Requena-Komuro Maï-Carmen, Marshall Charles R, Bond Rebecca L, Russell Lucy L, Greaves Caroline, Moore Katrina M, Agustus Jennifer L, Benhamou Elia, Sivasathiaseelan Harri, Hardy Chris J D, Rohrer Jonathan D, Warren Jason D
Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom.
Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom.
Front Neurol. 2020 Apr 21;11:291. doi: 10.3389/fneur.2020.00291. eCollection 2020.
Our awareness of time, specifically of longer intervals spanning hours, days, months, and years, is critical for ensuring our sense of self-continuity. Disrupted time awareness over such intervals is a clinical feature in a number of frontotemporal dementia syndromes and Alzheimer's disease, but has not been studied and compared systematically in these diseases. We used a semi-structured caregiver survey to capture time-related behavioral alterations in 71 patients representing all major sporadic and genetic syndromes of frontotemporal dementia, in comparison to 28 patients with typical Alzheimer's disease and nine with logopenic aphasia, and 32 healthy older individuals. Survey items pertained to apparent difficulties ordering past personal events or estimating time intervals between events, temporal rigidity and clockwatching, and propensity to relive past events. We used a logistic regression model including diagnosis, age, gender, and disease severity as regressors to compare the proportions of individuals exhibiting each temporal awareness symptom between diagnostic groups. Gray matter associations of altered time awareness were assessed using voxel-based morphometry. All patient groups were significantly more prone to exhibit temporal awareness symptoms than healthy older individuals. Clinical syndromic signatures were identified. While patients with typical and logopenic Alzheimer's disease most frequently exhibited disturbed event ordering or interval estimation, patients with semantic dementia were most prone to temporal rigidity and clockwatching and those with behavioral variant frontotemporal dementia commonly exhibited all these temporal symptoms as well as a propensity to relive past events. On voxel-based morphometry, the tendency to relive past events was associated with relative preservation of a distributed left-sided temporo-parietal gray matter network including hippocampus. These findings reveal a rich and complex picture of disturbed temporal awareness in major dementia syndromes, with stratification of frontotemporal dementia syndromes from Alzheimer's disease. This is the first study to assess symptoms of altered temporal awareness across frontotemporal dementia syndromes and provides a motivation for future work directed to the development of validated clinical questionnaires, analysis of underlying neurobiological mechanisms and design of interventions.
我们对时间的感知，尤其是对跨越数小时、数天、数月和数年的较长时间间隔的感知，对于确保我们的自我连续性意识至关重要。在数小时、数天、数月和数年这样的时间间隔内，时间感知紊乱是多种额颞叶痴呆综合征和阿尔茨海默病的临床特征，但在这些疾病中尚未进行系统的研究和比较。我们使用了一项半结构化的照顾者调查问卷，以了解71名代表额颞叶痴呆所有主要散发性和遗传性综合征的患者与时间相关的行为改变，同时纳入了28名典型阿尔茨海默病患者、9名语义性失语症患者以及32名健康老年人作为对照。调查问卷的项目涉及在安排过去个人事件顺序或估计事件之间的时间间隔时明显存在的困难、时间僵化和频繁看时钟的行为，以及重温过去事件的倾向。我们使用了一个逻辑回归模型，将诊断、年龄、性别和疾病严重程度作为回归变量，以比较不同诊断组中出现每种时间感知症状的个体比例。使用基于体素的形态测量法评估时间感知改变与灰质的关联。所有患者组出现时间感知症状的倾向均显著高于健康老年人。我们识别出了临床综合征特征。典型和语义性失语型阿尔茨海默病患者最常出现事件排序或时间间隔估计紊乱，语义性痴呆患者最容易出现时间僵化和频繁看时钟的行为，而行为变异型额颞叶痴呆患者通常会出现所有这些时间症状以及重温过去事件的倾向。基于体素的形态测量法显示，重温过去事件的倾向与包括海马体在内的左侧颞顶叶分布式灰质网络的相对保留有关。这些发现揭示了主要痴呆综合征中时间感知紊乱的丰富而复杂的情况，额颞叶痴呆综合征与阿尔茨海默病得以区分。这是第一项评估额颞叶痴呆综合征中时间感知改变症状的研究，为未来开发经过验证的临床问卷、分析潜在神经生物学机制以及设计干预措施的工作提供了动力。
