Prevalence, characteristics, and survival of frontotemporal lobar degeneration syndromes

Abstract

Objectives: To estimate the lifetime risk, prevalence, incidence, and mortality of the principal clinical syndromes associated with frontotemporal lobar degeneration (FTLD) using revised diagnostic criteria and including intermediate clinical phenotypes.

Methods: Multisource referral over 2 years to identify all diagnosed or suspected cases of frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), or corticobasal syndrome (CBS) in 2 UK counties (population 1.69 million). Diagnostic confirmation used current consensus diagnostic criteria after interview and reexamination. Results were adjusted to the 2013 European standard population.

Results: The prevalence of FTD, PSP, and CBS was 10.8/100,000. The incidence and mortality were very similar, at 1.61/100,000 and 1.56/100,000 person-years, respectively. The estimated lifetime risk is 1 in 742. Survival following diagnosis varied widely: from PSP 2.9 years to semantic variant FTD 9.1 years. Age-adjusted prevalence peaked between 65 and 69 years at 42.6/100,000: the age-adjusted prevalence for persons older than 65 years is double the prevalence for those between 40 and 64 years. Fifteen percent of those screened had a relevant genetic mutation.

Conclusions: Key features of this study include the revised diagnostic criteria with improved specificity and sensitivity, an unrestricted age range, and simultaneous assessment of multiple FTLD syndromes. The prevalence of FTD, PSP, and CBS increases beyond 65 years, with frequent genetic causes. The time from onset to diagnosis and from diagnosis to death varies widely among syndromes, emphasizing the challenge and importance of accurate and timely diagnosis. A high index of suspicion for FTLD syndromes is required by clinicians, even for older patients.

Figure 1. Prevalence of FTLD-associated syndromes

(A) The local authorities in England, with enlargement of the PiPPIN catchment area in the East of England. The asterisks mark the 2 cities (Norfolk and Cambridge) within the catchment area. The color code indicates crude prevalence rates of FTLD-associated clinical syndromes for each local authority. (B) Crude prevalence rates for the major FTLD-associated syndromes by age and (C) by age and syndrome. (D) Total number of prevalence cases for each syndrome. bvFTD = behavioral variant frontotemporal dementia; CBS = corticobasal syndrome; FTLD = frontotemporal lobar degeneration; nfvPPA = nonfluent agrammatic variant primary progressive aphasia; other PPA = other primary progressive aphasia; PiPPIN = Pick's Disease and Progressive Supranuclear Palsy: Prevalence and Incidence; PSP = progressive supranuclear palsy; svPPA = semantic variant primary progressive aphasia. (A) Contains National Statistics data © Crown copyright and database right [2013]; contains Ordnance Survey data © Crown copyright and database right [2013].

Figure 2. Survival with FTLD-associated syndromes

Mean duration from the onset of symptoms to the diagnosis of a neurodegenerative disorder (blue); to the specific diagnosis of an FTLD-associated syndrome (gold); and to death (green) for all 60 patients who have died since the start of the PiPPIN Study. Inserted figures indicate the mean duration of each phase for each syndrome and all patients combined. bvFTD = behavioral variant frontotemporal dementia; CBS = corticobasal syndrome; FTLD = frontotemporal lobar degeneration; nfvPPA = nonfluent agrammatic variant primary progressive aphasia; PSP = progressive supranuclear palsy; svPPA = semantic variant primary progressive aphasia.

Figure 3. Incidence of FTLD-associated syndromes

(A) Incidence of FTLD-associated syndromes by age at onset (green bars) and by age at diagnosis (blue bars). (B) Distribution of incident cases by clinical syndrome (n = 53). bvFTD = behavioral variant frontotemporal dementia; CBS = corticobasal syndrome; FTLD = frontotemporal lobar degeneration; nfvPPA = nonfluent agrammatic variant primary progressive aphasia; other PPA = other primary progressive aphasia logopenic variant (n = 2) and unclassifiable (n = 2); PSP = progressive supranuclear palsy; svPPA = semantic variant primary progressive aphasia.