Differential Diagnosis of Dementia with Lewy Bodies and Alzheimer Disease Using Combined MR Imaging and Brain Perfusion Single-Photon Emission Tomography

摘要

BACKGROUND AND PURPOSE: Diagnostic performance by MR imaging or by SPECT alone in discriminating DLB patients from AD patients has been estimated previously. However, the performance of a combination of MR imaging and SPECT has not yet been evaluated. Our aim was to evaluate the usefulness of combining MR imaging and SPECT to discriminate mild DLB from AD. MATERIALS AND METHODS: Nineteen patients with mild DLB and 19 age- and cognitive decline–matched patients with mild AD underwent both SPECT and MR imaging. Hippocampal, occipital, and striatal volume and SPECT count ratios were compared. Linear discriminant and ROC analyses were performed by using the parameters of striatal volume and the occipital SPECT ratio. RESULTS: The striatal volume ratio in the DLB group was significantly lower than that in the AD group. The occipital SPECT ratio in the DLB group was lower than that in the AD group. The mean area under the ROC curve from combined MR imaging and SPECT (AUC = 0.898) was higher than that from MR imaging (AUC = 0.679) or SPECT (AUC = 0.798) alone. CONCLUSIONS: By combining MR imaging and SPECT, we were able to distinguish patients with mild DLB from those with AD with a high level of accuracy. Our findings suggest that combining MR imaging and SPECT modalities is a useful and practical approach for diagnostically differentiating DLB from AD. Abbreviations: AD, Alzheimer disease • AUC, area under the curve • AVSIS, automated volumetry of segmented image system • DLB, dementia with Lewy bodies • 123I-FP-CIT, iodine 123-N-omega-fluoropropyl-2β-carbomethoxy-3 β-(4-iodophenyl)-nortropane • GM, gray matter • 123I, iodine 123 • MMSE, Mini-Mental State Examination • PD, Parkinson disease • PET, positron-emission tomography • ROC, receiver operating characteristic • SBD, Simulated Brain Data Base • SPECT, single-photon emission CT • SPM, statistical parametric mapping • TIV, total intracranial volume • VOI, volume of interest • WM, white matter The number of patients diagnosed with neurodegenerative dementia has increased in societies in which the average age of the population has risen. DLB is the second most prevalent form of neurodegenerative dementia following AD, and its clinical diagnosis is based on revised consensus criteria.1 An essential neuropathologic feature of DLB is the presence of Lewy bodies in cortical and brain stem structures, such as the substantia nigra and locus coeruleus.2–5 The central diagnostic criterion for DLB is dementia, defined as a progressive cognitive decline of sufficient magnitude to interfere with normal social or occupational functions. The core diagnostic features of DLB are the following: 1) fluctuating cognition with pronounced variations in attention and alertness, 2) recurrent visual hallucinations that are typically well-formed and detailed, and 3) spontaneous features of parkinsonism. The presence of 2 of 3 core features is sufficient for a diagnosis of probable DLB.1 Clinically distinguishing patients with DLB from those with AD, however, is difficult because of overlapping clinical and pathologic features.3–5 This is especially so during the early stages of illness. For example, because psychosis is usually defined as delusions and/or hallucinations, accurate differentiation of psychosis may be difficult at early stages of both diseases.6,7 The accurate identification and differentiation of patients with DLB and AD are particularly important because of the development of interventions and specific pharmacologic treatments and outcome evaluations. Occipital abnormalities in glucose metabolism and cerebral perfusion are also a characteristic neuropathologic feature of DLB. This has been demonstrated by using SPECT and PET.8–10 Recent studies have reported dopamine transporter loss in the striatal, caudate, and posterior putamen in patients with DLB.11,12 Many studies investigating AD have found volume decreases in medial temporal structures and cerebral blood flow reductions in temporoparietal areas.13 Few studies, however, have reported the usefulness of cerebral regional volume measurement with MR imaging for discriminating AD from DLB.14 The aim of the present study was to discriminate DLB and AD by means of regional cerebral volume and perfusion measures by combining MR imaging and SPECT techniques. Materials and Methods Nineteen patients with mild DLB (8 men and 11 women) and 19 patients with mild AD (8 men and 11 women), matched for age, sex, and MMSE score, were retrospectively selected from patients admitted to the infirmary of our institution for the evaluation of dementia from April 2004 to March 2006. The institutional ethics board approved the study. The requirement for a participant's informed consent was waived due to the retrospective nature of the study and because it was solely observational. All patients underwent a neurologic and psychiatric examination by 2 neurologists and/or psychiatrists followed by an MR imaging brain scan and a standard neuropsychological examination. Because all the subjects were initial patients, none of them were given any drugs at the examinations. The criteria for diagnosing and managing DLB were revised in 2005.1 This study dealt directly with morphologic and functional findings of DLB. To avoid sample-selection bias, we used DLB inclusion criteria based on the diagnostic criteria from 1996.15 These criteria do not refer to MR imaging and SPECT techniques, while the new criteria include morphologic and functional examinations. The DLB inclusion criteria used in this study were the following: 1) a diagnosis of probable DLB by using the criteria of the Consortium on DLB International Workshop published in 199616, 2) absence of evidence of focal brain lesions on MR images, and 3) an MMSE score of >20. These criteria include 3 core features (fluctuating cognitive functions, recurrent visual hallucinations, and spontaneous parkinsonism), any 2 of which are necessary for a diagnosis of probable DLB. All patients were examined comprehensively by both neurologists and psychiatrists; and standard neuropsychological examinations, routine laboratory tests, electroencephalography, and cranial MR imaging examinations were performed. Staff physicians closely monitored fluctuation of cognitive functions over a 1-month admission in terms of MMSE performance, activities of daily living, and episodic confusion. Psychiatric and behavioral symptoms were assessed with a structured interview of a caregiver and the Neuropsychiatric Inventory,17 and they were monitored during the patient's hospital stay by staff physicians. Parkinsonism was rated as positive when 1 of the following features were present: resting tremor, cogwheel or lead-pipe rigidity detectable without reinforcement, bradykinesia, and loss of postural reflexes. The inclusion criteria for AD were the following: 1) a diagnosis of probable AD by using the National Institute of Neurologic and Communicative Disorders and Stroke/Alzheimer Disease and Related Disorders Association criteria,16 2) absence of evidence of focal brain lesions on MR images, and 3) an MMSE score of