Prevalence of frontotemporal lobar degeneration in an isolated population: the Vallecamonica study

Abstract

The study of neurodegenerative diseases, such as frontotemporal lobar degeneration (FTLD), in isolated populations represents a privileged point of view for identifying new causative genes and pathogenetic mechanisms. Vallecamonica is a valley located in the Brescia province (Northern Italy), which experienced isolation until the end of World War II. The aims of the present work were (1) to estimate the prevalence of FTLD in Vallecamonica, (2) to determine the monogenic FTLD forms, and (3) to identify FTLD cases with no evidence of known pathogenetic mutations and the related clinical features. Patients meeting current clinical criteria for FTLD were considered. Mutation analysis for microtubule associated protein tau (MAPT) and progranulin (PGRN) genes was performed, as well as serum PGRN dosage. On the census day, 42 FTLD patients were alive, resulting in an overall disease prevalence of 35 per 100 inhabitants. Thirty-one out of 42 patients underwent sequencing analysis. Five patients carried PGRN Thr272fs mutation and one patient MAPT P301L mutation. There were no differences in term of age at onset and gender between this group and mutation carriers, but the latter had greater family history for dementia (100%, P = 0.01). In Vallecamonica, we detected a higher prevalence of FTLD compared with that already reported in other populations. A founder effect or a genetic drift might be considered for an allelic enrichment. Ongoing study aims to identify the presence of a new genetic form in those FTLD patients without known pathogenetic mutations in this isolated population.

Dementia in Latin America: Epidemiological Evidence and Implications for Public Policy

“…In general, the exact prevalence of FTD is unknown. The prevalence estimated in studies with outpatients and in European memory centers ranges from 0.002% to 0.031%; from 0.078% to 1.56%, and from 0.054% to 0.135% between 45 years and 64 years, 65 years and 74 years, and at ≥75 years respectively (Rosso et al, 2003; Gilberti et al, 2012). However, recent community-based studies suggest that FTD may be more common than previously estimated (Bernardi et al, 2012).…”

The epidemiology of frontotemporal dementia

“…Nevertheless, within the last decade prevalence and incidence data have accumulated from population studies conducted in Canada (Feldman et al, 2003), Japan (Ikejima et al, 2009), Italy (Bernardi et al, 2012; Borroni et al, 2010; Gilberti et al, 2012) the Netherlands (Rosso, Kaat, Baks, & Joosse, 2003a), Spain (Garre-Olmo et al, 2010), the United Kingdom (Harvey, Skelton-Robinson, & Rossor, 2003; Mercy, Hodges, Dawson, Barker, & Brayne, 2008; Ratnavalli, Brayne, Dawson, & Hodges, 2002) and the United States (Knopman, Petersen, Edland, Cha, & Rocca, 2004). These data are summarized in Tables 1 and 2.…”

“…Most relied on medical record linkage and coding, a few utilized passive surveillance and disease registries (Borroni et al, 2010; Garre-Olmo et al, 2010; Gilberti et al, 2012), and fewer still recruited and examined subjects (Bernardi et al, 2012; Feldman et al, 2003). This has spawned non-trivial variation in sampling frames and methodologies, as well as in case ascertainment strategies.…”

“…Table 1 shows that prevalence estimates of FTD have varied widely, ranging from 2.0/100,000 in Zuid-Holland (Rosso et al, 2003a) to 31/100,000 in Vallemonica (Gilberti et al, 2012). This wide variation can be explained: many report point-prevalence and some cumulative prevalence; there are differences in the age distribution of FTD; there are also differences in sampling frames and ascertainment methods (thus differences in proportions of missed cases and misclassifications); and there are regional variations in the risk factors for FTD.…”

Cognitive Profile of C9orf72 in Frontotemporal Dementia and Amyotrophic Lateral Sclerosis

“…Regarding the sex distribution of FTD, there is a disagreement, as to whether there is a male predominance [22][23][24][25][26][27]. FTD is further subclassified by symptoms and presentation into two main categories: behavioral variant (bvFTD) and the language variant primary progressive aphasia (PPA) which is further divided into semantic dementia (SD) and progressive nonfluent aphasia (PNFA).…”