Katsumi Yuta, Eckbo Ryan, Chapleau Marianne, Wong Bonnie, McGinnis Scott M, Touroutoglou Alexandra, Dickerson Bradford C, Putcha Deepti
Frontotemporal Disorders Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02115, USA.
Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA 94158, USA.
medRxiv. 2024 Oct 16:2024.10.15.24315270. doi: 10.1101/2024.10.15.24315270.
Posterior Cortical Atrophy (PCA) is a clinical syndrome characterized by progressive visuospatial and visuoperceptual impairment. As the neurodegenerative disease progresses, patients lose independent functioning due to the worsening of initial symptoms and development of symptoms in other cognitive domains. The timeline of clinical progression is variable across patients, and the field currently lacks robust methods for prognostication. Here, evaluated the utility of MRI-based cortical atrophy as a predictor of longitudinal clinical decline in a sample of PCA patients.
PCA patients were recruited through the Massachusetts General Hospital Frontotemporal Disorders Unit PCA Program. All patients had cortical thickness estimates from baseline MRI scans, which were used to predict longitudinal change in clinical impairment assessed by the CDR Sum-of-Boxes (CDR-SB) score. Multivariable linear regression was used to estimate the magnitude of cortical atrophy in PCA patients relative to a group of amyloid-negative cognitively unimpaired participants. Linear mixed-effects models were used to test hypotheses about the utility of baseline cortical atrophy for predicting longitudinal clinical decline.
Data acquired from 34 PCA patients (mean age = 65.41 ± 7.90, 71% females) and 24 controls (mean age = 67.34 ± 4.93, 50% females) were analyzed. Sixty-two percent of the PCA patients were classified as having mild cognitive impairment (CDR 0.5) at baseline, with the rest having mild dementia (CDR 1). Each patient had at least one clinical follow-up, with the mean duration of 2.78 ± 1.62 years. Relative to controls, PCA patients showed prominent baseline atrophy in the posterior cortical regions, with the largest effect size observed in the visual network of the cerebral cortex. Cortical atrophy localized to the dorsal attention network, which supports higher-order visuospatial function, selectively predicted the rate of subsequent clinical decline.
These results demonstrate the utility of a snapshot measure of cortical atrophy of the dorsal attention network for predicting the rate of subsequent clinical decline in PCA. If replicated, this topographically-specific MRI-based biomarker could be useful as a clinical prognostication tool that facilitates personalized care planning.
后皮质萎缩（PCA）是一种临床综合征，其特征为进行性视觉空间和视觉感知障碍。随着神经退行性疾病的进展，由于初始症状的恶化以及其他认知领域症状的出现，患者会失去独立生活能力。临床进展的时间线因患者而异，目前该领域缺乏可靠的预后评估方法。在此，我们评估了基于MRI的皮质萎缩作为PCA患者纵向临床衰退预测指标的效用。
通过麻省总医院额颞叶疾病单元PCA项目招募PCA患者。所有患者均有基线MRI扫描的皮质厚度估计值，这些值用于预测由CDR总和方框（CDR-SB）评分评估的临床损害的纵向变化。多变量线性回归用于估计PCA患者相对于一组淀粉样蛋白阴性且认知未受损参与者的皮质萎缩程度。线性混合效应模型用于检验关于基线皮质萎缩预测纵向临床衰退效用的假设。
分析了从34例PCA患者（平均年龄 = 65.41 ± 7.90，71%为女性）和24例对照（平均年龄 = 67.34 ± 4.93，50%为女性）获取的数据。62%的PCA患者在基线时被分类为轻度认知障碍（CDR 0.5），其余为轻度痴呆（CDR 1）。每位患者至少有一次临床随访，平均随访时间为2.78 ± 1.62年。相对于对照组，PCA患者在后部皮质区域显示出明显的基线萎缩，在大脑皮质视觉网络中观察到的效应量最大。局限于支持高阶视觉空间功能的背侧注意网络的皮质萎缩选择性地预测了随后临床衰退的速度。
这些结果证明了背侧注意网络皮质萎缩的快照测量对于预测PCA患者随后临床衰退速度的效用。如果得到重复验证，这种基于MRI的具有地形特异性的生物标志物可作为一种临床预后工具，有助于个性化护理计划。
