What is dementia diagnosis research?

Researchers are very interested in developing and improving techniques which can sensitively, reliably and accurately diagnose dementia, and differentiate between the distinct types of dementia.

In the past, diagnosis of specific dementia pathology such as Alzheimer’s disease was only confirmed retrospectively upon autopsy. Results of cognitive tests and other clinical features formed the basis of a probable diagnosis. However, these cognitive tests are limited in their ability to differentiate early signs of dementia from normal cognitive decline with ageing. Misdiagnosis of different forms of dementia based on cognitive tests may occur, and cognitive tests alone do not reliably detect when multiple forms of dementia are present.

In the last 15 years, new developments in brain imaging with magnetic resonance imaging (MRI, fMRI),and positron emission tomography (PET, PiB-PET) have allowed clinicians to detect some of the hallmark signs of various dementias with greater precision, enabling more accurate differential diagnosis.

Diagnosis research is progressing rapidly, and improvements and standardisations in the diagnosis of dementias will likely be introduced to the public in the near future.

Why is diagnosis research important?

Whilst there are currently no treatments targeting the underlying processes in dementia, evidence suggests that the window of opportunity for any such treatment to be effective would likely be limited to earlier stages of dementia.

Future treatments will likely be specific to particular types of dementia. Such treatments may slow or stop brain pathology and cognitive decline; restoration of lost cognitive abilities is likely to occur in earlier stages of dementia. Timely, accurate differential diagnoses at the very earliest stages will provide greater opportunity for targeted treatment and greater chance of preserving cognitive function and slowing or stopping deterioration.

Some researchers are using brain imaging with large numbers of people yet to be diagnosed with dementia, in order to identify early biomarkers that are associated with prodromal* changes and future dementia risk. It is hoped that imaging may help to identify people at higher risk for developing dementia, and that this could provide an even greater opportunity for prevention and treatment.

What is required in order to conduct diagnosis research more effectively?

Research into diagnosis with biological tests involves discovering new biomarkers, or finding more sensitive and reliable ways of detecting known biomarkers. Research into discovering biomarkers associated with prodromal or pre-dementia will likely require imaging the brains of large numbers of volunteers over 60 who are at an elevated risk of dementia.

Diagnostic tests need to be validated on large numbers of people before they can be used clinically. This involves testing large numbers of people, both those with no cognitive impairment and those with dementia and cognitive impairment, and comparing the results of these tests to a gold-standard test. Participants are sometimes invited to donate their brains to research after they die as the gold-standards tests require autopsy.

An example of a dementia diagnosis study

Impact of multiple pathologies on the threshold for clinically overt dementia (Acta Neuropathologica; Kapasi, DeCarli, & Schneider, 2017)

A recent review of large cohort studies has shown that the majority of people with suspected diagnoses of Alzheimer’s disease based on cognitive and clinical evaluation, actually have multiple forms of dementia present.

Participants had generously volunteered to donate their brains to research after death. Whilst they were alive, participants had received a clinical diagnosis of no cognitive impairment, mild cognitive impairment (MCI), or Alzheimer’s disease not long before the time of death. The average age at the time of death in this study was 89.

After a neuropathologist had examined the brains of deceased volunteers, at least one form of brain pathology was diagnosed in a majority of people who were assessed as having no cognitive impairment. The most commonly found brain pathology was signs of vascular insult, followed by changes typically associated with Alzheimer’s disease, and then changes associated with other dementias.

In people who had earlier received a diagnosis of MCI, the majority had evidence of vascular dementia, with about a third showing evidence of Alzheimer’s disease.

Interestingly, in people who were clinically diagnosed with probable Alzheimer’s, neuropathological test at autopsy revealed 82% had Alzheimer’s with at least one other form of dementia present (most commonly Vascular dementia). Another 15% of people clinically diagnosed with probable Alzheimer’s did not have Alzheimer’s disease, and had another form of dementia. Only 3% of people with a probable Alzheimer’s diagnosis had Alzheimer’s disease and no other forms of dementia.

This study highlights the large amount of mixed pathology, or multiple types of dementia present in cases of clinically suspected dementia. It is actually uncommon for a single type of dementia to be present without another type also being present. Some study participants had brain pathology without obvious cognitive symptoms in testing, suggesting possible cognitive reserve. The study also highlights the diagnostic limitations of clinical diagnosis. This has major implications for future treatments. Sensitive and specific diagnostic methods are needed for accurate diagnoses and appropriate application of targeted therapies. Biological diagnoses based on neuroimaging techniques such as MRI and PET techniques have greater accuracy than cognitive tests, and are becoming more widespread.

*Prodromal refers to people with deteriorating cognitive function, but below the threshold for Alzheimer’s diagnosis, and with a positive biomarker for amyloid.

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