What is the role of MRI in the diagnosis of Alzheimer disease?

Updated: Apr 12, 2018
  • Author: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS; Chief Editor: L Gill Naul, MD  more...
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MRI is able to identify structural changes, including patterns of atrophy, that characterize neurodegenerative diseases, and can distinguish these from other causes of cognitive impairment, such as infarcts, space-occupying lesions, and hydrocephalus. [31]

Rates of whole brain and hippocampal atrophy from MRI scans can aid in disease diagnosis and tracking of pathologic progression in neurodegenerative diseases. Many studies have shown that cerebral atrophy is significantly greater in patients with Alzheimer disease than in persons without it. However, the variability of atrophy in the normal aging process makes it difficult to use MRI as a definitive diagnostic technique. [32, 33, 34, 23]  (See the images below.)

Coronal, T1-weighted magnetic resonance imaging (M Coronal, T1-weighted magnetic resonance imaging (MRI) scan in a patient with moderate Alzheimer disease. Brain image reveals hippocampal atrophy, especially on the right side.
Axial, T2-weighted magnetic resonance imaging (MRI Axial, T2-weighted magnetic resonance imaging (MRI) scan of the brain reveals atrophic changes in the temporal lobes.
Axial, T2-weighted magnetic resonance imaging (MRI Axial, T2-weighted magnetic resonance imaging (MRI) scan shows dilated sylvian fissure resulting from adjacent cortical atrophy, especially on the right side.
Axial, T1-weighted magnetic resonance imaging (MRI Axial, T1-weighted magnetic resonance imaging (MRI) scan shows a dilated sylvian fissure caused by adjacent cortical atrophy.
Axial, T1-weighted magnetic resonance imaging (MRI Axial, T1-weighted magnetic resonance imaging (MRI) scan shows bilateral cortical atrophy with accentuated cortical sulci; there is decreased involvement in the posterior aspect.
Axial, T1-weighted magnetic resonance imaging (MRI Axial, T1-weighted magnetic resonance imaging (MRI) scan shows bilateral cortical atrophy with accentuated cortical sulci; there is decreased involvement in the posterior aspect.

Fox et al used an automated technique that is potentially applicable, in the clinical setting, to subtractiom MRI scans obtained an average of 1 year apart. They observed that there was a significant difference between the rate of change in patients with Alzheimer disease and the rate in control subjects. With MRI, sensitivity and specificity were approximately 90% for predicting the decline in dementia. [35]

Changes in hippocampal volume, shape, symmetry and activation are reflected by cognitive impairment. [29] Early MRI studies to evaluate the size of the hippocampus in patients with Alzheimer disease relative to control subjects showed large reductions in hippocampal volumes (approximately 50%) and high sensitivity and specificity for classification. [36] Over time, enlargement of the temporal horns, as well as of the third and lateral ventricles, was noted in patients with Alzheimer disease as compared with control subjects.

On structural MRI, atrophy of the entorhinal cortex is already present in MCI. In the autosomal dominant forms of Alzheimer disease, the rate of atrophy of the medial temporal structures differentiates affected individuals from control subjects as early as 3 years before the clinical onset of cognitive impairment. The accelerated annual rate of brain atrophy is a surrogate tool for evaluating new therapies in small samples that may save time and resources.

MRI measurements of the hippocampus, amygdala, cingulate gyrus, head of the caudate nucleus, temporal horn, lateral ventricles, third ventricle, and basal forebrain yield a predictive rate of 77% for conversion to Alzheimer disease from questionable Alzheimer disease. [37, 38]

Functional MRI (fMRI) techniques can be used to measure cerebral perfusion. Dynamic susceptibility contrast (DSC) MRI consists of the passage of a concentrated bolus of a paramagnetic contrast agent that sufficiently distorts the local magnetic field to cause a transient loss of signal with pulse sequences, especially T2-weighted sequences. The passage of contrast material is imaged over time by sequential rapid imaging of the same section. In animal studies, the rate of change of signal intensity over time gives a measure directly proportional to cerebral blood volume. Studies in humans have shown a correlation between PET and DSC MRI scan results, as well as between cerebral blood volumes measured with DSC MRI and perfusion on single-photon emission computed tomography (SPECT) scanning.

Studies have been performed using MRI with echo-planar imaging and signal targeting with attenuation radiofrequency (EPISTAR) in patients with Alzheimer disease. Focal areas of hypoperfusion were in the posterior temporoparieto-occipital regions. Ratios of signal intensity in the parieto-occipital and temporo-occipital areas to signal intensity on whole section were significantly lower in the patients with Alzheimer disease than in those without it. The parieto-occipital ratios were not correlated with the severity of dementia, as measured by using the Blessed Dementia Scale Information Memory Concentration subset.

With fMRI, structural imaging can be done by using the same imaging plane, field of view, and section thickness. Activational fMRI studies have included blood oxygenation level–dependent (BOLD) imaging, which uses changes in the level of oxygenated hemoglobin in capillary beds to depict areas of regional brain activation. In Alzheimer disease, fMRI activation in the hippocampal and prefrontal regions is decreased.

On fMRI, paradigms activate a larger area of parietotemporal association cortex in persons at high risk for Alzheimer disease than in others, whereas the entorhinal cortex activation is relatively low in MCI. [39]

The techniques are reasonably sensitive and specific in differentiating Alzheimer disease from changes resulting from normal aging, and studies with pathologic confirmation show good sensitivity and specificity in differentiating Alzheimer disease from other dementias. These techniques can also be used to detect abnormalities in asymptomatic or presymptomatic individuals, and they may help in predicting the decline to dementia.

Atlthough hippocampal volume has been shown in MRI studies to be associated with cognitive impairment in patients with Alzheimer disease, hippocampal texture has also been shown to be a predictor of conversion of mild cognitive impairment to Alzheimer disease, according to the Alzheimer's Disease Neuroimaging Initiative.  [40]


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