From the Department of Neurology (G.T., Y.C., P.A.L., J.C.F., H.W.H., B.L.M., J.C.R., A.M.S., A.L.B., H.J.R., K.P.R.), Memory and Aging Center, University of California, San Francisco; Department of Neurology (B.S.A.), Case Western Reserve University, Cleveland, OH; Frontotemporal Disorders Unit (B.C.D., D.E.L., S.M.M., B.W.), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston; Department of Neurology (K.D.-R.), University of Washington, Seattle; Department of Neurology (L.K.F., R.H.G., D.S.K., B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (N.G.), Washington University, St. Louis, MO; Department of Epidemiology and Biostatistics (J.K.), University of California, San Francisco; Department of Psychiatry and Psychology (M.I.L.), Mayo Clinic, Rochester, MN; Department of Neurology (I.L.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Department of Pathology and Laboratory Medicine (I.R.M.), University of British Columbia, Vancouver, Canada; Departments of Psychiatry and Psychology (O.P.), and Neurology (Z.K.W.), Mayo Clinic, Jacksonville, FL.
Neurology. 2022 Aug 1;99(5):e488-e499. doi: 10.1212/WNL.0000000000200582.
Changes in social behavior are common symptoms of frontotemporal lobar degeneration (FTLD) and Alzheimer disease syndromes. For early identification of individual patients and differential diagnosis, sensitive clinical measures are required that are able to assess patterns of behaviors and detect syndromic differences in both asymptomatic and symptomatic stages. We investigated whether the examiner-based Social Behavior Observer Checklist (SBOCL) is sensitive to early behavior changes and reflects disease severity within and between neurodegenerative syndromes.
Asymptomatic individuals and patients with neurodegenerative disease were selected from the multisite ALLFTD cohort study. In a sample of participants with at least 1 time point of SBOCL data, we investigated whether the Disorganized, Reactive, and Insensitive subscales of the SBOCL change as a function of disease stage within and between these syndromes. In a longitudinal subsample with both SBOCL and neuroimaging data, we examined whether change over time on each subscale corresponds to progressive gray matter atrophy.
A total of 1,082 FTLD pathogenic variant carriers and noncarriers were enrolled (282 asymptomatic, 341 behavioral variant frontotemporal dementia, 114 semantic and 95 nonfluent variant primary progressive aphasia, 137 progressive supranuclear palsy, and 113 Alzheimer disease syndrome). The Disorganized score increased between asymptomatic to very mild ( = 0.016, estimate = -1.10, 95% CI = -1.99 to -0.22), very mild to mild ( = 0.013, estimate = -1.17, 95% CI = -2.08 to -0.26), and mild to moderate/severe ( < 0.001, estimate = -2.00, 95% CI = -2.55 to -1.45) disease stages in behavioral variant frontotemporal dementia regardless of pathogenic variant status. Asymptomatic pathogenic gene variant carriers showed more reactive behaviors (preoccupation with time: = 0.001, estimate = 1.11, 95% CI = 1.06 to 1.16; self-consciousness: = 0.003, estimate = 1.77, 95% CI = 1.52 to 2.01) than asymptomatic noncarriers (estimate = 1.01, 95% CI = 0.98 to 1.03; estimate = 1.31, 95% CI = 1.20 to 1.41). The Insensitive score increased to a clinically abnormal level in advanced stages of behavioral variant frontotemporal dementia ( = 0.003, estimate = -0.73, 95% CI = -1.18 to -0.29). Higher scores on each subscale corresponded with higher caregiver burden ( < 0.001). Greater change over time corresponded to greater fronto-subcortical atrophy in the semantic-appraisal and fronto-parietal intrinsically connected networks.
The SBOCL is sensitive to early symptoms and reflects disease severity, with some evidence for progression across asymptomatic and symptomatic stages of FTLD syndromes; thus, it may hold promise for early measurement and monitoring of behavioral symptoms in clinical practice and treatment trials.
This study provides Class II evidence that the SBOCL is sensitive to early behavioral changes in FTLD pathogenic variants and early symptomatic individuals in a highly educated patient cohort.
社会行为的改变是额颞叶变性（FTLD）和阿尔茨海默病综合征的常见症状。为了早期识别个体患者和进行鉴别诊断，需要使用能够评估行为模式并在无症状和有症状阶段检测综合征差异的敏感临床措施。我们研究了基于检查者的社会行为观察检查表（SBOCL）是否对早期行为变化敏感，并反映神经退行性综合征内和之间的疾病严重程度。
从多地点 ALLFTD 队列研究中选择无症状个体和神经退行性疾病患者。在至少有 1 次 SBOCL 数据的参与者样本中，我们研究了 SBOCL 的混乱、反应和不敏感子量表是否随这些综合征内和之间的疾病阶段而变化。在具有 SBOCL 和神经影像学数据的纵向亚样本中，我们检查了每个子量表随时间的变化是否与进行性灰质萎缩相对应。
共纳入了 1082 名 FTLD 致病性变异携带者和非携带者（282 名无症状、341 名行为变异额颞叶痴呆、114 名语义和 95 名非流利变异原发性进行性失语症、137 名进行性核上性麻痹和 113 名阿尔茨海默病综合征）。混乱评分在行为变异额颞叶痴呆的无症状到轻度（ = 0.016，估计值 = -1.10，95%CI = -1.99 至 -0.22）、轻度到轻度（ = 0.013，估计值 = -1.17，95%CI = -2.08 至 -0.26）和轻度到中度/重度（<0.001，估计值 = -2.00，95%CI = -2.55 至 -1.45）疾病阶段之间增加，无论致病性变异状态如何。无症状致病性基因变异携带者表现出更多的反应性行为（关注时间： = 0.001，估计值 = 1.11，95%CI = 1.06 至 1.16；自我意识： = 0.003，估计值 = 1.77，95%CI = 1.52 至 2.01）比无症状非携带者（估计值 = 1.01，95%CI = 0.98 至 1.03；估计值 = 1.31，95%CI = 1.20 至 1.41）更多。不敏感评分在行为变异额颞叶痴呆的晚期达到临床异常水平（ = 0.003，估计值 = -0.73，95%CI = -1.18 至 -0.29）。每个子量表的得分越高，与照顾者负担越重（<0.001）。随着时间的推移，变化越大，与语义评估和额顶叶固有连接网络的额皮质下萎缩越大。
SBOCL 对 FTLD 综合征的早期症状和疾病严重程度敏感，在无症状和有症状阶段有一定的进展证据；因此，它可能有望在临床实践和治疗试验中早期测量和监测行为症状。
本研究提供了 II 级证据，表明 SBOCL 对高度教育患者队列中 FTLD 致病性变异和早期症状个体的早期行为变化敏感。
