Progression of Behavioral Disturbances and Neuropsychiatric Symptoms in Patients With Genetic Frontotemporal Dementia.
Progression of Behavioral Disturbances and Neuropsychiatric Symptoms in Patients With Genetic Frontotemporal Dementia.
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DOI：
10.1001/jamanetworkopen.2020.30194
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发表时间：
2021-01-04
影响因子：
13.8
通讯作者：
Genetic FTD Initiative (GENFI)
中科院分区：
文献类型：
--
作者：
Benussi A;Premi E;Gazzina S;Brattini C;Bonomi E;Alberici A;Jiskoot L;van Swieten JC;Sanchez-Valle R;Moreno F;Laforce R;Graff C;Synofzik M;Galimberti D;Masellis M;Tartaglia C;Rowe JB;Finger E;Vandenberghe R;de Mendonça A;Tagliavini F;Santana I;Ducharme S;Butler CR;Gerhard A;Levin J;Danek A;Otto M;Frisoni G;Ghidoni R;Sorbi S;Le Ber I;Pasquier F;Peakman G;Todd E;Bocchetta M;Rohrer JD;Borroni B;Genetic FTD Initiative (GENFI)
额颞叶痴呆不同基因变异患者的行为和神经精神症状演变是否不同？在这项对232例遗传性额颞叶痴呆患者的队列研究中，与C9orf72和GRN携带者相比，MAPT变异患者表现出大多数行为症状的最高频率和严重程度。焦虑和抑郁在GRN和MAPT携带者中最为常见；幻觉，尤其是听觉和视觉，在C9orf72携带者中最常见。这些发现表明，行为和神经精神障碍在常见的额颞叶痴呆基因变异之间存在差异，并且在疾病过程中具有不同的轨迹。本队列研究使用来自欧洲和加拿大三期额颞叶痴呆研究诊所的数据来评估不同形式的遗传性额颞叶痴呆的行为症状的频率和严重程度及其进展。行为障碍是额颞叶痴呆（FTD）的核心特征；然而，在遗传性FTD中，整个病程的症状进展并没有很好地表征。目的探讨不同形式的遗传性FTD的行为症状频率、严重程度及其演变和进展。这项纵向队列研究是国际遗传FTD计划（GENFI），于2012年1月30日至2019年5月31日在英国、荷兰、比利时、法国、西班牙、葡萄牙、意大利、德国、瑞典、芬兰和加拿大的23个多中心专科三级FTD研究诊所进行。参与者包括232例症状性FTD基因变异携带者的连续样本，其中115例为C9orf72变异，78例为GRN变异，39例为MAPT变异。共有101名携带者进行了至少1次随访评估（总共400次评估）。基因变异只有在被认为是致病的情况下才包括在内。行为和神经精神症状在整个病程中进行评估，并从症状开始进行评估。分层广义线性混合模型用于模拟行为和神经精神测量作为疾病持续时间和变异的函数。在232例FTD患者中，115例（49.6%）有C9orf72扩张(评估时的中位数[四分位数间距（IQR）]年龄为64.3[57.5-69.7]岁；男性72人（62.6%）；115例白人患者（100%），78例（33.6%）有GRN变异（中位[IQR]年龄63.4[58.3-68.8]岁；40例女性[51.3%]；77例白人患者[98.7%]），39例（16.8%）有MAPT变异（中位[IQR]年龄56.3[49.9-62.4]岁；25例男性[64.1%]；37例白人患者[94.9%]）。所有核心行为症状，包括去抑制、冷漠、移情丧失、顽固行为和高品质，在所有基因变异携带者（50%的患者）中都有高表达，冷漠是整个病程中最常见和最严重的症状之一（51.7%-100%的患者）。与C9orf72携带者（去抑制者占51.7% ~ 95.8%，强迫行为者占34.5% ~ 75.0%）和GRN携带者（去抑制者占38.2% ~ 100%，强迫行为者占20.6% ~ 100%）相比，MAPT变异患者表现出大多数行为症状的频率和严重程度最高，特别是去抑制（79.3% ~ 100%）和强迫行为（64.3% ~ 100%）。除了行为症状外，遗传性FTD患者还经常报告神经精神症状：焦虑和抑郁在GRN携带者（23.8%-100%的患者）和MAPT携带者（26.1%-77.8%的患者）中最常见；幻觉，尤其是听觉和视觉，在C9orf72携带者中最常见（10.3%-54.5%）。大多数行为和神经精神症状在疾病的早期中期增加，在疾病的晚期趋于稳定，除了抑郁，在C9orf72携带者中稳步下降，以及抑郁和焦虑，仅在晚期GRN携带者中激增。这项队列研究表明，行为和神经精神障碍在常见的FTD基因变异之间存在差异，并且在整个疾病过程中具有不同的轨迹。这些发现对于为患者和护理人员提供咨询以及设计遗传性FTD的疾病改善治疗试验具有重要意义。
Do behavioral and neuropsychiatric symptoms evolve differently in patients with distinct genetic variations for frontotemporal dementia? In this cohort study of 232 patients with genetic frontotemporal dementia, patients with MAPT variants showed the highest frequency and severity of most behavioral symptoms compared with C9orf72 and GRN carriers. Anxiety and depression were most common in GRN and MAPT carriers; hallucinations, particularly auditory and visual, were most common in C9orf72 carriers. These findings suggest that behavioral and neuropsychiatric disturbances differ between the common frontotemporal dementia gene variations and have different trajectories through the course of disease. This cohort study uses data from tertiary frontotemporal dementia research clinics across Europe and Canada to assess the frequency and severity of behavioral symptoms and their progression in different forms of genetic frontotemporal dementia. Behavioral disturbances are core features of frontotemporal dementia (FTD); however, symptom progression across the course of disease is not well characterized in genetic FTD. To investigate behavioral symptom frequency and severity and their evolution and progression in different forms of genetic FTD. This longitudinal cohort study, the international Genetic FTD Initiative (GENFI), was conducted from January 30, 2012, to May 31, 2019, at 23 multicenter specialist tertiary FTD research clinics in the United Kingdom, the Netherlands, Belgium, France, Spain, Portugal, Italy, Germany, Sweden, Finland, and Canada. Participants included a consecutive sample of 232 symptomatic FTD gene variation carriers comprising 115 with variations in C9orf72, 78 in GRN, and 39 in MAPT. A total of 101 carriers had at least 1 follow-up evaluation (for a total of 400 assessments). Gene variations were included only if considered pathogenetic. Behavioral and neuropsychiatric symptoms were assessed across disease duration and evaluated from symptom onset. Hierarchical generalized linear mixed models were used to model behavioral and neuropsychiatric measures as a function of disease duration and variation. Of 232 patients with FTD, 115 (49.6%) had a C9orf72 expansion (median [interquartile range (IQR)] age at evaluation, 64.3 [57.5-69.7] years; 72 men [62.6%]; 115 White patients [100%]), 78 (33.6%) had a GRN variant (median [IQR] age, 63.4 [58.3-68.8] years; 40 women [51.3%]; 77 White patients [98.7%]), and 39 (16.8%) had a MAPT variant (median [IQR] age, 56.3 [49.9-62.4] years; 25 men [64.1%]; 37 White patients [94.9%]). All core behavioral symptoms, including disinhibition, apathy, loss of empathy, perseverative behavior, and hyperorality, were highly expressed in all gene variant carriers (>50% patients), with apathy being one of the most common and severe symptoms throughout the disease course (51.7%-100% of patients). Patients with MAPT variants showed the highest frequency and severity of most behavioral symptoms, particularly disinhibition (79.3%-100% of patients) and compulsive behavior (64.3%-100% of patients), compared with C9orf72 carriers (51.7%-95.8% of patients with disinhibition and 34.5%-75.0% with compulsive behavior) and GRN carriers (38.2%-100% with disinhibition and 20.6%-100% with compulsive behavior). Alongside behavioral symptoms, neuropsychiatric symptoms were very frequently reported in patients with genetic FTD: anxiety and depression were most common in GRN carriers (23.8%-100% of patients) and MAPT carriers (26.1%-77.8% of patients); hallucinations, particularly auditory and visual, were most common in C9orf72 carriers (10.3%-54.5% of patients). Most behavioral and neuropsychiatric symptoms increased in the early-intermediate phases and plateaued in the late stages of disease, except for depression, which steadily declined in C9orf72 carriers, and depression and anxiety, which surged only in the late stages in GRN carriers. This cohort study suggests that behavioral and neuropsychiatric disturbances differ between the common FTD gene variants and have different trajectories throughout the course of disease. These findings have crucial implications for counseling patients and caregivers and for the design of disease-modifying treatment trials in genetic FTD.
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影响因子：
11
作者：
Cheran, Gayathri;Silverman, Hannah;Huey, Edward D.
通讯作者：
Huey, Edward D.
DOI：
10.1016/s1474-4422(14)70324-2
发表时间：
2015-03
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Rohrer JD;Nicholas JM;Cash DM;van Swieten J;Dopper E;Jiskoot L;van Minkelen R;Rombouts SA;Cardoso MJ;Clegg S;Espak M;Mead S;Thomas DL;De Vita E;Masellis M;Black SE;Freedman M;Keren R;MacIntosh BJ;Rogaeva E;Tang-Wai D;Tartaglia MC;Laforce R Jr;Tagliavini F;Tiraboschi P;Redaelli V;Prioni S;Grisoli M;Borroni B;Padovani A;Galimberti D;Scarpini E;Arighi A;Fumagalli G;Rowe JB;Coyle-Gilchrist I;Graff C;Fallström M;Jelic V;Ståhlbom AK;Andersson C;Thonberg H;Lilius L;Frisoni GB;Pievani M;Bocchetta M;Benussi L;Ghidoni R;Finger E;Sorbi S;Nacmias B;Lombardi G;Polito C;Warren JD;Ourselin S;Fox NC;Rossor MN;Binetti G
通讯作者：
Binetti G
DOI：
10.1093/brain/awx101
发表时间：
2017-06-01
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Lansdall CJ;Coyle-Gilchrist ITS;Jones PS;Vázquez Rodríguez P;Wilcox A;Wehmann E;Dick KM;Robbins TW;Rowe JB
通讯作者：
Rowe JB
影响因子：
11
作者：
Bozeat, S;Gregory, CA;Hodges, JR
通讯作者：
Hodges, JR
影响因子：
9.9
作者：
Rohrer, J. D.;Guerreiro, R.;Rossor, M. N.
通讯作者：
Rossor, M. N.