Butts Alissa M, Machulda Mary M, Martin Peter, Przybelski Scott A, Duffy Joseph R, Graff-Radford Jonathan, Knopman David S, Petersen Ronald C, Jack Clifford R, Lowe Val J, Josephs Keith A, Whitwell Jennifer L
Department of Neurology, Division of Neuropsychology, Medical College of Wisconsin, Milwaukee, WI, USA.
External Research Collaborator, Mayo Clinic, Rochester, MN, USA.
J Alzheimers Dis Rep. 2022 Aug 5;6(1):479-491. doi: 10.3233/ADR-220010. eCollection 2022.
The hippocampus and temporal lobe are atrophic in typical amnestic Alzheimer's disease (tAD) and are used as imaging biomarkers in treatment trials. However, a better understanding of how temporal structures differ across atypical AD phenotypes and relate to cognition is needed.
Our goal was to compare temporal lobe regions between tAD and two atypical AD phenotypes (logopenic progressive aphasia (LPA) and posterior cortical atrophy (PCA)), and assess cognitive associations.
We age and gender-matched 77 tAD participants to 50 LPA and 27 PCA participants, all of which were amyloid-positive. We used linear mixed-effects models to compare FreeSurfer-derived hippocampal volumes and cortical thickness of entorhinal, inferior and middle temporal, and fusiform gyri, and to assess relationships between imaging and memory, naming, and visuospatial function across and within AD phenotype.
Hippocampal volume and entorhinal thickness were smaller bilaterally in tAD than LPA and PCA. PCA showed greater right inferior temporal and bilateral fusiform thinning and LPA showed greater left middle and inferior temporal and left fusiform thinning. Atypical AD phenotypes differed with greater right hemisphere thinning in PCA and greater left hemisphere thinning in LPA. Verbal and visual memory related most strongly to hippocampal volume; naming related to left temporal thickness; and visuospatial related to bilateral fusiform thickness. Fewer associations remained when examined within AD group.
Atypical AD phenotypes are associated with greater thinning of lateral temporal structures, with relative sparing of medial temporal lobe, compared to tAD. These findings may have implications for future clinical trials in AD.
在典型遗忘型阿尔茨海默病(tAD)中,海马体和颞叶会出现萎缩,并在治疗试验中用作影像学生物标志物。然而,我们需要更好地了解颞叶结构在非典型AD表型之间如何不同以及与认知的关系。
我们的目标是比较tAD与两种非典型AD表型(语义性进行性失语(LPA)和后皮质萎缩(PCA))之间的颞叶区域,并评估认知关联。
我们将77名tAD参与者按年龄和性别匹配50名LPA参与者和27名PCA参与者,所有参与者均为淀粉样蛋白阳性。我们使用线性混合效应模型比较来自FreeSurfer的海马体积以及内嗅、颞下和颞中回及梭状回的皮质厚度,并评估AD表型之间及内部影像与记忆、命名和视觉空间功能之间的关系。
tAD双侧海马体积和内嗅皮质厚度均小于LPA和PCA。PCA表现为右侧颞下回和双侧梭状回更薄,LPA表现为左侧颞中回和颞下回以及左侧梭状回更薄。非典型AD表型有所不同,PCA右侧半球更薄,LPA左侧半球更薄。言语和视觉记忆与海马体积的相关性最强;命名与左侧颞叶厚度相关;视觉空间功能与双侧梭状回厚度相关。在AD组内检查时,相关性较少。
与tAD相比,非典型AD表型与外侧颞叶结构更薄有关,内侧颞叶相对保留。这些发现可能对未来AD的临床试验有影响。