Drzezga Alexander, Grimmer Timo, Henriksen Gjermund, Stangier Isabelle, Perneczky Robert, Diehl-Schmid Janine, Mathis Chester A, Klunk William E, Price Julie, DeKosky Steve, Wester Hans-Jürgen, Schwaiger Markus, Kurz Alexander
Department of Nuclear Medicine, Technische Universität, München, Ismaninger Str. 22, D-81675 Munich, Germany.
Neuroimage. 2008 Jan 15;39(2):619-33. doi: 10.1016/j.neuroimage.2007.09.020. Epub 2007 Sep 21.
Semantic dementia (SD) is a rare clinical syndrome, assigned to the group of frontotemporal lobar degenerations (FTLD). Histopathological analysis has not revealed the deposition of amyloid plaques in the majority of SD cases, in contrast to dementia of the Alzheimer type (AD). However, based on clinical examination alone a reliable differentiation of the underlying pathology cannot be guaranteed, i.e. AD and SD may be confused in some cases. Our aim was to determine, whether AD and SD can be differentiated in vivo by means of amyloid plaque PET imaging. In groups of AD and SD patients, matched for gender, age and overall degree of cognitive impairment, cerebral glucose metabolism was examined with [(18)F]Fluorodeoxyglucose (FDG)-PET and cerebral amyloid plaque density was assessed using [(11)C]6-OH-BTA-1 (PIB)-PET. A volume-of-interest analysis (VOI), using the cerebellum as a reference region, and voxel-based statistical group comparisons (SPM2) were carried out between the patient groups and matched groups of healthy controls. To control for a potential influence of atrophy on the PET findings, a correction of partial volume effects was performed. Characteristic patterns of hypometabolism could be demonstrated in both clinically defined AD and SD with some regional overlap and subtle differences (AD: bilateral posterior cingulate, temporoparietal and frontal cortex; SD: left>right polar temporal, frontal mesial cortex). Compared with healthy controls, significant [(11)C]PIB amyloid plaque tracer binding was observed only in patients with AD (in bilateral temporoparietal, frontal and posterior cingulate cortex and the precuneus) but not in SD. This difference in amyloid plaque deposition could be reproduced in direct statistical comparison of AD and SD and clearly extended the metabolic differences between the patient groups. These findings support the notion that SD can be diagnosed in vivo as a separate entity from AD using amyloid plaque imaging. In general, amyloid plaque PET may complement neuropsychological assessment regarding reliable differential diagnosis of AD and FTLD dementias based on characterization of underlying pathology and may improve the definition of individual prognosis and the selection of patients for scientific trials.
语义性痴呆（SD）是一种罕见的临床综合征，属于额颞叶变性（FTLD）组。与阿尔茨海默病型痴呆（AD）不同，组织病理学分析在大多数SD病例中未发现淀粉样斑块沉积。然而，仅基于临床检查不能保证对潜在病理进行可靠区分，即AD和SD在某些情况下可能混淆。我们的目的是确定能否通过淀粉样斑块PET成像在活体中区分AD和SD。在性别、年龄和认知障碍总体程度相匹配的AD和SD患者组中，用[（18）F]氟脱氧葡萄糖（FDG）-PET检查脑葡萄糖代谢，并用[（11）C]6-羟基-BTA-1（PIB）-PET评估脑淀粉样斑块密度。在患者组与匹配的健康对照组之间进行了以小脑为参考区域的感兴趣区分析（VOI）和基于体素的统计组间比较（SPM2）。为控制萎缩对PET结果的潜在影响，进行了部分容积效应校正。在临床定义的AD和SD中均可显示出代谢减低的特征性模式，存在一些区域重叠和细微差异（AD：双侧后扣带回、颞顶叶和额叶皮质；SD：左侧>右侧极颞叶、额叶内侧皮质）。与健康对照组相比，仅在AD患者中观察到显著的[（11）C]PIB淀粉样斑块示踪剂结合（在双侧颞顶叶、额叶和后扣带回皮质以及楔前叶），而在SD患者中未观察到。淀粉样斑块沉积的这种差异在AD和SD的直接统计比较中得以重现，并明显扩大了患者组之间的代谢差异。这些发现支持这样一种观点，即使用淀粉样斑块成像可在活体中将SD诊断为与AD不同的独立实体。总体而言，淀粉样斑块PET可能有助于神经心理学评估，基于潜在病理特征对AD和FTLD痴呆进行可靠的鉴别诊断，并可能改善个体预后的定义以及科学试验患者的选择。
