% 0期刊文章%一个欧v Billette %加布里埃尔·齐格勒% Merita Aruci Hartmut Schutze % %一个一个茉莉花m . Kizilirmak %安妮Richter % Slawek Altenstein % Frederic Brosseron克劳迪娅·巴特尔% % Arturo Cardenas-Blanco %一个彼得Dechent菲利普Dahmen % %劳拉Dobisch %一个克劳斯Fliessbach % Silka黎明Freiesleben %文策尔Glanz %一个朵琳Goerß%的约翰迪伦海恩斯% Michael T . Heneka % Ingo Kilimann %一个Okka Kimmich %一个Christoph Laske Luca Kleineidam % %一个Andrea Lohse % Ayda Rostamzadeh %一个卡洛琳Metzger %马蒂亚斯·h·蒙克%奥利弗·彼得斯%一个约瑟夫造粒机卢卡斯价格% %一个克劳斯Scheffler %安雅施耐德%安妮卡Spottke %一个阿尔弗雷多·拉米雷斯艾克Jakob Spruth % %一个桑德拉Roske %尼娜罗伊% Stefan Teipel %迈克尔·瓦格纳%一个Jens Wiltfang % Steffen Wolfsgruber % Renat Yakupov %一个彼得Zeidman % %弗兰克安杰森Bjorn h . Schott % Emrah Duzel %一个安妮马斯河% DELCODE研究小组的代表% T Novelty-Related fMRI反应个人楔前叶和内侧颞区域的阿尔茨海默病的风险% D R 10.1212 / WNL 2022%。0000000000200667 % J首页神经病学% P e775-e788 % V 99% N 8% X背景和目标我们评估是否novelty-related fMRI内侧颞叶区域的活动和楔前叶遵循一个倒u形的模式在提高阿尔茨海默病(AD)的临床表现正如前面建议的风险。具体来说,我们检测潜在的活动增加与更高的广告风险由于个人主观认知能力下降(SCD)或轻度认知障碍(MCI)。我们进一步测试是否活动差异诊断相关组占广告或脑萎缩的CSF标记。方法我们研究60 - 88岁的499名参与者从德国神经退行性疾病纵向认知障碍和老年痴呆症研究中心(DELCODE)接受了task-fMRI。参与者包括163认知正常(健康控制、HC)人,222年SCD, 82 MCI, 32临床诊断轻度AD患者。CSF水平β-amyloid 42/40比率和phosphorylated-tau181从232名参与者。我们提出分析用于评估novelty-related活动(小说>非常熟悉的场景)内嗅皮层、海马,楔前叶以及整个大脑voxel-wise分析。首先,一般线性模型测试fMRI活动参与者组之间的差异。互补的回归模型进行二次记忆障碍和活动之间的关系。第二,活动与广告脑脊液生物标记和脑容量的关系进行了分析。 Analyses were controlled for age, sex, study site, and education.Results In the precuneus, we observed an inverted U-shaped pattern of novelty-related activity across groups, with higher activity in SCD and MCI compared with HC, but not in patients with AD who showed relatively lower activity than MCI. This nonlinear pattern was confirmed by a quadratic relationship between memory impairment and precuneus activity. Precuneus activity was not related to AD biomarkers or brain volume. In contrast to the precuneus, hippocampal activity was reduced in AD dementia compared with all other groups and related to AD biomarkers.Discussion Novelty-related activity in the precuneus follows a nonlinear pattern across the clinical spectrum of increased AD risk. Although the underlying mechanism remains unclear, increased precuneus activity might represent an early signature of memory impairment. Our results highlight the nonlinearity of activity alterations that should be considered in clinical trials using functional outcome measures or targeting hyperactivity.AD=Alzheimer disease; AIC=Akaike information criterion; ANOVA=analysis of variance; CERAD=Consortium to Establish a Registry of AD; DMN=default mode network; FWE=family-wise error; FWHM=full width at half maximum; GLM=general linear model; GM=gray matter; HC=healthy control; MANCOVA=multivariate analysis of covariance; MCI=mild cognitive impairment; MMSE=Mini-Mental State Examination; MNI=Montreal Neurological Institute; MTL=medial temporal lobe; ROI=region of interest; SCD=subjective cognitive decline; SPM=statistical parametric mapping; VBM=voxel-based morphometry %U //www.ez-admanager.com/content/neurology/99/8/e775.full.pdf