Indiana University School of Medicine, Indianapolis, IN, USA.
CNS Drugs. 2012 Oct 1;26(10):841-70. doi: 10.2165/11640070-000000000-00000.
Frontotemporal lobar degeneration (FTLD) describes a spectrum of clinically, pathologically and genetically heterogeneous neurodegenerative disorders of unknown aetiology. FTLD spectrum disorders collectively represent a leading cause of early-onset dementia, with most cases presenting between 45 and 64 years of age. FTLD is characterized by progressive changes in behaviour, executive dysfunction and/or language impairment and can be differentiated clinically into three frontotemporal dementia (FTD) syndromes as follows: (i) behavioural variant (bvFTD); (ii) semantic dementia (SD); and (iii) progressive nonfluent aphasia (PNFA). Additionally, there is a significant clinical, pathological and genetic overlap between FTD and motor neuron disease/amyotrophic lateral sclerosis (FTD-ALS) and the atypical parkinsonian syndromes, progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). bvFTD is characterized by progressive behavioural impairment and a decline in executive function with frontal lobe-predominant atrophy, SD by a loss of object knowledge with prominent anomia and asymmetrical atrophy of the anterior temporal lobes and PNFA by expressive or motor speech deficits with predominantly left peri-sylvian atrophy. Recent advances in molecular biology and immunohistochemical staining techniques have further classified the FTLD spectrum disorders based upon the predominant neuropathological protein into three main categories: (i) microtubule-associated protein tau (FTLD-TAU); (ii) TAR DNA-binding protein-43 (FTLD-TDP); and (iii) fused in sarcoma protein (FTLD-FUS). Up to 40% of FTD patients report a family history of neurodegenerative illness, and one-third to one-half of familial cases of FTD follow an autosomal dominant inheritance pattern. Mutations in MAPT, PGRN, TARDBP, VCP and CHMP2B have been described, along with a recently identified C9ORF72 hexanucleotide repeat expansion. To date, there are no US FDA-approved treatments or disease-modifying therapies for FTD. Pharmacological strategies have focused on neurotransmitter replacement and modulation for the treatment of behavioural, motor and cognitive symptoms of FTD, and include selective serotonin reuptake inhibitors (SSRIs), atypical antipsychotics, acetylcholinesterase inhibitors and glutamate NMDA receptor antagonists. At present, adequate management of FTD symptoms involves a combination of pharmacological therapy with behavioural, physical and environmental modification techniques.
额颞叶变性（FTLD）描述了一组临床上、病理学上和遗传学上表现出未知病因的异质性神经退行性疾病。FTLD 谱障碍共同构成了早发性痴呆的主要原因，大多数病例发生在 45 至 64 岁之间。FTLD 的特征是行为、执行功能和/或语言障碍的进行性变化，临床上可分为三种额颞叶痴呆（FTD）综合征，如下所示：（i）行为变异型（bvFTD）；（ii）语义性痴呆（SD）；和（iii）进行性非流利性失语症（PNFA）。此外，FTD 与运动神经元病/肌萎缩性侧索硬化症（FTD-ALS）以及非典型帕金森综合征、进行性核上性麻痹（PSP）和皮质基底节综合征（CBS）之间存在显著的临床、病理和遗传重叠。bvFTD 的特征是进行性行为障碍和执行功能下降，伴有额叶优势萎缩，SD 表现为物体知识丧失，伴有明显的命名障碍和前颞叶不对称萎缩，PNFA 表现为表达或运动言语缺陷，伴有左外侧裂周围优势萎缩。分子生物学和免疫组织化学染色技术的最新进展进一步根据主要神经病理学蛋白将 FTLD 谱障碍分类为三类：（i）微管相关蛋白 tau（FTLD-TAU）；（ii）TAR DNA 结合蛋白 43（FTLD-TDP）；和（iii）肉瘤融合蛋白（FTLD-FUS）。多达 40%的 FTD 患者有神经退行性疾病的家族史，三分之一至一半的家族性 FTD 遵循常染色体显性遗传模式。已经描述了 MAPT、PGRN、TARDBP、VCP 和 CHMP2B 的突变，以及最近发现的 C9ORF72 六核苷酸重复扩展。迄今为止，美国食品和药物管理局（FDA）尚未批准用于 FTD 的治疗方法或疾病修饰疗法。药物治疗策略侧重于 FTD 行为、运动和认知症状的神经递质替代和调节，包括选择性 5-羟色胺再摄取抑制剂（SSRIs）、非典型抗精神病药、乙酰胆碱酯酶抑制剂和谷氨酸 NMDA 受体拮抗剂。目前，充分管理 FTD 症状需要将药物治疗与行为、物理和环境改变技术相结合。
