Department of Neurosciences, Central Clinical School, Monash University, Melbourne, Australia.
Department of Medicine and Radiology, The University of Melbourne, Parkville, Australia.
J Alzheimers Dis. 2023;94(1):19-38. doi: 10.3233/JAD-221171.
Behavioral variant frontotemporal dementia (bvFTD) belongs to the spectrum of frontotemporal lobar degeneration (FTLD) and is characterized by frontal dysfunction with executive deficits and prominent socioemotional impairments. Social cognition, such as emotion processing, theory of mind, and empathy may significantly impact daily behavior in bvFTD. Abnormal protein accumulation of tau or TDP-43 are the main causes of neurodegeneration and cognitive decline. Differential diagnosis is difficult due to the heterogeneous pathology in bvFTD and the high clinicopathological overlap with other FTLD syndromes, especially in late disease stages. Despite recent advances, social cognition in bvFTD has not yet received sufficient attention, nor has its association with underlying pathology. This narrative review evaluates social behavior and social cognition in bvFTD, by relating these symptoms to neural correlates and underlying molecular pathology or genetic subtypes. Negative and positive behavioral symptoms, such as apathy and disinhibition, share similar brain atrophy and reflect social cognition. More complex social cognitive impairments are probably caused by the interference of executive impairments due to increasing neurodegeneration. Evidence suggests that underlying TDP-43 is associated with neuropsychiatric and early social cognitive dysfunction, while patients with underlying tau pathology are marked by strong cognitive dysfunction with increasing social impairments in later stages. Despite many current research gaps and controversies, finding distinct social cognitive markers in association to underlying pathology in bvFTD is essential for validating biomarkers, for clinical trials of novel therapies, and for clinical practice.
行为变异型额颞叶痴呆（bvFTD）属于额颞叶变性（FTLD）谱系，其特征是额功能障碍伴执行功能缺陷和突出的社会情感障碍。社会认知，如情绪处理、心理理论和同理心，可能会显著影响 bvFTD 患者的日常行为。tau 或 TDP-43 的异常蛋白积累是神经退行性变和认知能力下降的主要原因。由于 bvFTD 的异质性病理学和与其他 FTLD 综合征的高临床病理重叠，尤其是在疾病晚期，鉴别诊断较为困难。尽管最近取得了进展，但 bvFTD 的社会认知仍未得到足够重视，其与潜在病理学的关系也未得到充分研究。本综述通过将这些症状与神经相关性以及潜在的分子病理学或遗传亚型联系起来，评估了 bvFTD 的社会行为和社会认知。阴性和阳性行为症状，如冷漠和抑制障碍，具有相似的脑萎缩，反映了社会认知。更复杂的社会认知障碍可能是由于执行功能障碍的干扰导致的，而执行功能障碍是由于神经退行性变的增加引起的。有证据表明，潜在的 TDP-43 与神经精神和早期社会认知功能障碍有关，而潜在 tau 病理学患者的特征是强烈的认知功能障碍，随着社会障碍的增加，在疾病后期更为明显。尽管存在许多当前的研究空白和争议，但在 bvFTD 中找到与潜在病理学相关的独特社会认知标志物对于验证生物标志物、新型疗法的临床试验以及临床实践都至关重要。
