Large-scale wrong diagnosis: New form of dementia mimics Alzheimer’s

A newly diagnosed form of dementia is being confused with Alzheimer's, potentially compromising research.

A newly diagnosed form of dementia is being confused with Alzheimer's, potentially compromising research. Photo: Getty

Millions of people are walking around thinking they have Alzheimer’s disease – and they don’t. Unfortunately, this isn’t a good news story.

What they have instead is a newly diagnosed form of dementia that mimics the symptoms of Alzheimer’s, but is caused by a different mechanism in the brain.

This has implications for dementia researchers because an unknown number of participants in clinical drug trials wouldn’t have actually had Alzheimer’s, therefore compromising results and perhaps even masking what may have otherwise been positive outcomes.

In other words, what might have been promising avenues of treatment were prematurely abandoned.

Where Alzheimer’s is characterised by plaques caused by the build-up of beta amyloid proteins, and neurofibrillary tangles composed of a protein called tau, the new condition, called LATE, is characterised by the presence of a different protein in the brain, named TDP-43.

LATE because it affects the oldest of the old

The name LATE comes from “Limbic-predominant Age-related TDP-43 Encephalopathy”, but it was actually conceived more as a strategy to raise awareness of the condition’s existence.

To what extent these different forms of dementia have been misdiagnosed and confused isn’t known. The situation is further complicated by the existence of yet another Alzheimer’s mimicking disease called PART discovered in 2014: Patients with PART don’t have the beta amyloid plaques, but do have the tau protein tangles.

Consider this: In 2017, researchers from the Memory and Ageing Centre at the University of California in San Francisco presented early results of a four-year project that involves testing more than 18,000 people with mild cognitive impairment or dementia to see if their brains contain the beta amyloid plaques and are en route to developing Alzheimer’s.

They did this using positron emission tomography (PET) scans.

Ordinarily, the presence of the plaques are only confirmed during an autopsy – with diagnoses of Alzheimer’s being made from an assessment of symptoms, because PET scans are expensive.

Of the first 4000 people tested, the Californian researchers found plaques in only 54.3 per cent of mild cognitive impairment patients and 70.5 per cent of dementia patients.

Extent of wrong diagnoses unknown

The researchers concluded that a substantial number of patients being treated for Alzheimer’s may not have it at all.

Associate Professor Michael Woodward, Dementia Australia Honorary Medical Adviser. Photo: Austin Health

Associate Professor Michael Woodward is head of aged and residential care services at Austin Health, a geriatrician in private practice at Donvale Rehabilitation Hospital, and Dementia Australia honorary medical adviser.

“There’s no doubt that the evidence suggests there is a significant number of older people, particularly over the age of 80, that have non-Alzheimer’s pathology even though they would be clinically diagnosed as having Alzheimer’s – and this doesn’t mean they’re not affected, they’ve still got significant memory and functional problems,” Professor Woodward told The New Daily.

“But it also suggests what we have to do is better design our diagnostic techniques.”

For patients going into research studies, he said: “We have to be sure that they have the disease being targeted. We have to be very careful that people with LATE don’t get into Alzheimer’s trials.”

Risk of side effects from wrong medication

Professor Woodward was concerned some patients may be overly excited by this news.

“People who are significantly cognitively impaired over 80 shouldn’t say, ‘Wow, I don’t have Alzheimer’s, it’s another condition’. They’re still cognitively impaired, and they still have difficulties in day-to-day living.”

He said most treatments are only modestly effective and in practical terms, it doesn’t matter all that much if they have a different diagnosis.

“Although it’s true to say we don’t want to give people side effects from medications when you’re treating them for conditions they don’t actually have,” he said.

Professor Woodward said as many as 30 per cent of older adults with late-onset dementia might have this new condition.

Other researchers have suggested that a quarter of all people over 85 have LATE and not know it.

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