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.     

Brain Proton MRS is Correlated with Financial Abilities in Patients with Alzheimer’s Disease

Persons with Alzheimer’s disease (AD) demonstrate frank impairments in the performance of everyday functional abilities. However, the neuroanatomic and neuro-metabolic correlates of these functional deficits in mild AD are largely unknown. Using 3-Tesla proton magnetic resonance spectroscopy (¹H-MRS) of the posterior cingulate gyrus in 14 patients with mild AD and 14 healthy adult controls, we sought to determine the brain metabolic correlates of financial impairments in mild AD. Both N-acetylaspartate (NAA) and choline-containing compounds (Cho) were found to be abnormal in mild AD. In AD patients, NAA showed a positive correlation with financial abilities, while Cho showed a possible negative correlation with financial abilities. These findings suggest that metabolic abnormalities of posterior cortical paralimbic regions may reflect the underlying neuropathological processes that are instrumental in the degradation of financial abilities in mild AD. Proton MRS could offer a means to track brain changes associated with functional change in mild AD.     

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.     

A comprehensive review of proton magnetic resonance spectroscopy studies in dementia and Parkinson's disease

We reviewed the literature of proton magnetic resonance spectroscopy (MRS) in dementia and Parkinson's disease (PD) and quantitatively compared the reported values of the markers N-acetyl aspartate (NAA), choline, and myo-Inositol between control and disease groups. We analysed a total of 27 reports in dementia. Combining the quantitative data from these showed a relative decrease of 15% in NAA level in the temporal lobe tissue in patients with Alzheimer's disease (AD) compared with controls. The rest of the brain showed a seemingly uniform 10% decrease in NAA levels in AD compared with controls. myo-Inositol was raised by about 15%, again uniformly throughout the brain, but there was no evidence for changed levels of choline. We found 15 reports of MRS in PD, which show a small decrease (5%) in the NAA level in the lentiform nucleus compared with controls. In progressive supranuclear palsy (PSP), there is a greater decrease in NAA levels in the frontal region and the lentiform nucleus. This may aid in the diagnosis of PSP. Further research is needed to determine spectroscopic changes in other dementias, to monitor how markers change with disease progression and to establish clinical utility.     

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.     

In vivo proton magnetic resonance spectroscopy of the temporal lobe in Alzheimer's disease

PURPOSE: Prior proton magnetic resonance spectroscopy (MRS) studies have consistently reported decreased brain n-acetyl aspartate (NAA) levels and increased myo-inositol (mI) levels in subjects with Alzheimer's disease (AD) relative to healthy comparison subjects. These studies have usually been conducted in small and homogeneous populations of patients with established Alzheimer's disease. Few studies have tested the usefulness of this finding in a general population seeking evaluation for memory loss and other cognitive declines. We designed a study to evaluate the significance of single-voxel proton MRS findings in these patients with memory loss and other cognitive declines. GENERAL METHOD: Thirty-five subjects with a primary complaint of memory loss and other cognitive declines were consecutively referred over a period of 13 months to a specialty clinic. Patients with a diagnosis of mild to moderate probable Alzheimer's disease (N = 22), non-Alzheimer's dementia (depression, multiinfarct dementia, Parkinson's Disease, Korsakoff's Psychosis, and bipolar disorder; N = 13), and healthy comparison subjects (N = 18) were examined with respect to possible differences in metabolites using proton MRS in a 3.4-ml anterior temporal lobe voxel. FINDINGS: The Alzheimer's disease group had 10.7% lower NAA/creatine (Cr) ratios relative to the healthy comparison group and 9.4% lower NAA/creatine relative to the non-Alzheimer's dementia group (15.0% lower NAA/creatine relative to the depression subgroup of the non-Alzheimer's dementia group). There were no significant differences in choline (Cho) or myo-inositol ratios among the groups. There were significant correlations between NAA/creatine ratios and mini-mental status exam (MMSE) scores in subjects with Alzheimer's disease (t = 2.41, p = 0.032) but not in subjects with non-Alzheimer's dementia or in its depression subgroup. CONCLUSIONS: This study found a reduction in the neuronal marker NAA in the anterior temporal lobe of patients diagnosed with probable Alzheimer's disease, using a short add-on proton MRS exam. This change was not observed in patients whose memory loss and other cognitive declines were not attributed to Alzheimer's disease, suggesting that it may aid in the diagnosis or detection of Alzheimer's disease.     

Brain N-acetylaspartate is reduced in Parkinson disease with dementia

Persons with Parkinson disease (PD) are at risk of developing dementia. Of the dementias affecting patients with PD, PD with dementia (PDD) is not well understood, although brain imaging studies to date have observed characteristic patterns of brain atrophy. Metabolic differences have been observed in magnetic resonance spectroscopy (MRS) studies comparing patients with PDD to nondemented PD patients, although it is unclear whether PDD patients have abnormally low MRS ratios compared with healthy age-matched adults. In this study, 12 patients with PDD, 12 patients with PD and no dementia, and 12 age-matched healthy older adults underwent MRS of the posterior cingulate gyrus. Patients with PDD showed lower N-acetylaspartate/creatine (NAA/Cr) compared with controls (P=0.004) and compared with nondemented PD patients (P=0.003). No abnormalities were observed in choline/Cr or myo-Inositol/Cr. NAA/Cr was correlated with mental status in patients with PD and in patients with PDD (r=0.56; P=0.029). The findings suggest that reduced NAA/Cr of the posterior cingulate could be used as a marker for dementia in patients with PD. Future studies investigating the utility of brain MRS as a predictor of dementia in PD and comparing brain metabolism in PDD with other dementias seem warranted.     

Localized proton magnetic resonance spectroscopy of a cerebellar tumor in a two-year-old child

Noninvasive localized proton magnetic resonance spectroscopy (MRS) was used for differential diagnosis of a focal brain lesion in a 2.5-year-old girl. The clinical signs were a mild head tilt and neck pain. Magnetic resonance imaging (MRI) revealed a lesion in the right hemisphere of the cerebellum, but its nature remained obscure. In this lesion quantitative determinations of cerebral metabolites by fully relaxed, short-echo-time proton MRS revealed markedly lowered N-acetylaspartate (NAA) and pronounced elevations of choline-containing compounds (Cho) and myo-inositol (Ins), whereas metabolite concentrations in cortical gray matter and white matter were within normal ranges. The metabolite pattern of the lesion indicated loss of vital neuroaxonal tissue (low NAA) and enhanced glial proliferation (high Cho and Ins), which, together with the MRI morphology, suggested a brain tumor. The diagnosis was established by neurosurgical exploration and total extirpation of the tumor. Histology confirmed an astrocytoma (WHO II). After 2 weeks' recovery the child was discharged with no neurological signs.     

Short echo time single-voxel 1H magnetic resonance spectroscopy in magnetic resonance imaging-negative temporal lobe epilepsy: different biochemical profile compared with hippocampal sclerosis

Single-voxel proton magnetic resonance spectroscopy (1H MRS) has shown abnormalities in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS). Many TLE patients, however, do not have HS or other lesions on quantitative magnetic resonance imaging (MRI) (MRI-negative). Fifteen control subjects, 15 patients with unilateral HS, and 15 MRI-negative TLE patients underwent 1H MRS at an echo time of 30 msec on a 1.5-T GE Signa scanner. Voxels were tailored to the individual hippocampi. N-Acetylaspartate (NAA), creatine, choline, total glutamate plus glutamine (Glx), and myo-inositol (Ins) were quantitated by using an external standard and LCModel, a user-independent quantitation method. Normal ranges were defined as the control mean +/- 2.5 SD. In HS patients, 12 of 15 had abnormally low NAA in sclerotic hippocampi; 3 of these 12 also had abnormally low NAA contralaterally. Abnormally low NAA/Ins ratios lateralized the side affected by HS in 7 of 15 patients, without any bilateral abnormalities. In 15 MRI-negative TLE patients, 4 had abnormally low hippocampal NAA ipsilateral to seizure onset, 1 of whom had abnormally low NAA bilaterally. Analysis of groups of subjects showed a bilateral decrease in NAA, most marked in patients with HS and on the side of seizure onset. The mean NAA/Ins ratio was lower in patients with HS than in control subjects and in MRI-negative patients. The concentration of Glx was higher ipsilateral to seizure onset in MRI-negative patients than in HS patients. Quantitative short echo time 1H MRS identified abnormalities in 87% of patients with HS and 27% of MRI-negative TLE patients in concordance with other lateralizing data. In individual and group comparisons, 1H MRS described a metabolite profile in the hippocampi of MRI-negative TLE patients that was different from patients with HS, with an increase in Glx and a less marked decrease in NAA than was seen in HS.     

MRI and MRS alterations in the preclinical phase of murine prion disease: association with neuropathological and behavioural changes

Prion diseases are fatal chronic neurodegenerative diseases. Previous qualitative magnetic resonance imaging (MRI) and spectroscopy (MRS) studies report conflicting results in the symptomatic stages of the disease, but little work has been carried out during the earlier stages of the disease. Here we have used the murine ME7 model of prion disease to quantitatively investigate MRI and MRS changes during the period prior to the onset of overt clinical signs (20+ weeks) and have correlated these with pathological and behavioural abnormalities. Using in vivo MRI, at the later stages of the preclinical period (18 weeks) the diffusion of tissue water was significantly reduced, coinciding with significant microglial activation and behavioural hyperactivity. Using in vivo MRS, we found early (12 weeks) decreases in the ratio of N-acetyl aspartate to both choline (NAA/Cho) and creatine (NAA/Cr) in the thalamus and hippocampus, which were associated with early behavioural deficits. Ex vivo MRS of brain extracts confirmed and extended these findings, showing early (8-12 weeks) decreases in both the neuronal metabolites NAA and glutamate, and the metabolic metabolites lactate and glucose. Increases in the glial metabolite myo-inositol were observed at later stages when microglial and astrocyte activation is substantial. These changes in MRI and MRS signals, which precede overt clinical signs of disease, could provide insights into the pathogenesis of this disease and may enable early detection of pathology.     

Thalamic proton magnetic resonance spectroscopy in vegetative state induced by traumatic brain injury

OBJECTIVES: To determine whether proton magnetic resonance spectroscopy (MRS), a newer radiographic technology, would be useful in the evaluation of the thalamus of patients in vegetative states resulting from traumatic brain injury. METHODS: 14 victims of severe traumatic brain injury who were in the vegetative state and whose magnetic resonance images of the thalamus were normal underwent bilateral thalamic proton (MRS) studies. The N-acetyl aspartate to creatine (NAA:Cr) and choline to creatine (Cho:Cr) ratios were obtained for each patient. The proton thalamic MRS findings of patients who were in a persistent vegetative state (n = 8) and in patients who had regained awareness after being in the vegetative state (n = 6) were compared with proton thalamic MRS findings in five healthy volunteers. RESULTS: While conventional magnetic resonance imaging suggested that each patient had a normal thalamus, proton MRS indicated that the thalamus of each patient in the series was damaged. The NAA:Cr ratio was significantly lower in the thalami of both the patients who remained in a persistent vegetative state for the duration of the study and in those who regained awareness after being in the vegetative state (p < 0.001). In addition, NAA:Cr ratios were lower in the group of patients who remained in a persistent vegetative state than in the group of patients who regained awareness after being in the vegetative state (p < 0.001). CONCLUSIONS: Results suggest that the NAA:Cr ratio within the thalamus is significant and that thalamic MRS may be helpful when attempting to determine the degree of severity of neuronal and axonal injury in patients in the vegetative state.     

Hippocampal pathology in schizophrenia: magnetic resonance imaging and spectroscopy studies

The hippocampus is a site of previously reported structural and functional abnormalities in schizophrenia. We used magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) to measure gray matter volumes, the neuronal marker N-acetylaspartate (NAA), and the combination of glutamate (Glu), glutamine (Gln), and gamma-aminobutyric acid (GABA), designated Glx. Measurements were obtained of the medial temporal lobe, centered on the hippocampus, in 10 male patients with schizophrenia (3 neuroleptic-medicated and 7 medication-free), and 10 matched normal volunteers. MRI volumetric measurements and MRS data obtained with short echo time (TE=20 ms) one-dimensional STEAM chemical shift imaging (CSI) on a GE 1.5 Tesla Signa system were analyzed. A laterality index ?(L-R)/(L+R) was generated from the ratio of Glx to choline-containing compounds (Cho) to test asymmetry changes. Reliability of the MRS measures was assessed with five test-retest studies of healthy volunteers and showed coefficients of variation (CV) in the range of 36-44% for the MRS ratios and standard deviations (S.D.) of 0.15-0.17 for the laterality indices. The Glx/Cho laterality index showed a relative right-sided excess in this region in the patients (-0.23+/-0.20) compared to the controls (+0.06+/-0.20), which was not confounded by tissue composition or placement variability of the MRS voxels. Hippocampal volume deficit and asymmetry were not significant, and other MRS measures showed no differences between patients and controls. The preliminary finding of a lateralized abnormality in Glx is consistent with postmortem findings of asymmetric neurochemical temporal lobe abnormalities in schizophrenia.     

Magnetic resonance spectroscopy.

Magnetic resonance spectroscopy (MRS) complements magnetic resonance imaging (MRI) as a non-invasive means for the characterization of tissue. While MRI uses the signal from hydrogen protons to form anatomic images, proton MRS uses this information to determine the concentration of brain metabolites such as N-acetyl aspartate (NAA), choline (Cho), creatine (Cr) and lactate in the tissue examined. The most widely used clinical application of MRS has been in the evaluation of central nervous system disorders.MRS has its limitations and is not always specific but, with good technique and in combination with clinical information and conventional MRI, can be very helpful in diagnosing certain entities. For example, a specific pattern of metabolites can be seen in disorders such as Canavan's disease, creatine deficiency, and untreated bacterial brain abscess. MRS may also be helpful in the differentiation of high grade from low grade brain tumors, and perhaps in separating recurrent brain neoplasm from radiation injury.     

Correlation study of optimized voxel-based morphometry and (1)H MRS in patients with mesial temporal lobe epilepsy and hippocampal sclerosis

Purpose:

To assess whether structural and metabolic brain abnormalities are correlated in MTLE/HS syndrome.

Methods:

Optimized voxel‐based morphometry (VBM) of gray matter concentration (GMC) and gray matter volume (GMV) and proton magnetic resonance spectroscopy measurements from both‐sided hippocampal and thalamic regions were performed in 20 MTLE/HS patients and 20 sex‐ and age‐matched healthy controls. The local GMC and GMV values were calculated in both the affected and unaffected hippocampi and ipsilateral and contralateral thalami in patients and healthy subjects, and these were compared. VBM variables and NAA, NAA/Cr and NAA/(Cr+Cho) values from the investigated brain regions were correlated.

Results:

(1) Analysis revealed significantly more extensive GMV reduction than GMC reduction in patients' affected hippocampus. In addition, significant GMV reduction was observed in the ipsilateral thalamus in MTLE/HS patients. (2) Significant decreases in all VBM and MRS variables were revealed in the affected hippocampus. Whilst practically normal GMC values were revealed in patients' both‐sided thalamic regions, a significant decrease in local GMV and metabolic measurements were found in the patients' ipsilateral thalamus. (3) Pearson's correlations between structural and metabolic abnormalities were significant for the ipsilateral thalamus only.

Conclusion:

Structural and metabolic abnormalities as detected by optimized voxel‐based morphometry and ¹H MRS in hippocampal and thalamic regions are only partially correlated in MTLE/HS patients. It seems therefore reasonable that both methods reflect different aspects of brain pathology, which, at least to some degree, might be independently ongoing. Hum Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.

     

The profile of hippocampal metabolites differs between Alzheimer's disease and subcortical ischemic vascular dementia, as measured by proton magnetic resonance spectroscopy

Alzheimer's disease (AD) and subcortical ischemic vascular dementia (SIVD) have overlapping pathologies and risk factors, but their underlying neurodegenerative mechanisms are basically different. We performed magnetic resonance spectroscopy (MRS) to study metabolite differences between the two diseases in vivo. The subjects were 31 patients with SIVD and 99 with AD. Additionally, 45 elderly subjects were recruited as controls. We measured N-acetylaspartate (NAA), glutamine and glutamate (Glx), and myoinositol (mIns) concentration quantitatively using a 1.5-T MR scanner. N-acetylaspartate and Glx concentrations decreased in the hippocampus and cingulate/precuneal cortices (PCC) in both AD and SIVD patients, and the NAA decrease in the hippocampus was more prominent in AD than in SIVD. Interestingly, the pattern of mIns concentration changes differed between the two disorders; mIns was increased in AD but not increased in SIVD. If one differentiates between AD and SIVD by the mIns concentration in the hippocampus, the area under the receiver operating characteristic curve was 0.95, suggesting a high potential for discrimination. Our results suggest that proton MRS can provide useful information to differentiate between AD and SIVD. The difference of mIns concentrations in the hippocampus and PCC seems to reflect the different neurodegenerative mechanisms of the two disorders.     

Clinically benign multiple sclerosis despite large T2 lesion load: can we explain this paradox?

Magnetic resonance imaging (MRI) techniques such as magnetization transfer imaging and magnetic resonance spectroscopy (MRS) may reveal otherwise undetectable tissue damage in multiple sclerosis (MS) and can serve to explain more severe disability than expected from conventional MRI. That an inverse situation may exist where non-conventional quantitative MRI and MRS metrics would indicate less abnormality than expected from T2 lesion load to explain preserved clinical functioning was hypothesized. Quantitative MRI and MRS were obtained in 13 consecutive patients with clinically benign MS (BMS; mean age 44 +/- 9 years) despite large T 2 lesion load and in 15 patients with secondary progressive MS (SPMS; mean age 47 +/- 6 years) matched for disease duration. The magnetization transfer ratio (MTR), magnetization transfer rate (kfor), brain parenchymal fraction (BPF) and brain metabolite concentrations from proton MRS were determined. BMS patients were significantly less disabled than their SPMS counterparts (mean expanded disability status score: 2.1 +/- 1.1 versus 6.2 +/- 1.1; P < 0.001) and had an even somewhat higher mean T2 lesion load (41.2 +/- 27.1 versus 27.9 +/- 24.8 cm3; P = 0.19). Normal appearing brain tissue histogram metrics for MTR and kfor, mean MTR and kfor of MS lesions and mean BPF were similar in BMS and SPMS patients. Levels of N-acetyl-aspartate, choline and myoinositol were comparable between groups. This study thus failed to explain the preservation of function in our BMS patients with large T2 lesion load by a higher morphologic or metabolic integrity of the brain parenchyma. Functional compensation must come from other mechanisms such as brain plasticity.     

Selective reduction of N-acetylaspartate in medial temporal and parietal lobes in AD

BACKGROUND: Both AD and normal aging cause brain atrophy, limiting the ability of MRI to distinguish between AD and age-related brain tissue loss. MRS imaging (MRSI) measures the neuronal marker N-acetylaspartate (NAA), which could help assess brain change in AD and aging. OBJECTIVES: To determine the effects of AD on concentrations of NAA, and choline- and creatine-containing compounds in different brain regions and to assess the extent NAA in combination with volume measurements by MRI improves discrimination between AD patients and cognitively normal subjects. METHODS: Fifty-six patients with AD (mean age: 75.6 +/- 8.0 years) and 54 cognitively normal subjects (mean age: 74.3 +/- 8.1 years) were studied using MRSI and MRI. RESULTS: NAA concentration was less in patients with AD compared with healthy subjects by 21% (p < 0.0001) in the medial temporal lobe and by 13% to 18% (p < 0.003) in parietal lobe gray matter (GM), but was not changed significantly in white matter and frontal lobe GM. In addition to lower NAA, AD patients had 29% smaller hippocampi and 11% less cortical GM than healthy subjects. Classification of AD and healthy subjects increased significantly from 89% accuracy using hippocampal volume alone to 95% accuracy using hippocampal volume and NAA together. CONCLUSION: In addition to brain atrophy, NAA reductions occur in regions that are predominantly impacted by AD pathology.     

The relationship between MRI and PET changes and cognitive disturbances in MS

Cognitive dysfunction in multiple sclerosis (MS) is present in approximately 50% of the patients. Only moderate correlations have been found between cognitive dysfunction and T(2) lesion load, black holes or atrophy. Cognitive dysfunction in MS is probably related to the overall disease burden of the brain including abnormalities in normal appearing white matter (NAWM) and cortical grey matter, which is undetected with conventional magnetic resonance imaging (MRI). Hence, imaging techniques that embrace such abnormalities are needed to achieve better correlation with cognitive dysfunction. MR spectroscopy (MRS) performed with multi-slice echo planar spectroscopic imaging (EPSI) and PET measurements of brain metabolism as the cortical cerebral metabolic rate of glucose are imaging methods that are able to provide information on axonal loss or dysfunction in both MS lesions and in NAWM and cortical grey matter. Measurements of global NAA using multi-slice EPSI is a new promising method for measurement of the global neuron capacity and can be repeated with only little discomfort and without any risk for the patient.     

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.     

Structural and metabolic damage in brains of patients with SPG11-related spastic paraplegia as detected by quantitative MRI

The goal of this work was to assess brain structural and metabolic abnormalities of subjects with SPG11 and their relevance to clinical disability by using quantitative magnetic resonance (MR) metrics. Autosomal recessive hereditary spastic paraplegia (AR-HSP) with thin corpus callosum and cognitive decline is a complex neurological disorder caused by mutations in the SPG11 gene in most cases. Little is known about the process leading to corticospinal and white matter degeneration. We performed conventional MRI/MR spectroscopic imaging ((1)H-MRSI) examinations in 10 HSP patients carrying an SPG11 mutation and in 10 demographically matched healthy controls (HC). We measured in each subject cerebral white matter hyperintensities (WMHs), normalized global and cortical brain volumes, and (1)H-MRSI-derived central brain levels of N-acetylaspartate (NAA) and choline (Cho) normalized to creatine (Cr). Clinical disability was assessed according to patients' autonomy in walking. Conventional MRI showed WMHs in all patients. Global brain volumes were lower in patients than in HC (p < 0.001). Decreased values were diffusely found also in cortical regions (p < 0.01). On (1)H-MRSI, NAA/Cr values were lower in SPG11 patients than in HC (p = 0.002). Cho/Cr values did not differ between patients and HC. Cerebral volume decreases and NAA/Cr in the corona radiata correlated closely with increasing disability scores (p < 0.05). Quantitative MR measures propose that widespread structural and metabolic brain damage occur in SPG11 patients. The correlation of these MR metrics with measures of patients' disease severity suggests that they might represent adequate surrogate markers of disease outcome.