Proxies of cognitive reserve and their effects on neuropsychological performance in patients with mild cognitive impairment

Cognitive reserve (CR) modulates the relationship between clinical and pathological phenotypes by restricting the negative effect of cerebral lesions on cognition, according to the CR hypothesis. In this study, we evaluated 18 healthy subjects and 21 patients with mild cognitive impairment (MCI) using conventional MRI, magnetic resonance spectroscopy (MRS), the Mini-Mental State Examination (MMSE), the Wechsler Memory Scale (WMS), and the Montreal Cognitive Assessment (MoCA). The MMSE, WMS and MoCA assessments were repeated 1 year later. The MRS analysis results showed that the N-acetyl-aspartate peak area (NAA; t = 5.122, P < 0.001) and the NAA/creatine (Cr), NAA/myo-inositol (mI) and NAA/choline (Cho) ratios were significantly changed in patients with MCI compared with the control subjects (all P < 0.01). The MoCA was significantly related to the NAA/Cho ratio (R = 0.443), the NAA/Cr ratio (R = 0.533), and the NAA peak area (R = 0.814; all P < 0.05), but was unrelated to the NAA/mI ratio (R = 0.400, P = 0.072). We found that the hippocampal volume was significantly correlated with the MoCA, WMS and MMSE (R = 0.704, 0.677, 0.542 respectively; all P < 0.05). Education level had a positive effect on changes in the MoCA, MMSE, and WMS 1 year later. We believe that MoCA and WMS results, MRI hippocampal volume and other related indicators (NAA peak area, NAA/Cr ratio, NAA/mI ratio, and NAA/Cho ratio) may reflect the degree of CR capacity, and that the number of years of education can significantly affect the changes in cognitive function in patients with MCI. Therefore, increasing levels of education and life skills training can help increase CR, reduce the risk of MCI, and slow down the appearance of clinical manifestations and clinical progress in patients with MCI.     

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.     

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.     

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。     

Multimodal imaging in diagnosis of Alzheimer's disease and amnestic mild cognitive impairment: value of magnetic resonance spectroscopy, perfusion, and diffusion tensor imaging of the posterior cingulate region

The purpose of this study was to assess metabolic, perfusion, and microstructural changes within the posterior cingulate area in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) using advanced MR techniques such as: spectroscopy (MRS), perfusion weighted imaging (PWI), and diffusion tensor imaging (DTI). Thirty patients with AD (mean age 71.5 y, MMSE 18), 23 with aMCI (mean age 66 y, MMSE 27.4), and 15 age-matched normal controls (mean age 69 y, MMSE 29.5) underwent conventional MRI followed by MRS, PWI, and DTI on 1.5 Tesla MR unit. Several metabolite ratios (N-acetylaspartate [NAA]/creatine [Cr], choline [Ch]/Cr, myoinositol [mI]/Cr, mI/NAA, mI/Cho) as well as parameters of cerebral blood volume relative to cerebellum and fractional anisotropy were obtained in the posterior cingulate region. The above parameters were correlated with the results of neuropsychological tests. AD patients showed significant abnormalities in all evaluated parameters while subjects with aMCI showed only perfusion and diffusion changes in the posterior cingulate area. Only PWI and DTI measurements revealed significant differences among the three evaluated subject groups. DTI, PWI, and MRS results showed significant correlations with neuropsychological tests. DTI changes correlated with both PWI and MRS abnormalities. Of neuroimaging methods, DTI revealed the highest accuracy in diagnosis of AD and aMCI (0.95, 0.79) followed by PWI (0.87, 0.67) and MRS (0.82, 0.47), respectively. In conclusion, AD is a complex pathology regarding both grey and white matter. DTI seems to be the most useful imaging modality to distinguish between AD, aMCI, and control group, followed by PWI and MRS.     

Comparative diagnostic utility of different MR modalities in mild cognitive impairment and Alzheimer's disease

This study compares the diagnostic accuracy of magnetic resonance (MR)-based hippocampal volumetry, single voxel (1)H MR spectroscopy ((1)H MRS) and MR diffusion-weighted imaging (DWI) measurements in discriminating patients with amnestic mild cognitive impairment (MCI), Alzheimer's disease (AD) and normally aging elderly. Sixty-one normally aging elderly, 24 MCI and 22 AD patients underwent MR-based hippocampal volumetry, (1)H MRS and DWI. (1)H MRS voxels were placed over both of the posterior cingulate gyri, and N-acetyl aspartate (NAA)/creatine (Cr), myoinositol (MI)/Cr and NAA/MI ratios were obtained. Apparent diffusion coefficient (ADC) maps were derived from DWI, and hippocampal borders were traced to measure hippocampal ADC. At 80% specificity, the most sensitive single measurement to discriminate MCI (79%) and AD (86%) from controls was hippocampal volumes. The most sensitive single measurement to discriminate AD from MCI was posterior cingulate gyrus NAA/Cr (67%). At high specificity (>85-90%), combinations of MR measures had superior diagnostic sensitivity compared with any single MR measurement for the AD vs. control and control vs. MCI comparisons. The MR measures that best discriminate more from less affected individuals along the cognitive continuum from normal to AD vary with disease severity. Selection of imaging measures used for clinical assessment or monitoring efficiency of therapeutic intervention should be tailored to the clinical stage of the disease.     

A decrease in N-acetylaspartate and an increase in myoinositol in the anterior cingulate gyrus are associated with behavioral and psychological symptoms in Alzheimer's disease

BACKGROUND AND PURPOSE: The cognitive decline in Alzheimer's disease (AD) patients has been reported to involve alterations in the medial temporal lobe and the posterior cingulate gyrus. On the other hand, the neurochemical pathologies of the behavioral and psychological symptoms of dementia (BPSD) have not been sufficiently discussed. The aim of this study was to clarify the pathologies of BPSD in AD patients. METHODS: Thirty patients with probable AD were included and underwent the following assessments: Mini Mental State Examination (MMSE), Clock Drawing Test (CDT), Story Recall Test (SRT), Behavioral pathology in Alzheimer's disease (BEHAVE-AD) and proton MRS ((1)H-MRS). None of them had been medicated for BPSD. RESULTS: The MRS study revealed that MMSE, CDT, and SRT scores were positively related to N-acetyl-aspartate (NAA)/creatine(Cr) and negatively related to myoinositol (mI)/Cr in the posterior cingulate gyrus, but not in the anterior cingulate gyrus. On the other hand, the scores obtained in two categories of BEHAVE-AD (delusional thought/ activity disturbances) were negatively related with NAA/Cr and positively related with mI/Cr in the anterior cingulate gyrus, but not in the posterior cingulate gyrus. CONCLUSION: We conclude that BPSD and the decline in cognitive function in AD might have separate pathologies.     

壳聚糖、磷脂酰胆碱对轻度认知功能障碍患者脑组织氢质子磁共振波谱成像的影响

目的观察壳聚糖、磷脂酰胆碱对轻度认知功能障碍(MCI)患者海马氢质子磁共振波谱成像(1H-MRSI)的影响。方法对15例MCI患者(MCI组)和15名正常老年人(正常对照组)进行海马1H-MRSI检查。给予MCI组患者壳聚糖、磷脂酰胆碱治疗2个月后对其进行复查,比较N-乙酰天门冬氨酸(NAA)/肌酸(Cr)、胆碱(Cho)/Cr、肌醇(mI)/Cr的比值。结果与正常对照组相比,MCI组服药前、后NAA/Cr比值显著降低,mI/Cr比值显著升高(均P<0.05),Cho/Cr的差异无统计学意义。MCI组治疗后的NAA/Cr比值较治疗前明显升高(P<0.05),mI/Cr比值明显降低(P<0.05),Cho/Cr比值治疗前后的差异无统计学意义。结论1H-MRSI显示,壳聚糖和磷脂酰胆碱能改善脑组织的代谢,可能对MCI有一定的治疗作用。     

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.     

脑白质疏松症患者认知功能与海马代谢关系的研究

目的探讨脑白质疏松症患者认知损害与海马代谢间的关系。方法对108例性别、受教育程度和脑血管病危险因素相匹配且有记忆力减退主诉的患者进行神经心理学评价,通过氢质子磁共振波谱测量左侧海马区N-乙酰天冬氨酸/肌酸、肌醇/肌酸、胆碱复合物/肌酸,以及谷氨酸和谷氨酰胺复合物α峰/肌酸比值,以观察与记忆相关脑区的代谢物变化。结果脑白质疏松症组患者简易智能状态检查量表(24.00)和蒙特利尔认知评价量表(16.50)中位数评分低于对照组(27.00和21.00),组间差异有统计学意义(均P=0.000);其中以视觉执行能力(1.00:3.00)、注意力(4.00:5.00)、语言(1.00:2.00)、延迟回忆(0.00:2.00)等项评分降低最为显著(P<0.05或P<0.01)。韦氏记忆量表中文修订版进一步测验显示,脑白质疏松症组患者瞬时记忆(5.06±2.86)和短时记忆(32.76±13.31)评分均显著低于对照组[(7.68±4.41)和(46.95±1481)],且差异具有统计学意义(P<0.05或p<0.01);左侧海马区N-乙酰天冬氨酸、肌醇、胆碱复合物与肌酸比值测定,两组差异无统计学意义(P>0.05)。结论脑白质疏松症引起的认知损害主要表现为视觉执行能力、注意力、语言及记忆(瞬时记忆和短时记忆)显著降低,未发现这一改变与左侧海马代谢变化有关。     

Regional metabolic patterns in mild cognitive impairment and Alzheimer's disease: A 1H MRS study

BACKGROUND: Mild cognitive impairment (MCI) is a recently described transitional clinical state between normal aging and AD. Assuming that amnestic MCI patients had pathologic changes corresponding to an early phase and probable AD patients to a later phase of the disease progression, the authors could approximate the temporal course of proton MR spectroscopic (1H MRS) alterations in AD with a cross-sectional sampling scheme. METHODS: The authors compared 1H MRS findings in the superior temporal lobe, posterior cingulate gyri, and medial occipital lobe in 21 patients with MCI, 21 patients with probable AD, and 63 elderly controls. These areas are known to be involved at different neurofibrillary pathologic stages of AD. RESULTS: The N-acetylaspartate (NAA)/creatine (Cr) ratios were significantly lower in AD patients compared to both MCI and normal control subjects in the left superior temporal and the posterior cingulate volumes of interest (VOI) and there were no between-group differences in the medial occipital VOI. Myoinositol (MI)/Cr ratios measured from the posterior cingulate VOI were significantly higher in both MCI and AD patients than controls. The choline (Cho)/Cr ratios measured from the posterior cingulate VOI were higher in AD patients compared to both MCI and control subjects. CONCLUSION: These findings suggest that the initial 1H MRS change in the pathologic progression of AD is an increase in MI/Cr. A decrease in NAA/Cr and an increase in Cho/Cr develop later in the disease course.     

Similar 1H magnetic resonance spectroscopic metabolic pattern in the medial temporal lobes of patients with mild cognitive impairment and Alzheimer disease

Structures of the medial temporal lobes are recognized to play a central role in memory processing and to be the primary sites of deterioration in Alzheimer disease (AD). Mild cognitive impairment (MCI) represents potentially an intermediate state between normal aging and AD. Proton magnetic resonance spectroscopy (MRS) was used to examine brain metabolic changes in patients with AD and MCI in the medial temporal lobes (MTLs), parietotemporal cortices (PTCs) and prefrontal cortices (PFCs). Fourteen patients with MCI, 14 patients with mild AD and 14 age- and sex-matched control subjects were studied. Patients with AD and MCI demonstrated significant reductions of NAA/H(2)O and Cho/H(2)O in the left MTL relative to control subjects. Patients with AD showed mI/H(2)O increases relative to patients with MCI and control subjects in all six regions investigated, and a statistically significant mI/H(2)O increase was measured in the right PTC. Patients with AD and MCI demonstrated the same metabolic pattern in the left MTL, suggesting a similar pathological process underlying memory impairment. Increased mI signal appears to be a neurochemical abnormality associated mostly with AD and the dementia process. Some interhemispheric metabolite asymmetries were increased in AD patients.     

MR spectroscopy in monitoring the treatment of Wilson's disease patients

The aim of this study was to determine the effectiveness of brain proton magnetic resonance spectroscopy (¹H‐MRS) for monitoring therapy in Wilson's disease (WD) patients. Voxels were located in the globus pallidus (right, left). We followed 17 newly diagnosed WD cases for 1‐year period. During this observation period, 6 neurological and 9 hepatic patients improved, while 2 neurological patients deteriorated. The pretreatment ¹H‐MRS analysis showed a statistically significant lower level of mI/Cr, NAA/Cr, and higher Lip/Cr in all WD patients with improvement compared with controls. In patients with hepatic signs, a statistically significant increase of mI/Cr and Glx/Cr was observed in the second (1 year posttreatment) ¹H‐MRS. In patients with neurological improvement after treatment in the follow‐up ¹H‐MRS, a statistically significant increase of NAA/Cr was noted. During neurological deterioration, a decrease of Glx/Cr and NAA/Cr was seen, in contrast to another neurologically impaired patient with liver failure exacerbation, where a decrease of mI/Cr and increase of Glx/Cr was observed. The alternations of NAA/Cr ratio in neurologically impaired patients and mI/Cr and Glx/Cr in patients with liver failure could be a sensitive marker of the clinical recovery and deterioration in those WD patients. ¹H‐MRS is a technique that can be used for accurate monitoring of treatment efficacy in WD patients. © 2008 Movement Disorder Society     

Rôle de l’impulsivité dans la relation entre surpoids et TDAH chez l’enfant : étude exploratoire des caractéristiques cliniques,neuropsychologiques et neurobiochimiques

ObjectivesRelationship between Attention Deficit Hyperactivity Disorder (ADHD) and obesity in adults and children had previously been established in research studies. Brain imaging studies pointed out the important role of the prefrontal region in both ADHD and obesity. However, the underlying link between ADHD and obesity is not well understood. The hypothesis that impulsivity could play a role has been explored in clinical studies of ADHD and Binge Eating Disorders or Loss of Control Eating, with contradictory results. Our study aims to compare children with ADHD and obesity to children with ADHD and normal weight. We propose to compare these two populations with clinical, neuropsychological and brain spectroscopy investigation, focusing specifically on impulsivity items.MethodTen children presenting overweight or obesity were selected from a larger population of children with ADHD (5–12y) and paired with regard to gender and age with ten children with ADHD and normal weight from the same population. Conners Rating scales version parents (CPRS) and teachers (CTRS), Conners’ Continuous Performance Test II (CPT-II), and Magnetic Resonance Spectroscopy (MRS) metabolites in five regions of interest (left and right prefrontal, left and right striatal and left cerebellum regions) were measured for all the children. For MRS, ratio to creatinine levels of following metabolites were measured: glycerophosphocholine + phosphocholine/creatinine (GPC + PCh/Cr), glutamate + glutamine (Glu + Gln/Cr), myoinositol (mI/Cr) et N-acétylaspartate + N-acétylaspartylglutamate (NAA + NAAG/Cr).ResultsHyperactivity/Impusivity and Conners Global Index (CGI) subscales of Conners rating scales showed a higher rate of impulsivity in children with ADHD and obesity as compared to children with ADHD and normal weight. Neuropsychological results were comparable in the two groups. Finally, MRS showed a higher GPC + PCh/Cr ratio in right prefrontal cortex in children with ADHD and obesity as compared to children with ADHD and normal weight.ConclusionsOur results are concordant with the hypothesis that impulsivity could be the link between obesity and ADHD in a population of children with ADHD. The right prefrontal regions seem to be areas of interests that need more research in the study of the link between obesity and ADHD.     

Volume,metabolites and neuroinflammation of the hippocampus in bipolar disorder – A combined magnetic resonance imaging and positron emission tomography study

BackgroundThe hippocampus is one of the brain regions that is involved in several pathophysiological theories about bipolar disorder (BD), such as the neuroinflammation theory and the corticolimbic metabolic dysregulation theory. We compared hippocampal volume and hippocampal metabolites in bipolar I disorder (BD-I) patients versus healthy controls (HCs) with magnetic resonance imaging (MRI) and spectroscopy (MRS). We post hoc investigated whether hippocampal volume and hippocampal metabolites were associated with microglial activation and explored if potential illness modifying factors affected these hippocampal measurements and whether these were associated with experienced mood and functioning.Materials and methodsTwenty-two BD-I patients and twenty-four HCs were included in the analyses. All subjects underwent psychiatric interviews as well as an MRI scan, including a T1 scan and PRESS magnetic resonance spectroscopy (MRS). Volumetric analysis was performed with Freesurfer. MRS quantification was performed with LC Model. A subgroup of 14 patients and 11 HCs also underwent a successful [¹¹C]-(R)-PK11195 neuroinflammation positron emission tomography scan.ResultsIn contrast to our hypothesis, hippocampal volumes were not decreased in patients compared to HC after correcting for individual whole-brain volume variations. We demonstrated decreased N-acetylaspartate (NAA) + N-acetyl-aspartyl-glutamate (NAAG) and creatine (Cr) + phosphocreatine (PCr) concentrations in the left hippocampus. In the explorative analyses in the left hippocampus we identified positive associations between microglial activation and the NAA + NAAG concentration, between alcohol use and NAA + NAAG concentration, between microglial activation and the depression score and a negative relation between Cr + PCr concentration and experienced occupational disability. Duration of illness associated positively with volume bilaterally.ConclusionCompared to HCs, the decreased NAA + NAAG concentration in the left hippocampus of BD-I patients suggests a decreased neuronal integrity in this region. In addition we found a positive relation between microglial activation and neuronal integrity in vivo, corresponding to a differentiated microglial function where some microglia induce apoptosis while others stimulate neurogenesis.     

脑白质疏松症患者认知功能与海马代谢关系的研究

目的探讨脑白质疏松症患者认知损害与海马代谢间的关系。方法对108例性别、受教育程度和脑血管病危险因素相匹配且有记忆力减退主诉的患者进行神经心理学评价,通过氢质子磁共振波谱测量左侧海马区N-乙酰天冬氨酸／肌酸、肌醇／肌酸、胆碱复合物／肌酸,以及谷氨酸和谷氨酰胺复合物a峰／肌酸比值,以观察与记忆相关脑区的代谢物变化。结果脑白质疏松症组患者简易智能状态检查量表（24．00）和蒙特利尔认知评价量表（16．50）中位数评分低于对照组（27．00和21．00）,组间差异有统计学意义（均P=0．000）;其中以视觉执行能力（1．00：3．00）、注意力（4．00：5．00）、语言（1．00：2．00）、延迟回忆（0．00：2．00）等项评分降低最为显著（P〈0．05或P〈0．01）。韦氏记忆量表中文修订版进一步测验显示,脑白质疏松症组患者瞬时记忆（5．06±2．86）和短时记忆（32．76±13．31）评分均显著低于对照组[（7．68±4．41）和（46．95±14．81）],且差异具有统计学意义（P〈0．05或P〈0．01）;左侧海马区N-乙酰天冬氨酸、肌醇、胆碱复合物与肌酸比值测定,两组差异无统计学意义（P〉0．05）。结论脑白质疏松症引起的认知损害主要表现为视觉执行能力、注意力、语言及记忆（瞬时记忆和短时记忆）显著降低,未发现这一改变与左侧海马代谢变化有关。     

Comparative evaluation of MRS and SPECT in prognostication of patients with mild to moderate head injury

Magnetic resonance spectroscopy (MRS) and single-photon emission computed tomography (SPECT) have only been individually studied in patients with head injury. This study aimed to comparatively assess both in patients with mild to moderate head injury. Patients with a Glasgow Coma Scale (GCS) score of 9–14 who underwent MRS and/or SPECT were evaluated in relation to various clinical factors and neurological outcome at 3 months. There were 56 SPECT (Tc99m-ethylcysteinate dimer [ECD]) studies and 41 single voxel proton MRS performed in 53 patients, with 41 patients having both. Of the 41 who underwent MRS, 13 had a lower N-acetyl-aspartate/creatine (NAA/Cr) ratio, 14 had a higher choline (Cho)/Cr ratio, 19 were normal, and nine had bilateral MRS abnormalities. Of the 56 who underwent SPECT, 22 and 19 had severe and moderate hypoperfusion, respectively. Among those in Traumatic Coma Data Bank CT scan category 1 and 2, 50% had MRS abnormalities, whereas 64% had SPECT hypoperfusion, suggesting greater incremental validity of SPECT over MRS. In univariate analyses, GCS, moderate/severe hypoperfusion and bilateral SPECT changes were found to have significant association with unfavorable outcome (odds ratio 13.2, 15.9, and 4.4, and p values <0.01, 0.01, and 0.05, respectively). Patients with lower NAA/Cr ratio in MRS had more unfavorable outcomes, however this was not significant. In multivariate analysis employing binary logistic regression, GCS and severe hypoperfusion on SPECT were noted to have significant association with unfavorable outcome, independent of age, CT scan category, and MRS abnormalities (p values = 0.02 and 0.04, respectively). To conclude, ECD-SPECT seems to have greater sensitivity, incremental validity and prognostic value than single voxel proton MRS in select patients with head injury, with only severe hypoperfusion in SPECT significantly associated with unfavorable outcome independent of other confounding factors.     

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.     

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.