Changes in brain structure, function and molecular processes occur several years before clinical symptoms of Alzheimer’s disease (AD) become apparent.
The big question then, is can you detect patients who are cognitively normal, but will go on to develop AD before they show symptoms, i.e. pre-symptomatic patients? The answer is “Yes” according to results published in the April 19, 2011 issue of Neurology by Brad Dickerson and colleagues.
In this small study, the team of researchers from two centers (Massachusetts General Hospital and Rush University in Chicago) followed a small sample of cognitively normal (CN) subjects over time with magnetic resonance imaging (MRI) and then sought to identify what structural changes had taken place in those subjects who were initially cognitively normal, but went on to develop AD, on average 11.1 years later.
The researchers found that changes in brain cortical thickness were associated with AD:
AD-signature cortical thinning in CN-AD converters in both samples was remarkably similar, about 0.2 mm (p < 0.05)
They concluded that:
By focusing on cortical regions known to be affected in AD dementia, subtle but reliable atrophy is identifiable in asymptomatic individuals nearly a decade before dementia, making this measure a potentially important imaging biomarker of early neurodegeneration.
Some of the limitations of this research and questions that come to mind are:
- Small sample size: only 8 individuals who developed AD and 25 in the cognitively normal control group.
- Reproducibility: the 0.2mm difference seen is small and the extent to which other centers may be able to reproduce this measurement is uncertain
- Accuracy of detection: in any screening tool the issue of false positives and negatives arises i.e. in a larger sample size will there be a margin for error that results in some people being included in the pre-symptomatic AD group, when they may be normal? Also will the proposed measurement remain valid in a large population of patients with other disease symptoms and chronic illnesses?
- Validity of biomarker: are the changes in cortical thickness causally linked to AD or just an incidental correlation i.e. is this a valid biomarker?
Brad Dickerson in the excellent Neurology podcast available with this publication clearly sees this currently as a research tool, especially given the requirement for considerable computer power to make these types of cortical measurements in the brain. The podcast interview is well worth listening to.
The MRI biomarker proposed by Dickerson is therefore not something that is really applicable to screen the general population at the moment.
However, the promise from this and other biomarker research is that at some point in the not too distant future we will be able to detect those at risk of developing AD. Those patients could then be given neuroprotective drugs that may delay the onset of the clinical symptoms of AD such as memory loss and cognitive impairment.
Biomarkers that identify those at risk of developing AD will also be useful as inclusion and screening tools for clinical trials of drugs aimed at slowing disease progression in pre-symptomatic patients.
Alzheimer’s disease has been called “The challenge of the Second Century,” we still have a long way to go before this is overcome.
Story Source: BBC Health
Dickerson, B., Stoub, T., Shah, R., Sperling, R., Killiany, R., Albert, M., Hyman, B., Blacker, D., & deToledo-Morrell, L. (2011). Alzheimer-signature MRI biomarker predicts AD dementia in cognitively normal adults Neurology, 76 (16), 1395-1402 DOI: 10.1212/WNL.0b013e3182166e96