*These authors contributed equally as co-first authors.
These authors contributed equally as co-senior authors.
Neurology. 2023 Jan 17;100(3):e286-e296. doi: 10.1212/WNL.0000000000201403. Epub 2022 Oct 3.
Patients with primary progressive aphasia (PPA) have gradually progressive language deficits during the initial phase of the illness. As the underlying neurodegenerative disease progresses, patients with PPA start losing independent functioning due to the development of nonlanguage cognitive or behavioral symptoms. The timeline of this progression from the mild cognitive impairment stage to the dementia stage of PPA is variable across patients. In this study, in a sample of patients with PPA, we measured the magnitude of cortical atrophy within functional networks believed to subserve diverse cognitive and affective functions. The objective of the study was to evaluate the utility of this measure as a predictor of time to subsequent progression to dementia in PPA.
Patients with PPA with largely independent daily function were recruited through the Massachusetts General Hospital Frontotemporal Disorders Unit. All patients underwent an MRI scan at baseline. Cortical atrophy was then estimated relative to a group of amyloid-negative cognitively normal control participants. For each patient, we measured the time between the baseline visit and the subsequent visit at which dementia progression was documented or last observation. Simple and multivariable Cox regression models were used to examine the relationship between cortical atrophy and the likelihood of progression to dementia.
Forty-nine patients with PPA (mean age = 66.39 ± 8.36 years, 59.2% females) and 25 controls (mean age = 67.43 ± 4.84 years, 48% females) were included in the data analysis. Greater baseline atrophy in not only the left language network (hazard ratio = 1.47, 95% CI = 1.17-1.84) but also in the frontoparietal control (1.75, 1.25-2.44), salience (1.63, 1.25-2.13), default mode (1.55, 1.19-2.01), and ventral frontotemporal (1.41, 1.16-1.71) networks was associated with a higher risk of progression to dementia. A multivariable model identified contributions of the left frontoparietal control (1.94, 1.09-3.48) and ventral frontotemporal (1.61, 1.09-2.39) networks in predicting dementia progression, with no additional variance explained by the language network (0.75, 0.43-1.31).
These results suggest that baseline atrophy in cortical networks subserving nonlanguage cognitive and affective functions is an important predictor of progression to dementia in PPA. This measure should be included in precision medicine models of prognosis in PPA.
原发性进行性失语症（PPA）患者在疾病的初始阶段会逐渐出现语言缺陷。随着潜在的神经退行性疾病的发展，由于非语言认知或行为症状的发展，PPA 患者开始失去独立功能。从轻度认知障碍阶段到 PPA 的痴呆阶段的进展时间因患者而异。在这项研究中，我们在一组 PPA 患者中测量了与多种认知和情感功能相关的功能网络内皮质萎缩的程度。研究的目的是评估该测量值作为预测 PPA 后续向痴呆进展的时间的指标的效用。
通过马萨诸塞州综合医院额颞叶障碍科招募了具有基本独立日常生活功能的 PPA 患者。所有患者均在基线时接受 MRI 扫描。然后相对于一组淀粉样阴性认知正常的对照组来估计皮质萎缩。对于每位患者，我们测量了从基线就诊到随后记录痴呆进展或最后观察之间的时间。简单和多变量 Cox 回归模型用于检查皮质萎缩与向痴呆进展的可能性之间的关系。
49 名 PPA 患者（平均年龄=66.39±8.36 岁，59.2%女性）和 25 名对照者（平均年龄=67.43±4.84 岁，48%女性）纳入数据分析。基线时左侧语言网络（危险比=1.47，95%CI=1.17-1.84）以及额顶叶控制网络（1.75，1.25-2.44）、突显网络（1.63，1.25-2.13）、默认模式网络（1.55，1.19-2.01）和腹侧额颞叶网络（1.41，1.16-1.71）的更大萎缩与向痴呆进展的风险更高相关。多变量模型确定了左侧额顶叶控制网络（1.94，1.09-3.48）和腹侧额颞叶网络（1.61，1.09-2.39）在预测痴呆进展中的贡献，语言网络（0.75，0.43-1.31）没有解释额外的差异。
这些结果表明，非语言认知和情感功能相关皮质网络的基线萎缩是 PPA 向痴呆进展的重要预测指标。该测量值应纳入 PPA 预后的精准医学模型中。
