Neuroimaging in Alzheimer disease: an evidence-based review

Current clinical criteria (DSM-IIIR and NINCDS-ADRDA) for the diagnosis of dementia and AD are reliable; however, these criteria remain to be validated by clinicians of different levels of expertise at different clinical settings. Structural neuroimaging has an important role in initial evaluation of dementia for ruling out potentially treatable causes. Although CT is the appropriate choice when brain tumors, subdural hematoma, or normal pressure hydrocephalus is suspected, MR imaging is more sensitive to the white-matter changes in vascular dementia. The diagnostic accuracy of PET, SPECT, 1H MRS, and MR volumetry of the hippocampus for distinguishing patients with AD from healthy elderly individuals is comparable to the accuracy of a pathologically confirmed clinical diagnosis. Sensitivity of PET for distinguishing patients with dementia with Lewy bodies from AD, however, is higher than that of clinical evaluation; similarly, SPECT and 1H MRS may be adjuncts to clinical evaluation for distinguishing patients with frontotemporal dementia from those with AD. Neuroimaging is valuable in predicting future development of AD in patients with MCI and in carriers of the ApoE epsilon 4 allele who are at a higher risk of developing AD than are cognitively normal elderly individuals. Quantitative MR techniques (e.g., MR volumetry, DWI, magnetization transfer MR imaging, and 1H MRS) and PET are sensitive to the structural and functional changes in the brains of patients with MCI, and hippocampal volumes on MR imaging are associated with future development of AD in these individuals. PET is also sensitive to the regional metabolic decline in the brains of carriers of the ApoE epsilon 4 allele. The longitudinal decrease of whole brain and hippocampal volumes on MR imaging, NAA levels on 1H MRS, cerebral glucose metabolism on PET, and cerebral blood flow on SPECT are associated with rate of cognitive decline in patients with AD. These neuroimaging markers may be useful for monitoring symptomatic progression in groups of patients with AD for drug trials. Furthermore, antemortem MR-based hippocampal volumes correlate with the pathologic stage of AD, and the rate of hippocampal volume loss on MR imaging correlates with clinical disease progression in the cognitive continuum from normal aging to MCI and to AD. Hence, as an in vivo correlate of pathologic involvement, structural imaging measures are potential surrogate markers for disease progression in patients with established AD and in patients with prodromal AD, who will benefit most from disease-modifying therapies underway.     

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.     

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.     

Magnetic resonance spectroscopy in AD

Proton MR spectroscopy (MRS) studies have found both decreased N-acetylaspartate (NAA) and increased myo-inositol in the occipital, temporal, parietal, and frontal regions of patients with AD, even at the early stages of the disease. This diffuse NAA decline is independent of regional atrophy and probably reflects a decrease in neurocellular viability. Reports of such metabolite changes are now emerging in the mild cognitive impairment prodrome and in investigation of the medial temporal lobe. In vivo quantitation of neural choline in AD has been inconclusive because of poor test-retest repeatability. Less robust evidence using phosphorous MRS has shown significant phosphocreatine decline and increments in the cell membrane phosphomonoesters in the early, and possibly asymptomatic, stages of the disease. These phosphorous metabolite disturbances normalize with disease progression. Phosphodiester concentration has been found to correlate strongly with AD plaque counts. MRS of AD has therefore introduced new pathophysiologic speculations. Studies of automated MRS for AD diagnosis have reported high sensitivity and moderate specificity, but are yet to test prospective samples and should be extended to include at least two MRS regions of interest. MRS has promise for predicting cognitive status and monitoring pharmacologic efficacy, and can assess cortical and subcortical neurochemical change.     

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.     

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.     

Proton magnetic resonance spectroscopy in Alzheimer's disease, a review

Alzheimer disease (AD), a progressive neurodegenerative disorder, is the most common cause of dementia in the elderly. Current consensus statements have emphasized the need for early recognition of AD. In vivo magnetic resonance spectroscopy (MRS) has recently opened new possibilities for noninvasively assessing metabolic and functional correlates of dementia in research and clinical settings. The purpose of this article is to provide a conceptual review, covering the principles of MRS and main pathological findings related to AD. H1 MRS has the possibility of being a neuroimaging marker because the potential clinical applications in patients with AD include a role in early diagnosis and differential diagnosis of AD, a role in prognosis of disease severity, a role in predicting future progression to AD in patients with mild cognitive impairment and tracking disease progression. MRS can also help in the evaluation of treatment effects and in the development of new therapies. In conclusion, H1 MRS has great potential in becoming an adjunct to clinical evaluation and management of dementia in the future. Nevertheless, there is still need for further research for the implementation of this neuroimaging technique in the management of dementia.     

Proton magnetic resonance spectroscopy of the brain in dementia

Proton magnetic resonance spectroscopy (MRS) allows accurate and noninvasive biochemical assay of living tissues. In vivo measurements provided by MRS have greatly enhanced our understanding of the pathophysiology of dementia. Increases in choline and myo-inositol (markers of membrane turnover) have been demonstrated in several studies on patients with Alzheimer's disease (AD), suggesting the presence of a significant cellular membrane (and glial) pathology in this disorder. Large decreases in brain N-acetylaspartate (NAA) (a marker of neuroaxonal integrity) are commonly seen in AD as well as in other forms of dementia in cerebral gray and white matter, indicating the presence of significant axonal damage. Since greater NAA decreases have been demonstrated in brains of patients with clinically more severe disease, NAA could provide an index relevant to patients' clinical status. Brain metabolic changes can be independent of abnormalities detected by conventional magnetic resonance imaging (MRI), since proton MRS may show a normal metabolic pattern in patients with mild neurological impairment and severe MRI abnormalities. However, quantitative measurements of regional brain volumes can be useful in the diagnosis of dementia. Thus, proton MRS, alone or combined with new quantitative magnetic resonance techniques, can provide sensitive indices able to monitor disease progresson or effects of drug therapy.     

Cognition in multiple sclerosis: relevance of lesions,brain atrophy and proton MR spectroscopy

The overall burden of brain MRI-visible lesions does not fully account for cognitive impairment in multiple sclerosis (MS). Several MRI studies have highlighted the importance of brain damage in the normal-appearing brain tissue. Brain atrophy (global, cortical, white and deep grey matter) is related to cognitive deficits in MS patients and this holds true since the earliest disease stages. Non-conventional MRI techniques such as proton MR spectroscopy have related metabolic changes in specific brain areas to specific cognitive deficits. Overall, data provided by MRI support the notion that cognitive disturbances need to be considered for a more complete clinical characterisation of patients with MS, including those with “benign” MS.     

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.     

Magnetic resonance spectroscopyin vivo: applications in neurological disorders

Magnetic resonance (MR) spectroscopy (MRS) is performed using the same magnets and computers as conventional MR imaging (MRI), However, unlike conventional MRI, which provides structural information, MRS provides chemical information that represents pathologically specific measures useful for diagnosis and monitoring of patients affected by neurological disorders. This review will focus on selected clinical applications of MRS that have been demonstrated to have clinical use. These include phosphorus MRS of muscle to diagnose metabolic muscle disease, and proton MRS of brain to lateralize temporal lobe epilepsy, to classify brain tumors, and to evaluate the natural history and pathology of multiple sclerosis.     

Magnetic resonance spectroscopy in focal epilepsy: 31P and 1H spectroscopy.

Magnetic resonance spectroscopy (MRS) is rapidly becoming a clinical and research tool in epilepsy. Animal studies have demonstrated metabolic abnormalities in the interictal and ictal state showing energy depletion and changes in neuronal compounds. Similarly, clinical studies have demonstrated consistent abnormalities involving energy (31P) and cellular dependent (1H) compounds. Phosphorus MRS (31P) shows lateralizing metabolic dysfunction in approximately 65-75 p. 100 of patients with temporal lobe epilepsy (PCr/Pi). Proton MRS (1H) using single-voxel or chemical shift imaging has demonstrated a high sensitivity in lateralizing temporal lobe epilepsy (65-96 p. 100) with bilateral changes seen in 35-45 p. 100 of patients. The role of MRS in extra-temporal lobe epilepsy is less accurate because of the spatial limitations of current techniques. Further advances in this field promise to improve the clinical utility of MRS in epilepsy.     

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.     

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.     

The role of MRI in dementia

Neuroimaging techniques aimed at studying structural changes of the brain may provide useful information for the diagnosis and the clinical management of patients with dementia. Magnetic resonance imaging (MRI) may show abnormalities amenable to surgical treatment in a significant percentage of patients with cognitive impairment. MRI may also assist the differential diagnosis in dementia associated with metabolic or inflammatory diseases.MRI has the potential to detect focal signal abnormalities which may assist the clinical differentiation between Alzheimer's disease (AD) and vascular dementia (VaD). Severe temporal atrophy, hyperintensities involving the hippocampal or insular cortex, and gyral hypointense bands are more frequently noted in AD. Basal ganglionic/thalamic hyperintense foci, thromboembolic infarctions, confluent white matter and irregular periventricular hyperintensities are more common in VaD.The high sensitivity of MRI in detecting T2 hyperintense lesions and the low specificity off white matter lesions have resulted in a poor correlation between MRI findings and both neuropathological and clinical manifestations. In particular, MRI has disclosed a series of white matter focal changes in the elderly population, which are not necessarily associated with cognitive dysfunction.The recent advent of a new MRI method sensitive to the microstructural changes of white matter, the so-called diffusion tensor imaging, may be helpful in correlating clinical manifestations with white matter abnormalities.     

Magnetic resonance spectroscopic imaging in temporal lobe epilepsy: neuronal dysfunction or cell loss?

BACKGROUND: Magnetic resonance spectroscopy (MRS) has demonstrated consistent metabolic abnormalities in temporal lobe epilepsy. The reason for decreases in N-acetylated compounds are thought to be related to neuronal hippocampal cell loss as observed in hippocampal sclerosis. However, mounting evidence suggest that the N-acetylated compound decreases may be functional and reversible. OBJECTIVE: To establish whether the metabolic changes measured by MRS correlate to hippocampal cell loss in temporal lobe epilepsy. SUBJECTS AND METHODS: We prospectively performed quantitative hippocampal MR imaging volumetry and MRS imaging in 33 patients with intractable mesial temporal lobe epilepsy who were undergoing surgery. A neuronal-glial ratio of cornu ammonis and fascia dentata was obtained and correlated while validating the pathologic analysis by comparisons with specimens of age-matched autopsy control-case hippocampus (n = 14). RESULTS: The neuronal-glial ratio of the patient group was statistically significantly lower than in the control group for the cornu ammonis region (P<.001). Correlations of hippocampal volumes with cornu ammonis and neuronal-glial ratios revealed a significant interdependence (P<.01). However, correlations of the resected hippocampal creatine-N-acetylated compound ratio with the cornu ammonis or fascia dentata neuronal-glial ratios showed no significant interdependence (P>.8). CONCLUSIONS: Our findings support the concept that the metabolic dysfunction measured by MRS imaging and the hippocampal volume loss detected by MR imaging volumetry do not have the same neuropathologic basis. These findings suggest that the MRS imaging metabolic measures reflect neuronal and glial dysfunction rather than neuronal cell loss as previously assumed.     

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.     

Neuroprotective effect of the free radical scavenger MCI-186 in patients with cerebral infarction: Clinical evaluation using magnetic resonance imaging and spectroscopy.

A newly developed free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), holds promise for clinical application. We clinically evaluated the effect of MCI-186 on cerebral infarction by using magnetic resonance imaging (MRI) and proton MR spectroscopy (MRS). Six patients with large supratentorial infarction were evaluated with sequential MRI and proton MRS. These patients were also administered MCI-186 for 14 days after ischemic insult (MCI-186 group). The findings were compared with those for patients who had supratentorial infarctions equivalent in size to those in the MCI-186 group but who had received only conventional therapy. The course of change of the size of infarction was evaluated by MRI, and the metabolic changes following cerebral infarction were evaluated by proton MRS. As a result, there was no significant difference between the initial size of infarction in the conventionally treated group and that in the MCI-186 treated groups, nor did the groups show significant difference in the sequential changes depicted by MRI in the area of infarction, midline shift, or amount of edema. However, on MRS, the N-acetyl aspartate signal was significantly higher in the MCI-186 group than in the conventionally treated patients. In conclusion, MCI-186 has an effect of preservation of N-acetyl-aspartate, which is thought to be a neuronal marker, in cerebral infarction.     

Association of life activities with cerebral blood flow in Alzheimer disease: implications for the cognitive reserve hypothesis

BACKGROUND: Regional cerebral blood flow (CBF), a good indirect index of cerebral pathologic changes in Alzheimer disease (AD), is more severely reduced in patients with higher educational attainment and IQ when controlling for clinical severity. This has been interpreted as suggesting that cognitive reserve allows these patients to cope better with the pathologic changes in AD. OBJECTIVE: To evaluate whether premorbid engagement in various activities may also provide cognitive reserve. DESIGN: We evaluated intellectual, social, and physical activities in 9 patients with early AD and 16 healthy elderly controls who underwent brain H(2)(15)O positron emission tomography. In voxelwise multiple regression analyses that controlled for age and clinical severity, we investigated the association between education, estimated premorbid IQ, and activities, and CBF. RESULTS: In accordance with previous findings, we replicated an inverse association between education and CBF and IQ and CBF in patients with AD. In addition, there was a negative correlation between previous reported activity score and CBF in patients with AD. When both education and IQ were added as covariates in the same model, a higher activity score was still associated with more prominent CBF deficits. No significant associations were detected in the controls. CONCLUSIONS: At any given level of clinical disease severity, there is a greater degree of brain pathologic involvement in patients with AD who have more engagement in activities, even when education and IQ are taken into account. This may suggest that interindividual differences in lifestyle may affect cognitive reserve by partially mediating the relationship between brain damage and the clinical manifestation of AD.     

颅内多发病灶的立体定向活检术后病理学结果与MRS结果的比较分析

目的探讨立体定向活检术及磁共振波谱成像（MRS）在颅内多发病灶定性诊断中的临床价值。方法回顾性分析37例经MRI、MRS和立体定向活检术后病理学检查确诊的颅内多发病灶患者的临床资料,其中行有框架定向活检术22例,无框架神经导航定向活检术15例。结果 37例均获得明确病理学诊断,其中低级别胶质瘤19例,高级别胶质瘤8例,淋巴瘤3例,多发脱髓鞘3例,炎性病灶2例,转移癌2例。术后出现癫痫发作1例,活检靶点少量出血1例。病理学诊断与MRS诊断符合率为83.8%（31/37）,误诊率为16.2%（6/37）。结论 MRS在颅内多发病灶的诊断中具有较高的准确性,但仍有一定的误诊率;立体定向活检术微创、安全,在颅内多发病灶的诊断中具有决定性的意义;MRS的代谢变化在活检术靶点选择上具有一定的指导价值。