Soichiro Shimizu

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

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.

Cerebral microbleeds in Binswanger's disease: a gradient-echo T2*-weighted magnetic resonance imaging study.

We investigated the incidence and the number of microbleeds (MBs) on T2*-weighted gradient-echo magnetic resonance imaging in 30 Binswangers disease (BD) patients with diffuse white matter lesions and a varying degree of lacunar infarction, 51 multiple lacunar stroke (MLS) patients with multiple lacunar infarction and no or mild white matter lesions, and 59 elderly controls. MBs were found in 23 (77%) patients with BD, 26 (51%) patients with MLS, and 5 (8%) controls, and the incidence and the number of MBs were significantly greater in the BD group compared with MLS and control groups. Patients with BD had a more widespread location of MBs. More specifically, MBs were commonly found in areas within or surrounded by white matter lesions of the patients with BD. When 81 patients from both the BD and MLS groups were analyzed, logistic regression analysis showed that number of lacunar infarct, severity of white matter hyperintensity, and use of antiplatelet agents were significantly associated with MBs. Patients with BD exhibited a high frequency and number of MBs, indicating advanced bleeding-prone microangiopathy within the brain, which should be taken into account in treatment and management.

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.

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.

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 Alzheimers 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. Signifi cant 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.

Neuroanatomical correlates of unawareness of memory deficits in early Alzheimer's disease.

Background/Aims: To investigate neuroanatomical substrates of unawareness of memory deficits in patients with early Alzheimer’s disease (AD). Methods: We compared regional perfusion deficits between AD patients with awareness (n = 19) and unawareness (n = 19). SPECT data were analyzed by statistical brain imaging method. Results: Statistical maps demonstrated a more extensive and severe reduction in perfusion in the unaware group than in the aware group. Quantitative analysis demonstrated a significant difference between the groups in the right subcallosal, anterior cingulate and cingulate gyri and left orbital, subcallosal, and anterior cingulate gyri. Conclusion: Functional damage to the inferior, medial and orbital frontal lobes as well as the anterior cingulate gyri may be associated with the lack of awareness in patients with early AD.

Association Between ApoE Phenotypes and Telomere Erosion in Alzheimer’s Disease

Although several reports suggest that Alzheimers disease (AD) is associated with shortened telomere length, the clinical relevance of this has not yet been fully elucidated. This study was conducted to clarify the correlation of telomere length with clinical characteristics and ApoE phenotypes in 74 AD patients. Telomere length was determined from genomic DNA extracted from whole blood by quantitative real-time polymerase chain reaction. We found no significant difference in telomere length between the AD and non-dementia elderly control (n = 35) groups. Furthermore, no significant correlation was found among telomere length and the severity of cognitive decline and disease duration, age, or gender difference. However, telomere length was significantly shorter in AD patients with the ApoE4 homozygote than in those with the ApoE4 heterozygote (p < .001) and noncarriers (p < .001). These findings suggest that shortened telomere length may be associated with the ApoE4 homozygote in AD patients.

Differences in magnetization transfer ratios of the hippocampus between dementia with Lewy bodies and Alzheimer's disease

We compared magnetization transfer ratios (MTRs) in the brains of patients with dementia with Lewy bodies (DLB) and Alzheimers disease (AD) to determine whether regional differences in the brain structures between DLB and AD are detectable with magnetization transfer imaging. Seventeen patients with DLB, 31 patients with AD and 18 elderly normal controls were included. Although no significant differences were found in MTRs in the frontal white matter between the three groups, MTRs in the hippocampus, parahippocampus, and posterior cingulate white matter in both patients with DLB and AD were significantly lower than those in age-matched control subjects. However, MTRs in the hippocampus of patients with DLB were significantly higher than those in patients with AD. Logistic regression analysis revealed that hippocampal MTR yielded a sensitivity of 76% and a specificity of 71% in discriminating DLB from AD. These results may reflect underlying histopathological differences with less severe neuronal degeneration in the hippocampus of DLB. MTR measurement of the hippocampus may contribute to the clinical differentiation between DLB and AD.