Benussi Alberto, Libri Ilenia, Premi Enrico, Alberici Antonella, Cantoni Valentina, Gadola Yasmine, Rivolta Jasmine, Pengo Marta, Gazzina Stefano, Calhoun Vince D, Gasparotti Roberto, Zetterberg Henrik, Ashton Nicholas J, Blennow Kaj, Padovani Alessandro, Borroni Barbara
Neurology Unit Department of Clinical and Experimental Sciences University of Brescia Brescia Italy.
Neurology Unit Department of Neurological and Vision Sciences ASST Spedali Civili Brescia Italy.
Alzheimers Dement (N Y). 2022 Jul 25;8(1):e12326. doi: 10.1002/trc2.12326. eCollection 2022.
The possibility to generalize our understandings on treatments and assessments to both familial frontotemporal dementia (f-FTD) and sporadic FTD (s-FTD) is a fundamental perspective for the near future, considering the constant advancement in potential disease-modifying therapies that target particular genetic forms of FTD. We aimed to investigate differences in clinical features, cerebrospinal fluid (CSF), and blood-based biomarkers between f-FTD and s-FTD.
In this longitudinal cohort study, we evaluated a consecutive sample of symptomatic FTD patients, classified as f-FTD and s-FTD according to Goldman scores (GS). All patients underwent clinical, behavioral, and neuropsychiatric symptom assessment, CSF biomarkers and serum neurofilament light (NfL) analysis, and brain atrophy evaluation with magnetic resonance imaging.
Of 570 patients with FTD, 123 were classified as f-FTD, and 447 as s-FTD. In the f-FTD group, 95 had a pathogenic FTD mutation while 28 were classified as GS = 1 or 2; of the s-FTD group, 133 were classified as GS = 3 and 314 with GS = 4. f-FTD and s-FTD cases showed comparable demographic features, except for younger age at disease onset, age at diagnosis, and higher years of education in the f-FTD group (all < .05). f-FTD showed worse behavioral disturbances as measured with Frontal Behavioral Inventory (FBI) negative behaviors (14.0 ± 7.6 vs. 11.6 ± 7.4, = .002), and positive behaviors (20.0 ± 11.0 vs. 17.4 ± 11.8, = .031). Serum NfL concentrations were higher in patients with f-FTD (70.9 ± 37.9 pg/mL) compared to s-FTD patients (37.3 ± 24.2 pg/mL, < .001), and f-FTD showed greater brain atrophy in the frontal and temporal regions and basal ganglia. Patients with f-FTD had significantly shorter survival than those with s-FTD (= .004).
f-FTD and s-FTD are very similar clinical entities, but with different biological mechanisms, and different rates of progression. The parallel characterization of both f-FTD and s-FTD will improve our understanding of the disease, and aid in designing future clinical trials for both genetic and sporadic forms of FTD.
Do clinical features and biomarkers differ between patients with familial frontotemporal dementia (f-FTD) and sporadic FTD (s-FTD)?In this cohort study of 570 patients with FTD, f-FTD and s-FTD share similar demographic features, but with younger age at disease onset and diagnosis in the f-FTD group.f-FTD showed higher serum neurofilament light concentrations, greater brain damage, and shorter survival, compared to s-FTD.f-FTD and s-FTD are very similar clinical entities, but with different cognitive reserve mechanisms and different rates of progression.
鉴于针对特定基因形式的额颞叶痴呆（FTD）的潜在疾病修饰疗法不断取得进展，在不久的将来，将我们对治疗和评估的理解推广至家族性额颞叶痴呆（f-FTD）和散发性FTD（s-FTD）是一个基本观点。我们旨在研究f-FTD和s-FTD在临床特征、脑脊液（CSF）和血液生物标志物方面的差异。
在这项纵向队列研究中，我们评估了一组有症状的FTD患者连续样本，根据戈德曼评分（GS）分为f-FTD和s-FTD。所有患者均接受了临床、行为和神经精神症状评估、CSF生物标志物和血清神经丝轻链（NfL）分析，以及磁共振成像脑萎缩评估。
在570例FTD患者中，123例被分类为f-FTD，447例为s-FTD。在f-FTD组中，95例有致病性FTD突变，28例被分类为GS = 1或2；在s-FTD组中，133例被分类为GS = 3，314例为GS = 4。f-FTD和s-FTD病例在人口统计学特征上具有可比性，但f-FTD组发病年龄、诊断年龄更小，受教育年限更长（均P <.05）。f-FTD在额叶行为量表（FBI）阴性行为方面表现出更严重的行为障碍（14.0±7.6对11.6±7.4，P =.002），阳性行为方面也是如此（20.0±11.0对17.4±11.8，P =.031）。与s-FTD患者（37.3±24.2 pg/mL，P <.001）相比，f-FTD患者血清NfL浓度更高，且f-FTD在额叶、颞叶区域和基底节表现出更严重的脑萎缩。f-FTD患者的生存期明显短于s-FTD患者（P =.004）。
f-FTD和s-FTD是非常相似的临床实体，但具有不同的生物学机制和不同的进展速度。对f-FTD和s-FTD进行并行特征描述将增进我们对该疾病的理解，并有助于为FTD的遗传和散发性形式设计未来的临床试验。
家族性额颞叶痴呆（f-FTD）和散发性FTD患者的临床特征和生物标志物有差异吗？在这项对570例FTD患者的队列研究中，f-FTD和s-FTD具有相似的人口统计学特征，但f-FTD组发病和诊断年龄更小。与s-FTD相比，f-FTD血清神经丝轻链浓度更高、脑损伤更严重、生存期更短。f-FTD和s-FTD是非常相似的临床实体，但具有不同的认知储备机制和不同的进展速度。
