Singh Neha Atulkumar, Martin Peter R, Graff-Radford Jonathan, Sintini Irene, Machulda Mary M, Duffy Joseph R, Gunter Jeffrey L, Botha Hugo, Jones David T, Lowe Val J, Jack Clifford R, Josephs Keith A, Whitwell Jennifer L
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA.
Brain Commun. 2023 Jun 14;5(4):fcad184. doi: 10.1093/braincomms/fcad184. eCollection 2023.
Posterior cortical atrophy and logopenic progressive aphasia are atypical clinical presentations of Alzheimer's disease. Resting-state functional connectivity studies have shown functional network disruptions in both phenotypes, particularly involving the language network in logopenic progressive aphasia and the visual network in posterior cortical atrophy. However, little is known about how connectivity differs both within and between brain networks in these atypical Alzheimer's disease phenotypes. A cohort of 144 patients was recruited by the Neurodegenerative Research Group at Mayo Clinic, Rochester, MN, USA, and underwent structural and resting-state functional MRI. Spatially preprocessed data were analysed to explore the default mode network and the salience, sensorimotor, language, visual and memory networks. The data were analysed at the voxel and network levels. Bayesian hierarchical linear models adjusted for age and sex were used to analyse within- and between-network connectivity. Reduced within-network connectivity was observed in the language network in both phenotypes, with stronger evidence of reductions in logopenic progressive aphasia compared to controls. Only posterior cortical atrophy showed reduced within-network connectivity in the visual network compared to controls. Both phenotypes showed reduced within-network connectivity in the default mode and sensorimotor networks. No significant change was noted in the memory network, but a slight increase in the salience within-network connectivity was seen in both phenotypes compared to controls. Between-network analysis in posterior cortical atrophy showed evidence of reduced visual-to-language network connectivity, with reduced visual-to-salience network connectivity, compared to controls. An increase in visual-to-default mode network connectivity was noted in posterior cortical atrophy compared to controls. Between-network analysis in logopenic progressive aphasia showed evidence of reduced language-to-visual network connectivity and an increase in language-to-salience network connectivity compared to controls. Findings from the voxel-level and network-level analysis were in line with the Bayesian hierarchical linear model analysis, showing reduced connectivity in the dominant network based on diagnosis and more crosstalk between networks in general compared to controls. The atypical Alzheimer's disease phenotypes were associated with disruptions in connectivity, both within and between brain networks. Phenotype-specific differences in connectivity patterns were noted in the visual network for posterior cortical atrophy and the language network for logopenic progressive aphasia.
后部皮质萎缩和语义性进行性失语是阿尔茨海默病的非典型临床表现。静息态功能连接研究表明，这两种表型均存在功能网络破坏，特别是语义性进行性失语涉及语言网络，而后部皮质萎缩涉及视觉网络。然而，对于这些非典型阿尔茨海默病表型中脑网络内部以及脑网络之间的连接性差异，我们知之甚少。美国明尼苏达州罗切斯特市梅奥诊所的神经退行性疾病研究小组招募了144名患者，并对他们进行了结构和静息态功能磁共振成像检查。对空间预处理后的数据进行分析，以探究默认模式网络以及突显、感觉运动、语言、视觉和记忆网络。在体素和网络层面进行数据分析。采用针对年龄和性别进行调整的贝叶斯分层线性模型来分析网络内部和网络之间的连接性。在两种表型的语言网络中均观察到网络内部连接性降低，与对照组相比，语义性进行性失语中连接性降低的证据更为明显。与对照组相比，仅后部皮质萎缩在视觉网络中显示出网络内部连接性降低。两种表型在默认模式和感觉运动网络中均显示出网络内部连接性降低。记忆网络未发现显著变化，但与对照组相比，两种表型的突显网络内部连接性均略有增加。与对照组相比，后部皮质萎缩的网络间分析显示视觉与语言网络连接性降低，视觉与突显网络连接性降低。与对照组相比，后部皮质萎缩中视觉与默认模式网络连接性增加。语义性进行性失语的网络间分析显示与对照组相比，语言与视觉网络连接性降低，语言与突显网络连接性增加。体素层面和网络层面分析的结果与贝叶斯分层线性模型分析一致，表明基于诊断的优势网络连接性降低，总体上与对照组相比，网络之间的串扰更多。非典型阿尔茨海默病表型与脑网络内部以及脑网络之间的连接性破坏有关。在后部皮质萎缩的视觉网络和语义性进行性失语的语言网络中，注意到了连接模式的表型特异性差异。
