementia is currently diagnosed – the considerable overlap in symptoms means that at the moment it would be impossible for doctors to confidently distinguish between the two conditions. However, the findings could help explain why the hunt for a cure for Alzheimer’s has so far proved futile: it is possible that positive results were being diluted by the inclusion of patients with a different disease.
“Treatment trials of drugs that are designed to work against Alzheimer’s will not have any efficacy against LATE and this has important implications for the choice of participants in future trials,” said Howard.
James Pickett, the head of research at the Alzheimer’s Society, said: “This type of research is the first step towards more precise diagnosis and personalised treatment for dementia, much as we’ve started to see in other serious diseases such as breast cancer.”
The review is published in the journal Brain.
