Department of Radiology & Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands; Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
Neuroimage Clin. 2020;28:102504. doi: 10.1016/j.nicl.2020.102504. Epub 2020 Nov 19.
Alpha-synuclein often co-occurs with Alzheimer's disease (AD) pathology in Dementia with Lewy Bodies (DLB). From a dynamic [F]flortaucipir PET scan we derived measures of both tau binding and relative cerebral blood flow (rCBF). We tested whether regional tau binding or rCBF differed between DLB patients and AD patients and controls and examined their association with clinical characteristics of DLB.
Eighteen patients with probable DLB, 65 AD patients and 50 controls underwent a dynamic 130-minute [F]flortaucipir PET scan. DLB patients with positive biomarkers for AD based on cerebrospinal fluid or amyloid PET were considered as DLB with AD pathology (DLB-AD+). Receptor parametric mapping (cerebellar gray matter reference region) was used to extract regional binding potential (BP) and R, reflecting (AD-specific) tau pathology and rCBF, respectively. First, we performed regional comparisons of [F]flortaucipir BP and R between diagnostic groups. In DLB patients only, we performed regression analyses between regional [F]flortaucipir BP, R and performance on ten neuropsychological tests.
Regional [F]flortaucipir BP in DLB was comparable with tau binding in controls (p > 0.05). Subtle higher tau binding was observed in DLB-AD+ compared to DLB-AD- in the medial temporal and parietal lobe (both p < 0.05). Occipital and lateral parietal R was lower in DLB compared to AD and controls (all p < 0.01). Lower frontal R was associated with impaired performance on digit span forward (standardized beta, stβ = 0.72) and category fluency (stβ = 0.69) tests. Lower parietal R was related to lower delayed (stβ = 0.50) and immediate (stβ = 0.48) recall, VOSP number location (stβ = 0.70) and fragmented letters (stβ = 0.59) scores. Lower occipital R was associated to worse performance on VOSP fragmented letters (stβ = 0.61), all p < 0.05.
The amount of tau binding in DLB was minimal and did not differ from controls. However, there were DLB-specific occipital and lateral parietal relative cerebral blood flow reductions compared to both controls and AD patients. Regional rCBF, but not tau binding, was related to cognitive impairment. This indicates that assessment of rCBF may give more insight into disease mechanisms in DLB than tau PET.
在路易体痴呆（DLB）中，α-突触核蛋白常与阿尔茨海默病（AD）病理学共存。我们从动态[F]flortaucipir PET 扫描中得出了tau 结合和相对脑血流（rCBF）的测量值。我们测试了 DLB 患者与 AD 患者和对照组之间是否存在区域 tau 结合或 rCBF 差异，并检查了它们与 DLB 临床特征的关联。
18 名可能的 DLB 患者、65 名 AD 患者和 50 名对照组接受了 130 分钟的[F]flortaucipir PET 扫描。根据脑脊液或淀粉样 PET 有 AD 生物标志物阳性的 DLB 患者被认为是 DLB 合并 AD 病理学（DLB-AD+）。受体参数映射（小脑灰质参考区）用于提取区域结合潜力（BP）和 R，分别反映（AD 特异性）tau 病理学和 rCBF。首先，我们在诊断组之间进行了[F]flortaucipir BP 和 R 的区域比较。仅在 DLB 患者中，我们进行了区域[F]flortaucipir BP 和 R 与十项神经心理学测试表现之间的回归分析。
DLB 中的局部[F]flortaucipir BP 与对照组的 tau 结合相似（p>0.05）。与 DLB-AD-相比，DLB-AD+中内侧颞叶和顶叶的 tau 结合略高（均 p<0.05）。与 AD 和对照组相比，DLB 中的枕叶和外侧顶叶的 R 较低（均 p<0.01）。额叶 R 越低与数字跨度正向（标准化β，stβ=0.72）和类别流畅性（stβ=0.69）测试的表现越差有关。顶叶 R 越低与延迟（stβ=0.50）和即时（stβ=0.48）回忆、VOSP 数字位置（stβ=0.70）和片段字母（stβ=0.59）评分越低有关。枕叶 R 越低与 VOSP 片段字母的表现越差有关（stβ=0.61），均 p<0.05。
DLB 中的 tau 结合量很小，与对照组没有差异。然而，与对照组和 AD 患者相比，DLB 存在特定的枕叶和外侧顶叶相对脑血流减少。与认知障碍相关的是区域 rCBF，而不是 tau 结合。这表明与 tau PET 相比，评估 rCBF 可能会更深入地了解 DLB 中的疾病机制。
