The Application On Magnetic Resonance Spectroscopy In Mild Cognitive Impairment And Alzheimer’s Disease

Background With an aging population that is getting increasingly older, the prevalence of dementia is increasing. Alzheimer disease(AD) is the most common form of dementia. It is a neurodegenerative disease first described by Alois Alzheimer in 1907. AD is characterized by progressive loss of cognitive function as well as a distinct pathological profile of neurofibrillary tangles and amyloid plaques that begins in the mediotemporal lobe and limbic areas as early as decades before clinical diagnosis. Unfortunately, the diagnosis of dementia is typically made at a stage in which the underlying pathology has reached an advanced and irreversible state. In the past decade, Mild Cognitive Impairment(MCI) has been identified as an early stage on the path towards dementia.It is an intermediate clinical stage along the cognitive spectrum between healthy aging and dementia that many consider to be prodromal AD. As the burden of AD is projected to increase in the near future, the interest in MCI as a predictor has also increased manifold.MCI may thus be important to predict the development of dementia at a stage when it can still be treated, thereby stopping or at least delaying the progression to dementia. The molecular neuropathology of Alzheimer disease and MCI is thought to precede structural brain alteration by several years. Hence, measurements of tissue metabolism may be sensitive biomarkers of very early disease processes in AD and MCI. Magnetic resonance spectroscopy(MRS)is a novel technique that provides a detailed picture in the vivo biochemistry of the brain. MRS has many advantages. The MRS spectrum is easily obtained from a conventional MRI machine requiring relatively little time and it is sensitive to regional changes in metabolites even that is subtle.Also it is non-invasive and free from radiation.The technique of MRS enhances the sensitivity and specificity of differentiating MCI or ADfrom healthy subjects.Objective 1. To address the possible role of brain regional metabolic differences among different types of MCI(A-MCI,V-MCI) and normal controls.2. The second objective is to compare the characters in the cognitive impairment between A-MCI and V-MCI and to find the differences.3. The third objective is to examine the relationship between metabolite measures and cognitive test results.4.To investigate whether there would be a consistent pattern that would consolidate and highlight the changes in AD and demonstrate the utility and value on MRS in the early diagnosi of AD.Methods 1. Brain regional metabolites in patients with amnestic mild cognitive impairment(A-MCI),vascular mild cognitive impairment(V-MCI) and normal controls were measured via proton magnetic resonance spectroscopy(1H MRS) technique. Twenty-eight patients with A-MCI, 24 patients with V-MCI and 34 normal controls(NC) were tested by a battery of neuropsychological screens and accepted a MRI scan at first. All the subjects underwent the single voxel1 H MRS on a 3.0-T-scanner(Signa; GE Medical Systems, Milwaukee, WI) with the regions of interest(ROIs) located in the left frontal lobe, left basal ganglia and left hippocampus.2.We integrated the published literature using meta-analysis to identify patterns of metabolite changes in AD from January 2000 to December 2014. A search was performed in the Pub Med, and Cochrane databases using the keywords “Mild cognitive impairment AND magnetic resonance spectroscopy, MCI AND metabolites”.The search was limited to English language and Chinese studies only. Additionally, the reference lists of all included studies were examined for relevant publications. Twenty-nine MRS studies(with a total of 859 AD patients and 1063 healthy controls) were classified according to brain regions. The data was analyzed using STATA software version 11.0(Stata Corp, College Station, TX, USA). Hedges’ g was used as standard mean deviation in a random effect model. The I2 statistic is derived from Cochran’s Q and is more intuitive to interpret.It describes the percentage of variation due to heterogeneity. Heterogeneity was assessed by the I2statistic. Heterogeneity is said to be low(I2<50%), or high(I2>50%). Indicates significant result at p≤0.05.A meta-analysis was performed only when there were at least three studies in one category(i.e., specific metabolite in a brain region).Results 1.There was no significant differences among the groups in age,gender and education years. But the prevalence of hypertension was significantly higher in the A-MCI as well as in the V-MCI groups than that in the control group. 2. The CAMCOG-C and MMSE scores in A-MCI and V-MCI were significantly lower in comparison with that in NC(P < 0.01). There were multi-domain cognitive impairment both in A-MCI and V-MCI,but not single-domain.3. The A-MCI showed lower NAA/CR ratio in the left hippocampus. In V-MCI, NAA/CR ratio in the left frontal lobe was reduced.NAA/CR ratio in the left basal ganglia among 3 groups has no statistical differences.CHO/CR and MI/CR among 3 groups have no statistical differences.4. There was a significant correlation between recent memory score and the NAA/CR ratio in the left hippocampus in A-MCI.In V-MCI, NAA/CR ratio in the left frontal lobe was positively correlated with the cognitive score evaluated with Cambridge Cognitive Examination-Chineseversion(CAMCOG-C) and its subscores of orientation, praxi, language and language comprehension.5.Contrasted to healthy control(HC),N-Acetyl Aspartate(NAA) measures in AD were consistently reduced in the posterior cingulated(PC),hippocampus,parietal grey matter(PGM) and frontal grey matter(FGM),but no difference in paratrigonal white matter(PWM). Choline(CHO) was reduced in the hippocampus. Myo-inositol(MI) concentration was raised in the PC. No difference on creatine was found between AD and HC. NAA/CR ratio was consistently reduced in the hippocampus, PC, PWM and temporal lobe.MI/CR ratio was raised in PWM and PC.NAA/MI ratio was reduced in the PC.CHO/CR ratio was raised in the PC.MI/NAA ratio was raised in the PC.Conclusions 1.The NAA/Cr ratio was significantly reduced in hippocampus in A-MCI and significantly decreased in frontal lobe in V-MCI. The reduced NAA/Cr was positively correlated with the cognitive function. Multi-domain cognitive impairment not only existed in A-MCI but also in V-MCI. In conclusion,1HMRS may be a useful tool for differentiating A-MCI and V-MCI.2. The results from the meta-analysis revealed robust metabolite changes in some ROIs in patients with AD. N-Acetyl Aspartate may be the most reliable marker for the differentiation of AD subjects from healthy elderly, though myo-inositol,choline, and the ratios may also contribute towards the diagnosis.