09 Nov, 2022 Read Time: 3 mins

Predicting dementia based on mild cognitive impairment and biomarkers

Mild cognitive impairment alone is not an indicator of Alzheimer’s disease and cannot be used to predict future progression to dementia. To obtain a much more accurate diagnosis of Alzheimer’s disease and prognosis, it is necessary to test for amyloid, tau, and neurodegeneration, explained Professor Wiesje van der Flier, Amsterdam at EAN 2022.

Mild cognitive impairment alone does not indicate Alzheimer’s disease

Dementia is the end stage of Alzheimer’s disease (AD) after decades of development of Alzheimer’s disease neuropathology,1 said Professor van der Flier.

50% of individuals with mild cognitive impairment do not develop dementia4

Mild cognitive impairment (MCI) is the stage in AD that develops immediately before dementia,2 especially in older people.3 It was originally developed as a syndrome construct based on memory or other cognitive impairment, but not the general cognitive impairment required for a diagnosis of AD dementia, explained Professor van der Flier.

A more accurate prediction about whether an individual is likely to develop dementia is provided by measuring biomarkers5

However, MCI is associated with other conditions such as depression2 and only 50% of patients with MCI develop AD dementia over 3 years.4

 

Biomarkers for Alzheimer’s disease

A more accurate prediction about whether an individual with MCI has AD and is likely to progress to AD dementia is provided by measuring biomarkers. Alzheimer’s disease is now therefore seen as not just as a syndromal construct but as a biological construct,5 Professor van der Flier explained.

Earlier diagnosis provides the opportunity for therapeutic interventions to prevent progression to dementia

AD can be defined by its underlying pathophysiology using the ATN (amyloid-tau-neurodegeneration) framework enabling diagnosis before the development of dementia,5 so opening up opportunities for early intervention to prevent progression to dementia, said Professor van der Flier. The ATN biomarkers include:

  • Amyloid — measured using positron emission tomography (PET), cerebrospinal fluid (CSF) amyloid-beta (Aβ) 42/40
  • Tau — measured using PET, CSF phospho-tau (ptau)
  • Neurodegeneration — measured using magnetic resonance imaging (MRI), fluorodeoxyglucose PET5

 

Biomarkers can help inform prediction of risk for dementia

Risk of dementia is associated with increasing age, a lower mini-mental state examination test, more brain atrophy, and higher biomarker levels4

A study of 525 patients of patients with MCI has shown that the 3-year risk of progression to AD dementia is higher for patients who are older, have a lower mini-mental state examination test, have more atrophy on MRI, and have higher biomarker levels.4

However, it is not easy to explain an individual’s probability for developing AD dementia based on these risk factors to patients? said Professor van der Flier. Professor van der Flier and her colleagues have therefore developed a Web-based risk prediction tool called ADappt that takes into account MCI and ATN-based biomarker levels.

The tool provides patients with an individually tailored communication sheet explaining the results of their tests and a graphical representation showing their risk per 100 people in the same situation of developing AD dementia over 1 year and 3 years.6,7

ADappt helps inform individual prognosis7

ADappt has been particularly useful for informing individual prognosis, said Professor van der Flier, and provides reassurance for patients who are unlikely to develop AD dementia.

Although currently only available for academic use, ADappt is undergoing feasibility studies and will then be subject to a European validation study to see if it improves patient care, concluded Professor van der Flier.

References

  1. Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):280–92.
  2. Petersen RC. Mild cognitive impairment. Continuum (Minneap Minn). 2016;22(2 Dementia):404–18.
  3. Visser PJ, Kester A, Jolles J, Verhey F. Ten-year risk of dementia in subjects with mild cognitive impairment. Neurology. 2006;67(7):1201–7.
  4. van Maurik IS, Zwan MD, Tijms BM, et al; Alzheimer’s Disease Neuroimaging Initiative. Interpreting biomarker results in individual patients with mild cognitive impairment in the Alzheimer’s Biomarkers in Daily Practice (ABIDE) project. JAMA Neurol. 2017;74(12):1481–91.
  5. Jack CR Jr, Bennett DA, Blennow K, et al; Contributors. NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14(4):535–62.
  6. van Maurik IS, Vos SJ, Bos I, et al; Alzheimer’s Disease Neuroimaging Initiative. Biomarker-based prognosis for people with mild cognitive impairment (ABIDE): a modelling study. Lancet Neurol. 2019;18(11):1034–44.
  7. van Maurik IS, Visser LN, Pel-Littel RE, et al. Development and usability of ADappt: web-based tool to support clinicians, patients, and caregivers in the diagnosis of mild cognitive impairment and Alzheimer disease. JMIR Form Res. 2019;3(3):e13417.

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