Behavioral-variant frontotemporal dementia Distinct phenotypes with unique functional profiles
Behavioral-variant frontotemporal dementia Distinct phenotypes with unique functional profiles
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DOI：
10.1212/wnl.0000000000004215
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发表时间：
2017-08-08
期刊：
影响因子：
9.9
通讯作者：
Mioshi, Eneida
中科院分区：
文献类型：
--
作者：
O'Connor, Claire M.;Landin-Romero, Ramon;Mioshi, Eneida
目的：识别行为变异型额颞叶痴呆 (bvFTD) 的不同行为表型，并阐明功能、神经影像学和住院护理安置进展方面的差异。方法：对 88 名 bvFTD 患者进行聚类分析，应用去抑制和冷漠水平（剑桥行为量表修订版）来识别表型亚组。检查组间（Kruskal-Wallis、Mann-Whitney U）功能差异（痴呆症残疾评估）和住院护理安置时间（生存分析）。对 bvFTD 患者与健康对照 (n = 30) 以及表型亚组之间的皮质厚度差异（全脑 MRI）进行了分析。结果：确定了四个表型亚组：原发性严重冷漠 (n = 26)、严重冷漠和抑制解除 (n = 26)、轻度冷漠和抑制解除 (n = 27) 以及原发性重度抑制解除 (n = 9).与仅轻度冷漠或严重去抑制的患者相比，具有严重冷漠表型的患者功能受损更严重，脑萎缩更严重。进一步的影像学分析表明，右侧颞中区对于去抑制的发展至关重要，这种关联与疾病进展和严重冷漠的情况下仍然存在。最后，不同表型之间没有发现入院时间的差异。结论：这项研究表明，bvFTD 的不同临床行为表型具有不同的功能衰退特征和不同的相关皮质变化模式。这些发现强调了冷漠在功能障碍中的重要性，强调了右颞区在去抑制中的作用，并表明残疾可能是针对减少冷漠的治疗的敏感结果指标。这些表型还可以支持对预后和临床管理的理解。
Objective: To identify distinct behavioral phenotypes of behavioral-variant frontotemporal dementia (bvFTD) and to elucidate differences in functional, neuroimaging, and progression to residential care placement.Methods: Eighty-eight patients with bvFTD were included in a cluster analysis applying levels of disinhibition and apathy (Cambridge Behavioural Inventory-Revised) to identify phenotypic subgroups. Between-group (Kruskal-Wallis, Mann-Whitney U) functional differences (Disability Assessment for Dementia) and time to residential care placement (survival analyses) were examined. Cortical thickness differences (whole-brain MRI) were analyzed in patients with bvFTD vs healthy controls (n = 30) and between phenotypic subgroups.Results: Four phenotypic subgroups were identified: primary severe apathy (n = 26), severe apathy and disinhibition (n = 26), mild apathy and disinhibition (n = 27), and primary severe disinhibition (n = 9). Patients with severely apathetic phenotypes were more functionally impaired and had more extensive brain atrophy than those with mild apathy or severe disinhibition alone. Further imaging analyses indicated that the right middle temporal region is critical for the development of disinhibition, an association that remains with disease progression and in the context of severe apathy. Finally, no difference in time to residential care admission was found between phenotypes.Conclusions: This study reveals that different clinical behavioral phenotypes of bvFTD have differing profiles of functional decline and distinct patterns of associated cortical changes. These findings emphasize the importance of apathy in functional impairment, highlight the role of the right temporal region in disinhibition, and suggest that disability may be a sensitive outcome measure for treatments targeting reduction of apathy. These phenotypes could also support understanding of prognosis and clinical management.