Regional cerebral blood flow deficits in mild Alzheimer's disease using high resolution single photon emission computerized tomography

In spite of its wide availability, single photon emission computerized tomography (SPECT) scanning is uncommonly used in the assessment of Alzheimer's disease (AD) and related dementias. In light of recent advances in scanning protocols and image analysis, SPECT needs to be re-examined as a tool in the diagnosis of dementia. A total of 18 subjects with early AD and 10 healthy elderly control subjects were examined with high resolution SPECT during the performance of a simple word discrimination task. SPECT images were coregistered with individual magnetic resonance imaging scans, allowing delineation of predetermined neuroanatomical Regions of Interest (ROI). There was a gradation of regional cerebral blood flow (rCBF) values in both groups, with the lowest values being in the hippocampus and the highest in the striatum, thalamus and cerebellum. Compared to healthy controls, AD subjects demonstrated lower relative rCBF in parietal and prefrontal cortices. Analysis of individual ROI demonstrated bilateral reduction of rCBF in prefrontal poles, posterior temporal and anterior parietal cortex, and unilateral reduction of rCBF in left dorsolateral prefrontal cortex, right posterior parietal cortex and the left cingulate body. There were no significant differences for hippocampal, occipital or basal ganglia rCBF. Discriminant function analysis indicated that rCBF in the prefrontal polar regions achieved the best classification of cases. SPECT has utility in the diagnostic assessment of AD if standardized and semiquantitative techniques are used.     

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.     

Diagnosing Alzheimer's disease in elderly,mildly demented patients: the impact of routine single photon emission computed tomography

Based on the observation of bilateral temporoparietal hypoperfusion in Alzheimer's disease (AD), single photon emission computed tomography (SPECT) is advocated by some as a powerful diagnostic tool in the evaluation of demented patients. We studied whether routine brain SPECT in elderly, mildly demented outpatients increases the a priori diagnostic sensitivity and specificity of a careful clinical examination.^99mTc-HMPAO SPECT imaging was performed in 110 patients for a first evaluation for dementia. A semiquantitative measure of temporoparietal (TP) perfusion was calculated as the ratio of the activity in the temporoparietal cortex to activity in the cerebellum. A diagnosis of probable AD according to the McKhann criteria was made in 68 patients (mean age of 79.3 years) based on the results of a clinical examination, ancillary investigations and a 6-month follow-up. TP perfusion was significantly lower in AD patients than in 18 age-matched, non-demented controls. However, at a specificity of 89%, sensitivity was only 43% for detecting probable AD. The clinicians judged that SPECT had contributed to the final diagnosis in only 8% of the demented patients investigated. Routine brain SPECT in elderly, mildly demented outpatients does not contribute substantially to diagnostic accuracy after a careful clinical examination using current diagnostic criteria. Clinical guidelines have to be developed for the use of SPECT in patients with (suspected) dementia.     

Regional cerebral blood flow in patients with orally localized somatoform pain disorder: a single photon emission computed tomography study

Aim: Somatoform pain disorder is characterized by persistent and chronic pain at one or more sites without an associated general medical condition and in which psychological factors are thought to play a role. This study aimed to investigate the pathological features of somatoform pain disorder localized to the oral region by single photon emission computed tomography (SPECT). Methods: Ten patients (nine females and one male; average age 55.0 ± 14.4 years) having somatoform pain disorder with oral symptoms participated. SPECT was performed using N‐isopropyl‐4‐[¹²³I] iodoamphetamine intravenous injections, and regional cerebral blood flow (rCBF) was assessed by three‐dimensional stereotactic surface projections. We also selected 12 healthy individuals (seven females and five males; average age 61.8 ± 13.2 years) to act as controls. Results: Both the patient and control groups showed no atrophy or infarction on CT or magnetic resonance imaging. The patient group showed higher rCBF in the subcortical area, especially in the thalamus and cingulate gyri, than the control group. In contrast, the patient group showed lower rCBF in the bilateral frontal and occipital lobes as well as in the left temporal lobe. Conclusions: These results suggest that the biological process involved in somatoform pain disorder of the oral region is characterized by changes in limbic and cortical functions. The finding that somatoform pain disorder with oral symptoms is associated with brain functional changes will help to develop treatment regimes for this disorder and clarify the underlying pathology.     

Amlodipine lowers blood pressure without significant effect on cerebral blood flow in hypertensive patients with a history of stroke: a quantitative single photon emission computed tomography study

Appropriate antihypertensive therapy is important to prevent cerebrovascular disease. The purpose of the present study was to investigate the effect of such therapy on cerebral blood flow in stroke patients. Twenty hypertensive patients with a history of ischemic stroke received amlodipine 2.5 or 5 mg daily for 12 weeks. Blood pressure and cerebral blood flow as measured by ¹³³Xe single photon emission computed tomography at baseline and were compared at 12 weeks. There were statistically significant reductions in both systolic (167.0 to 140.9 mm Hg) and diastolic (97.8 to 81.8 mm Hg) blood pressures after 12 weeks of amlodipine treatment. No statistically significant effect was observed on cerebral blood flow (46.7 to 46.9 ml/100g brain/min). A weak but statistically significant change was observed in cerebellar blood flow (44.1 to 46.9 ml/100g brain/min). We concluded that amlodipine reduces blood pressure without affecting cerebral blood flow in hypertensive patients with a history of ischemic stroke. Investigation about its effect on cerebellar blood flow is mandatory.     

The pattern of regional cerebral blood flow during alcohol withdrawal - a single photon emission tomography study with 99mTc-HMPAO

Cerebral blood flow was investigated during alcohol withdrawal in 15 male alcoholics by single photon emission computerized tomography with ^99mTc-HMPAO and compared with the results of a second study 3 weeks later when all symptoms of withdrawal had disappeared and when the patients had been free of medication for at least 1 week. Slice images were reconstructed parallel to the orbitomeatal plane, and tracer activity was analyzed in 8 regions of interest per hemisphere. During alcohol withdrawal a special pattern of cerebral blood flow distribution could be observed. Relative perfusion was elevated in both inferior temporal regions, whereas it was reduced in the superior temporal region of both hemispheres. The changes of cerebral blood flow distribution did not correlate with neuropsychological findings nor with the severity of withdrawal syndrome.     

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.     

Cerebral blood flow changes in general paresis following penicillin treatment: a longitudinal single photon emission computed tomography study

Three cases of general paresis were successfully treated with high-dose penicillin. In all cases, cerebrospinal fluid cell counts decreased to normal and mental status improved rapidly. Cerebrospinal fluid protein concentrations decreased and IQ scores and overall levels of functioning improved gradually over 1 year. Regional cerebral blood flow (CBF) changes were analyzed longitudinally for 1 year using single photon emission computed tomography (SPECT). Autoradiography method and region of interest (ROI) analyses were used for quantitative CBF assessment and 3D stereotactic surface projections (3D-SSP) analyses were used for qualitative CBF pattern assessment. 3D-SSP could not reveal remarkable CBF pattern changes through the courses. The ROI analyses showed remarkable CBF decreases in all brain regions 1 month after the treatment, which recovered to normal levels 1 year after the treatment. These results suggest that remarkable decreases of quantitative CBF counts reflect the disappearance of encephalitis, while their gradual recovery reflects the gradual improvement of cerebral functional activity. As Treponema pallidum infection affects whole brain and CBF changes globally, quantitative CBF assessment may be more efficient than qualitative CBF pattern analyses for the purpose of understanding the pathophysiology of general paresis.     

Combined cerebral blood flow effects of a cholinergic agonist (milameline) and a verbal recognition task in early Alzheimer's disease

RU 35926/CI-979 (milameline) is a partial muscarinic agonist with promnestic effects in animal models. Preliminary animal studies suggest that this agent has the capacity to reverse cholinergic dysfunction and that it may impact on regional cerebral blood flow (rCBF). A total of 10 subjects with Alzheimer's disease (AD) of mild severity underwent high resolution split-dose single photon emission computed tomography (SPECT) during performance of a verbal recognition and control task, both before and after 18 weeks treatment with melameline or placebo. SPECT images were coregistered with individual's magnetic resonance imaging scans allowing extraction of rCBF values from multiple anatomical regions of interest (ROI). The effect of milameline was examined in eight individuals who were found after unblinding to be taking active drug. Effects of milameline were most apparent in the frontal regions, basal ganglia and thalamus. In the group as a whole, the greatest increase in rCBF due to milameline treatment was observed in the left globus pallidus. Response to milameline treatment was associated with increases in rCBF in the cingulate gyrus bilaterally, and less so for the left thalamus. Milameline-related increases in rCBF values were exaggerated by the verbal recognition task. Milameline has a demonstrable effect on cerebral blood flow in mild AD. Consistent with emerging animal data, the effects on rCBF appear most prominent in frontal and subcortical regions in AD subjects. The effects on rCBF appear to be augmented by the performance of a cognitively demanding task, raising the possibility that such tasks could assist in building an awareness of the functional neuropsychopharmacology of drugs designed for cognitive enhancement.     

Hot water epilepsy: Phenotype and single photon emission computed tomography observations

We studied the anatomical correlates of reflex hot water epilepsy (HWE) using multimodality investigations viz. magnetic resonance imaging (MRI), electroencephalography (EEG), and single photon emission computed tomography (SPECT). Five men (mean age: 27.0 ΁ 5.8 years) with HWE were subjected to MRI of brain, video-EEG studies, and SPECT scan. These were correlated with phenotypic presentations. Seizures could be precipitated in three patients with pouring of hot water over the head and semiology of seizures was suggestive of temporal lobe epilepsy. Ictal SPECT showed hyperperfusion in: left medial temporal — one, left lateral temporal — one, and right parietal — one. Interictal SPECT was normal in all five patients and did not help in localization. MRI and interictal EEG was normal in all the patients. The clinical and SPECT studies suggested temporal lobe as the seizure onset zone in some of the patients with HWE.     

Residual striatal dopaminergic nerve terminals in very long‐standing Parkinson's disease: A single photon emission computed tomography imaging study

Molecular imaging studies of Parkinson's disease (PD) progression mostly focus on the first 5 years after disease onset, demonstrating rapid initial nigrostriatal neuronal loss. The fate of residual functional dopaminergic nerve terminals in patients with long‐standing PD has not yet been specifically explored. Therefore, we performed [¹²³I]‐FP‐CIT single photon emission computed tomography (SPECT) in 15 patients with very long‐standing PD (mean disease duration 20.6 ± 6.3 years). Measurable uptake of [¹²³I]‐FP‐CIT was still detected in the striata of all patients. As seen in early stages, reduction of tracer uptake in the putamen was more prominent than in the caudate nucleus. Asymmetry in tracer uptake between the two putamen and caudate nuclei was preserved. These findings indicate that degeneration of dopaminergic neurons in PD is not total even after many years of illness. Data should be considered in exploring underlying causes of progressive loss of nigrostriatal dopaminergic neurons and development of future novel dopaminergic therapeutic strategies in PD. © 2010 Movement Disorder Society     

Relationship between psychiatric symptoms and regional cerebral blood flow in patients with mild Alzheimer's disease

Background: Behavioral and psychological symptoms of dementia (BPSD) are frequently observed in patients with dementia and often cause serious problems. However, the cause of BPSD has not yet been elucidated. Moreover, the precise evaluation of BPSD in mild dementia has not been studied in any great detail. In the present study, we investigated the relationship between psychiatric symptoms and regional cerebral blood flow (rCBF) in patients with mild Alzheimer's disease (AD). Methods: The present study included 47 patients (20 men and 27 women) who were diagnosed with mild AD. Mean patient age was 72.8 ± 8.2 years. Single photon emission computed tomography (SPECT) with ^99mTc‐ethyl cysteinate dimer (^99mTc‐ECD) was performed in all patients. The SPECT data were analyzed using a three‐dimensional stereotactic region of interest template, which evaluated CBF in 24 segments. Psychiatric symptoms were evaluated in patients using the Brief Psychiatric Rating Scale. Each psychiatric symptom was designated as ‘symptom present’ in cases in which the BPRS item score was more than 3. We compared 10 segments of rCBF in symptom‐present patients with those in symptom‐absent patients. Results: Motor retardation was the most common psychiatric symptom (36.2%), followed by depression (19.1%), anxiety (17.0%), emotional withdrawal (17.0%), and somatic concern (14.9%). Alzheimer's disease patients with motor retardation exhibited a tendency towards lower rCBF in seven segments (left callosomarginal, bilateral parietal, bilateral angular, and bilateral temporal). However, no specific tendency was observed in depression, anxiety, and somatic concern. Conclusions: In the present study, we observed a tendency for decreased brain perfusion in patients with motor retardation. Further studies are necessary to confirm that this trend contributes to the appearance of psychiatric symptoms in patients with mild AD.     

脑血管性痴呆与帕金森病神经心理学测验和脑单光子发射计算机断层扫描的对照研究

目的　研究脑血管性痴呆（ Ｖ Ｄ） 与帕金森病（ Ｐ Ｄ） 在神经心理学测验及脑单光子发射计算机断层扫描（ Ｓ Ｐ Ｅ Ｃ Ｔ） 的诊断和鉴别诊断的意义。方法　对３０ 例 Ｖ Ｄ、３１ 例 Ｐ Ｄ 和３０ 名正常老年人（ Ｎ Ａ） 进行神经心理学测验和 Ｓ Ｐ Ｅ Ｃ Ｔ 检查并比较检测结果。结果　神经心理学各项总分 Ｖ Ｄ 组最低［ 除积木测验（ Ｂ Ｄ） 外］ , Ｐ Ｄ 组次之, Ｎ Ａ 组最高;３ 组间差异均有非常显著性（ Ｆ＝ １８６７ ～６３９５ , Ｐ＜００１） 。在 Ｓ Ｐ Ｅ Ｃ Ｔ的检查中, Ｖ Ｄ 除额叶、左丘脑和右枕叶外余各脑区血流灌注均低于 Ｎ Ａ 组（ Ｐ＜００５） , Ｐ Ｄ 则为顶叶、颞叶、基底节和丘脑血流灌注低于 Ｎ Ａ 组（ Ｐ＜ ００５） 。结论　 Ｖ Ｄ 和 Ｐ Ｄ 的神经心理学测验和脑 Ｓ Ｐ Ｅ Ｃ Ｔ各有其特点,这两项检查可作为诊断和鉴别诊断 Ｖ Ｄ 和 Ｐ Ｄ 的辅助手段。     

The effects of tacrine on regional cerebral blood flow in Alzheimer's disease

Regional cerebral blood flow (rCBF) was studied in nine patients with Alzheimer's disease before and after treatment with tacrine. A small but significant improvement in cognitive functioning on the drug was not accompanied by significant changes in rCBF for the group as a whole. However, when the analysis was repeated excluding the only patient who showed no clinical response to the drug a significant increase in rCBF was seen to the right posterior temporal area. This preliminary study shows that some caution is necessary when interpreting studies of rCBF as changes in cognitive functioning may not always be accompanied by parallel changes in rCBF. Separate analysis of drug responders and non-responders may be a fruitful area for further research.     

Quantification analysis of 123I-IPT single photon emission computed tomography uptake in the striatum of parkinsonism with the standard magnetic resonance template

This study evaluated the striatal specific binding ratio (SBR), the anterior to posterior ratio of the striatum (APR) and its reproducibility by employing a template-based registration (TBR) method using the coregistered to the standard T1 magnetic resonance (MR) template (SMRT) as a replacement for the MR image of each patient. The 123I-IPT single photon emission computed tomography (SPECT) images of 30 patients with Idiopathic Parkinson's disease (IPD) and 11 normal controls were analyzed. The region of interest (ROI) was positioned manually in the same slice showing the highest striatal activity using the manual ROI method, while the ROI were positioned automatically in the mid striatal slice of the SPECT image coregistered to the SMRT. The SBR obtained using the TBR method showed a strong correlation with those using the manual method in all groups: normal controls (r = 0.851, P = 0.001), early IPD (r = 0.841, P < 0.001), and severe IPD (r = 0.702, P = 0.007). The APR obtained by the TBR correlated with those using the manual method in only the early IPD (r = 0.72, P = 0.001), while those obtained using the manual method showed no correlation in the three groups (P > 0.05). The reproducibility (rmsCV) of the TBR method was 7.2% (normal controls, 5.2%; mild IPD, 4.2%; severe IPD, 10.8%), while the reproducibility of the manual method was 31% (normal controls, 19.7%; mild IPD, 21.7%; severe IPD, 46.2%). This shows that the use of 123I-IPT SPECT for assessing IPD is affected by the method used to position the striatal ROI. This study showed that the TBR method using the SMRT is useful in diagnosing the IPD and assessing the disease severity with a high reproducibility, indicating a possibility of using the TBR method as a good replacement for the manual method.     

Cerebral blood flow in spinocerebellar degenerations: a single photon emission tomography study in 28 patients

We used single photon emission tomography to study regional cerebral perfusion in patients with different forms of spinocerebellar degeneration: 6 patients with Friedreich’s ataxia (FA), 6 with early-onset cerebellar ataxia with retained tendon reflexes (EOCA), 5 with autosomal dominant cerebellar ataxia type 1 (ADCA I) and 11 with idiopathic late-onset cerebellar ataxia (ILOCA). The results were related to clinical and magnetic resonance imaging (MRI) findings. Cerebellar hypoperfusion was constant in ADCA I and frequent in patients with other spinocerebellar degenerations. Brain stem hypoperfusion was constant in ADCA I, frequent in ILOCA patients with pontocerebellar atrophy and absent in FA and EOCA. FA and EOCA often showed a reduction in the parietotemporal cortex blood flow, which was not related to cortical atrophy. ILOCA patients had an asymmetric pattern in the temporal areas with decreased blood flow in the right side only. Caudate hypoperfusion was found in ADCA I patients. Cerebral atrophy did not account for changes in regional blood flow, which probably indicate early involvement of cerebral structures. Received: 26 August 1997 Received in revised form: 22 January 1998 Accepted: 27 January 1998     

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.     

Quantitative assessment of cerebral hemodynamics using single photon emission computed tomography with venous blood sampling

Objective

Quantitative cerebral blood flow (CBF) measured by single photon emission computed tomography (SPECT) with arterial blood sampling is one of the most reliable methods to assess the hemodynamics in individual patients. SPECT with venous blood sampling is less invasive. The present study compared the measurement of CBF using N-isopropyl-p-(iodine-123)-iodoamphetamine SPECT with venous blood sampling and with arterial blood sampling in patients with major cerebral artery occlusive disease.

Methods

Two normal subjects and 14 patients with major cerebral artery occlusive disease underwent SPECT with arterial and venous blood sampling. The microsphere method was used for quantitative SPECT imaging. Whole brain radioactivity was corrected when the detectors rotated in the forward direction (F₁–F₇). Venous sampling was performed 30 min after radiotracer injection. Arterial blood radioactivity was estimated by multiple regression analysis from these parameters. The cerebrovascular reactivity to acetazolamide was also measured.

Results

Multiple regression analysis established the following formula:

Ca₁₀=−1.099F₁+1.629F₂−2.143F₃−2.766F₄−1.208F₅+2.113F₆+3.259F₇+1.241Cv₃₀+94.958${\text{Ca}}_{10}=-1.099{\text{F}}_1+1.629{\text{F}}_2-2.143{\text{F}}_3-2.766{\text{F}}_4-1.208{\text{F}}_5+2.113{\text{F}}_6+3.259{\text{F}}_7+1.241{\text{Cv}}_{30}+94.958$     

Lack of initiative and interest in Alzheimer's disease: a single photon emission computed tomography study

Apathy is defined as a lack of motivation. The aim of this study was to investigate the relation between two major dimensions of apathy (lack of initiative and lack of interest) and brain perfusion. in patients with Alzheimer's disease (AD). Brain perfusion was measured by single photon emission tomography (SPECT). Thirty-one AD patients were included. Lack of initiative and interest were assessed with the Apathy Inventory. Nineteen AD subjects presented a lack of initiative and interest pathological score whereas 12 AD subjects did not. The lack of initiative and interest score correlated significantly with the right frontal and the right inferior temporal lobes. The AD patients with lack of initiative and interest showed a significantly lower perfusion in the right anterior cingulate than the AD patients without lack of initiative and interest. These results derive from rather small subgroups of patients but have the interest to dismantle the complementary aspects of emotion and motivation in apathy and suggest that the latter one is more related to cingulate area.