Frontotemporal lobar degeneration: current perspectives

Abstract

The term frontotemporal lobar degeneration (FTLD) refers to a group of progressive brain diseases, which preferentially involve the frontal and temporal lobes. Depending on the primary site of atrophy, the clinical manifestation is dominated by behavior alterations or impairment of language. The onset of symptoms usually occurs before the age of 60 years, and the mean survival from diagnosis varies between 3 and 10 years. The prevalence is estimated at 15 per 100,000 in the population aged between 45 and 65 years, which is similar to the prevalence of Alzheimer’s disease in this age group. There are two major clinical subtypes, behavioral-variant frontotemporal dementia and primary progressive aphasia. The neuropathology underlying the clinical syndromes is also heterogeneous. A common feature is the accumulation of certain neuronal proteins. Of these, the microtubule-associated protein tau (MAPT), the transactive response DNA-binding protein, and the fused in sarcoma protein are most important. Approximately 10% to 30% of FTLD shows an autosomal dominant pattern of inheritance, with mutations in the genes for MAPT, progranulin (GRN), and in the chromosome 9 open reading frame 72 (C9orf72) accounting for more than 80% of familial cases. Although significant advances have been made in recent years regarding diagnostic criteria, clinical assessment instruments, neuropsychological tests, cerebrospinal fluid biomarkers, and brain imaging techniques, the clinical diagnosis remains a challenge. To date, there is no specific pharmacological treatment for FTLD. Some evidence has been provided for serotonin reuptake inhibitors to reduce behavioral disturbances. No large-scale or high-quality studies have been conducted to determine the efficacy of non-pharmacological treatment approaches in FTLD. In view of the limited treatment options, caregiver education and support is currently the most important component of the clinical management.

Efficacy of memantine on neuropsychiatric symptoms associated with the severity of behavioral variant frontotemporal dementia: A six-month, open-label, self-controlled clinical trial

“…According to the survey of epidemiology, from the time of symptom onset, the mean survival in all FTLD is estimated to range from 6.6 to 11.0 years. The mean survival from time of clinical diagnosis of FTLD is estimated to range between 3 and 4 years, which means that patients with FTLD admitted to hospital will progress to a moderate or severe stage in no more than 3 and 4 years (20,21). The majority of studies have focused on the effects of memantine on mild-to-moderate (MMSE score, >15) FTLD and have neglected its possible benefits for the treatment of patients in moderate-to-severe stages of FTLD (16).…”

Behavioral Evolution of Progressive Semantic Aphasia in Comparison with Nonfluent Aphasia

“…Frontotemporal lobar degeneration (FTLD) is a heterogeneous cause of dementia starting in the 5th and 6th decades of life, with a positive family history seen in about 40% of the cases [1,2,3]. In the past few years, diagnostic criteria have been revised for the three most common clinical phenotypes, which include the behavioral variant (bvFTD) [4] and two types of primary progressive aphasia (PPA): the nonfluent and the semantic variant [5].…”

“…These phenotypes can be distinguished based on predominant clinical features that correlate with different patterns of atrophy on neuroimaging. bvFTD is associated with bilateral orbitofrontal atrophy, while semantic PPA is associated with anterior temporal lobe atrophy (frequently asymmetric), and nonfluent PPA with left perisylvian atrophy [1,2,3,4,5,6]. The genetic causes and underlying pathology associated with the behavioral and the nonfluent PPA phenotype are heterogeneous.…”

“…The genetic causes and underlying pathology associated with the behavioral and the nonfluent PPA phenotype are heterogeneous. Semantic PPA is more consistently correlated with TAR DNA-binding protein pathology, the family history is usually weak, and no genetic markers have been linked to date [1,2,3,7,8]. …”

Modulation of Amyloid β-Protein (Aβ) Assembly by Homologous C-Terminal Fragments as a Strategy for Inhibiting Aβ Toxicity

“…Classic examples are Alzheimer's, 5 Parkinson's, 6 and Huntington's 7 diseases. The number of recognized proteinopathies has been increasing gradually as additional abnormal protein deposits have been found in multiple other diseases, such as different variants of amyotrophic lateral sclerosis, frontotemporal dementia, 8 mental disorders, 9 and preeclampsia. 10 …”