Diagnosing mild cognitive impairment (MCI) is more important than ever, experts say

Increasing recognition of MCI as an early stage on the continuum of Alzheimer’s disease (AD) in some patients has led experts to call for improved diagnosis of MCI, while research examines ways to halt or slow the disease process following early diagnosis.

In ‘MCI on the Alzheimer’s continuum’, one of a series of Mind Changers podcasts hosted on the recently launched ADBioHub, Prof Philip Morris (Medical Director of the Gold Coast Memories Disorder Clinic) and A/Prof Michael Woodward (Head of Aged and Residential Care Services at Austin Health in Melbourne) discussed how our understanding of MCI is changing as clinical research pushes the threshold for diagnosis earlier in the disease continuum.

Defining MCI

MCI is defined as declines in performance of one or more cognitive domains with the preservation of functional independence.¹ MCI may be amnestic (i.e. affecting memory) or non-amnestic (i.e. not affecting memory).² While the person or their family members will have noticed a change in cognition, it is not so severe that it affects their independence in everyday activities.²

If the person progresses to cognitive decline that results in difficulties managing their everyday life, this is then classified as dementia.² The differential diagnosis between normal ageing and MCI, as between MCI and mild dementia, is challenging because the boundaries are inherently arbitrary along the disease continuum.²

Significance of amnestic MCI

Amnestic and non-amnestic forms of MCI have a number of different underlying causes with a range of variable outcomes.³ In a subset of patients with amnestic MCI, this represents the prodromal stage of dementia due to AD.³

As explained by A/Prof Michael Woodward in ‘MCI on the Alzheimer’s continuum‘, “We know from studies such as AIBL [the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing]… that over the next 3–5 years, at least 50% of people with MCI will develop dementia, usually due to AD.” ⁴

The role of biomarkers in the early diagnosis of AD

According to A/Prof Woodward, “We understood that AD gets more severe as time goes on from the very beginning, but this idea of earlier stages – preclinical and prodromal stages of AD – has only been defined over the last 20 to 25 years, in particular, as a result of studies such as AIBL [the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing] and ADNI [the Alzheimer’s Disease Neuroimaging Initiative]… Through the use of biomarkers and other tests we are now getting a much more comprehensive picture of what happens in AD.”

Indeed, research on biomarkers has allowed the AD continuum to be divided into three overlapping areas:⁵

1. Preclinical AD in which individuals show no cognitive impairment, but have biomarker evidence of the AD disease process.
2. MCI due to AD whereby individuals meet the clinical criteria for MCI and have varying levels of biomarker specificity for AD.
3. AD dementia in which individuals meet the clinical criteria for dementia and similarly have varying degrees of biomarker support.

Prof Morris described the currently available biomarker evidence of AD as follows:⁶

• Brain atrophy on MRI, particularly of the temporal lobe and hippocampus
• Reduced glucose metabolism in certain parts of the brain (the posterior cingulate, precuneus and the temporal and parietal lobes) shown with PET studies
• Increased levels of amyloid-β and tau proteins in the brain (shown with PET scans), and decreased level of amyloid-β and elevated phosphorylated tau and total tau levels in the cerebrospinal fluid (collected via spinal tap)

According to A/Prof Michael Woodward, “From the AIBL study we have found for instance that if you have both a positive amyloid PET scan and you have atrophy on MRI then you have about 100 times greater chance of developing dementia over the next 3 years than if you don’t have either of those.” ⁴

Benefits of early diagnosis

According to a report published in The Lancet in 2020, modifying 12 risk factors might prevent or delay up to 40% of dementias.⁷ These include smoking, obesity, depression, physical inactivity, diabetes, alcohol consumption and low social contact.⁷

Prof Morris highlighted that, “The availability of biomarkers will help clinicians make the diagnosis of AD earlier in the disease continuum, thereby allowing for the early implementation of lifestyle interventions, with the potential to prevent or reduce progression.”

In addition to facilitating lifestyle modification (e.g. cardiovascular risk factor control, aerobic exercise and mental activity) to prevent or reduce progression to dementia, early diagnosis of the subset of patients with MCI who are at increased risk of developing AD may allow for improved access to clinical trials, and provide opportunities for counselling and future planning.

A/Prof Woodward stated, “I think it’s always important to have a look at the early stages of diseases. In fact, a lot of the bang for our buck in healthcare comes from approaching diseases earlier rather than waiting for them to fully manifest.”

He explained that it is not helpful to discount or ignore forgetfulness or amnestic signs in older patients in the belief that there is nothing that can be done. “These sorts of attitudes unfortunately lead to delays in diagnosis, delays in recognition of what’s going on,” he said.

Learn more about how our understanding of MCI is changing as clinical research pushes the threshold for diagnosis earlier in the disease continuum in the ADBioHub Mind Changers podcast ‘Mild cognitive impairment (MCI) on the Alzheimer’s continuum’.

References:

1. Petersen RC. J Intern Med2004;256:183–94.
2. DSM Guide Wikia. Major and Mild Neurocognitive Disorders. Available at: https://dsm.wikia.org/wiki/Major_and_Mild_Neurocognitive_Disorders#DSM-5. Accessed June 2021.
3. Petersen RC. Continuum (Minneap Minn) 2016;22:404–18.
4. The Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing, AIBL, accessed 23 June 2021 <https://aibl.csiro.au/>
5. Clifford R et al. Alzheimers Dement 2011;7:257–62.
6. Dubois B et al. Lancet Neurol 2021;20:484–96.
7. Livingston G et al. Lancet 2020;396:413–46.