Evaluation of treatment effects in Alzheimer's and other neurodegenerative diseases by MRI and MRS

Abstract

Neurodegeneration refers to a large clinically and pathologically heterogeneous disease entity associated with slowly progressive neuronal loss in different anatomical and functional systems of the brain. Neurodegenerative diseases often affect cognition, e.g. Alzheimer's disease (AD), dementia with Lewy bodies and vascular dementia, or different aspects of the motor system, e.g., amyotrophic lateral sclerosis, Parkinson's disease and ataxic disorders. Owing to increasing knowledge about the mechanisms leading to neurodegeneration, the development of treatments able to modify the neurodegenerative process becomes possible for the first time. Currently, clinical outcome measures are used to assess the efficacy of such treatments. However, most clinical outcome measures have a low test-retest reliability and thus considerable measurement variance. Therefore, large patient populations and long observation times are needed to detect treatment effects. Furthermore, clinical outcome measures cannot distinguish between symptomatic and disease-modifying treatment effects. Therefore, alternative biomarkers including neuroimaging may take on a more important role in this process. Because MR scanners are widely available and allow for non-invasive detection and quantification of changes in brain structure and metabolism, there is increasing interest in the use of MRI/MRS to monitor objectively treatment effects in clinical trials of neurodegenerative diseases. Particularly volumetric MRI has been used to measure atrophy rates in treatment trials of AD because the relationship between atrophic changes and neuron loss is well established and correlates well with clinical measures. More research is needed to determine the value of other MR modalities, i.e. diffusion, perfusion and functional MRI and MR spectroscopy, for clinical trials with neuroprotective drugs.

Evaluation of functional MRI markers in mild cognitive impairment

“…Elevated mI in MCI patients might be associated with glial activation and inflammation in the pathology of AD. 6,10,20 Therefore, an elevated mI followed later by a decreased NAA level might imply that glial activation preceded neuronal loss or dysfunction in MCI. 10 Furthermore, we found that ADC values increased incrementally among the controls, MCI and AD patients.…”

Proton magnetic resonance spectroscopy and cognition in patients with spastin mutations

“…We used independent-samples t-test with a 5% significance level to (4,8,34) f,m,m +/+/− +/+/+ C (12) f − + D (14) f − + E (19,20,22,28) f compare means in the two groups. The Pearson correlation coefficient was used to analyze associations between continuous variables.…”

“…Proton magnetic resonance spectroscopy (MRS) [18][19][20][21] has proved useful in investigating neurodegenerative diseases, but has so far only been performed in complicated forms of HSP [22,23]. Our hypothesis was that SPG4-HSP leads to cerebral changes reflecting a pathological process involving specific parts of the brain, among them motor cortex and frontal white matter.…”

Proton Magnetic Resonance Spectroscopy of the Central Nervous System

“…1 H-MRS has been demonstrated to be highly specific and sensitive to the diagnosis of Alzheimer's dementia (AD) [15]. Reduction in NAA is the most frequent 1 H-MRS finding in AD [84,85]. Single Voxel 1 H-MRS studies have consistently found reductions in NAA/Cr ratio in the hippocampal formation [85] as well as other temporal regions [86] and the posterior cingulate gyrus [87].…”