■阿尔茨海默病(AD)下游萎缩的异质性主要与病理标志有关(Aβ,tau)和共病(脑血管负担)独立。然而,每种病理在确定萎缩模式方面的比例贡献尚不清楚.我们使用两个最近概念化的维度评估了萎缩的异质性:与Aβ相关的典型性(中心的典型AD萎缩和极端的异常非典型萎缩,包括海马保留模式的边缘)和严重程度(从最小萎缩到弥漫性典型AD萎缩的总体神经变性),tau,和脑血管负担。
■我们在AD连续体上纳入了149个Aβ+个体(认知正常,前驱AD,AD痴呆)和来自ADNI的163个Aβ-认知正常个体。我们对基于MRI的萎缩的异质性进行了建模,并具有典型性(海马与皮质体积之比)和严重程度(总灰质体积)的连续尺度。偏相关模型研究了典型性/严重程度与(a)Aβ(全局AβPETcentloid)的关联,tau(全球tauPETSUVR),脑血管(总脑白质低张量)负担(B)四个认知域(记忆,执行功能,语言,视觉空间复合材料)。使用多元回归,我们评估了每种病理负荷和典型性/严重程度与认知的相关性.
■(A)在AD连续体中,控制Aβ后,典型性(r=-0.31,p<0.001)和严重性(r=-0.37,p<0.001)与tau负荷相关,脑血管负担和年龄。研究结果表明,在边缘占优势的萎缩和弥漫性萎缩中,tau病理更大。(b)典型性与记忆(r=0.49,p<0.001)和语言评分(r=0.19,p=0.02)相关。严重程度与记忆有关(r=0.26,p<0.001),执行功能(r=0.24,p=0.003)和语言得分(r=0.29,p<0.001)。研究结果暗示海马保留和最小萎缩模式的认知表现更好。超越典型性/严重性,tau负担而不是Aβ和脑血管负担解释了认知。
■在AD连续体中,在考虑Aβ和脑血管负担后,基于萎缩的严重程度与tau负担的相关性强于典型性。记忆中的认知表现,执行功能和语言领域由典型性和/或严重性以及tau病理学解释。典型性和严重程度可能不同地反映了由tau病理学引起的负担,而不是在研究AD异质性时需要考虑的Aβ或脑血管病理学。
UNASSIGNED: Heterogeneity in downstream atrophy in Alzheimer\'s disease (AD) is predominantly investigated in relation to pathological hallmarks (Aβ, tau) and co-pathologies (cerebrovascular burden) independently. However, the proportional contribution of each pathology in determining atrophy pattern remains unclear. We assessed heterogeneity in atrophy using two recently conceptualized dimensions: typicality (typical AD atrophy at the center and deviant atypical atrophy on either extreme including limbic predominant to hippocampal sparing patterns) and severity (overall neurodegeneration spanning minimal atrophy to diffuse typical AD atrophy) in relation to Aβ, tau, and cerebrovascular burden.
UNASSIGNED: We included 149 Aβ + individuals on the AD continuum (cognitively normal, prodromal AD, AD dementia) and 163 Aβ- cognitively normal individuals from the ADNI. We modeled heterogeneity in MRI-based atrophy with continuous-scales of typicality (ratio of hippocampus to cortical volume) and severity (total gray matter volume). Partial correlation models investigated the association of typicality/severity with (a) Aβ (global Aβ PET centiloid), tau (global tau PET SUVR), cerebrovascular (total white matter hypointensity volume) burden (b) four cognitive domains (memory, executive function, language, visuospatial composites). Using multiple regression, we assessed the association of each pathological burden and typicality/severity with cognition.
UNASSIGNED: (a) In the AD continuum, typicality (r = -0.31, p < 0.001) and severity (r = -0.37, p < 0.001) were associated with tau burden after controlling for Aβ, cerebrovascular burden and age. Findings imply greater tau pathology in limbic predominant atrophy and diffuse atrophy. (b) Typicality was associated with memory (r = 0.49, p < 0.001) and language scores (r = 0.19, p = 0.02). Severity was associated with memory (r = 0.26, p < 0.001), executive function (r = 0.24, p = 0.003) and language scores (r = 0.29, p < 0.001). Findings imply better cognitive performance in hippocampal sparing and minimal atrophy patterns. Beyond typicality/severity, tau burden but not Aβ and cerebrovascular burden explained cognition.
UNASSIGNED: In the AD continuum, atrophy-based severity was more strongly associated with tau burden than typicality after accounting for Aβ and cerebrovascular burden. Cognitive performance in memory, executive function and language domains was explained by typicality and/or severity and additionally tau pathology. Typicality and severity may differentially reflect burden arising from tau pathology but not Aβ or cerebrovascular pathologies which need to be accounted for when investigating AD heterogeneity.