1H-MRS evaluation of metabolism in Alzheimer's disease and vascular dementia

Proton magnetic resonance spectroscopy (1H-MRS) allows major metabolites to be measured noninvasively in defined regions of the living brain, and can detect biochemical abnormalities where conventional structural imaging appears normal. MRS can be performed in 10 min as part of a clinical MRI examination. Biochemical abnormalities in Alzheimer's Disease (AD), vascular dementia (VaD) and other primary degenerative dementias have been investigated using MRS. Characteristic and consistent abnormalities in AD are decreased N-acetyl aspartate (NAA) and elevated myo-inositol (mI) in the mesial temporal and parieto-occipital cortex. These are thought to represent neuronal loss/dysfunction and gliosis, in anatomic distributions which reflect early pathological involvement and atrophy patterns in AD. Less consistent disturbances of glutamine and glutamate (Glx) and choline-containing compounds (Cho) have also been reported. Similar changes are seen in VaD; mostly in white matter, whereas in AD they predominate in cortical grey matter. The regional distribution of grey matter involvement may differ between AD and other degenerative dementias. Hence, both the nature and anatomic distribution of metabolite abnormalities contribute to diagnostic discrimination with MRS. NAA/mI ratios from short echo time spectra of the posterior cingulate region cortex discriminate reliably between AD subjects, normal individuals and those with VaD, and provides a useful clinical test, as an adjunct to structural imaging. Elevated mI is detected in mild cognitive impairment (MCI) and quantitative metabolite measures correlate with degrees of cognitive impairment in AD; these suggest a possible role for MRS in early diagnosis and for surrogate biochemical markers for monitoring disease progression and therapeutic response.     

1H-MRS asymmetry changes in the anterior and posterior cingulate gyrus in patients with mild cognitive impairment and mild Alzheimer's disease

Alzheimer's disease (AD) is the most common cause of dementia worldwide. Amnestic mild cognitive impairment (aMCI) is often the prodromal stage to AD. Most patients with aMCI harbor the pathologic changes of AD and demonstrate transition to AD at a rate of 10%–15% per year. Patients with AD and aMCI experience progressive brain metabolite changes. Accumulating evidence indicates that the asymmetry changes of left and right brain happen in the early stage of AD. However, the features of asymmetry changes in both anterior cingulate gyrus (ACG) and posterior cingulate gyrus (PCG) are still unclear. Here, we examine the left–right asymmetry changes of metabolites in ACG and PCG. Fifteen cases of mild AD patients meeting criteria for probable AD of NINDS-ADRDA, thirteen cases of aMCI according to the Mayo Clinic Alzheimer's Disease Research Center criteria, and sixteen cases of age-matched normal controls (NC) received Proton magnetic resonance spectroscopy (¹H-MRS) for measurement of NAA/mI, NAA/Cr, Cho/Cr, and mI/Cr ratios in the PCG and ACG bilaterally. We analyzed ¹H-MRS data by paired t-test to validate the left–right asymmetry of ¹H-MRS data in the PCG and ACG. In AD, there was a significant difference in mI/Cr between the left and right ACG (P < 0.001) and the left and right PCG (P = 0.007). In aMCI, there was a significant difference in mI/Cr between the left and right ACG (P < 0.001). In NC, there were no differences in the ratio value of metabolites NAA/mI, NAA/Cr, Cho/Cr, and mI/Cr between the left and right ACG and PCG. Thus, the left–right asymmetry of mI/Cr in the ACG and PCG may be an important biological indicator of mild AD.     

Reproducibility of magnetic resonance spectroscopy in correlation with signal-to-noise ratio

An increased amount of myoinositol (mI) relative to creatine (Cr) by proton MR spectroscopy ((1)H-MRS) measurement gives a useful aid for the diagnosis of Alzheimer's disease (AD). Previous results of test-retest measurement of mI, however, have shown variability more than twice as large as for other metabolites. The aims of this study were to analyze test-retest variability of (1)H-MRS measurements in correlation with signal-to-noise ratio (SNR). Ten subjects clinically suspected of mild AD were examined twice (2-14 days apart) with (1)H-MRS measurements of voxels placed at anterior and posterior cingulate cortex. The percent differences between two measurements (%differences) of mI/Cr showed a significant linear trend to decrease as average SNR increased, but %differences of N-acetylaspartate (NAA)/Cr and choline (Cho)/Cr did not. The average of %differences was 10.5, 15.0 and 20.8 for NAA/Cr, Cho/Cr, and mI/Cr, respectively, indicating a prominent deterioration of mI/Cr measurement reproducibility, which decreased to 6.96, 15.4 and 9.87, respectively, when the analysis was limited to measurements with SNR over 25. The results indicate that MRS measurements with high SNR should be used to obtain reliable assessments of mI/Cr as accurate diagnostic indicator of AD in clinical MR examinations.     

Proton spectroscopy in Alzheimer's disease and cognitive impairment not dementia: a community study

OBJECTIVE: To describe the proton magnetic resonance spectroscopy (1H-ERM) data in Alzheimer's disease (AD) and Cognitive Impairment Not Dementia (CIND) in a community sample. METHOD: We investigated subjects with AD (n=6), CIND (n=7) and normal control (n=7). 1H-ERM was performed with single voxel (8 cm3) placed in temporal, parietal and occipital regions and studied metabolites were: N-acetylaspartate (NAA), creatine (Cr), choline (Cho) and myo-inositol (mI). RESULTS: NAA concentration was higher in control subjects than AD and intermediated in CIND patients. Cho parietal plus occipital and Cr parietal plus Cho occipital classified correctly 92.3% of subjects Control vs AD. Temporal mI classified 78.6% of subjects between Control vs CIND. CONCLUSION: Spectroscopy can be used in the diagnosis and follow-up of individuals with cognitive impairment; evaluation of community subjects may show different patterns of brain metabolites distribution.     

Reduced NAA in the thalamus and altered membrane and glial metabolism in schizophrenic patients detected by 1H-MRS and tissue segmentation

Functional and structural abnormalities in the thalamus as well as a generalized phospholipid membrane disorder have been implicated in the pathogenesis of schizophrenic psychosis. To determine whether thalamic neuronal abnormalities and altered membrane-associated metabolites can be detected in schizophrenic patients, we used in vivo proton magnetic resonance spectroscopy (1H-MRS) in 32 acutely-ill, medicated schizophrenic patients and 17 age-matched controls. Thalamic and white matter metabolite concentrations (myo-inositol (mI), choline-containing compounds (Cho), total creatine (Cr) and N-acetylaspartate (NAA)) were estimated and corrected for atrophy (CSF) and gray and white matter contributions (GM, WM) by use of image-based voxel segmentation. Thalamic NAA was significantly reduced in schizophrenic patients, whereas Cho and mI were significantly increased in the parietal white matter. White matter Cr was significantly elevated in patients and correlated positively with the brief psychiatric rating scores (BPRS). Regional metabolite levels were inversely associated with GM and WM content reaching significance for mI and Cr in the thalamus and Cho and NAA in the white matter. Reduced NAA in the left thalamus of schizophrenic patients confirms and extends previous spectroscopic data and agrees well with histologic and imaging findings of reduced neuronal density and volume. Elevated Cho in line with 31P-MRS studies suggests increased myelin degradation thus further supporting a generalized membrane disorder in schizophrenic patients. In addition, we demonstrate the need to correct metabolite concentrations for regional tissue composition in studies employing patients with altered brain morphology.     

MRI和磁共振波谱在肝性脑病的应用价值

目的探讨MRI和磁共振波谱(1H-MRS)在肝性脑病中的应用价值。方法对6例肝性脑病患者行MRI和1H-MRS检查,检测基底节MRS的N-乙酰天门冬氨酸(NAA)、肌酸(Cr)、胆碱(Cho)、谷氨酰胺复合物(Glx)、肌醇(mI)的峰值,计算Cho、mI、NAA与Cr的比值,并与5名正常对照者比较。结果 MRI检查显示,6例肝性脑病患者双侧基底节T1WI均出现高信号,其中1例累及内囊、2例累及尾状核、1例累及中脑被盖;5例患者T2WI未见明显异常信号,1例患者因并发弥漫性脑水肿T2WI出现广泛高信号影。1H-MRS显示,肝性脑病组双侧基底节Cho峰、mI峰、Cho/Cr和mI/Cr显著低于正常对照组,Glx峰显著高于正常对照组(P<0.01～0.005);两组NAA/Cr比较差异无统计学意义。结论 MRI显示双侧基底节T1WI高信号是肝性脑病特征性改变。1H-MRS能准确地反映其脑代谢物质水平的变化。     

Altered white and gray matter metabolism in CADASIL: a proton MR spectroscopy and 1H-MRSI study

OBJECTIVE: Subcortical white matter hyperintensities (WMH) and small cystic lesions are the radiologic hallmark of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary angiopathy causing stroke in young adults. To further characterize the cerebral pathology in vivo we analyzed metabolite concentrations in normal and abnormal appearing brain tissue using single and multiple voxel proton MR spectroscopy (1H-MRS and 1H-MRSI). METHODS: Twenty patients with CADASIL and 21 age-matched controls were studied with 1H-MRSI at the level of the centrum semiovale; short echo time 1H-MRS was performed in six patients (WMH) and 10 controls. LCModel fits were used to estimate absolute and relative concentrations of N:-acetylaspartate (NAA), choline-containing compounds (Cho), total creatine (Cr) within WMH, normal appearing white matter (NAWM), and cortical gray matter (GM) as well as myo-inositol (mI) and lactate in WMH. RESULTS: 1H-MRSI-Patients with CADASIL showed significantly reduced NAA, Cho, Cr, and total metabolite content (Met(tot)) in WMH and NAWM. Normalization to Met(tot) revealed that NAA/Met(tot) was reduced in all regions, whereas Cho and Cr were relatively elevated in WMH. Short echo time 1H-MRS showed decreased NAA, Cr, Met(tot), and NAA/Met(tot) and elevated mI/Met(tot) and lactate in WMH. Metabolite changes were larger in severely affected subjects. Rankin scores correlated negatively with NAA/Met(tot) (all regions) and NAA/Cho (WMH), and positively with Cho/Met(tot) (WMH) and Cr/Met(tot) (NAWM). CONCLUSION: Marked metabolic abnormalities were observed in abnormal and normal appearing white matter in patients with CADASIL. The findings suggest axonal injury, enlarged extracellular spaces, myelin loss, and gliosis. The cortical abnormalities may reflect structural damage or functional neuronal impairment secondary to white matter pathology. NAA reductions were correlated with clinical disability emphasizing the clinicopathologic relevance of axonal injury in CADASIL.     

麻痹性痴呆患者磁共振波谱与认知障碍的相关研究

目的应用氢质子磁共振波谱(1H-proton magnetic resonance spectroscopy,1H-MRS)技术,探索麻痹性痴呆(general paresis of the insane,GPI)患者海马区代谢物水平特点。方法纳入GPI患者52例,健康中老年对照(normal control,NC)38例进行双侧海马区1H-MRS检查,比较N-乙酰天门冬氨酸(N-acetylaspartate,NAA)/肌酸、胆碱/肌酸,NAA/胆碱,胆碱/NAA和肌醇/肌酸的水平;并同日进行简易精神状态检查(MMSE)、蒙特利尔认知检查量表(Mo CA)量表评定,探索GPI患者海马区代谢物水平与病程严重程度的相关性。结果 GPI和NC两组比较:GPI组的双侧海马区NAA/Cr水平较NC组明显下降,差异有统计学意义(P0.001)。不同痴呆程度的GPI患者比较:重度痴呆组左侧海马区NAA/Cr水平较轻度痴呆组明显下降,差异有统计学意义(P0.001)。重度痴呆组右侧海马区的Cho/Cr和m I/Cr较轻度痴呆组升高(P0.05)。GPI组左侧海马区的NAA/Cr与MMSE、Mo CA呈正相关(P0.001)。结论 GPI患者均存在双侧海马区神经元损伤。且痴呆程度越重,左侧海马神经元损害越严重。     

Focal and lateralized subcortical abnormalities in unipolar major depressive disorder: an automated multivoxel proton magnetic resonance spectroscopy study.

BACKGROUND: The results of prior proton magnetic resonance spectroscopy ((1)H-MRS) studies in unipolar major depressive disorder (MDD) evaluating choline (Cho)/creatine (Cr) and N-acetyl-L-aspartate (NAA)/Cr ratios are mixed. These single-voxel or one-dimensional chemical-shift imaging (CSI) nonautomated (1)H-MRS studies has been unable to evaluate global or lateralized abnormalities in neuronal or membrane function. Using automated multivoxel two-dimensional CSI (1)H-MRS techniques, we tested the hypothesis that patients with MDD have focal neuronal and membrane abnormalities localized in the subcortical region. METHODS: Whole brain and subcortical measures of Cho, NAA, Cr, and myo-inositol (mI) were obtained in 18 patients with MDD and 20 control subjects using automated two-dimensional CSI (1)H-MRS. RESULTS: Compared with control subjects, MDD patients had a significantly lower mean NAA/Cr amplitude in the caudate and a significantly higher mean Cho/Cr amplitude in the putamen, particularly on the right side. No differences were observed for global whole brain measurements. CONCLUSIONS: The findings support reduced neuronal viability or function in the caudate and altered membrane phospholipid metabolism in the putamen for patients with MDD. Our results are consistent with prior magnetic resonance imaging, positron emission tomography, and postmortem reports of focal and lateralized abnormalities of the basal ganglia in MDD.     

急性脑梗死后血管性认知障碍的磁共振波谱研究

目的应用质子磁共振波谱(1 H-MRS)技术,探讨急性脑梗死后血管性认知障碍(VCI)患者的颅内物质代谢变化与认知损害的关系。方法对86例脑梗死患者(脑梗死组)及21名健康对照者(对照组)进行简易精神状态检查量表(MMSE)和蒙特利尔认知评分量表(MoCA)评分,并计算其视空间及执行功能评分。根据认知评分结果,将脑梗死组分为脑梗死后认知功能正常组(NCI)、脑梗死后VCI非痴呆组(VCIND)、脑梗死后痴呆组。对脑梗死组及健康对照进行1 H-MRS检查,测定右额叶、左颞叶、左丘脑及顶枕叶交界处N-乙酰天冬氨酸(NAA)/肌酸(Cr)、肌醇(mI)/Cr及胆碱复合物(Cho)/Cr比值,并分析脑梗死组物质代谢比值与认知评分(MoCA评分、视空间及执行功能)间的相关性。结果 (1)与对照组(左颞叶及左丘脑NAA/Cr 1.53±0.08、1.52±0.10)相比,VCIND组左颞叶及左丘脑NAA/Cr(1.46±0.07、1.47±0.07)降低(P=0.001、P=0.006);与VCIND组右额叶1.46±0.10比较,梗死后痴呆组右额叶、左颞叶及左丘脑NAA/Cr(1.38±0.14、1.39±0.06、1.42±0.09)降低(分别P<0.001、P<0.001、P=0.003)。对照组及NCI组间的各区域物质代谢比值无统计学差异(均P>0.05)。(2)所有脑梗死患者中,除右额叶Cho/Cr外,余各感兴趣区物质代谢比值与MoCA评分间均相关,其中以左颞叶、左丘脑NAA/Cr值与MoCA评分的相关性为著(分别r=0.566,P<0.001;r=0.485,P<0.001);除右额叶、丘脑及顶枕叶交界处Cho/Cr外,余各物质代谢比值与视空间及执行功能评分间相关,其中亦以左颞叶及左丘脑NAA/Cr值的相关性为著(分别NAA/Cr为r=0.591,P<0.001;r=0.491,P<0.001)。结论左丘脑及左颞叶代谢异常可能为VCI患者认知损害的早期关键环节之一,随着VCI病变进展可能整个皮质及皮质下环路区域都将出现代谢异常。     

Brain metabolism differs in Alzheimer's disease and Parkinson's disease dementia

BackgroundFew comparative studies exist of metabolic brain changes among neurodegenerative illnesses. We compared brain metabolic abnormalities in Alzheimer's disease (AD) and in Parkinson's disease with dementia (PDD) as measured by proton magnetic resonance spectroscopy (MRS).MethodsTwelve patients with idiopathic PDD, 22 patients with probable mild AD, and 61 healthy older controls underwent posterior cingulate MRS.ResultsPatients with AD exhibited reduced N-acetyl aspartate (NAA)/creatine (Cr) (P < .05) and increased choline (Cho)/Cr (P < .05) and myo-inositol (mI)/Cr (P < .01) compared with controls. Patients with PDD exhibited reduced NAA/Cr (P < .05) and glutamate (Glu)/Cr (P < .01) compared with controls. There was reduced Glu/Cr in PDD compared with AD (P < .01).ConclusionsPatients with AD and patients with PDD exhibited distinct brain metabolic MRS profiles. Findings suggest that comparison of brain MRS profiles across dementias provides useful direction for future study.     

Effects of Alzheimer disease on fronto-parietal brain N-acetyl aspartate and myo-inositol using magnetic resonance spectroscopic imaging

Previous magnetic resonance (MR) spectroscopy studies of Alzheimer disease (AD) reporting reduced N-acetyl aspartate (NAA) and increased myo-Inositol (mI) used single voxel techniques, which have limited ability to assess the regional distribution of the metabolite abnormalities. The objective of this study was to determine the regional distribution of NAA and mI alterations in AD by using MR spectroscopic imaging. Fourteen patients with AD and 22 cognitively normal elderly were studied using structural MR imaging and MR spectroscopic imaging. Changes of NAA, mI, and various metabolite ratios were measured in frontal and parietal lobe gray matter (GM) and white matter. This study found: (1) when compared with cognitively normal subjects, AD patients had increased mI and mI/creatine (Cr) ratios primarily in parietal lobe GM, whereas frontal lobe GM and white matter were spared; (2) in the same region where mI was increased, AD patients had also decreased NAA and NAA/Cr ratios, replicating previous findings; (3) however, increased mI or mI/Cr ratios did not correlate with decreased NAA or NAA/Cr ratios; and (4) using mI/Cr and NAA/Cr together improved sensitivity and specificity to AD from control as compared with NAA/Cr alone. In conclusion, decreased NAA and increased mI in AD are primarily localized in parietal lobe GM regions. However, the NAA and mI changes are not correlated with each other, suggesting that they represent different processes that might help staging of AD.     

Single voxel magnetic resonance spectroscopy at 3 Tesla in a memory disorders clinic: early right hippocampal NAA/Cr loss in mildly impaired subjects

In this study, we use magnetic resonance spectroscopy (MRS) at 3 Tesla to measure N-acetyl aspartate (NAA), myo-inositol (mI) and choline (Cho) to creatine (Cr) ratios in R (right) and L (left) hippocampi (H) in 8 mildly memory impaired (MMI), 6 probable Alzheimer's Disease (PRAD), and 17 control subjects. NAA/Cr was significantly reduced in the RH in the MMI group and bilaterally in the PRAD group vs. controls. No other metabolite differences were noted between the three groups. Five MMI subjects have converted to PRAD in follow-up. These findings suggest that RH NAA/Cr ratios measured at 3 Tesla may be a sensitive marker of future progression to dementia in a clinically defined population with isolated memory complaints.     

Maturation of limbic regions in Asperger syndrome: a preliminary study using proton magnetic resonance spectroscopy and structural magnetic resonance imaging

People with autistic spectrum disorders (ASD, including Asperger syndrome) may have developmental abnormalities in the amygdala-hippocampal complex (AHC). However, in vivo, age-related comparisons of both volume and neuronal integrity of the AHC have not yet been carried out in people with Asperger syndrome (AS) versus controls. We compared structure and metabolic activity of the right AHC of 22 individuals with AS and 22 healthy controls aged 10-50 years and examined the effects of age between groups. We used structural magnetic resonance imaging (sMRI) to measure the volume of the AHC, and magnetic resonance spectroscopy ((1)H-MRS) to measure concentrations of N-acetyl aspartate (NAA), creatine+phosphocreatine (Cr+PCr), myo-inositol (mI) and choline (Cho). The bulk volume of the amygdala and the hippocampus did not differ significantly between groups, but there was a significant difference in the effect of age on the hippocampus in controls. Compared with controls, young (but not older) people with AS had a significantly higher AHC concentration of NAA and a significantly higher NAA/Cr ratio. People with AS, but not controls, had a significant age-related reduction in NAA and the NAA/Cr ratio. Also, in people with AS, but not controls, there was a significant relationship between concentrations of choline and age so that choline concentrations reduced with age. We therefore suggest that people with AS have significant differences in neuronal and lipid membrane integrity and maturation of the AHC.     

MRS in relation to hippocampal volume in the oldest old

The MRS brain metabolite ratio N-acetylaspartate (NAA)/myo-inositol (mI) is reported to be decreased in AD. MRS was used to study medial temporal and parietal regions in 60 cognitively healthy subjects older than 85 years. Subjects with small hippocampal volumes, a putative risk factor for dementia, had significantly lower NAA/mI in parietal and temporal lobes compared with other subjects. Neuropsychological tests and APOE genotype did not correlate with MRS ratios. MRS measures are candidate biomarkers for dementia risk.     

氢质子磁共振波谱对Alzheimer病神经生化改变的分析

目的研究Alzheimer病(Alzheimerdisease,AD)的氢质子磁共振波谱分析改变,并与认知正常的老年志愿者(normalcognition,NC)进行比较。方法对AD组21例及NC组20名被观察者行磁共振波谱分析,测定双侧海马、颞顶叶联合区的N乙酰天门冬氨酸(N acetylaspartate,NAA)、胆碱(choline,Cho)和肌醇(myo inositol,mI)与肌酸(creatine,Cr)的比值。采用SPSS11.5软件进行统计分析。结果AD组和NC组双侧海马和颞顶联合区的NAA/Cr差异有显著性(P<0.05),双侧海马和左侧颞顶叶联合区的mI/Cr差异有显著性(P<0.05),双侧海马和颞顶叶联合区的Cho/Cr差异无显著性(P<0.05)。只有左侧海马的NAA/Cr水平下降与AD的严重程度呈正相关(r=0.470,P<0.05)。结论磁共振波谱分析可发现AD海马及颞顶联合区的NAA/Cr、mI/Cr改变,左侧海马NAA/Cr的减低可帮助评价AD的严重程度。     

Cortical brain metabolism as measured by proton spectroscopy is related to memory performance in patients with amnestic mild cognitive impairment and Alzheimer's disease

AIMS: To investigate the relationship between verbal memory performance and brain metabolism as determined by proton spectroscopy ((1)H-MRS) in selected cortical brain regions. To characterize metabolite abnormalities across the continuum of degenerative disease from mild impairment to dementia. METHODS: 27 controls, 27 amnestic mild cognitive impairment (aMCI) patients and 35 Alzheimer's disease (AD) patients. Verbal memory was assessed with the Text Memory Test, the Wordlist Learning Test (WL-Learning Test), and with a memory screening test, the Memory Alteration Test (M@T). Single-voxel (1)H-MRS was obtained in the posterior cingulate (P-CING), left temporal pole (L-TPOLE) and left posterior temporoparietal region (L-TPAR). RESULTS: WL-Learning Test scores were inversely associated with myoinositol/creatine ratios (mI/Cr) in the L-TPAR (r = -0.404, p < 0.002). Negative associations were also observed between M@T global scores and mI/Cr in the P-CING (r = -0.42; p < 0.001), L-TPOLE (r = -0.34; p < 0.005) and L-TPAR (r = -0.46; p < 0.001). A positive association was found between M@T scores and N-acetylaspartate concentrations in the P-CING (r = 0.33; p < 0.003). CONCLUSION: Verbal learning performance is related to metabolic changes in cortical brain regions known to be involved in the neurodegenerative process of aMCI and AD.     

Cognitive impairment: classification by 1H magnetic resonance spectroscopy.

1H magnetic resonance spectroscopy (MRS) allows accurate and non-invasive in vivo metabolic study, and is a useful tool for the diagnosis of different forms of dementias. Cognitive impairment pathologies have been almost exclusively studied with MRS by comparison with healthy without a global comparison amongst Alzheimer disease (AD), vascular dementia, mild cognitive impairment (MCI) and major depression patients with cognitive impairment. Whereas decrease of N-acetylaspartate (NAA) and increase myo-Inositol (mI) at different brain locations by 1H MRS are common features of AD, Choline (Cho) alterations have been inconclusive. In our study, 64 patients with cognitive impairment were evaluated by 1H MRS using two echo times (31 and 136 ms). There were statistical differences between dementia (AD and vascular dementia) and non-dementia (MCI and depression) spectra at posterior cingulate gyrus. Cho/Cr, mI/Cr and NAA/Cr have been valuables for the differentiation amongst the different cognitive impairment entities. NAA/mI provides the best area under the ROC curve with the highest sensitivity (82.5%) and specificity (72.7%) in diagnosing AD. NAA/mI and mI/Cr ratios differed amongst the four cognitive impairment degenerative pathologies. Metabolic MRS differences found amongst patients with cognitive impairment entities can be useful to differentiate between AD, vascular dementia, MCI and depression.     

(1)H-MR spectroscopy differentiates mild cognitive impairment from normal brain aging

This study aimed to characterize the white matter biochemical profile of healthy elderly subjects, mild cognitive impairment (MCI) subjects, and early Alzheimer's disease (AD) patients. We used proton magnetic resonance spectroscopy ((1)H-MRS) to measure myo-inositol, creatine, N-acetylaspartate (NAA) and choline levels from a volume of interest located in the paratrigonal white matter bilaterally. A significantly higher myo-inositol/creatine ratio was found in MCI subjects and AD patients than in controls. The NAA/creatine ratio was reduced in AD patients in the left hemisphere compared to control subjects. The choline/creatine ratio was not significantly different among the three groups. These data suggest that MCI is different from normal brain aging, having a white matter biochemical pattern similar to AD.     

Longitudinal metabolic and cognitive changes in mild cognitive impairment patients

Advancements in clinical therapies have identified the need for biomarkers of early Alzheimer disease that distinguish the earliest stages of pathology and target those patients who are likely to gain the most benefit. The aim of this study was to characterize the longitudinal metabolic changes measured by 1H magnetic resonance spectroscopy in correlation to neuropsychologic indices of episodic memory, attention and mental processing speed, language facility, and executive function in subjects with mild cognitive impairment (MCI). Quantitative 1H magnetic resonance spectroscopy of the posterior cingulate gyrus was performed and repeated at 11.56+/-4.3 months. N-acetyl aspartate (NAA), total choline (Cho), total creatine (Cr), myo-inositol (mI), and glutamate/glutamine (Glx) metabolite levels were measured, corrected for cerebrospinal fluid dilution, and ratios calculated in MCI and cognitively normal subjects. In the first study, MCI subjects showed lower NAA levels, NAA/Cho, and NAA/mI ratios and increased Cho/Cr and mI/Cr compared with controls. In the follow-up study, 36% of the MCI subjects [atypical MCI (atMCI)] showed interval increases in NAA, Cr, and Glx levels compared with 64% of MCI subjects (typical MCI) who showed an interval decrease in NAA, Cr, and Glx. Both MCI subgroups had higher Clinical Dementia Rating scores and lower scores on episodic memory, phonemic, and semantic word fluency tasks, compared with controls. The annualized rate of change in metabolic and cognitive status did not differ between normal aging and MCI subjects. atMCI subjects showed significant negative correlations between metabolite levels and executive function task scores, with NAA/mI showing a significant positive correlation with phonemic and semantic word fluency. There were no significant correlations between metabolite levels and cognitive performance in tMCI subjects; however, NAA/mI and mI/Cr were negatively correlated with executive function tasks. These results indicate 2 distinct evolving metabolite profiles that correlate with changes in executive function and can be used to differentiate MCI from normal aging.