Feature Article

Could MRI aid in predicting Alzheimer's disease?

Roughly 5.7 million Americans are currently living with Alzheimer's disease.1 This number is expected to increase to 14 million by the year 2050. It is the sixth leading cause of death in the United States. Alzheimer's is incurable and disease progression can only be slowed with treatment.

What is Alzheimer's disease?

Normally, the brain changes as a person ages, and often people will notice some cognition issues. However, Alzheimer's is the most common form of dementia and typically manifests as severe memory and cognition issues.2,3,4 Initially, patients may experience problems with short term memories, confusion, or forgetfulness. As time passes, these will become more frequent. People with Alzheimer's disease may experience trouble with memory, thinking and reasoning, making judgments and decisions, planning and performing familiar tasks and changing personality and behavior.

Alzheimer's is believed to be caused by genetic, lifestyle, and environmental facts which affect the brain over time.3 There are three genetic mutations which almost guarantee a person will develop Alzheimer's. If a parent or sibling has Alzheimer's, a patient has a slightly higher risk of developing the disease. Although scientists are not sure what causes Alzheimer's, they do know that changes in the brain manifest long before the first signs of memory loss. A brain affected by Alzheimer's has fewer cells and connections among surviving cells. Over time, an Alzheimer's patient's brain begins to shrink.

There are two abnormalities that appear in the brains of Alzheimer's patients: plaques and tangles.3,4 Plaques are clumps of protein (beta-amyloid) which damage and destroy brain cells.Plaques also interfere with cell-to-cell communication and the collection of beta-amyloid on brain cells is a prime suspect for the cause of Alzheimer's-related death. Tangles occur when threads of tau protein twist inside brain cells and hinder internal support and transportation of nutrients. These tangles are also intrinsically tied to the death of brain cells. Tangles and plaques are typically developed in small quantities in healthy people but appear in much larger quantities in Alzheimer's patients.

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MRI and Alzheimer's disease

Physicians cannot use plaques and tangles to diagnose Alzheimer's disease, because plaques and tangles are only observable when brain tissue is put under the microscope. 5This is also true for a variety of other molecular and cellular changes that occur in the brain of someone with Alzheimer's. Because of this, doctors have developed screening tests to predict the declination of cognitive function. Traditionally, this is done using Mini-Mental State Examinations (MMSE) and APOE-e4 genotyping.

Throughout an MMSE, medical personnel asks questions designed to test everyday cognitive function.6 The patient is then given a score from 1-30. The lower the score the more severe the dementia. On average, the score for patients with Alzheimer's decreases two to four points each year. The accuracy rate for MMSE is about 78%.7

APOE-e4 is the strongest risk gene for Alzheimer's and is used in trials to identify people at a higher risk of developing Alzheimer's.5 The APOE-e4 genotyping is done through blood-work. If a patient has this gene mutation, it does not mean they will develop Alzheimer's. The accuracy rate for APOE-e4 testing is roughly 70-71% accurate.7,8

At this year's RSNA conference in Chicago, Illinois, researchers reported that a study of fractional anisotropy in the brain could potentially predict Alzheimer's disease through MRI.7,8,9 Fractional Anisotropy measures how water molecules move along white matter tracts in the brain, which corresponds to white matter integrity, and is therefore important for physicians working with dementia patients. White matter loses integrity as dementia damages the brain. Lower fractional anisotropy means the brain has been damaged more.

The study involved 61 people who were about the age of 75.7,8,9 The study was conducted over an average of 2.6 years. Of these patients, 31 had normal-looking baseline scans and follow-up scans. The other 30 patients showed declining cognitive function. The researchers used MRI with diffusion tensor imaging (DTI) for their scans, which measures the random motion of water molecules (diffusion) under different types of gradients. This method allows for a more accurate measure of white matter structures than traditional MRI. The study reports that DTI scans were 89% accurate in predicting the cognitive outcome for patients, which is a higher accuracy rate than both MMSE and APOE-e4 genotyping. An additional study was conducted involving about 40 of the original study's patients. In this secondary study, the accuracy of DTI in predicting Alzheimer's was 95%.

Diffusion tensor imaging has proven 89-95% accurate in predicting cognitive decline in patients with Alzheimer's. Compared to the standard methods, MMSE and APOE-e4 testing, DTI is at least 10% more accurate. For a disease that causes cognitive issues for so many patients, tests with higher accuracy could lead to early detection and treatment which would slow the development of plaques and tangles. Ultimately, those 5.7 million Americans living with Alzheimer's and those being newly diagnosed could potentially benefit greatly from this new screening method.

1. "2018 Alzheimer's disease facts and figures." Alzheimer's Association. 2018. Web. 5 December 2018. <https://www.alz.org/media/Documents/alzheimers-facts-and-figures-infographic.pdf>.

2. "Alzheimer's Disease Fact Sheet." NIA.NIH.gov. 17 August 2016. Web. 5 December 2018. <https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet>.

3. Mayo Clinic Staff. "Alzheimer's disease." MayoClinic.org. 30 December 2017. Web. 5 December 2018. <https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/symptoms-causes/syc-20350447>.

4. "What Is Alzheimer's?" Alzheimer's Association. Web. 5 December 2018. <https://www.alz.org/alzheimers-dementia/what-is-alzheimers>.

5. "Medical Tests." Alzheimer's Association. Web. 10 December 2018. <https://www.alz.org/alzheimers-dementia/diagnosis/medical_tests>.

6. "What Happens to the Brain in Alzheimer's Disease?" NIA.NIH.gov. 16 May 2017. Web. 10 December 2018. <https://www.nia.nih.gov/health/what-happens-brain-alzheimers-disease>.

7. Subrata Thakar. "MRI scans using diffusion tensor imaging can predict Alzheimer's disease." Radiology Business. 20 November 2018. Web. 5 December 2018. <https://www.radiologybusiness.com/topics/care-delivery/mri-diffusion-tensor-imaging-promising-alzheimers>.

8. Radiological Society of North America. "Researchers use MRI to predict Alzheimer's disease." EurekAlert.org. 20 November 2018. Web. 5 December 2018. <https://www.eurekalert.org/pub_releases/2018-11/rson-rum110718.php>.

9. Ed Susman. "Alzheimer's Disease May Be Found Earlier with MRI—Diffusion tensor imaging may indicate which patients are at risk." MedPage Today. 29 November 2018. Web. 5 December 2018. <https://www.medpagetoday.com/meetingcoverage/rsna/76583>.