Telomere length shortening in patients with dementia with Lewy bodies.

BACKGROUND AND PURPOSE: Shortened telomere length has been considered to be associated with various age-related diseases, especially in dementia such as Alzheimer's disease and vascular dementia. However, changes in telomere length in dementia with Lewy bodies (DLB) remain unclear. To elucidate these changes, we set out to determine telomere length in peripheral leukocytes as well as the level of urinary 8-hydroxy-deoxyguanosine (8-OHdG) as a marker of oxidative stress in DLB. METHODS: Blood samples were obtained from 33 patients with a clinical diagnosis of probable DLB and 35 age-matched, non-demented elderly controls (NEC). Telomere length was assessed by quantitative real-time polymerase chain reaction of genomic DNA extracted from leukocytes, whereas oxidative stress was assessed on the basis of urine 8-OHdG level, which was measured using high-performance liquid chromatography. RESULTS: Telomere length was significantly shorter in the DLB group than in the NEC group. Urinary 8-OHdG levels were significantly higher in the DLB group than in the NEC group. There was a negative correlation between telomere length and age in the DLB group; however, there were no significant relationships between telomere length and clinical findings including disease duration, severity of cognitive decline, presence or absence of fluctuation in cognitive function, visual hallucinations, and Parkinsonism. In both groups, the correlation between telomere length and urinary 8-OHdG levels was not significant. CONCLUSIONS: These findings indicate that the etiopathology of DLB is considered to be an accelerated aging process.

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.

Differences in clinical course between dementia with Lewy bodies and Alzheimer's disease.

BACKGROUND AND PURPOSE: To investigate whether there may be differences in the clinical course and changes in cognitive progression between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). METHODS: We compared the time from the first visit to endpoints (discontinuation of visits because of admission, death, or institutionalization) between 56 patients with DLB and 111 patients with AD. Mini-Mental State Examination (MMSE) scores of patients were every 12 months examined up to 60 months. RESULTS: Dementia with Lewy bodies had a significantly shorter time to reaching endpoints than those with AD (median time; 40 months vs. 52 months, P < 0.0001). The proportion of admission (or death) was significantly higher in DLB than in AD (30% vs. 14%, P < 0.05), while the difference in institutionalization in nursing homes did not reach statistical significance (25% vs. 17%). Rates of longitudinal MMSE score decline for DLB and AD groups were equivalent. CONCLUSION: Dementia with Lewy bodies had a greater risk of admission (or death) because of most commonly fall-related injuries and bronchopneumonia than AD, but the two groups did not differ in rate of cognitive decline.

Deep gray matter hyperperfusion with occipital hypoperfusion in dementia with Lewy bodies.

Although decreased occipital perfusion is a characteristic feature of dementia with Lewy bodies (DLB), not all patients with DLB show a significant decreased perfusion in the occipital lobe. We explored characteristics of perfusion changes to improve the identification of DLB, in addition to occipital hypoperfusion. Statistical image analysis of single photon emission computed tomography data was performed on 22 patients with DLB and 25 patients with Alzheimer's disease (AD). A significant decreased perfusion in the occipital lobe was found in 16 patients with DLB (72%) and three patients with AD (12%), while a significant increased perfusion in the deep gray matter (striatum and/or thalamus) was found in 18 patients with DLB (81%) and eight patients with AD (31%), respectively. Either occipital hypoperfusion or deep gray matter hyperperfusion was found in 21 patients with DLB (95%), while in nine patients with AD (35%), indicating a sensitivity of 95% and a specificity of 65% in discriminating DLB from AD. Our results suggest that the addition of deep gray matter hyperperfusion to occipital hypoperfusion may be useful in the clinical differentiation of DLB and AD.

Magnetization transfer measurements of the hippocampus in patients with Alzheimer's disease, vascular dementia, and other types of dementia.

BACKGROUND AND PURPOSE: Although atrophy of structures in the medial temporal lobe has been considered an indication of Alzheimer's disease (AD), atrophic changes on MR images have also been associated with other dementing diseases and are not specific to AD. This study was undertaken to determine whether characteristic alterations in the hippocampus of patients with AD are detectable with magnetization transfer (MT) imaging. METHODS: Coronal MT imaging was performed in 35 patients with probable AD, in 14 patients with vascular dementia, in 13 patients with other types of dementia, and in 23 control subjects to measure MT ratios of the hippocampus. Medial temporal lobe atrophy was graded subjectively on a five-point scale. RESULTS: Scores of medial temporal lobe atrophy in all dementia groups were significantly higher than those in control subjects, but no differences were found among the dementia groups. MT ratios in the hippocampus were significantly lower in patients with AD than in those with non-AD dementia and in the control subjects; however, no differences were found between the non-AD dementia patients and the control subjects. MT ratio measurements were better than visual analysis of atrophy for differentiating AD patients from those with non-AD dementia (an overall discrimination rate of 77% versus 65%). MT ratios significantly correlated with scores on the Mini-Mental State Examination and with medial temporal lobe atrophy in AD patients but not in patients with non-AD dementia. CONCLUSION: MT measurements may be more specific than visual analysis in detecting structural damage of the hippocampus in AD patients and might be useful in discriminating AD from vascular dementia and other types of dementia.

Diffusion-weighted MR imaging of the hippocampus and temporal white matter in Alzheimer's disease.

We investigated the changes in water diffusion in the hippocampus and the temporal white matter (the temporal stem) in eight patients with possible Alzheimer's disease (AD), 10 patients with probable AD, and 10 age-matched controls, using coronal diffusion-weighted magnetic resonance (MR) imaging. Apparent diffusion coefficients (ADCs) were derived for the three orthogonal axes and an index of diffusion anisotropy (IDA = ADC(max-min)/ADC(mean)) was then calculated. Although no significant differences were found in ADC and IDA values in the hippocampal body between controls and patients, vertical (superior-inferior) ADC values and ADC(mean) values in the temporal stem of patients with AD were significantly higher than those in controls, and IDA values were therefore significantly lower in patients with possible or probable AD than those in controls. Moreover, IDA values in the temporal stem were significantly correlated with the clinical severity. These results suggest that decreased fiber density, such as the disruption and loss of axonal membranes or myelin, occur early in the temporal stem, probably due to secondary degeneration related to grey matter pathology including the medial temporal lobe.

Magnetization transfer ratio in cerebral white matter lesions of Binswanger's disease.

We measured the magnetization transfer (MT) ratios in white matter lesions of Binswanger's disease (BD) and compared them with BD and with similar-appearing changes in non-demented elderly subjects and cerebral infarction. Four subject groups were studied: 30 patients with BD and periventricular hyperintensity (PVH) on MRI, 29 patients with ischemic cerebrovascular event with PVH but no dementia, 17 patients with old cerebral infarction, and 26 elderly control subjects. MT ratios were calculated for areas of PVH in BD and non-demented subjects, of infarction, and of normal-appearing white matter in controls. The decrease in MT ratios for areas in PVH of non-demented subjects and BD and in infarction compared with normal white matter in controls was 12, 20, and 35%, respectively. The MT ratio in PVH of BD was significantly lower than that in PVH of non-demented subjects, but not to the levels seen in areas of infarction. There was a significant high correlation between the Mini-Mental State Examination score and MT ratio for area of PVH (r = 0.790). MT ratio distinguishes PVH in BD patients from those in non-demented subjects, suggesting underlying histopathological differences. Tissue damage in white matter lesions of BD may be more severe than that in non-demented subjects, but not as much as with complete infarction.

Magnetization transfer measurements of the hippocampus in the early diagnosis of Alzheimer's disease.

We measured magnetization transfer ratios (MTRs) of the hippocampus in 38 patients with Alzheimer's disease (AD), including very mild (Clinical Dementia Rating [CDR] 0.5, n=12), mild (CDR 1, n=14), and moderate stages (CDR 2, n=12), and in 21 healthy elderly control subjects. Medial temporal lobe atrophy was graded subjectively on a five-point scale by two observers blinded to clinical data. Compared with the controls, each of the AD groups, including the very mild group, had significant atrophy of the medial temporal lobe and a decrease in MTRs of the hippocampus. Logistic regression analysis revealed that the overall discrimination rate with MTR measurement and visual analysis of the atrophy was 85% and 73% between the control group and the CDR 0.5 group, 89% and 80% between the control group and the CDR 1 group, and 100% and 91% between the control group and the CDR 2 group, respectively. MTR measurements may provide additional information in detecting structural damage of the hippocampus of AD and be helpful in providing improved diagnosis and early detection of AD.

Diffusion-weighted and magnetization transfer imaging of the corpus callosum in Alzheimer's disease.

We investigated structural changes of the corpus callosum in patients with Alzheimer's disease (AD) using sagittal diffusion-weighted (DW) and magnetization transfer (MT) imaging. Patients with AD (n=23) had a significantly decreased area only in the posterior portion of the corpus callosum. Apparent diffusion coefficient (ADC) values perpendicular to the commisural fiber orientation were significantly higher in the anterior portion of the corpus callosum without definite atrophy, as well as in the posterior portion with significant atrophy, in patients with AD than in controls (n=16) and thus diffusion in these regions showed a significantly lower degree of anisotropy in patients than in controls. MT ratios were also significantly lower in patients with AD in the anterior and posterior portions of the corpus callosum than in controls. These findings probably reflect structural changes in the corpus callosum including axonal loss and/or demyelination. DW and MT imagings may be useful in detecting degeneration of the corpus callosum in AD.

Diffusion-weighted magnetic resonance and magnetization transfer imaging in the assessment of ischemic human stroke.

We compared characteristic features in ischemic stroke lesions from the hyperacute to the chronic stage on diffusion-weighted (DW) and magnetization transfer (MT) images with those on T2-weighted (T2W) images, and assessed changes in apparent diffusion coefficient (ADC), MT effect (MTe), and T2 ratios (infarct/normal) over time. DW images were particularly useful for detecting hyperacute infarcts within 6 hours of onset and in distinguishing acute lesions from chronic lesions. ADC ratios were lower within 7 days after onset and rose toward 1.0 in the subacute phase, becoming relatively isotense on ADC maps, but elevated thereafter. Although MTe ratios were unchanged or only subtly changed in the acute stage, they became significantly lower in the subacute and chronic stages. These combined magnetic resonance (MR) techniques were useful in the assessment of ischemic stroke and facilitated the determination of the age of cerebral infarct.

Cerebrocerebellar relationships in normal subjects and patients with dementia of the Alzheimer type: a SPECT study.

The relationships between blood flow in the cerebrum and the cerebellum was investigated in 21 normal subjects and 21 patients with dementia of the Alzheimer type (DAT). In normal subjects, only asymmetry in the frontal cortical blood flow was significantly correlated with asymmetry in the contralateral cerebellar blood flow. However, a significant correlation between asymmetry in the cerebral cortical blood flow in many areas and the blood flow in the contralateral cerebellum in DAT patients was observed. These results suggest the existence of a functional relationship between the cerebrum and the cerebellum in both normal and DAT groups, mediated by neuronal mechanisms through crossed fiber pathways. However, there are regional differences in the cerebrocerebellar relationship in normal resting and pathological states.

Chemical control of Haematobia irritans with 0.5% topical ivermectin solution in cattle.

A field trial was conducted to evaluate the efficacy of a topical formulation of ivermectin administered at the dose of 500 micrograms/kg against horn flies (Haematobia irritans) in cattle. Eighty-eight cattle in four herds naturally exposed to horn flies were used in the trial. Replicates were formed of two herds. Within replicates, one herd was randomly allocated to the untreated control and the other to the ivermectin treatment group. Horn fly counts were taken on the treatment day (Day 0) and on Days 7, 14, 21, 28, and 35 post-treatment. There were no horn flies on any cattle in the treatment group, whereas all the control cattle were continuously infested by horn flies on each examination day.

[Wallenberg's syndrome caused by a brain tumor--a case report and literature review].

we report a patient with Wallenberg's syndrome caused by glioma of the lateral medulla oblongata, and review the literature for Wallenberg's syndrome associated with neoplastic disease. A 46-year-old man was admitted because of progressive dysphagia and vertigo. Neurological examination revealed atypical symptoms and signs of Wallenberg's syndrome on the right side, hypalgesia on the second and third divisions of the left trigeminal nerve, paresis of the right palate and uvula, and ataxia of the right extremities. Although CT showed no abnormality in the posterior fossa, MRI demonstrated a mass with abnormal signal intensities in the right dorsolateral portion of the medulla. Biopsy specimens showed astrocytoma (grade III). Based on the present case and a review of 10 previously reported cases of Wallenberg's syndrome caused by neoplastic disease, the clinical features of this syndrome are characterized by gradual development and steady progression of symptoms, non-classical or atypical symptomatology, numerous additional symptoms and signs depending on the site and size of tumors, and poor prognosis.

[Study of cerebral circulation and cerebrospinal fluid dynamics in a patient with agenesis of the corpus callosum using 123I-IMP SPECT and cine-mode MRI].

A right-handed, 77-year-old man, complaining of dizziness, was diagnosed as agenesis of the corpus callosum (ACC) by MRI, which demonstrated a complete defect of the corpus callosum (CC) with symmetrical enlargement of the posterior horns of the bilateral ventricles (colpocephy) and focal hypo-plasticity of the frontal lobes. Neurological examination revealed only mild impairment of mental function and poor transfer of tactile form-board learning from the right hand to the left hand. As to the cerebral circulation detected by 123I-IMP SPECT, isotope distribution corresponded to the MRI brain images, though the defects were clearly seen on the medial surfaces of the bilateral frontal lobes, so interhemispheric fissure seemed to be opened widely. IV-DSA revealed hypo-vascularity in the anterior territory of the anterior cerebral arteries. These findings suggested that this localized defect was due to hypo-vascularity and focal hypo-plasticity of the frontal lobes. On the other hand, cine-mode MRI findings that no signal-void phenomenon was found between the third ventricle and the longitudinal fissure indicated no shunt in cerebrospinal fluid.

[Atrophy and magnetization transfer ratio of the corpus callosum in patients with Alzheimer's disease].

We compared atrophy and magnetization transfer ratio (MTR) in the corpus callosum in patients with Alzheimer's disease and age-matched normal subjects. Fifteen patients with Alzheimer's disease and fourteen normal subjects received MRI. The corpus callosum was divided into three parts (anterior, middle, and posterior portions) on midsagittal slice, and their areas on T2-weighted reversed images and MTR on magnetization transfer contrast images in each portion were measured. The area and MTR decreased significantly in the posterior portion in patients with Alzheimer's disease. In the anterior portion, MTR decreased significantly, but although the area showed no significant change. In the middle portion, the area and MTR showed no significant change. MTR and the area was correlated in each portion in patients with Alzheimer's disease. The score of Hasegawa dementia scale-revised (HDS-R) and the area of the middle, posterior and total of corpus callosum were significantly related. The score of HDS-R and MTR in the anterior portion of corpus callosum were significantly related. The present study revealed decreases in MTR in the anterior portion of the corpus callosum of patients with Alzheimer's disease although the area showed no significant change, and this change suggests the increase in free water and/or the decrease in bound water in tissues, probably due to demyelination and axonal degeneration.

[Magnetization transfer imaging of periventricular white matter lesions in patients with multi-infarct dementia].

Using magnetization transfer (MT) imaging, we studied the underlying pathological conditions of periventricular hyperintense (PVH) white matter changes seen on T2-weighted MR images of patients with multi-infarct dementia. Twenty-two patients with multiple lacunar infarcts and PVH lesions, including 11 with dementia (diagnosed as multi-infarct dementia) and 11 without dementia, and 10 control subjects (with multiple lacunes, but no PVH lesion) were studied using the MT technique. MT ratios (MTRs) were calculated for PVH lesions (normal-appearing frontal white matter in controls) and the genu of the corpus callosum. Signal intensities on T2-weighted images in PVH lesions of patients were significantly higher than those in normal-appearing white matter of controls, while there were no significant differences in signal intensity in the genu of the corpus callosum among the dementia, non-dementia and control groups. However, MTRs in patients with PVH lesions were significantly lower than those in controls, and MTRs in demented patients were significantly lower than those in non-demented patients. Moreover, MTRs in the genu of the corpus callosum of demented patients were significantly lower than in those in non-demented patients and controls. MTRs in PVH lesions and the genu of the corpus callosum significantly correlated with Hasegawa's dementia scale score. These results suggest that there is some difference in histopathologic changes of PVH lesions between demented and non-demented patients and that the pathological substrate in the corpus callosum may play a role in inducing cognitive decline. Studies with MT imaging may allow the characterization of different pathological conditions that cannot be visualized by conventional MRI.

[Diffusional anisotropy in the cerebral white matter in Alzheimer-type dementia].

To investigate changes in water diffusion in the cerebral white matter in Alzheimer-type dementia (AD), diffusion MRI studies were performed on 11 patients with AD without hyperintensity lesions on T2-weighted images, and 10 age-matched controls. In the anterior and posterior white matter around the lateral ventricule, and the splenium of the corpus callosum, the apparent diffusion coefficients (ADCs), in which the diffusion gradient was applied perpendicular to the predominant fiber direction, were significantly higher in patients with AD than in the controls. However, those in which the diffusion gradient was applied parallel to the predominant fiber direction, there were no significant difference in ADCs between patients and controls. Therefore, diffusional anisotropy was lost in the white matter. These results suggest that demyelination occurs in patients with AD even in apparently normal white matter (without signal abnormalitis). Degeneration related to grey matter encephalopathy may be a possible explanation of the demyelinating process in the white matter.

[Diffusion MRI study of cerebral white matter lesions in patients with Binswanger's disease].

We performed diffusion MRI studies in 14 patients with extensive ischemic leukoencephalopathy, including 9 with dementia (diagnosed as Binswanger's disease), and 5 without dementia, and 8 age-matched controls. Apparent diffusion coefficients (ADCs) in anterior and posterior periventricular white matter were significantly higher in demented and non-demented patients than in the controls, and diffusion anisotropy disappeared in patients because of the high ratio of the diffusion coefficients perpendicular to the nerve fibers to those parallel to the nerve fibers. ADCs in the corpus callosum were significantly higher in demented patients that in non-demented patients and controls. Therefore, diffusion anisotropy disappeared only in demented (Binswanger's disease) patients. These results suggest that the cerebral white matter lesions in Binswanger's disease reflect a decrease of nerve fibers and diffuse myelin loss, and that the loss of nerve fibers in the corpus callosum may play a role in inducing cognitive decline. Diffusion MRI may be useful in the pathophysiological evaluation of cerebral white matter lesions.

[Differences of neuroimaging between early-onset and late-onset Alzheimer-type dementia].

Several studies have shown that the symptomatology and the neuropathological and neurochemical changes of early-onset Alzheimer's disease (EAD) differ from those of late-onset Alzheimer's disease (LAD). The aim of the present study is to examine differences in SPECT and MRI findings between EAD and LAD. Cerebral blood flow and patterns on SPECT, and deep white matter lesions and cerebral atrophy on MRI in 17 patients with EAD were compared with 30 patients with LAD without cerebrovascular risk factors. Temporoparietal activity ratio, divided by cerebellum, on SPECT imaging in patients with EAD was significantly lower than in patients with LAD. In a qualitative assessment of perfusion patterns, bilateral temporoparietal hypoperfusion, which is typical in AD, was seen more frequently in patients with EAD than in those with LAD. Among white matter changes in MRI, the score of white matter hyperintensity was significantly higher in LAD than in EAD patients. However, there was no significant difference between periventricular hyperintensity scores. Though ventricular enlargement did not differ significantly in EAD and LAD, cortical atrophy scores in LAD were significantly higher than in EAD. Cortical atrophy scores were significantly higher in patients with atypical perfusion patterns on SPECT, (e.g. global hypoperfusion in addition to temporoparietal change), than in patients with typical perfusion pattern. These results indicate that functional and morphological imagings in LAD differ with those in EAD, probably due to less-prominent neuropathological degeneration combined with age-related alterations.

[Diagnosis of Alzheimer's disease using brain SPECT with three-dimensional stereotactic surface projections].

We compared the diagnostic usefulness of three-dimensional stereotactic surface projection (3D-SSP) with that of standard transaxial images in brain SPECT in patients with Alzheimer's disease (AD). The subjects consisted of 69 patients with AD and 60 patients with non-AD, including vascular dementia, Parkinson's disease with dementia, frontotemporal dementia, other dementing diseases and neuropsychiatric diseases. Standard transaxial section and 3D-SSP SPECT images with N-isopropyl-p-[123I] iodoamphetamine were blindly interpreted by three examiners and were classified into the following three patterns: typical AD, atypical AD, and not indicative AD patterns. The 3D-SSP images demonstrated reductions of cerebral blood flow in the parieto-temporal association cortex and posterior cingulate gyrus more clearly and easily than the standard transaxial images. The diagnostic sensitivity and specificity were 93% and 85% with 3D-SSP and 83% and 82% with standard transaxial section respectively. 3D-SSP was especially useful for early or atypical AD which showed no characteristic perfusion abnormalities on standard transaxial images. These results suggest that SPECT with 3D-SSP provides an sensitive as well as accurate tool for the diagnosis of AD.