Imaging the Neural Network Connectivity on Patients With Mild Cognitive Impairment
Condition: Mild Cognitive Impairment
MeSH terms: Cognitive Dysfunction
Study type: Observational

Summary: 
      The hypothesis tested if the diffusion properties in the base line, such as mean diffusivity
      or kurtosis, can differentiate two subtypes of MCI and predict the clinical outcome in
      Patients. The hypothesis further supports the correlation of the measured diffusion
      properties and the disease severity. We therefore proposed to investigate the potential value
      of diffusion properties as a possible tool to monitor the disease progression. The disease
      related changes in neural connectivity will be investigated.

        1. The diffusion MRI could provide an improved diagnosis of Alzheimer's Disease and Mild
           cognitive Impairment.

           Explanation:

           The deposition of the macromolecules such as beta amyloid in the brain and the
           associated neuron death of the patient could lead to observable changes in tissue
           microenvironment. The related changes would lead to alterations in either the amplitude
           or distribution of water diffusion. In turn it could be detected in diffusion tensor and
           kurtosis.

        2. aMCI is a preclinical state of AD and dMCI is from a different etiology, which can be
           differentially diagnosis by MRI. Diffusion Imaging could help to predict the clinical
           outcome Explanation
    

Detailed description: 
      Mild Cognitive Impairment (MCI) referred to a decline of cognition in elder adults that are
      not of sufficient magnitude to meet the criteria for dementia. It is usually regarded as a
      transition state between patients of Alzheimer's Disease (AD) and the age matched healthy
      adults. It is a heterogeneous syndrome which can be divided into two subtypes: amnestic and
      dysexecutive. This 3 year proposal continues from a NSc funded project, in which we reported
      that the amnestic MCI could involve global white matter changes and therefore could be a
      preclinical status to AD. In contrast, no compromise in white matter status was found in
      patients of dysexecutive MCI. Therefore we proposed to further investigate the phenomena in
      this project.

      The subjects will be divided into 3 groups: 30 patients with amnestic MCI, 30 with
      dysexecutive MCI and 30 healthy age-matched normal controls. Comprehensive neuropsychological
      examinations will be performed after detailed clinical history and physical screening,
      including Mini-Mental Status Examination, Clinical Dementia Rating and the Cognitive
      Abilities Screening Instrument. Successful candidate will be examined by 3T MRI, including
      diffusion imaging and high resolution T1 weighted anatomical images.

      The current project proposed to examine the sensitivity and specificity of diffusion Magnetic
      Resonance Imaging, in the diagnosis of MCI and differential diagnosis of two subtypes. Both
      the conventional tensor derived indices and diffusion kurtosis will be compared. This is due
      to the fact that in a recently publication in Radiology, we reported an improved diagnostic
      performance on neurodegenerative disease from diffusion kurtosis than diffusion tensor.
      Secondly we will examine the regional changes of diffusion properties and correlated with the
      white matter involvement in patients. High resolution track density images will be
      implemented and compared with the susceptibility weighted imaging in an effort to address the
      underlying changes in pathophysiology. In the third year, the prognostic value of diffusion
      MRI will be determined. The optimal cutoff value of diffusion MRI in the prediction of
      conversion to Alzheimer's disease will be reported. The diffusion properties in patients with
      early conversion (the 2nd year) and late conversion (the 3rd year) will be compared.

      It is expected that changes in diffusion can be used as an image based surrogate marker
      during the neurodegenerative process. The new insight into the temporal evolution of the
      diffusion MRI might help to understand the underlying etiology and pathophysiology between
      the amnestic and dysexecutive MCI patients, which can contribute to an early intervention
      strategy and might ultimately lead to an effective treatment.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patient will be recruited from the movement disorder clinics in ChangGung memorial hospital
        LinKou. The healthy control will be recruited from the local community in northem Taiwan.
      
Keywords: Amnestic mild cognitive impairment; Dysexecutive mild cognitive impairment; Diffusion MRI