Association of Cognitive and Behavioral Features Between Adults With Tuberous Sclerosis and Frontotemporal Dementia
Association of Cognitive and Behavioral Features Between Adults With Tuberous Sclerosis and Frontotemporal Dementia
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DOI：
10.1001/jamaneurol.2019.4284
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发表时间：
2020-03-01
期刊：
影响因子：
29
通讯作者：
Kao, Aimee W.
中科院分区：
文献类型：
--
作者：
Liu, Andy J.;Staffaroni, Adam M.;Kao, Aimee W.
重要性 患有结节性硬化症的个体可能会出现一种进行性神经精神综合征，称为结节性硬化症相关神经精神疾病。结节性硬化症相关的神经精神疾病症状与额颞叶痴呆的临床标准重叠，但尚未探讨两者之间的关联。目的 探讨结节性硬化症相关神经精神疾病与额颞叶痴呆之间的潜在关联。设计、设置和参与者病例对照研究，2017 年至 2019 年在旧金山加利福尼亚大学进行一项观察性临床研究，招募了智商正常的结节性硬化症患者，他们接受了全面的临床评估，包括神经心理学测试、脑脊髓液生物标志物分析和结构神经影像学。该研究纳入了符合结节性硬化症临床标准、智商正常、患有额颞叶痴呆的成年人或健康对照者。主要结果和措施结节性硬化症相关神经精神疾病检查表严重程度评分、神经心理学测试评分、脑脊液中磷酸化 tau (181)、总 tau、淀粉样蛋白 β 42 和神经丝轻链的浓度。对部分患者进行了淀粉样蛋白和 tau 正电子发射断层扫描。结果 纳入 18 名结节性硬化症患者（平均 [SD] 年龄，48 岁 [9.54]；13 名女性 [72%]）、16 名额颞叶痴呆患者（60 [6.93] 岁；7 名女性 [44%]）和 18 名健康对照者（63 [3.85] 岁；9 名女性 [50%]）。当比较结节性硬化症和额颞叶痴呆队列时，结节性硬化症相关的神经精神疾病检查表和神经心理学测试结果没有显着差异。与健康对照个体相比，结节性硬化症患者的脑脊液磷酸化 tau(181) 和神经丝轻链水平升高，平均值分别为 32 pg/mL 和 2300 pg/mL。所有 3 名患有结节性硬化症的患者均接受了氟 1B 标记的弗洛托西吡 tau 正电子发射断层扫描神经影像学检查，结果显示额叶和颞区存在[F-18]弗洛托西吡结合升高的点状病灶。结论和相关性 患有结节性硬化症的成人表现出与额颞叶痴呆的表型重叠。这些结果支持结节性硬化症相关神经精神疾病和额颞叶痴呆之间可能存在的临床连续性，并强调了神经发育和神经退行性过程之间潜在的病理生理学联系。定量神经心理学测试和结节性硬化症相关神经精神疾病检查表，可能辅以脑脊髓液和成像生物标志物，可用于筛查和预测结节性硬化症成人患者神经退行性过程的风险。本研究探讨了结节性硬化症相关神经精神疾病与额颞叶痴呆之间的潜在关联。疾病是否符合神经退行性疾病额颞叶痴呆 (FTD) 的标准？结果 在这项病例对照研究中，定量临床测量表明，患有结节性硬化症相关神经精神疾病的成年人表现出与 FTD 相似的行为和认知困难。与 FTD 相比，结节性硬化症患者的脑脊液生物标志物有显着重叠，同样，这些受试者的一部分表现出 tau PET 配体氟 1B 标记的弗洛托西吡的点状局灶性保留。意义 应该对患有结节性硬化症的成年人进行额外的纵向研究，以评估患神经退行性疾病（如 FTD）的风险。
Importance Individuals with tuberous sclerosis complex can develop a progressive neuropsychiatric syndrome known as tuberous sclerosis-associated neuropsychiatric disorders. Tuberous sclerosis-associated neuropsychiatric disorders symptoms overlap with clinical criteria for frontotemporal dementia, yet the association between the 2 has not been explored. Objective To investigate the potential association between tuberous sclerosis-associated neuropsychiatric disorders and frontotemporal dementia. Design, Setting, and Participants Case-control study that enrolled patients with tuberous sclerosis complex with normal IQs in an observational clinical study at the University of California, San Francisco, from 2017 to 2019 where they underwent a comprehensive clinical evaluation including neuropsychologic testing, cerebral spinal fluid biomarker profiling, and structural neuroimaging. The study included adults who fulfilled the clinical criteria for tuberous sclerosis complex and had normal IQs, had frontotemporal dementia, or were healthy control individuals. Main Outcomes and Measures Tuberous sclerosis-associated neuropsychiatric disorders checklist severity score, neuropsychologic test scores, cerebral spinal fluid concentrations of phosphorylated tau(181), total tau, amyloid-beta 42, and neurofilament light chain. Amyloid and tau positron emission tomography scans were obtained in a subset of patients. Results Eighteen patients with tuberous sclerosis complex (mean [SD] age, 48 years [9.54]; 13 women [72%]), 16 with frontotemporal dementia (60 [6.93] years; 7 women [44%]) and 18 healthy control individuals (63 [3.85] years; 9 women [50%]) were included. The tuberous sclerosis-associated neuropsychiatric disorders checklist and neuropsychological test results were not significantly different when the tuberous sclerosis complex and frontotemporal dementia cohorts were compared. The tuberous sclerosis complex cohort exhibited elevated cerebral spinal fluid phosphorylated tau(181) and neurofilament light chain with a mean of 32 pg/mL and 2300 pg/mL, respectively, when compared to healthy control individuals. All 3 patients with tuberous sclerosis complex who underwent fluorine 1B-labeled flortaucipir tau positron emission tomographic neuroimaging showed punctate foci of elevated [F-18]flortaucipir binding in the frontal and temporal regions. Conclusions and Relevance Adults with tuberous sclerosis complex showed phenotypic overlap with frontotemporal dementia. The results support a possible clinical continuum between tuberous sclerosis-associated neuropsychiatric disorders and frontotemporal dementia and highlights a potential pathophysiological link between neurodevelopmental and neurodegenerative processes. Quantitative neuropsychological testing and the tuberous sclerosis-associated neuropsychiatric disorders checklist, potentially supplemented by cerebral spinal fluid and imaging biomarkers, could be used to screen and prognosticate for risk of a neurodegenerative process in adult patients with tuberous sclerosis complex.This study investigates the potential association between tuberous sclerosis-associated neuropsychiatric disorders and frontotemporal dementia.Question Do individuals with tuberous sclerosis-associated neuropsychiatric disorders meet criteria for the neurodegenerative disease frontotemporal dementia (FTD)? Findings In this case-control study, quantitative clinical measurements showed that adults with tuberous sclerosis-associated neuropsychiatric disorders exhibit behavioral and cognitive difficulties similar to those seen in FTD. Compared with FTD, significant overlap in cerebrospinal fluid biomarkers was seen in patients with tuberous sclerosis complex, and similarly, a subset of these subjects demonstrated punctate focal retention of the tau PET ligand fluorine 1B-labeled flortaucipir. Meaning Additional longitudinal studies should be performed on adults affected with tuberous sclerosis complex to assess risk for developing a neurodegenerative disease such as FTD.