The incidence estimates for CS-FTLD were clustered in a tight range, but the prevalence estimates differed by a factor of 10. We believe that the low estimates of prevalence (Rosso et al. 2003
; Ikejima et al. 2009
) resulted from insensitive diagnostic criteria and inadequate recognition. Indeed, the studies that reported lower prevalence estimates were ones that used the older 1994 criteria (The Lund and Manchester Groups 1994
). It is possible that the very high estimates of prevalence in persons over age 65 years in some studies (Borroni et al. 2010
; Garre-Olmo et al. 2010
) do not reflect neuropathological FTLD and therefore represent an overdiagnosis of bvFTD. Neuropathological studies typified by the large multicenter study (Rascovsky et al. 2011
) simply do not support the contention that most FTLDs occur in persons over age 65. Based on the best available data, we believe that the most plausible figures are that roughly 60% of CS-FTLD occurs in the 45–64-year-old age range, and that the prevalence of CS-FTLD is 15–22 per 100,000 in that age range.
Because of the rarity of PPA and bvFTD, none of the studies reviewed here employed active case detection methods. Instead, they all relied on passive surveillance and case detection by medical record review. The basis for claiming that a prevalence or incidence could be calculated was that each study was able to define a geographic catchment area for their case review and claim that any case of FTLD in a resident of the catchment region that was diagnosed would have been captured by their methodology.
The main threat to the validity of these observations is the accuracy of clinical diagnoses. Undercounting of cases is a distinct possibility because the clinical detection of bvFTD or PPA requires a level of expertise in behavioral neurology that is possessed by few neurologists and even fewer non-neurologists. We believe that the very low estimate of CS-FTLD prevalence from Ibaraki, Japan (Ikejima et al. 2009
) reflected the use of insensitive diagnostic criteria for, and, simultaneously, a limited awareness of, the clinical syndromes of FTLD in the practitioners in Ibaraki.
Overdiagnosis and misclassification of bvFTD or PPA are also possible and could occur if some of the cases that were labeled clinically as bvFTD or PPA were actually due to the pathology of Alzheimer’s disease, Lewy body disease, or cerebrovascular disease. A number of the behavioral features of bvFTD may occur in the dementia of AD or in dementia with Lewy bodies. AD pathology sometimes occurs in persons diagnosed clinically with bvFTD or PPA (Mesulam et al. 2008
; Forman et al. 2006
; Davies et al. 2005
; Hodges et al. 2004
; Knopman et al. 2005
It is not possible to estimate quantitatively the extent of under- or overdiagnosis of CS-FTLD syndromes. To resolve both misclassification problems, very large, longitudinal clinical–pathological studies would be required that were free of biases during recruitment that would compromise the estimates. Patients with dementia of any presumed etiology would have to be recruited and followed to death and autopsy confirmation of diagnosis.
The similarities in prevalence and incidence of CS-FTLD syndromes and Alzheimer’s disease (AD) in younger persons are notable. Our estimates of CS-FTLD prevalence are lower than a prevalence of AD of 35 per 100,000 in the 45–64-year age range in London, UK (Harvey et al. 2003
). Unlike any of the other studies, the Japanese study found the prevalence of vascular dementia exceeded that of dementia due to AD, 38.6 vs. 22.3 per 100,000 persons in the 45–64-year age range (Ikejima et al. 2009
Each of the incidence studies (Knopman et al. 2004
; Mercy et al. 2008
; Garre-Olmo et al. 2010
) also analyzed cases of dementia due to AD. Incidence rates of CS-FTLD were similar to rates observed for AD: 4.2 per 100,000 person-years in 45–64 year olds in Cambridge (Mercy et al. 2008
) and 5.7 per 100,000 person-years in 30–64 year olds in Girona (Garre-Olmo et al. 2010
). The Rochester, MN study found that CS-FTLD and AD incidence rates were identical in 50–59 year olds; in contrast, the incidence of AD considerably exceeded CS-FTLD in the 60–69-year-old age range (88.9 for AD versus 8.9 per 100,000 person-years for CS-FTLD) (Knopman et al. 2004
A study of progressive supranuclear palsy from the UK reported a prevalence rate of 25 per 100,000 in a population of 55 years and older, a value similar to our estimate of CS-FTLD (Nath et al. 2001
). The incidence of ALS in three European countries in the 65–84-year-old age range was greater than five new cases per 100,000 person-years (Logroscino et al. 2010
), higher than the peak rate for CS-FTLD reported in the three incidence studies described above.
In summary, our review of these studies suggests that prevalence rates of CS-FTLD range between 15 and 22 per 100,000, incidence rates are between 2.7 and 4.0 per 100,000 person-years, and between 20,000 and 30,000 persons in the USA have CS-FTLD.