Role of MRI in diagnosis of mild cognitive impairment, and Alzheimer’s disease

Diagnosis of mild cognitive impairment(MCI) and Alzheimer’s disease (AD) is generally a clinical diagnosis, but with the aids of Magnetic resonance imaging (MRI), it has great value of sensitivity and specificity with MRI alone reaching more than 90% [ref1]. How MRI help in diagnosis? and what structural images is expected and used in the diagnosis of both MCI and AD? and can they be differentiated based on MRI?

Several autopsy has show that medial temporal lobe is affected earliest in AD and has positive relationship with MRI results [ref2]. From the study provided by The Alzheimer’s Disease Neuroimaging Initiative (ADNI), which is a multi-center study assessing neuroimaging in diagnosis and longitudinal monitoring, has done study on several region of interest, especially medial temporal lobe which include hippocampus and entorhinal cortex. Other region include amygdala, parietal and temporal cortex. In AD and MCI, there is reduction in global gray matter density, also in bilateral hippocampal and amygdalar volumes and entorhinal cortex thickness. The most significant atrophic changes is seen in medial temporal lobe, with hippocampus most significantly involved especially the left hippocampus. However these were obtained through voxel-based morphometry (VBM) and automated parcellation methods. [ref3] These finding correlate in several other studies. [ref4][ref5][ref6]

MRI-based atrophy recognition is a valid method with several reason [ref7]. Patterns of gray matter loss are correlated with neurofibrillary tangle (NFT) pathology seen in AD[ref5][ref8][ref9]. The clinical presentation of AD correlates with the distribution and pattern of atrophic changes in the brain [ref10][ref11]. Moreover, the Braak staging of NFT correlate with the changes of medial temporal lobe atrophy (MTA) [ref5][ref12]. The severity of MTA also correlate well with the severity of AD, by using a standardized MTA visual scale rating system introduced by Scheltens et al. in 1992 [ref13][ref2] and comparing with MMSE score. This visual rating system is reliable and has been suggested to be use in clinical setting, and it is comparable , if not better than volumetric study [ref14][ref15]. Besides that, MTA can be used to differentiate dementia dues to AD from others such as dementia with Lewy bodies, and corticobasal degeneration [ref5]. Therefore we can say that medial temporal lobe atrophy is a important tool for diagnosis of AD, with severity indicator, which can be easily done by using visual rating scale introduced by Scheltens et al.

20121231-105226.jpg

Image above shown the updated visual rating scale of MTA, ranging from 0(no atrophy) to 4(severe atrophy). Image obtained from [ref27].

20121231-111939.jpg

Image shown the Braak’s staging of neurofibrillary tangle deposition in AD. Obtained from [ref30].

Since we know the role of MRI in AD, how about MCI? It has been documented that MCI has relatively lower medial temporal atrophy effect size than AD based on volumetric MRI study [ref16][ref17][ref18]. However such differentiating factor or scoring is not well defined for clinical application. How about visual rating scale of MTA? High MTA scores were associated with clinical dementia with sensitivity was 63% and specificity 69% for AD, scoring of less than 2 is not frequently associated with dementia [ref19]. This mean we can somehow use MTA score to differentiate between MCI and AD. In one study, it shows that mean MTA cut score of 1.33 yielded an optimal sensitivity/specificity of 85%/82% for probable AD subjects and 80%/82% for amnestic MCI subjects [ref20]. Similarly, it is not well defined of the cut off value for MTA scores to differentiate MCI and AD, nor its reliability in clinical practice. More importantly, is the role of MTA in the value of predicting conversion from MCI to AD. In clinically diagnosed MCI but remain stable throughout the time of investigation shown no significant atrophic changes compared to the group where MCI is later progressed to AD[ref21][ref22]. MTA rating has strong association with conversion of MCI to AD [ref12][ref23][ref24][ref25]. In one study, it is found that there is a hazard ratio of 1.5 for conversion to dementia for every point increased in atrophy score based on visual rating scale of MTA [ref26]. However, other studies have concluded that other region has more predictive role than hippocampus, such as the entrorhinal cortex, lateral temporal, and parietal cortex [ref25][ref27][ref28][ref29].

In summary, MRI can aids in the diagnosis of AD, by increasing its sensitivity and specificity, also to differentiate from other causes of dementia; mainly by focusing on medial temporal lobe atrophy (MTA). Similar method can be apply to MCI, but differentiating MCI from AD based on MTA is still not yet clearly defined for clinical practice. MTA visual rating scale is easily applicable and has high sensitivity and specificity for not just diagnosing but also predicting the conversion of MCI to AD.

references.

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