Demographic, clinical, biomarker, and neuropathological correlates of posterior cortical atrophy: an international cohort study and individual participant data meta-analysis.
Demographic, clinical, biomarker, and neuropathological correlates of posterior cortical atrophy: an international cohort study and individual participant data meta-analysis.
复制标题
后皮质萎缩的人口统计学、临床、生物标志物和神经病理学相关性：一项国际队列研究和个体参与者数据荟萃分析。
DOI：
10.1016/s1474-4422(23)00414-3
复制
发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Grinber
中科院分区：
文献类型：
--
作者：
Chapleau,Marianne;LaJoie,Renaud;Yong,Keir;Agosta,Federica;Allen,IsabelElaine;Apostolova,Liana;Best,John;Boon,BaaylaDC;Crutch,Sebastian;Filippi,Massimo;Fumagalli,GiorgioGiulio;Galimberti,Daniela;Graff-Radford,Jonathan;Grinber
背景后皮质萎缩是一种罕见的综合征，其特征是早期、显著和进行性的视觉感知和视觉空间处理障碍。这种疾病与阿尔茨海默病的潜在神经病理学特征有关，但大规模的生物标志物和神经病理学研究很少。我们的目的是描述人口统计学，临床，生物标志物和神经病理学相关的后皮质萎缩在一个大型的国际coherent.MethodsWe检索PubMed之间的数据库成立和2021年8月1日，所有已发表的研究后皮质萎缩和相关术语。我们从这些研究中确定了研究中心，并要求在第一次诊断访视时从研究的相应作者或研究中心负责人处获得的去识别的个体参与者数据（已发表和未发表）。入选标准是由当地中心和阿尔茨海默病生物标志物（PET或CSF）的可用性定义的后皮质萎缩的临床诊断，或尸检诊断。并非所有患有后皮质萎缩的个体都符合共识标准，使用中心特定程序或在共识标准制定之前进行诊断。我们获得了人口统计学、临床、生物流体、神经影像学和神经病理学数据。使用逆方差荟萃分析方法合并连续变量的平均值;仅纳入一个变量有一名以上参与者的研究中心。使用限制性最大似然模型计算二元变量的合并比例。Heterodynamics量化usingI2.FindingsWe确定了55个研究中心，从1353篇论文，29个中心响应我们的要求。另外七个中心是通过阿尔茨海默氏症协会的广告招募的。我们从16个国家的36个研究中心获得了1092名受试者的数据，其他研究中心没有回应我们最初的邀请参加这项研究。症状发作时的平均年龄为59.4岁（95%CI 58.9 - 59.8;I2=77%），60%（56-64;I2=35%）为女性，80%（72-89;I2=98%）表现为单纯后皮质萎缩综合征。81%（95% CI 75-87;I2=78%）的CSF中β淀粉样蛋白阳性（来自28个中心的536例受试者），而65%（56-75;I2 =87%）的CSF中磷酸化tau阳性（来自29个中心的503例受试者）。淀粉样蛋白-PET（来自24个中心的299名受试者）阳性率为94%（95% CI 90-97;I2=15%），而tau-PET（来自13个中心的170名受试者）阳性率为97%（93-100;I2=12%）。尸检时（来自13个中心的145名参与者），最常见的神经病理学诊断是阿尔茨海默病（94%，95%CI 90-97;I2=0%），具有脑淀粉样血管病的常见共同病理（71%，54-88;I2=89%），路易体病（44%，25-62;I2=77%）和脑血管损伤（42%，24-60岁; I2=88%）。解释这些数据表明后皮质萎缩通常表现为单纯的，对潜在的阿尔茨海默病病理学高度特异性的迟发性痴呆综合征。需要进一步的工作来了解是什么驱动认知脆弱性和进展率，通过调查性别，遗传学，发病前认知优势和弱点以及大脑网络完整性的贡献。
BackgroundPosterior cortical atrophy is a rare syndrome characterised by early, prominent, and progressive impairment in visuoperceptual and visuospatial processing. The disorder has been associated with underlying neuropathological features of Alzheimer's disease, but large-scale biomarker and neuropathological studies are scarce. We aimed to describe demographic, clinical, biomarker, and neuropathological correlates of posterior cortical atrophy in a large international cohort.MethodsWe searched PubMed between database inception and Aug 1, 2021, for all published research studies on posterior cortical atrophy and related terms. We identified research centres from these studies and requested deidentified, individual participant data (published and unpublished) that had been obtained at the first diagnostic visit from the corresponding authors of the studies or heads of the research centres. Inclusion criteria were a clinical diagnosis of posterior cortical atrophy as defined by the local centre and availability of Alzheimer's disease biomarkers (PET or CSF), or a diagnosis made at autopsy. Not all individuals with posterior cortical atrophy fulfilled consensus criteria, being diagnosed using centre-specific procedures or before development of consensus criteria. We obtained demographic, clinical, biofluid, neuroimaging, and neuropathological data. Mean values for continuous variables were combined using the inverse variance meta-analysis method; only research centres with more than one participant for a variable were included. Pooled proportions were calculated for binary variables using a restricted maximum likelihood model. Heterogeneity was quantified usingI2.FindingsWe identified 55 research centres from 1353 papers, with 29 centres responding to our request. An additional seven centres were recruited by advertising via the Alzheimer's Association. We obtained data for 1092 individuals who were evaluated at 36 research centres in 16 countries, the other sites having not responded to our initial invitation to participate to the study. Mean age at symptom onset was 59·4 years (95% CI 58·9–59·8;I2=77%), 60% (56–64;I2=35%) were women, and 80% (72–89;I2=98%) presented with posterior cortical atrophy pure syndrome. Amyloid β in CSF (536 participants from 28 centres) was positive in 81% (95% CI 75–87;I2=78%), whereas phosphorylated tau in CSF (503 participants from 29 centres) was positive in 65% (56–75;I2=87%). Amyloid-PET (299 participants from 24 centres) was positive in 94% (95% CI 90–97;I2=15%), whereas tau-PET (170 participants from 13 centres) was positive in 97% (93–100;I2=12%). At autopsy (145 participants from 13 centres), the most frequent neuropathological diagnosis was Alzheimer's disease (94%, 95% CI 90–97;I2=0%), with common co-pathologies of cerebral amyloid angiopathy (71%, 54–88;I2=89%), Lewy body disease (44%, 25–62;I2=77%), and cerebrovascular injury (42%, 24–60;I2=88%).InterpretationThese data indicate that posterior cortical atrophy typically presents as a pure, young-onset dementia syndrome that is highly specific for underlying Alzheimer's disease pathology. Further work is needed to understand what drives cognitive vulnerability and progression rates by investigating the contribution of sex, genetics, premorbid cognitive strengths and weaknesses, and brain network integrity.FundingNone.