Brain Imaging and Alzheimer's Disease Prediction

Enhanced early detection of risk for Alzheimer's dementia and other forms of dementia is key to prevention and early intervention.

Brain imaging holds promise as a pre-clinical disease risk assessment tool in Alzeimer's dementia.

Dementia risk has been linked to several brain imaging abnormalities found with magnetic resonance imaging. These abnormalities have included atrophy of the brain hippocampus, medial temporal lobe as well as white matter hyperintensities.

A recent study from France examined whether brain MRI findings can improve Alzheimer's and other dementia prediction over conventional known risk factors.

Here are the key elements of the design of this study:
Subjects: French citizens 65 years and old living at home participating in a longitudinal study of dementia with interviews two, four, six and ten years after baseline interview
Brain imaging: 1.5 Tesla MRI with estimation of white matter lesion volume, hippocampal volume (right and left summed) and total brain volume
Dementia diagnosis: all subjects screened at each interview, with targeted neuropsychological testing and neurologist consensus assessment
Standard dementia risk model variables: age, gender, education, smoking status, alcohol use, functional daily living skills, cognition screening tests, cardiovascular disease, diabetes status, systolic blood pressure and apolipoprotein epsilon 4 status.

The research team found a statistically significant smaller hippocampal and total brain volume at baseline in those later developing dementia. White matter lesion scores showed a trend (p.076) with later dementia.

However, adding the imaging data to the standard dementia risk model did not add statistically to the predictive power for all-cause dementia to the model.

The baseline imaging in this study took place around the year 1999 to 2000. Since then, more specific brain imaging tools targeted towards Alzheimer's have emerged including amyloid plaque markers. 

These enhanced imaging tools may have better power at adding power to our prediction models.

Readers with more interest in this research study can access the free full-text manuscript by clicking on the link in the citation below.

Photo of meerkats from the Cincinnati Zoo are from the author's files.

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Stephan BC, Tzourio C, Auriacombe S, Amieva H, Dufouil C, Alpérovitch A, & Kurth T (2015). Usefulness of data from magnetic resonance imaging to improve prediction of dementia: population based cohort study. BMJ (Clinical research ed.), 350 PMID: 26099688

Brain MRI White Matter Intensities: Clinical Significance

T2 White Matter Hyperintensity (Mild left, Extensive right)

Novel imaging findings emerge with the advancement of imaging techniques.  Commonly, the meaning of new imaging findings is unknown until further clinical research provides answers.  This situation describes the finding of white matter intensities on brain magnetic resonance imaging.  White matter intensities are relatively common in the aging brain as well as with a variety of clinical disorders.  Two manuscripts provide new insight into the clinical significance of this MRI finding.

Debette and Markus performed a metanalysis of the existing literature through November 2009 in a BMJ article published in early 2010.  Their study examined 46 longitudinal studies.  Often, when first discovered, white matter intensities occur in the context of relatively normal brain function.  But these lesions are not normal as they indicate an increased risk for the following outcomes (estimated as relative risk increases)

• Increased risk of stroke 3.5 (350% increase)
• Increased risk of dementia 1.9 (90% increase)
• Increased risk of death 2.0 (100% increase)

The Debette and Markus review noted that there was some support for white matter hyperintensities to be linked to neuropsychological deficits like global cognitive decline, impaired executive function and decreased processing speed.

The neuropsychological effects of white matter intensities is the subject of a manuscript by Murry and colleagues from the Mayo Clinic.  This study examined a total of 148 elderly (73-91 years of age) subjects with white matter intensities on MRI but without current dementia.  The subjects underwent a battery of neuropsychological tests.  Additionally, the specific brain region for the white matter hyperintensities was examined in relationship to cognitive performance.  The primary findings from this study were:

• Lower executive function was found with these lesions for all areas except for occipital white matter hyperintensities (executive function including planning and complex decision making skills)
• White matter hyperintensities (particularly parietal lobe) were correlated with Parkinson's disease scores for impaired gait, posture and postural stability)
• Higher white matter intensities in all regions except the occipital regions as well as subcortical and periventricular regions correlated with slowed visuomotor performance (Trail Making Test Part B) and reduce gait (walking) speed

So this study adds two important elements to understanding white matter intensities.  First location makes a difference and second, white matter intensities should not be just noted to be present or absent but an estimation of the burden (volume) of the lesions is informative.  This study also helps to quantitate the effect of white matter intensities on risk for Parkinsonian symptoms. 

Murray and colleagues conclude: "The selective nature of the functional deficits associated withWMHsuggests thatthe primary effect of WMH is to reduce the efficiency of neuronal signaling. This conclusion is strengthened by the fact that vastly different functional domains—cognition and gait—were affected, with the common theme being processing speed.

White matter MRI images from the BMJ 2010:341:c3666 an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license.

Debette, S., & Markus, H. (2010). The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis BMJ, 341 (jul26 1) DOI: 10.1136/bmj.c3666

Murray, M., Senjem, M., Petersen, R., Hollman, J., Preboske, G., Weigand, S., Knopman, D., Ferman, T., Dickson, D., & Jack, C. (2010). Functional Impact of White Matter Hyperintensities in Cognitively Normal Elderly Subjects Archives of Neurology, 67 (11), 1379-1385 DOI: 10.1001/archneurol.2010.280