Kimihiko Abe

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 Alzheimers 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.

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 Alzheimers 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.

Comparative value of brain perfusion SPECT and [123I]MIBG myocardial scintigraphy in distinguishing between dementia with Lewy bodies and Alzheimer’s disease

PurposeBoth decreased occipital perfusion on brain single-photon emission computed tomography (SPECT) and reduction in cardiac 123I-metaiodobenzylguanidine (MIBG) uptake are characteristic features of dementia with Lewy bodies (DLB), and potentially support the clinical diagnosis of DLB. The aim of this study was to compare the diagnostic value of these two methods for differentiation of DLB from Alzheimer’s disease (AD).MethodsThe study population comprised 19 patients with probable DLB and 39 patients with probable AD who underwent both SPECT with N-isopropyl-p-[123I]iodoamphetamine and MIBG myocardial scintigraphy. Objective and quantitative measurement of perfusion in the medial occipital lobe, including the cuneus and lingual gyrus, was performed by the use of three-dimensional stereotactic surface projections.ResultsMedial occipital perfusion was significantly decreased in the DLB group compared with the AD group. The mean heart/mediastinum ratios of MIBG uptake were significantly lower in the DLB group than in the AD group. Although SPECT failed to demonstrate significant hypoperfusion in the medial occipital lobe in five patients with DLB, marked reduction of MIBG uptake was found in all patients with DLB. Receiver operating characteristic analysis revealed that MIBG myocardial scintigraphy enabled more accurate discrimination between DLB and AD than was possible with perfusion SPECT.ConclusionMIBG myocardial scintigraphy may improve the sensitivity in the detection of DLB. In particular, this method may provide a powerful differential diagnostic tool when it is difficult to distinguish cases of DLB from AD using brain perfusion SPECT.

Cerebral microbleeds in Alzheimer’s disease

Sirs: T2*-weighted gradient-echo magnetic resonance imaging (MRI) is a highly sensitive technique for detecting hemosiderin deposits and thus remnants of intracerebral microbleeds (MBs), which are clearly visualized as small areas of signal loss. Postmortem correlative MRI and histopathological studies have confirmed that areas of signal loss on T2*-weighted images represent hemosiderin deposits [2, 7]. Several studies have revealed that patients with small artery disease of the brain, such as hypertensive microangiopathy and cerebral amyloid angiopathy, more often exhibit MBs on T2*-weighted MRI [3, 5, 7]. Since cerebral amyloid angiopathy is commonly found with an incidence of about 80 to 98 % in the brain of Alzheimer’s disease (AD) [4], we hypothesized that AD may show a predisposition to MBs. We obtained T2*-weighted MRI scans to determine the frequency, extent, and pattern of MBs in patients with AD. Patients were prospectively recruited for serial MRI scans from the Memory Disorder Clinic at the Department of Geriatric Medicine, Tokyo Medical University, between January 2002 and December 2002. Among patients studied, we identified 59 consecutive patients with AD (25 men and 34 women, aged 61 to 88 years). The clinical diagnosis of AD was based on the NINCDS-ADRDA criteria [6]. The mean Mini-Mental State Examination (MMSE) score (mean ± SD) was 17.9 ± 6.0 (5 to 26). Fifty-five consecutive patients who underwent MRI for observation of headache or dizziness without neurological deficits or cognitive impairment served as controls (22 men and 33 women, aged 58 to 88 years). MRI was performed on a 1.5 T superconducting magnet system (Siemens Magnetom Symphony). Nineteen contiguous axial 5-mmthick slices (1.5-mm interslice gap) were obtained with the following pulse sequence: (1) T1-weighted spin echo (TR, 450 ms; TE, 12 ms; FOV, 250 mm, matrix 256 256), (2) T2-weighted fast spin echo (TR, 3540 ms, TE, 106 ms; FOV, 250 mm, matrix 256 256), and (3) T2*weighted gradient echo (TR, 800 ms; TE, 26 ms, flip angle, 30°; FOV, 250 mm, matrix 256 256). Lacunar infarction was defined as a small deep lesion (usually less than 15 mm in diameter) with a high signal intensity on T2-weighted images and low signal intensity on T1-weighted images. White matter hyperintensities were classified as absent, punctate, early confluent, or confluent abnormalities according to Fazekas et al. [1]. In accordance with previous studies, MBs were defined on gradient-echo T2*weighted images as homogenous rounded lesions of signal loss with a diameter greater than 2 mm [5, 7]. The numbers of MBs were recorded in the following: deep gray matter (basal ganglia and thalamus), deep white matter, cortico-subcortical, and infratentorial regions (brain stem and cerebellum). Based on the numbers of MBs, the extent of MBs was graded as none [0], mild [1–5], moderate [6–10], or severe (≥11). All MR images were reviewed by the same observer blinded to clinical or laboratory data. There were no significant differences in age, sex, risk factors including hypertension and diabetes mellitus, lacunae, or the grade of LETTER TO THE EDITORS

Increased Water Diffusion in Cerebral White Matter in Alzheimer’s Disease

We investigated the changes in water diffusion in the cerebral white matter in 19 patients with Alzheimers disease (AD), including 11 without and 8 with periventricular hyperintensity (PVH) lesions, using diffusion-weighted magnetic resonance imaging (MRI). The apparent diffusion coefficients in the anterior and posterior white matter were significantly higher in the 19 AD patients than in the 10 age-matched controls. The apparent diffusion coefficients were higher in patients with PVH than in those without. The anisotropic ratios, defined as diffusion restricted perpendicular to the direction of the nerve fibers, were significantly higher in AD patients, even in those without PVH, than in the controls. Our results suggest that mild myelin loss occurs in AD patients even in the apparently normal white matter. A definite loss of myelin and axons, including incomplete infarction, occurs in the white matter, as seen on T2-weighted images as PVH. Studies with diffusion-weighted MRI may allow the characterization of different pathological processes and enable the demonstration of underlying white matter lesions in AD that cannot be visualized by conventional MRI.

Atrophy of the Substantia innominata on Magnetic Resonance Imaging Predicts Response to Donepezil Treatment in Alzheimer’s Disease Patients

To investigate whether atrophy of the substantia innominata as shown on magnetic resonance imaging (MRI), reflecting degeneration of cholinergic neurons in the nucleus basalis of Meynert, predicts response to donepezil treatment in patients with Alzheimer’s disease (AD), we studied correlations between the thickness of the substantia innominata and clinical efficacy. Eighty-two patients were divided into responders, including transiently and continuously responding groups, and nonresponders, based on the changes in the Mini-Mental State Examination (MMSE) score from baseline at 3 months and at 12 months. Atrophy of the substantia innominata was more pronounced in transiently and continuously responding groups than nonresponders, but no significant change in the thickness between transiently and continuously responding groups was found. The MMSE score changes from baseline at 3 months and at 12 months significantly inversely correlated with the thickness of the substantia innominata. Logistic regression analysis revealed that the overall discrimination rate with the thickness of the substantia innominata was 70% between responders and nonresponders. We conclude that atrophy of the substantia innominata on MRI helps to predict response to donepezil treatment in patients with AD.

Differentiation of Dementia with Lewy Bodies from Alzheimer’s Disease Using Brain SPECT

We compared regional cerebral blood flow (CBF) patterns in patients with dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) using single photon emission computed tomography (SPECT) and investigated the diagnostic utility of SPECT study in differentiating between DLB and AD. SPECT data on 20 patients with DLB and 75 patients with AD were analyzed using three-dimensional stereotactic surface projections. Regional CBF reduction was determined by quantitative analysis using stereotactic extraction estimation method. The DLB group showed a significant CBF reduction in the temporoparietal, frontal lobe and posterior cingulate, similar to the CBF pattern in the AD group, but regional CBF in the medial and lateral occipital lobes decreased significantly in patients with DLB compared with patients with AD. Receiver operating characteristic analysis revealed that regional CBF measurement of the medial occipital lobe, including the cuneus and lingual gyrus, yielded a sensitivity of 85% and a specificity of 85% in discriminating DLB from AD. Objective and quantitative CBF measurement in the medial occipital lobe may be useful in the clinical differentiation of DLB and AD.

The role of 123I-metaiodobenzylguanidine myocardial scintigraphy in the diagnosis of Lewy body disease in patients with dementia in a memory clinic.

Reduction in cardiac 123I-metaiodobenzylguanidine (MIBG) uptake is a characteristic feature of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), and is useful in distinguishing them from other neurodegenerative disorders. The aim of this study was to investigate the role of this method of scintigraphy in the differential diagnosis of dementia in our Memory Clinic. We performed MIBG scintigraphy in patients with dementia referred to the Memory Clinic and compared the heart-to-mediastinum (H/M) ratio of MIBG uptake. Thirty out of 32 patients with DLB and all 9 PD with dementia patients had reduced H/M ratios, whereas 37 out of 40 patients with Alzheimer’s disease had normal H/M ratios. Most patients with vascular dementia, frontotemporal dementia, and other dementias had normal H/M ratios. The overall sensitivity to positively identify patients with Lewy body disease (including DLB and PD with dementia) was 95%, and the specificity to distinguish them from patients with other types of dementias was 87%. MIBG scintigraphy showed a high sensitivity for the detection of Lewy body disease, and also a high specificity for discrimination from other types of dementia. The scintigraphy may provide a valuable and adjunctive method in the diagnosis of Lewy body disease and a differential diagnostic tool for patients with dementias.

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 Alzheimers 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.

MR features of the substantia innominata and therapeutic implications in dementias.

We measured the thickness of the substantia innominata using magnetic resonance imaging in 122 patients with Alzheimers disease (AD), 31 patients with dementia with Lewy bodies (DLB) and 34 patients with vascular dementia (VaD), and examined the correlates of cognitive response to donepezil. Although all dementia groups showed significant atrophy of the substantia innominata compared to 28 age-matched controls, atrophy was greater in the DLB group, but less in the VaD group than the AD group. Mini-Mental State Examination score changes at 12 weeks after donepezil administration inversely and significantly correlated with the thickness of the substantia innominata in patients with AD (n=103, r=-0.43, p<0.0001) and in patients with DLB (n=24, r=-0.57, p<0.01), but not in patients with VaD (n=12, r=-0.22, p>0.1). There may be some differences in cholinergic impairment among AD, DLB and VaD, reflecting cholinergic neuropathology. Clinical response to cholinergic therapy may be partly attributable to damaged cholinergic neurons in AD and DLB, but not in VaD, suggesting differences in the therapeutic implication of cholinergic system degeneration.