Cognitive and neuroimaging features and brain β-amyloidosis in individuals at risk of Alzheimer's disease (INSIGHT-preAD): a longitudinal observational study
Cognitive and neuroimaging features and brain β-amyloidosis in individuals at risk of Alzheimer's disease (INSIGHT-preAD): a longitudinal observational study
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DOI：
10.1016/s1474-4422(18)30029-2
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发表时间：
2018-04-01
期刊：
影响因子：
48
通讯作者：
Hampel, Harald
中科院分区：
文献类型：
--
作者：
Dubois, Bruno;Epelbaum, Stephane;Hampel, Harald
背景：需要进一步了解临床前阿尔茨海默病的危险因素和疾病进展的标志物。我们评估脑β-淀粉样变性和各种认知和神经影像学参数与临床前阿尔茨海默病患者认知功能下降进展之间的关联。方法INSIGHT-preAD是一项正在进行的单中心观察性研究，在Salpetriere医院，巴黎，法国。符合资格的参与者年龄为70-85岁，有主观记忆投诉，但认知和记忆未受损（简易精神状态检查[MMSE]评分>= 27，临床痴呆评定评分0，自由和暗示选择性提醒测试[FCSRT]总回忆评分>= 41）。我们根据基线时F-18-florbetapir PET上的脑淀粉样蛋白β沉积（阳性或阴性）对参与者进行分层。所有患者均接受了人口统计学、认知和心理行为、特征、APOE β 4等位基因携带状态、MRI脑结构和功能、F-18-氟脱氧葡萄糖（F-18-FDG）PET脑葡萄糖代谢和脑电图（EEG）事件相关电位的基线评估。可选择进行活动描记术和CSF检查。参与者每6个月进行一次临床、认知和心理行为评估，每12个月进行一次神经心理评估、EEG和活动记录，每24个月进行一次MRI、F-18-FDG和F-18-florbetapir PET。我们评估了β淀粉样蛋白沉积状态与基线和24个月时的测试结果以及30个月时的临床状态的相关性。前驱阿尔茨海默病的进展被定义为海马型的遗忘综合征。结果从2013年5月25日至2015年1月20日，我们招募了318名参与者，平均年龄为76.0岁（SD 3.5）。平均基线MMSE评分为28.67（SD 0.96），平均教育水平较高（评分>6 [SD 2]，量表1-8，其中1=幼儿学校，8=高等教育）。318名参与者中有88名（28%）显示淀粉样蛋白β沉积，其余则没有。在校正年龄、性别和教育水平后，淀粉样β亚组在任何心理行为、认知、活动记录、结构和功能神经影像学结果方面均无差异。
Background Improved understanding is needed of risk factors and markers of disease progression in preclinical Alzheimer's disease. We assessed associations between brain beta-amyloidosis and various cognitive and neuroimaging parameters with progression of cognitive decline in individuals with preclinical Alzheimer's disease.Methods The INSIGHT-preAD is an ongoing single-centre observational study at the Salpetriere Hospital, Paris, France. Eligible participants were age 70-85 years with subjective memory complaints but unimpaired cognition and memory (Mini-Mental State Examination [MMSE] score >= 27, Clinical Dementia Rating score 0, and Free and Cued Selective Reminding Test [FCSRT] total recall score >= 41). We stratified participants by brain amyloid beta deposition on F-18-florbetapir PET (positive or negative) at baseline. All patients underwent baseline assessments of demographic, cognitive, and psychobehavioural, characteristics, APOE epsilon 4 allele carrier status, brain structure and function on MRI, brain glucose-metabolism on F-18-fluorodeoxyglucose (F-18-FDG) PET, and event-related potentials on electroencephalo-grams (EEGs). Actigraphy and CSF investigations were optional. Participants were followed up with clinical, cognitive, and psychobehavioural assessments every 6 months, neuropsychological assessments, EEG, and actigraphy every 12 months, and MRI, and F-18-FDG and F-18-florbetapir PET every 24 months. We assessed associations of amyloid beta deposition status with test outcomes at baseline and 24 months, and with clinical status at 30 months. Progression to prodromal Alzheimer's disease was defined as an amnestic syndrome of the hippocampal type.Findings From May 25, 2013, to Jan 20, 2015, we enrolled 318 participants with a mean age of 76.0 years (SD 3.5). The mean baseline MMSE score was 28.67 (SD 0.96), and the mean level of education was high (score >6 [SD 2] on a scale of 1-8, where 1=infant school and 8=higher education). 88 (28%) of 318 participants showed amyloid beta deposition and the remainder did not. The amyloid beta subgroups did not differ for any psychobehavioural, cognitive, actigraphy, and structural and functional neuroimaging results after adjustment for age, sex, and level of education More participants positive for amyloid beta deposition had the APOE e4 allele (33 [38%] vs 29 [13%], p