Forgetting in dementia with and without subcortical lacunes

Alzheimer's disease (AD) and subcortical ischemic vascular disease (SIVD) are common causes of dementia, often co-occur, and can present quite similarly, making differential diagnosis clinically challenging. This study tested the hypothesis that patients with SIVD retain information better than AD patients. Participants were 35 dementia patients with subcortical lacunes (SIVD group), 27 dementia patients without lacunar infarction (AD group), and 56 normal controls. Results indicated that despite comparable levels of initial acquisition, AD patients showed more rapid forgetting. Further analysis indicated that memory patterns within the SIVD group were heterogeneous, with some participants exhibiting rapid forgetting and some exhibiting good retention. SIVD participants with good retention showed a trend for greater executive impairments relative to SIVD participants with rapid forgetting and AD participants. Results suggest that rapid forgetting in SIVD may imply concomitant AD, whereas the dementia in patients with good retention may be purely vascular in origin. Three SIVD patients with rapid forgetting followed to autopsy all had AD pathology, further supporting the link between memory patterns and AD.     

Identification of Alzheimer disease risk by functional magnetic resonance imaging

BACKGROUND: Functional magnetic resonance imaging plays a promising role in the preclinical characterization of Alzheimer disease (AD) for use in early diagnosis and in preventive drug trials. OBJECTIVE: To determine whether functional magnetic resonance imaging can reliably distinguish risk groups for AD among cognitively normal middle-aged adults. DESIGN: Cross-sectional case-control study. SETTING: University of California, San Diego, Alzheimer Disease Research Center participants and San Diego community volunteers. PARTICIPANTS: Twenty cognitively normal individuals (10 high risk and 10 low risk), aged 58 to 65 years, were divided into 2 groups based on the presence or absence of the apolipoprotein E epsilon4 allele and a positive family history of AD. MAIN OUTCOME MEASURES: Word pairs were presented in a blocked design alternating between conditions of novel pairs, repeated pairs, and fixation. Whole-brain differences in blood oxygenation level-dependent brain responses between conditions were compared across risk groups. RESULTS: Compared with the low-risk group, the high-risk group showed many areas of differential blood oxygenation level-dependent response in regions commonly associated with AD pathology (eg, the left medial temporal lobe). Furthermore, different patterns of association between left medial temporal lobe activity and memory performance were demonstrated. CONCLUSIONS: Results support a theory of up-regulation in neuronal memory systems in people at risk for AD many years before the typical age at disease onset. They further demonstrate that functional magnetic resonance imaging is a viable technique to identify persons at risk for AD.     

Pathological findings correlated with magnetic resonance imaging in subcortical arteriosclerotic encephalopathy (Binswanger''s disease).

Formalin-fixed brain slices from four cases of subcortical arteriosclerotic encephalopathy in which a firm diagnosis could be made both clinically and pathologically have been studied by magnetic resonance imaging (MRI). The slices were subsequently embedded in paraffin-wax or celloidin and sections were cut in the same plane as the MRI slices. There was a good correlation between the extent and severity of the abnormal MRI signal and the pathological changes. Areas of diffuse MRI abnormality corresponded with areas of axonal and myelin loss with gliosis, and small "lacune"-like lesions corresponded with lacunar infarcts histologically. Sparing of the subcortical U-fibres was seen histologically and on MRI. The abnormal signal probably originates from increased tissue water attributable to gliosis and an expanded extracellular space.     

In vivo evaluation of brain iron in Alzheimer disease using magnetic resonance imaging

BACKGROUND: The basal ganglia contain the highest levels of iron in the brain, and postmortem studies indicate a disruption of iron metabolism in the basal ganglia of patients with Alzheimer disease (AD). Iron can catalyze free radical reactions and may contribute to oxidative damage observed in AD brains. Treatments aimed at reducing oxidative damage have offered novel ways to delay the rate of progression and could possibly defer the onset of AD. Brain iron levels were quantified in vivo using a new magnetic resonance imaging method. METHODS: Thirty-one patients with AD and 68 control subjects participated in this study. A magnetic resonance imaging method was employed that quantifies the iron content of ferritin molecules (ferritin iron) with specificity through the combined use of high and low field-strength magnetic resonance imaging instruments. Three basal ganglia structures (caudate, putamen, and globus pallidus) and one comparison region (frontal lobe white matter) were evaluated. RESULTS: Basal ganglia ferritin iron levels were significantly increased in the caudate (P = .007; effect size, 0.69) and putamen (P = .008; effect size, 0.67) of AD subjects, with a trend toward an increase in the globus pallidus (P = .13). The increased basal ganglia ferritin iron levels were not a generalized phenomenon; white matter ferritin iron levels were unchanged in patients with AD (P = .50). CONCLUSIONS: The data replicate and extend prior results and suggest that basal ganglia ferritin iron levels are increased in AD. Prospective studies are needed to evaluate whether premorbid iron levels are increased in individuals who develop AD.     

阿尔茨海默病和血管性痴呆氢质子磁共振波谱研究

痴呆是一种获得性、持续性智能损害综合征,老年期痴呆主要包括阿尔茨海默病(Alzheimer disease,AD)和血管性痴呆(Vascular dementia,VD).AD是老年人最常见的痴呆类型,根据尸检病理研究,60%～70%的痴呆为此种类型[1].VD是第二大常见痴呆类型,约占痴呆类型的10%～20%[2],AD和VD病理过程不完全相同,但临床表现、危险因素、病理学所见、影像学特征存在一定程度的重叠[3],在临床上难以准确区分,鉴别诊断的困难长期存在.     

Quantitative magnetic resonance imaging and the severity of dementia in Alzheimer's disease

The T2 component of the magnetic resonance imaging (MRI) signal was measured in 11 brain loci in six elderly patients diagnosed as having probable Alzheimer's disease. T2 values and relative amount of periventricular high-intensity foci were significantly correlated with dementia severity, indicated by the Blessed-Roth Dementia Scale score. Although the mean T2 value for left hemispheric structures was more closely correlated with the dementia score, T2 values did not differ significantly in the right and left hemispheres or in gray and white matter. These findings suggest that more severe dementia in Alzheimer's disease is associated with more water in the brain.     

Neuroanatomic differences between dyslexic and normal readers on magnetic resonance imaging scans

The areas of six bilateral brain segments in the right and left hemispheres, on a horizontal brain section, and the area of subdivisions of the corpus callosum, on a midsagittal brain section, were measured on magnetic resonance images obtained from 21 dyslexic and 29 control subjects. In the entire group, the frontal half of the horizontal brain section showed asymmetry, with the right side being larger, whereas posteriorly only the occipital polar segment was asymmetrical, with the left side being larger. Dyslexic subjects exhibited asymmetry, with the right side greater than the left side, in contrast to the relatively symmetrical pattern that is normally observed in the midposterior segment that corresponds to the angular gyrus. In the corpus callosum, dyslexic subjects were found to have a larger splenium than nondyslexic subjects, and dyslexic female subjects were found to have a larger splenium than dyslexic male subjects. Because transcallosal pathways connecting the left and right angular gyrus regions traverse through the splenium of the corpus callosum, the above findings in dyslexic subjects suggest an anatomic abnormality in the angular gyrus region.     

The value of magnetic resonance imaging in the detection of type II hemorrhagic lacunes

Lacunar infarcts (lacunes) are small necrotic/cystic lesions of the brain associated with hypertension. Many are clinically silent, but some are associated with localizing symptoms and signs. Lacunes recently were classified into three types, namely, those resulting from small infarcts (type I), those arising as small hemorrhages (type II), and those due to dilatation of perivascular spaces (type III). The type II lacunes are thought to be much less common than those of type I. Type II lacunes have not previously been reported during life. We report a case of subacute type II lacune in the pontine tegmentum that was detected by magnetic resonance imaging and later verified by histopathologic examination. The patient was hypertensive and had numerous other type I lacunes. This case shows that the magnetic resonance imaging features of hemorrhagic lacunes are identical to those of small hemorrhages or small hemorrhagic infarcts and that magnetic resonance imaging is a useful tool in the detection of lacunes and their correlation with clinical neurologic symptoms and signs.     

Quantitative magnetic resonance imaging in patients with temporal lobe epilepsy

Quantitative brain changes on magnetic-resonance-weighted imaging (MRI) were studied in 30 patients with temporal lobe epilepsy (TLE) who showed negative findings on computed tomography and no visible abnormality on MRI, and 20 healthy controls in order to detect changes not visible by standard imaging. The patients with TLE showed a significant decrease in size and a significant increase in T1 values of the mesial temporal area in both hemispheres compared to controls who had normal values bilaterally. Patients with a current or past history of organic delusional disorder (ICD-10) resembling schizophrenia showed a significant increase in the size of the third ventricle. The data suggest that (a) there are atrophic changes in the mesial temporal areas of patients with TLE, reflecting an increased water content in these areas, (b) TLE patients often have bilateral atrophic changes in the mesial temporal areas, even if there is only unilateral abnormality of EEG, and (c) TLE patients with schizophrenia-like organic symptoms may have some structural changes around the third ventricle, including limbic system structures. Further research needs to clarify the exact structures involved and the factors responsible for these abnormalities.     

Structural brain differences between never-treated patients with schizophrenia, with and without dyskinesia, and normal control subjects: a magnetic resonance imaging study

BACKGROUND: In south India, abnormal movements indistinguishable from tardive dyskinesia have been observed in chronically ill patients with schizophrenia who have never received antipsychotic medication. The present study, using magnetic resonance imaging, examines brain structure in such patients, in those without dyskinesia, and in normal control subjects. METHODS: Chronically ill patients with schizophrenia with and without dyskinesia and controls were identified in villages south of Chennai, India (each group, n = 31). Patients' mental state was assessed by the Positive and Negative Syndrome Scale for schizophrenia, dyskinesia by the Abnormal Involuntary Movements Scale, and parkinsonism by the Simpson and Angus scale. In patients and controls, magnetic resonance imaging measured the volume of the caudate and lentiform nuclei and the lateral ventricle-hemisphere ratio. RESULTS: The left lentiform nucleus was significantly (11%) larger in patients with dyskinesia compared with controls, and the right lateral ventricle-hemisphere ratio was significantly (33%) larger in patients without dyskinesia compared with controls. In all 3 groups, there were significant positive correlations between age and ventricle-hemisphere ratio. In controls, but not in patients, there were significant negative correlations between age and the volume of the caudate and lentiform nuclei. CONCLUSIONS: Never-treated patients with dyskinesia may have striatal pathologic conditions and may represent a subgroup of patients with schizophrenia; in those without abnormal movements, cortical atrophy is more apparent. The schizophrenic process may interfere with normal age-related anatomical changes in the basal ganglia.     

Progressive microstructural alterations in subcortical nuclei in Parkinson's disease: A diffusion magnetic resonance imaging study

ObjectivesTo explore the microstructural alterations in subcortical nuclei in Parkinson's disease (PD) at different stages with diffusion kurtosis imaging (DKI) and tensor imaging and to test the performance of diffusion metrics in identifying PD.Methods108 PD patients (64 patients in early-stage PD group (EPD) and 44 patients in moderate-late-stage PD group (MLPD)) and 64 healthy controls (HC) were included. Tensor and kurtosis metrics in the subcortical nuclei were compared. Partial correlation was used to correlate the diffusion metrics and Unified Parkinson's Disease Rating Scale part-III (UPDRS-III) score. Logistic regression and receiver operating characteristic analysis were applied to test the diagnostic performance of the diffusion metrics.ResultsCompared with HC, both EPD and MLPD patients showed higher fractional anisotropy and axial diffusivity, lower mean kurtosis (MK) and axial kurtosis in substantia nigra, lower MK and radial kurtosis (RK) in globus pallidus (GP) and thalamus (all p < 0.05). Compared with EPD, MLPD patients showed lower MK and RK in GP and thalamus (all p < 0.05). MK and RK in GP and thalamus were negatively correlated with UPDRS-III score (all p < 0.01). The logistic regression model combining kurtosis and tensor metrics showed the best performance in diagnosing PD, EPD, and MLPD (areas under curve were 0.817, 0.769, and 0.914, respectively).ConclusionsPD has progressive microstructural alterations in the subcortical nuclei. DKI is sensitive to detect microstructural alterations in GP and thalamus during PD progression. Combining kurtosis and tensor metrics can achieve a good performance in diagnosing PD.     

Clinical and radiologic differences between primary intracerebral hemorrhage with and without microbleeds on gradient-echo magnetic resonance images

BACKGROUND: Microbleeds on gradient-echo magnetic resonance (MR) imaging reflect bleeding-prone microangiopathy. The microbleeds are frequently detected in patients with primary intracerebral hemorrhage (PICH). However, some patients do not have microbleeds. OBJECTIVE: To clarify the risk factors associated with microbleeds in PICH, thus providing insight into the pathogenesis of PICH. DESIGN: Prospective study. SETTING: Neurology department of a tertiary referral center.Patients A consecutive series of 107 patients with PICH. INTERVENTIONS: Gradient-echo MR imaging to determine distribution patterns and numbers of microbleeds. MAIN OUTCOME MEASURES: Clinical variables and the associated MR imaging abnormalities in patients with PICH with and without microbleeds. RESULTS: Patients with PICH who had microbleeds were significantly older (65.9 +/- 10.9 years) than those without microbleeds (53.9 +/- 13.0 years; P<.001), and previous stroke, medication with antithrombotics or anticoagulants, lacunes, and leukoaraiosis were more common in patients with microbleeds. However, potential triggering events tending to raise the blood pressure were more common in cases of PICH without microbleeds (18 [56.3%] vs 10 [15.4%]). In logistic regression analysis, age (odds ratio and 95% confidence interval: 1.07, 1.01-1.14), advanced leukoaraiosis (7.79, 1.05-57.74), number of lacunes (1.66, 1.21-2.28), and potential triggering events (0.18, 0.04-0.90) were independent risk factors associated with the presence of microbleeds in patients with PICH. CONCLUSIONS: Primary intracerebral hemorrhage without microbleeds was more common in younger patients with precipitating events, whereas PICH with microbleeds was more common in elderly patients with prominent ischemic change and frequent use of antithrombotics or anticoagulants. Our findings might help to determine the pathogenetic type for secondary prevention.     

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.     

Brain atrophy rates in Parkinson's disease with and without dementia using serial magnetic resonance imaging.

Increased rates of brain atrophy are seen in Alzheimer's disease, but whether rates are similarly increased in other dementias such as Parkinson's disease dementia (PDD) has not been well examined. We determined the rates of brain atrophy using serial magnetic resonance imaging (MRI) in PDD and compared this finding to rates seen in cognitively intact Parkinson's disease (PD) patients and age-matched control subjects. Thirty-one patients (PD = 18, PDD = 13) and 24 age-matched controls underwent serial volumetric 1.5 T MRI scans, approximately 1 year apart. Baseline and repeat scans were registered and quantification of the brain boundary shift integral was used to determine whole-brain atrophy rates. Rates of brain atrophy were significantly increased in PDD (1.12 +/- 0.98%/year) compared to PD (0.31 +/- 0.69%/year; P = 0.018) and control subjects (0.34 +/- 0.76%/year; P = 0.015). There were no differences in atrophy rates between controls and PD (P = 0.79). No correlations between increased atrophy rates and age or dementia severity (Mini-Mental State Examination score) were observed. Serial MRI may be a useful tool for monitoring disease progression in PDD and further studies should investigate its utility for early diagnosis.     

Regional N-acetylaspartate reduction in the hippocampus detected with fast proton magnetic resonance spectroscopic imaging in patients with Alzheimer disease

OBJECTIVE: To detect regional metabolic changes that resemble the expected spatial pattern of neuronal loss in patients with Alzheimer disease (AD). METHODS: Thirty-four patients with AD and 22 healthy control subjects were included in the study. Single-slice fast proton spectroscopic imaging was performed in parallel angulation to the temporal lobes. Proton spectra were selected from the hippocampus, the lateral temporal lobe, and the occipital lobe of both hemispheres to determine metabolite concentration of N-acetylaspartate (NAA), total creatine (tCr), including phosphocreatine and creatine, and choline-containing compounds (Cho). The metabolic ratios of NAA/tCr and Cho/tCr were calculated and compared between patients with AD and healthy volunteers. RESULTS: The NAA/tCr ratios were significantly reduced in the left (F(1,1) = 4.34, P =.04) and right hippocampus (F(1,1) = 9.96, P =.003) in patients with AD. The Cho/tCr ratios remained unchanged in both hippocampi. There was no significant change of either NAA/tCr or Cho/tCr in the lateral temporal and occipital lobes of patients with AD. CONCLUSION: This study provides evidence that fast proton spectroscopic imaging may detect the regional pattern of disturbed neuronal integrity in patients with AD with high spatial resolution in a short acquisition time.     

Adrenoleukodystrophy without adrenal insufficiency and its magnetic resonance imaging

Summary Fatty acids of plasma and erythrocyte membrane sphingomyelin were determined by gas chromatography-mass spectrometry in adrenoleukodystrophy (ALD) without adrenal insufficiency. Mass chromatogram tracing with the ion at m/z 143 [(CH₂)₆ COOH₃]⁺ showed increases of saturated very long chain fatty acids in plasma and erythrocyte membrane sphingomyelin in ALD. The C26:0/C22:0 ratios in plasma were 0.121, 0.057 and 0.007 in cases 1 and 2, and a control subject, respectively. The C26:0/C22:0 ratios in erythrocyte membrane sphingomyelin were 0.386, 0.211 and 0.093 in cases 1 and 2 and the control subject, respectively. The demyelinating process of ALD was clearly observed in both the inversion recovery 2100/500 and spin echo 2100/80 scans on magnetic resonance imaging. The magnetic resonance image in case 1 revealed widespread demyelinated lesions, involving almost the entire cerebrum and cerebellum, at 4 years after the onset, while that in case 2 revealed demyelinated lesions mainly limited to parieto-occipital areas at 1 year after the onset.