Amyloid burden and metabolic function in early-onset Alzheimer's disease: parietal lobe involvement
Amyloid burden and metabolic function in early-onset Alzheimer's disease: parietal lobe involvement
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DOI：
10.1093/brain/aws113
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发表时间：
2012-07-01
期刊：
影响因子：
14.5
通讯作者：
van Berckel, Bart N. M.
中科院分区：
文献类型：
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作者：
Ossenkoppele, Rik;Zwan, Marissa D.;van Berckel, Bart N. M.
早发性阿尔茨海默病通常表现出独特的认知特征，可能反映了潜在神经病理学的不同分布。本研究的目的是研究年龄与阿尔茨海默病患者体内原纤维淀粉样蛋白沉积和葡萄糖代谢之间的关系。对100名阿尔茨海默病患者和20名健康对照者进行动态[C-11]匹兹堡化合物b扫描（90分钟）和静态[F-18]氟脱氧葡萄糖扫描（15分钟）。以小脑灰质为参比组织，生成[C-11]匹兹堡化合物- b的参数化不可置换结合电位图像和[F-18]氟脱氧葡萄糖的标准化摄取值比图像。排除9例[C-11]匹兹堡化合物b阴性患者。其余患者根据诊断时的中位年龄（62岁）分为年轻组（n = 45，年龄：56 +/- 4岁）和老年组（n = 46，年龄：69 +/- 5岁）。年轻患者在视觉空间功能、注意力和执行功能综合评分上表现出更严重的损害（P < 0.05），而我们发现老年患者的记忆表现有更差的趋势（P = 0.11）。使用一般线性模型评估组间差异，其中年龄为受试者之间因素，区域（额叶、颞叶、顶叶、枕叶和后扣带皮层）为受试者内部因素，[C-11]匹兹堡化合物- b结合/[F-18]氟氧葡萄糖摄取为因变量。年龄对[C-11]匹兹堡化合物- b或[F-18]氟脱氧葡萄糖没有主要影响，这表明总的来说，淀粉样蛋白沉积或葡萄糖低代谢的程度在两组之间没有差异。[C-11]匹兹堡化合物- b结合和[F-18]氟脱氧葡萄糖摄取的区域分布（相互作用P均< 0.05）在两组之间存在差异，但主要是由于年轻患者顶叶皮层中[C-11]匹兹堡化合物- b结合增加而[F-18]氟脱氧葡萄糖摄取减少（P均< 0.05）。线性回归分析显示，年轻患者的视觉空间功能与顶叶[C-11]匹兹堡化合物- b结合之间呈负相关（标准化贝塔系数：-0.37），老年患者的视觉空间功能与枕叶结合之间呈负相关（标准化贝塔系数：-0.39）。对于[F-18]氟脱氧葡萄糖，发现年轻患者的顶叶摄取与视觉空间（标准化β值：0.55）、注意力（标准化β值：0.39）和执行功能（标准化β值：0.37）之间存在关联，老年患者的后扣带摄取与记忆之间存在关联（标准化β值：0.41，均P < 0.05）。这些体内研究结果表明，老年和年轻阿尔茨海默病患者的临床差异并不局限于下游过程的地形差异，而可能源于早期上游事件的不同分布。因此，年轻阿尔茨海默病患者顶叶淀粉样蛋白负荷的增加以及代谢功能障碍可能导致这些患者的独特认知特征。
Alzheimer's disease with early onset often presents with a distinct cognitive profile, potentially reflecting a different distribution of underlying neuropathology. The purpose of this study was to examine the relationships between age and both in vivo fibrillary amyloid deposition and glucose metabolism in patients with Alzheimer's disease. Dynamic [C-11]Pittsburgh compound-B (90 min) and static [F-18]fluorodeoxyglucose (15 min) scans were obtained in 100 patients with Alzheimer's disease and 20 healthy controls. Parametric non-displaceable binding potential images of [C-11]Pittsburgh compound-B and standardized uptake value ratio images of [F-18]fluorodeoxyglucose were generated using cerebellar grey matter as reference tissue. Nine [C-11]Pittsburgh compound-B-negative patients were excluded. The remaining patients were categorized into younger (n = 45, age: 56 +/- 4 years) and older (n = 46, age: 69 +/- 5 years) groups, based on the median age (62 years) at time of diagnosis. Younger patients showed more severe impairment on visuo-spatial function, attention and executive function composite scores (P < 0.05), while we found a trend towards poorer memory performance for older patients (P = 0.11). Differences between groups were assessed using a general linear model with repeated measures (gender adjusted) with age as between subjects factor, region (frontal, temporal, parietal and occipital and posterior cingulate cortices) as within subjects factor and [C-11]Pittsburgh compound-B binding/[F-18]fluorodeoxyglucose uptake as dependent variables. There was no main effect of age for [C-11]Pittsburgh compound-B or [F-18]fluorodeoxyglucose, suggesting that overall, the extent of amyloid deposition or glucose hypometabolism did not differ between groups. Regional distributions of [C-11]Pittsburgh compound-B binding and [F-18]fluorodeoxyglucose uptake (both P for interaction < 0.05) differed between groups, however, largely due to increased [C-11]Pittsburgh compound-B binding and decreased [F-18]fluorodeoxyglucose uptake in the parietal cortex of younger patients (both P < 0.05). Linear regression analyses showed negative associations between visuo-spatial functioning and parietal [C-11]Pittsburgh compound-B binding for younger patients (standardized beta: -0.37) and between visuo-spatial functioning and occipital binding for older patients (standardized beta: -0.39). For [F-18]fluorodeoxyglucose, associations were found between parietal uptake with visuo-spatial (standardized beta: 0.55), attention (standardized beta: 0.39) and executive functioning (standardized beta: 0.37) in younger patients, and between posterior cingulate uptake and memory in older patients (standardized beta: 0.41, all P < 0.05). These in vivo findings suggest that clinical differences between younger and older patients with Alzheimer's disease are not restricted to topographical differentiation in downstream processes but may originate from distinctive distributions of early upstream events. As such, increased amyloid burden, together with metabolic dysfunction, in the parietal lobe of younger patients with Alzheimer's disease may contribute to the distinct cognitive profile in these patients.