Frontotemporal dementia in The Netherlands: patient characteristics and prevalence estimates from a population-based study

Abstract

Since 1994, a population-based study of frontotemporal dementia (FTD) in The Netherlands has aimed to ascertain all patients with FTD, and first prevalence estimates based on 74 patients were reported in 1998. Here, we present new prevalence estimates after expansion of our FTD population to 245 patients, with emphasis on the prevalence in the province Zuid-Holland where the main study centre is located. All neurologists and physicians in nursing homes received a yearly postal enquiry about suspected FTD cases. FTD was diagnosed in 245 patients according to the Lund-Manchester criteria, supported by neuroimaging and neuropsychology. tau mutation analysis was performed in a subgroup of 154 patients (63%), and 40 out of 98 patients (41%) who died during follow-up were autopsied during the course of the study. The prevalence of FTD in the province Zuid-Holland was 3.6 per 100,000 at age 50-59 years, 9.4 per 100,000 at age 60-69 years and 3.8 per 100,000 at age 70-79 years. The median age at onset of the 245 patients (51% female) was 58.0 years (range 33-80 years). Dementia in one or more first-degree family members was found in 43% of patients and mutation analysis of the tau gene showed mutations in 34 patients (19 P301L, five L315R, four G272V, four R406W, one Delta K280 and one S320F), all with a positive family history for dementia (14% of the total population, 32% of patients with a positive family history). Pathological findings in the 40 autopsied patients consisted of dementia lacking distinctive histology in 22%, FTD with ubiquitin-positive inclusions in 33%, Pick's disease in 15% and tauopathy in the remaining 30% of patients, with tau mutations identified in more than half of the latter patients. We conclude that the prevalence of FTD in The Netherlands is higher than previously reported, confirming that FTD is more common than was previously thought. The finding of tau mutations in 32% of patients with a positive family history for dementia justifies mutation screening in FTD patients with a positive family history, while tau mutations in non-familiar cases are rare.

Cortical ubiquitin-positive inclusions in frontotemporal dementia without motor neuron disease: a quantitative immunocytochemical study

“…Despite several contributions based on small series, the presence of ubiquitin-related pathology within the cerebral cortex is still considered a rare phenomenon in typical FTD cases [2,6,15,18,21,22,24,34,35,40,47,48]. However, a recent population-based study of FTD in Netherlands indicated that 25% of typical FTD cases displayed ubiquitin-positive inclusions [36]. Our data go beyond these findings in that they indicate that the appearance of ubiquitin-positive inclusions and neurites is an age-unrelated phenomenon, which occurs in the majority of typical FTD cases mainly in the dentate gyrus of the hippocampus and to a lesser degree in the temporal and frontal neocortex.…”

“…This latter form is characterized clinically by the presence of MND with dementia and neuropathologically by the formation of ubiquitin-positive and tau-negative intraneuronal inclusions in hippocampus and subcortical structures [3,7,9,11,27,31,42,46]. However, ubiquitin-positive intraneuronal inclusions and dendrites have also been reported in familial [6,20,24,35] and in a few sporadic FTD cases in the absence of MND [2,15,18,21,22,36,40,47,48] as well as in FTDP-17 cases [17,28,35]. These observations question the specificity of ubiquitin-positive inclusions and their clinical relevance in the context of FTD.…”

Diagnostic utility of ASL‐MRI and FDG‐PET in the behavioral variant of FTD and AD

“…With an estimated prevalence of 15/100,000 in the age group of 45–64 years, FTLD represents a significant challenge for social welfare 1, 3. FTLD can present with a variety of syndromes, including progressive supranuclear palsy, corticobasal degeneration, and progressive aphasia, but the most common presentation is progressive change in personality with abnormalities in socioemotional behavior, referred to as the behavioral variant of frontotemporal dementia (bvFTD) 4.…”

Mutations other than null mutations producing a pathogenic loss of progranulin in frontotemporal dementia

“…Up to 50% of FTD patients have a positive family history of dementia, mainly with autosomal dominant inheritance [Chow et al, 1999;Poorkaj et al, 2001;Rosso et al, 2003]. The majority of FTD families have been linked to chromosome 17q21.…”