Department of Neurology & Alzheimer Center, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, the Netherlands.
Department of Epidemiology & Biostatistics, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, the Netherlands.
JAMA Neurol. 2018 Sep 1;75(9):1062-1070. doi: 10.1001/jamaneurol.2018.1346.
Previous studies have evaluated the diagnostic effect of amyloid positron emission tomography (PET) in selected research cohorts. However, these research populations do not reflect daily practice, thus hampering clinical implementation of amyloid imaging.
To evaluate the association of amyloid PET with changes in diagnosis, diagnostic confidence, treatment, and patients' experiences in an unselected memory clinic cohort.
DESIGN, SETTING, AND PARTICIPANTS: Amyloid PET using fluoride-18 florbetaben was offered to 866 patients who visited the tertiary memory clinic at the VU University Medical Center between January 2015 and December 2016 as part of their routine diagnostic dementia workup. Of these patients, 476 (55%) were included, 32 (4%) were excluded, and 358 (41%) did not participate. To enrich this sample, 31 patients with mild cognitive impairment from the University Medical Center Utrecht memory clinic were included. For each patient, neurologists determined a preamyloid and postamyloid PET diagnosis that existed of both a clinical syndrome (dementia, mild cognitive impairment, or subjective cognitive decline) and a suspected etiology (Alzheimer disease [AD] or non-AD), with a confidence level ranging from 0% to 100%. In addition, the neurologist determined patient treatment in terms of ancillary investigations, medication, and care. Each patient received a clinical follow-up 1 year after being scanned.
Primary outcome measures were post-PET changes in diagnosis, diagnostic confidence, and patient treatment.
Of the 507 patients (mean [SD] age, 65 (8) years; 201 women [39%]; mean [SD] Mini-Mental State Examination score, 25 [4]), 164 (32%) had AD dementia, 70 (14%) non-AD dementia, 114 (23%) mild cognitive impairment, and 159 (31%) subjective cognitive decline. Amyloid PET results were positive for 242 patients (48%). The suspected etiology changed for 125 patients (25%) after undergoing amyloid PET, more often due to a negative (82 of 265 [31%]) than a positive (43 of 242 [18%]) PET result (P < .01). Post-PET changes in suspected etiology occurred more frequently in patients older (>65 years) than younger (<65 years) than the typical age at onset of 65 years (74 of 257 [29%] vs 51 of 250 [20%]; P < .05). Mean diagnostic confidence (SD) increased from 80 (13) to 89 (13%) (P < .001). In 123 patients (24%), there was a change in patient treatment post-PET, mostly related to additional investigations and therapy.
This prospective diagnostic study provides a bridge between validating amyloid PET in a research setting and implementing this diagnostic tool in daily clinical practice. Both amyloid-positive and amyloid-negative results had substantial associations with changes in diagnosis and treatment, both in patients with and without dementia.
先前的研究已经评估了在选定的研究队列中淀粉样蛋白正电子发射断层扫描(PET)的诊断效果。然而,这些研究人群不能反映日常实践,因此阻碍了淀粉样蛋白成像的临床应用。
评估在未经选择的记忆门诊队列中,淀粉样蛋白 PET 与诊断变化、诊断信心、治疗和患者体验的相关性。
设计、地点和参与者:2015 年 1 月至 2016 年 12 月期间,866 名患者在 VU 大学医学中心的三级记忆诊所就诊,作为其常规诊断性痴呆评估的一部分,接受了氟-18 氟比他滨的淀粉样蛋白 PET 检查。其中 476 名(55%)患者被纳入研究,32 名(4%)患者被排除,358 名(41%)患者未参与。为了丰富这一样本,31 名来自乌得勒支大学医学中心记忆诊所的轻度认知障碍患者也被纳入研究。对于每位患者,神经科医生根据临床综合征(痴呆、轻度认知障碍或主观认知下降)和疑似病因(阿尔茨海默病[AD]或非 AD)确定了淀粉样蛋白 PET 检查前后的诊断,信心水平范围从 0%到 100%。此外,神经科医生还确定了患者的治疗方法,包括辅助检查、药物治疗和护理。每位患者在扫描后接受了为期 1 年的临床随访。
主要结局指标是淀粉样蛋白 PET 检查后诊断、诊断信心和患者治疗的变化。
在 507 名患者(平均[标准差]年龄,65 [8]岁;201 名女性[39%];平均[标准差]简易精神状态检查评分,25 [4])中,164 名(32%)患有 AD 痴呆,70 名(14%)患有非 AD 痴呆,114 名(23%)患有轻度认知障碍,159 名(31%)患有主观认知下降。242 名患者(48%)的淀粉样蛋白 PET 检查结果为阳性。125 名患者(25%)在接受淀粉样蛋白 PET 检查后病因疑似发生了变化,更多的是由于阴性(265 例中的 82 例[31%])而不是阳性(242 例中的 43 例[18%])PET 结果(P <.01)。年龄较大(>65 岁)的患者比年龄较小(<65 岁)的患者更有可能发生疑似病因的改变(74 例[29%]比 51 例[20%];P <.05)。诊断信心(SD)均值从 80(13)增加到 89(13%)(P <.001)。在 123 名患者(24%)中,淀粉样蛋白 PET 检查后患者的治疗发生了变化,主要与额外的检查和治疗有关。
这项前瞻性诊断研究在验证淀粉样蛋白 PET 在研究环境中的有效性和将该诊断工具应用于日常临床实践之间架起了一座桥梁。淀粉样蛋白阳性和阴性结果都与诊断和治疗的变化有很大的关联,无论是在有痴呆还是没有痴呆的患者中都是如此。