Epidemiology of early-onset frontotemporal dementia and molecular genetics of early-onset neurodegenerative dementia

In the thesis Epidemiology of early-onset frontotemporal dementia and molecular genetics of early-onset neurodegenerative dementia the epidemiology of frontotemporal dementia in Northern Ostrobothnia, Finland, was determined using the hospital discharge register from Oulu University Hospital and the population statistics for 2006–2010. In the study, there were 40 frontotemporal dementia patients, of whom 29 were 45–65 years old. In the age group 45–65 years old incidence was 5.5/100000 person-years and prevalence 20.5/100000 people at risk. The incidence and prevalence of early-onset frontotemporal dementia is rather high when compared to the results worldwide. The prevalence was similar than in Italy and higher than in England, Holland and Norway. This is the first study of incidence and prevalence of early-onset frontotemporal dementia in Finland. The results are useful in clinical diagnostics and in the evaluation of support and services.

Genes associated with Alzheimer’s disease, frontotemporal dementia and Parkinson’s disease were evaluated in the selected cohort of early-onset dementia patients using next generation sequencing. In Finland the most common mutation causing frontotemporal dementia is the C9orf72 repeat expansion that was excluded from the cohort. The patients of the cohort had memory disease or memory complaints in their family, their disease was rapidly progressive, or the onset was with atypical features. The variants of genes associated with Parkinson’s disease determined from the selected cohort were screened from 279 unselected early-onset dementia patients. The selected cohort of 39 patients carried two mutations (PSEN1 p.His163Arg ja MAPT p.Arg406Trp) that cause Alzheimer’s disease and frontotemporal dementia. Rare variants were found from PSEN1, PSEN2, TREM2, BIN1, APP, UBQLN2, GRN, MAPT, TMEM106B, LRRK2, SNCAIP, PARK2 ja GBA genes. The variants of genes associated with Parkinson disease were more common in the selected cohort than in the unselected cohort. The results indicate that the pathogenic mutations can be found from the patients whose age at onset is under 55. Based on the results it is also suggested that the rare variants of the genes associated with Parkinson’s disease may also be involved in the etiologies of Alzheimer´s disease and frontotemporal dementia.