Apolipoprotein E Genotype and Early Alzheimer''s Disease: A Longitudinal SPECT Study

BACKGROUND AND PURPOSE: To determine the association of the apolipoprotein E (APOE) genotype and longitudinal changes of regional cerebral blood flow (rCBF) in Alzheimer's disease (AD). Previous reports have yielded conflicting results concerning this association. METHODS: A retrospective cohort study was performed. rCBF was noninvasively measured using 99mTc-ethyl cysteinate dimer single-photon emission computed tomography in 23 patients with probable AD at the very early stage and at a mean interval of 24 months, as well as in 55 age-matched healthy volunteers. Patients were classified into 2 groups according to the presence of the epsilon 4 allele: 11 epsilon 4 carriers and 12 noncarriers. Correction for partial volume effects (PVEs) was performed in all patients using gray matter volume measured by magnetic resonance imaging. Statistical parametric mapping was used for the analysis of absolute rCBF data and the adjusted rCBF images of relative flow distribution. RESULTS: In the baseline study, both carriers and noncarriers showed significant decreases of absolute and adjusted rCBF in the psoterior cingulate gyri and precunei. After PVE correction, carriers showed a greater spread of areas with significant rCBF reduction from the parietotemporal to the frontal area than noncarriers during the follow-up period compared to healthy volunteers. Moreover, carriers showed a significant decline of absolute rCBF in the frontal cortex from the baseline to the follow-up study. CONCLUSIONS: The authors' study suggests that the APOE epsilon 4 allele is associated with the faster progression of AD, and PVE correction may be necessary for accurate assessments of SPECT studies of AD.     

Regional cerebral blood flow measured by99mTc-HMPAO SPECT differs in subgroups of Alzheimer's disease

Summary Alzheimer's disease (AD) is a heterogeneous entity. Identifying AD subtypes might have impact in patients' response to different treatment strategies. We designed a study to examine regional cerebral blood flow (rCBF) in AD subtypes. To identify AD subtypes, we performed a cluster analysis including performance on memory, language, visuospatial, praxis, and executive functions. The rCBF measured by^99mTc-HMPAO SPECT was referred to the cerebellum. We examined 35 patients fulfilling the NINCDS-ADRDA criteria of probable AD and 13 age and sex-matched healthy cognitively intact controls. AD patients were at the early stage of the disease, their mean Mini-Mental Status (MMS) score (S.D.) was 22.5 (3.6). The cluster analysis revealed two AD subgroups: AD1 (N=12) and AD2 (N=23). The subgroups did not differ in age, sex, or global clinical severity as assessed by MMS and Brief Cognitive Rating Scale (BCRS). Both subgroups had equally impaired memory. The AD2 group was inferior to the AD1 group on verbal, visuospatial, praxic, and executive functions. The AD1 group showed reduced rCBF ratios in the temporal and parietal cortices and the amygdala compared to controls. The AD2 group differed from controls in the rCBF ratios of frontal, temporal, parietal, occipital, basal ganglia, and amygdaloid regions bilateral and from AD1 in the rCBF ratios of frontal and temporal cortices. In AD patients, the rCBF ratios did not correlate with MMS or BCRS scores. In contrast, several significant correlations were found between decreases rCBF ratios and impairment of memory and other cognitive functions. In conclusion, a cluster analysis on neuropsychological test performance identified two AD subgroups that differed on the neuropsychological profile and on the rCBF in spite of similar global clinical severity.     

SPECT Follow-Up Study of Cerebral Blood Flow Changes During Donepezil Therapy in Patients with Alzheimer''s Disease

BACKGROUND AND PURPOSE: Treatment with acetylcholinesterase inhibitors (AchEIs) is beneficial for patients with Alzheimer's disease (AD). But the clinical response varies. Functional neuroimaging techniques might allow objective evaluation of the topographic correlates of the effect of therapy on brain functioning. We attempted to evaluate the possible correlation between regional cerebral blood flow (rCBF) differences in patients with AD and response to donepezil hydrochloride (Donepezil) therapy. METHODS: The subjects of this study were 51 consecutive patients with AD receiving Donepezil who underwent SPECT at baseline and 10-14 months later. We divided the patients into stabilized (n = 19) and nonstabilized (n = 32) subgroups based on changes in the Mini Mental State Examination (MMSE) score. Analysis of single-photon emission computed tomography (SPECT) data was done using 3-dimensional stereotactic surface projections (3D-SSP) and the stereotactic extraction estimation (SEE) method. We compared differences in rCBF between the two subgroups at baseline and follow-up, and between the baseline and follow-up in each subgroup. RESULTS: Significant correlation was recognized between the mean Z score changes of the left frontal lobe, left limbic lobe, and MMSE change. There were no significant baseline differences in rCBF in any region of the brain between the two subgroups. At the study endpoint, the nonstabilized subgroup showed lower rCBF in the lateral and medial frontal lobes, limbic lobe, lower lateral temporal lobe, and cingulate gyrus compared to the stabilized subgroup. Both patient groups showed a significant post-treatment increase over baseline values in the frontal lobe, and the stabilized group had more extensive and intense increases in the lateral and medial frontal lobes and orbital surface. CONCLUSIONS: Our study suggests that the diversity of clinical responses to Donepezil therapy in patients with AD is associated with rCBF changes, mainly in the frontal lobe. SPECT may be a promising tool to assess the impact of AchEI therapy on the brain function of patients with AD.     

Relationship between regional cerebral blood flow and verbal fluency in Alzheimer's disease

Category and letter verbal fluency tests are widely used for dementia detection and severity measure. Performances of these tasks have been regarded to be mainly associated with the left frontal lobe function. However, some recent studies suggest that there are different neuropsychological bases between these two tasks, and the brain region which contributes to these performances still remains unclear in Alzheimer's disease (AD). To clarify the neural basis of verbal fluency in AD, we examined the relationship between performances of these tasks and regional cerebral blood flow (rCBF). Twenty-five AD patients were administered verbal fluency tasks and single photon emission computed tomography (SPECT) scans. Thirteen cortical regions of interest were symmetrically defined in each hemisphere. Letter fluency scores were correlated significantly only with the left prefrontal (Brodmann's area (BA) 10-46) regional cerebral blood flow (rCBF). In contrast, category fluency scores were correlated most strongly with the left temporal rCBF and also with the left prefrontal (BA 10-46) rCBF. In conclusion, the present study suggests that left prefrontal (BA 10-46) dysfunction contributes to decline in both letter and category fluency scores in AD, while typical posterior dysfunction of AD has a closer relationship with decline in category fluency scores.     

阿尔茨海默病的脑血流灌注研究

目的探讨AD患者脑血流灌注的特征性变化。方法选择20例确诊AD患者和10例认知正常者,对所有入组对象行SPECT脑血流灌注显像检查,对所得图像进行视觉分析和半定量分析,比较两组对象各脑区血流灌注情况的差异,并比较AD患者左、右脑叶脑血流灌注的差异。结果 (1)视觉分析结果显示,AD组以颞叶或顶叶脑血流灌注减低为主,各占55%,其中双侧颞顶叶血流灌注减低者占15%,单侧颞顶叶血流灌注减低占20%。正常认知组SPECT影像学表现各异,额叶、颞叶、顶叶、枕叶、丘脑、基底节血流灌注减少情况均存在,各占10%。但无双侧颞顶叶血流灌注减少者,40%表现完全正常。(2)半定量分析结果显示,AD组在右额叶、双侧颞顶叶、右枕叶血流灌注显著低于正常认知组(P<0.05),以右侧颞叶血流灌注降低最明显,左右颞顶叶血流低灌注程度对比无显著性差异。结论 AD患者的SPECT特征性表现为双侧对称性颞顶叶血流低灌注,其中右侧颞叶血流灌注下降最严重。     

Comparative study of regional cerebral blood flow values measured by Xe CT and Xe SPECT

The regional cerebral blood flow (rBCF) values measured by stable xenon-enhanced computed tomography (Xe XT) and by radioactive xenon-133 single photon emission computed tomography (Xe SPECT) were compared in 16 patients with cerebral infarct. On the non-lesion side Xe SPECT recorded 10.7% higher rCBF values than Xe CT in the anterior cerebral artery territory while Xe CT recorded 9.6% higher values than Xe SPECT in the middle cerebral artery territory. These differences were not statistically significant. Although the rCBF values were almost the same no correlation was found between the two methods in the posterior cerebral artery territory and the basal ganglia. Only hemispheric CBF on the non-lesion side showed the same value and a good correlation between the Xe CT and the Xe SPECT. There was a good correlation in the hemispheric CBF values on the lesion side, too. The difference of rCBF between the non-lesion side and the lesion side was expressed smaller in the Xe SPECT than in the Xe CT. This is in agreement with the previous reports that Xe SPECT overestimates the flow in the low flow areas. The higher rCBF values in the anterior cerebral artery territory measured by the Xe SPECT was ascribed to the artifact from the radioactivities in the inhalation mask and the air passages as reported previously. In conclusion, there is no good correlation between the rCBF values measured by the Xe CT and by the Xe SPECT. Only hemispheric CBF shows a good correlation between the two methods.     

Impact of blood pressure changes in cerebral blood perfusion of patients with ischemic Moyamoya disease evaluated by SPECT

Our aim was to determine the impact of targeted blood pressure modifications on cerebral blood flow in ischemic moyamoya disease patients assessed by single-photon emission computed tomography (SPECT). From March to September 2018, we prospectively collected data of 154 moyamoya disease patients and selected 40 patients with ischemic moyamoya disease. All patients underwent in-hospital blood pressure monitoring to determine the mean arterial pressure baseline values. The study cohort was subdivided into two subgroups: (1) Group A or relative high blood pressure (RHBP) with an induced mean arterial pressure 10–20% higher than baseline and (2) Group B or relative low blood pressure (RLBP) including patients with mean arterial pressure 10–20% lower than baseline. All patients underwent initial SPECT study on admission-day, and on the following day, every subgroup underwent a second SPECT study under their respective targeted blood pressure values. In general, RHBP patients showed an increment in perfusion of 10.13% (SD 2.94%), whereas RLBP patients showed a reduction of perfusion of 12.19% (SD 2.68%). Cerebral blood flow of moyamoya disease patients is susceptible to small blood pressure changes, and cerebral autoregulation might be affected due to short dynamic blood pressure modifications.     

Regional cerebral blood flow change in a case of Alzheimer's disease with musical hallucinations

We examined alteration of regional cerebral blood flow (rCBF) in a case of Alzheimer's disease (AD) patient with musical hallucination. To detect regions related to musical hallucination, single–photon emission computed tomography (SPECT) imaging of the patient and nine sex, age, and cognitive functionmatched AD patients without delusions and hallucinations were compared using statistical parametric mapping 99 (SPM99). In comparison with controls, the patient had increased rCBF in left temporal regions and left angular gyrus. This profile could be relevant to the neuroanatomical basis of musical hallucinations. This work had been carried out at the Higher Brain Function Clinic of the Ehime University Hospital.     

The cerebral localization of neuropsychological impairment in Alzheimer's disease: a SPECT study

Summary Twenty-three patients with a clinical diagnosis of Alzheimer's disease were examined with a set of neuropsychological tests and with ^99mTc-hexamethyl-propyleneamineoxime (HMPAO) single photon emission computed tomography (SPECT). Correlations between test results and indices of regional HMPAO distribution were analysed by multidimensional scaling (MDS). Test results covaried positively with relative HMPAO uptake of frontal, inferior parietal and superior temporal regions but not, or in a negative way, with the remainder of the regions. When only positive correlations were analysed, MDS suggested two dimensions of organization: one was related to a dichotomy between frontal and temporo-parietal regions. The relationship of test results to this dimension was largely consistent with common neuropsychological knowledge. A second, less stringent dimension of organization opposed right and left hemisphere regions. The ordering of test results with respect to this dimension was only partly consistent with what is known about the lateralization of neuropsychological deficits from the study of localized brain lesions. The possibility is considered that these inconsistencies may reflect the effect of disproportionally severe involvement of extended cortical systems which modulates the sequels of localized brain damage.     

Intercorrelations of regional cerebral glucose metabolic rates in Alzheimer''s disease

Patterns of cerebral metabolic correlations were compared between 21 Alzheimer's disease patients and 21 healthy age-matched controls in the resting state. Cerebral metabolic rates for glucose were determined by positron emission tomography using [18F]2-fluoro-2-deoxy-D-glucose. Partial correlation coefficients, controlling for whole brain glucose metabolism, were evaluated between pairs of regional glucose metabolic rates in 59 brain regions. Reliable correlation coefficients were obtained with the 'jackknife' and 'bootstrap' statistical procedures. Compared with healthy controls, the Alzheimer patients had significantly fewer reliable partial correlation coefficients between frontal and parietal lobe regions, and more reliable correlations between the cerebellum and temporal lobe. The number of reliable correlations between many bilaterally symmetric brain regions was reduced in the Alzheimer patients, as compared with controls. These results suggest that in the early stages of Alzheimer's disease there is a breakdown of the organized functional activity between the two cerebral hemispheres, and between parietal and frontal lobe structures.     

颈动脉支架置入术对大脑皮质血流灌注量的影响

目的 研究颈动脉狭窄支架置入术对脑皮质血流灌注量的影响.方法 应用单光子发射计算机断层扫描(SPECT)对18例单侧颈动脉狭窄患者颈动脉支架置入术前后脑皮质血流灌注量进行检测.结果 患者术后双侧大脑前动脉、大脑中动脉、大脑后动脉供血区脑皮质血流灌注量均显著增加(均P<0.05);同时支架置入侧术后大脑中动脉、大脑后动脉供血区脑皮质血流灌注量比值较术前增加更明显(均P<0.05),但大脑前动脉供血区差异无统计学意义.结论 颈动脉狭窄支架置入术可使狭窄侧及对侧脑皮质血流灌注量增加,而狭窄侧大脑中动脉、后动脉增加幅度更明显.     

Activation of Multi-modal Cortical Areas Underlies Short-term Memory

We wanted to examine whether there are cortical fields active in short-term retention of sensory information, independent of the sensory modality. To control for selective attention, response selection and motor output, the cortical activity during short-term memory (STM) tasks was compared with that during detection (DT) tasks. Using positron emission tomography and [¹⁵O]-butanol as a tracer, we measured the regional cerebral blood flow in ten subjects during three STM tasks in which the subjects had to keep in mind: (i) the pitch of tones; (ii) frequencies of a vibrating stylus; and (iii) luminance levels of a monochrome light. Another group of ten subjects undertook three tasks in which subjects detected changes in similar stimuli. Six cortical fields were significantly more activated during STM than during DT. These fields were activated irrespective of sensory modality, and were located in the left inferior frontal gyrus, right superior frontal gyrus, right inferior parietal cortex, anterior cingulate, left frontal operculum and right ventromedial prefrontal cortex. Since the DT tasks and the STM tasks differed only with respect to the STM component, we conclude that the neuronal activity specifically related to retention of the stimuli during the delays was located in these six multi-modal cortical areas. Since no differences were observed in the sensory-specific association cortices, the results indicate further that the activity in the sensory-specific association cortices due to selective attention is not different from the activity underlying short-term retention of sensory information.     

Short-term longitudinal evaluation of cerebral blood flow in mild Alzheimer's disease

The aim of this study was to estabilish whether subtle changes in regional cerebral blood flow (rCBF) can be detected in patients with mild Alzheimer's disease (AD) over a period as short as three months. Aprospective evaluation of rCBF changes with HMPAO SPECT at baseline and after 3 and 6 months was carried out. Standard clinical dementia tests were performed in parallel. The study enrolled 13 patients with mild probable AD from an outpatient memory clinic. SPECT data collected at baseline and after three months were compared using Statistical Parametric Mapping (SPM). Significant clusters of rCBF decrement in the medial part of the temporal lobe in both hemispheres, in the orbital part of the right frontal lobe and in the inferior part of the right parietal lobe were observed. No significant differences were found using a region of interest (ROI) analysis. After six months SPM analysis showed larger clusters of significant decrement in the same areas. ROI analysis was now sensitive to the rCBF changes and significant differences were shown in all brain regions except the temporal lobes. SPM analysis of SPECT data can detect significant changes in rCBF in mild AD over a short time interval. This method might be of potential advantage for the early diagnosis of AD and for its differentiation from stable cognitive impairments. Received: 30 November 2002 / Accepted in revised form: 28 January 2003 Correspondence to: A. Venneri     

Neuroimaging findings in Alzheimer's disease

In the present article, the neuroimaging findings in Alzheimer's disease are summarized and experimental data from animals relating to metabolic changes in Alzheimer's disease (AD), particularly in the frontobasal cholinergic projections onto the cerebral cortex, are reviewed. Changes in glucose metabolism as well as in cerebral blood flow (CBF) are specific for AD, in which the parietotemporal association cortex shows metabolic suppression. This finding is used as a diagnostic aid in the clinical application of single photon emission computed tomography. In rare cases, limited suppression of metabolism and blood flow is also found in the unilateral medial temporal lobe or parietal lobe. Statistically, approximately 80% of cases of AD show a typical parietotemporal suppression pattern of CBF. This cortical metabolic and circulatory suppression has been attributed to cholinergic deprivation from the basal forebrain Mynert nucleus. Animal experiments have revealed transient cortical suppression of glucose metabolism in the frontal cortex after destruction of the basal forebrain cholinergic neurons by ibotenic acid. This suppression persists for approximately 1 week and returns to normal 1 month after operation. Thus, the typical neuroimaging findings in AD would not be due to deficient cholinergic projections from the basal forebrain.     

外伤性颅骨缺损修复前后灌注CT评价脑血流变化的研究

目的 探讨颅骨修复术对外伤性颅骨缺损患者脑血流动力学和神经症状的影响.方法 对14例外伤性颅骨缺损患者颅骨修复前后行脑灌注CT检查,比较修补侧基底节层面与侧脑室体部层面的底节区和颞叶皮层区4组感兴趣区,自身对照比较其rCBF均值差别,分别比较术前与术后7d,术前与术后6个月均值,并且对其神经症状变化情况进行随访.结果 (1)基底节层面底节区:术后7 d rCBF较术前有改善,P=0.044＜0.05;6个月随访rCBF较术前有改善,P=0.033＜0.05.(2)基底节层面颞叶皮层:术后7 d rCBF较术前有改善,P=0.001 ＜0.01;6个月随访rCBF较术前有改善,P=0.000 ＜0.01.(3)侧脑室体部层面底节区:术后7 d rCBF较术前无明显改善,P=0.275＞0.05;6个月随访rCBF较术前有明显改善,P=0.001 ＜0.05.(4)侧脑室体部层面颞叶皮层:术后7 d rCBF较术前无明显改善,P=0.064 ＞0.05;6个月随访rCBF较术前无明显改善,P=0.174＞0.05.其中发现靠近侧裂大血管处基底节水平层面脑组织血流因颅骨修复得以改善的程度更加明显.患者修复术后神经症状得到改善.结论 本研究应用灌注CT数据说明脑血管分布越密集,脑血流量恢复越明显,进一步充实完善了颅骨修复后脑血管储备功能改善的理论假说.     

Regional cerebral blood flow changes in patients with idiopathic REM sleep behavior disorder

Background: Recent studies have shown an association between rapid eye movement sleep behavior disorder (RBD) and neurodegenerative disorders, especially alpha‐synucleinopathies. Objective: We investigated regional cerebral blood flow (rCBF) changes using single photon emission computed tomography (SPECT) in patients with idiopathic RBD (iRBD), to determine functional brain alterations associated with the disorder. Methods: The SPECT data of 24 patients with iRBD were compared with those of 18 age‐matched normal controls using statistical parametric mapping 2. Results: We found decreased rCBF in the parietooccipital lobe (precuneus), limbic lobe, and cerebellar hemispheres in patients with iRBD, which is commonly seen in patients with Lewy body disease (Parkinson’s disease and dementia with Lewy bodies) or multiple system atrophy. Conclusion: Our SPECT study suggests that iRBD can be a presymptomatic stage of alpha‐synucleinopathies.     

Distinct cerebral cortical perfusion patterns in idiopathic normal-pressure hydrocephalus

The aims of the study are to evaluate idiopathic normal-pressure hydrocephalus (INPH)-related cerebral blood flow (CBF) abnormalities and to investigate their relation to cortical thickness in INPH patients. We investigated cortical CBF utilizing surface-based early-phase ¹⁸F-florbetaben (E-FBB) PET analysis in two groups: INPH patients and healthy controls. All 39 INPH patients and 20 healthy controls were imaged with MRI, including three-dimensional volumetric images, for automated surface-based cortical thickness analysis across the entire brain. A subgroup with 37 participants (22 INPH patients and 15 healthy controls) that also underwent ¹⁸F-fluorodeoxyglucose (FDG) PET imaging was further analyzed. Compared with age- and gender-matched healthy controls, INPH patients showed statistically significant hyperperfusion in the high convexity of the frontal and parietal cortical regions. Importantly, within the INPH group, increased perfusion correlated with cortical thickening in these regions. Additionally, significant hypoperfusion mainly in the ventrolateral frontal cortex, supramarginal gyrus, and temporal cortical regions was observed in the INPH group relative to the control group. However, this hypoperfusion was not associated with cortical thinning. A subgroup analysis of participants that also underwent FDG PET imaging showed that increased (or decreased) cerebral perfusion was associated with increased (or decreased) glucose metabolism in INPH. A distinctive regional relationship between cerebral cortical perfusion and cortical thickness was shown in INPH patients. Our findings suggest distinct pathophysiologic mechanisms of hyperperfusion and hypoperfusion in INPH patients.     

Sneddon syndrome: cerebral perfusion studies by Tc99m HM-PAO and SPECT

Sneddon syndrome is a non-inflammatory, non-atherosclerotic disease involving small and medium-sized arteries of the brain and of the skin. The arteriographic examination is often negative despite progressive impairment of the neurological status. In 3 patients with Sneddon syndrome cerebral perfusion was assessed with single photon emission computerized tomography (SPECT) and technetium⁹⁹m-hexamethylpropylenamineoxime (Tc⁹⁹ HM PAO). A correlation between clinical and SPECT finding was found, with significant focal reduction of regional cerebral blood flow (rCBF) in the two more severely affected patients.

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Sommario La sindrome di Sneddon è una malattia a carattere non infiammatorio e non aterosclerotico che colpisce le arterie cerebrali e cutanee di piccolo e medio calibro. L'esame angiografico è spesso negativo nonostante il carattere progressivo della malattia. In tre pazienti con diagnosi clinica di malattia di Sneddon è stata studiata la perfusione cerebrale mediante SPECT e tecnezio⁹⁹m-esametilpropilenamineossima (Tc⁹⁹m HM PAO). La SPECT ha dimostrato una migliore correlazione con il quadro clinico rispetto alla tomografia computerizzata, evidenziando riduzioni focali di perfusione nei due casi più gravi.

     

Longitudinal study of cerebral blood flow in Alzheimer's disease using single photon emission tomography

Ten patients with probable Alzheimer's disease were assessed at baseline and a mean 2 years later using a battery of neuropsychological tests, CT scans and Tc99m-HMPAO SPECT scans. The subjects had declined significantly in their functional indices. Cerebral perfusion measures declined in the parietal lobes, left hemisphere and whole brain, but the overall decline did not reach statistical significance. The decline in brain perfusion did not correlate significantly with the decline in various indices of neuropsychological function, either globally or for specific brain regions. The index of cerebral perfusion correlated significantly with global indices of neuropsychological function at baseline but not at follow-up. No single perfusion index was a significant predictor of clinical progression of dementia.     

Mapping of SPECT regional cerebral perfusion abnormalities in obsessive-compulsive disorder

Locations of cerebral perfusion abnormalities in obsessive-compulsive disorder (OCD) were mapped with single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). This report is a new, more thorough analysis of a previous study of these subjects that used region-of-interest methods. Ten obsessive-compulsive patients and seven age- and sex-matched control subjects were studied. Image sets were converted into stereotaxic space, normalized to each subject's mean cerebral value, then group averaged. Difference images were calculated and searched for regions with significant between-group cerebral perfusion differences. Obsessive-compulsive patients had significantly higher relative cerebral perfusion in medial-frontal and right frontal cortex and in cerebellum, and significantly reduced perfusion in right visual association cortex. Increased frontal Perfusion agrees with several prior reports. The caudate nucleus, which has been controversial in neuroimaging studies of OCD, did not display a difference between groups. The results of this study provide information about the locations and extents of cerebral perfusion abnormalities in OCD. Regional abnormalities were compared with those reported in prior functional neuroimaging studies. Issues related to OCD hyperfrontality and frontal lateralization of psychopathology are discussed. Normal caudate nucleus findings are considered in relation to prior functional imaging studies and hypotheses of OCD pathology. © 1994 Wiley-Liss, Inc.