What is it?
Frontotemporal dementia is a disorder of the frontal lobes and includes what was known as primary progressive aphasia. Although it occurs far less often than Alzheimer's disease, among dementia sufferers younger than 65 it is estimated to occur at about the same rate. In other words, frontotemporal dementia is, unlike the most common dementias, not a disorder of age. Most sufferers become symptomatic in their 50s and 60s.
Frontotemporal dementia generally begins with a focal symptom, such as aphasia, before (usually a number of years later) progressing to more generalized dementia.
There are several types of frontotemporal dementia. The most common (around 60% of FTD cases) is known as the behavioral variant (also, Pick's disease). This is characterized by impairment in social and emotional skills. The other 40% of FTD cases have language impairments -- about half of these suffer from semantic FTD, characterized by difficulties in remembering the meanings of words; the other half suffer from progressive nonfluent aphasia, characterized by difficulties in producing language (although they understand what they're trying to say).
In around 15% of FTD cases (most usually the behavioral variant), motor neurone disease also develops.
A large-scale epidemiological study1 in the Netherlands indicated frontotemporal dementia occurs at a rate of 1.1 per 100,000, with the prevalence highest among those ages 60 to 69, at 9.4 per 100,000. The prevalence among people ages 45 to 64 was estimated to be 6.7 per 100,000 (this was after autopsies caused the number of diagnosed cases to go up, with 17 of 50 patients undiagnosed in life). Unlike other forms of dementia, where most occurrences begin in older adults, symptoms began after age 65 in only 22% of patients. The median age of onset was 58, with a range from 33 to 80.
A family history of dementia was present in 43% of patients. Interestingly, whites accounted for 99% of all cases despite an ample nonwhite population.
A large U.K. study2 found prevalences of early-onset FTD and Alzheimer's were the same in the 45-64 population: 15 per 100,000. The mean age at onset of FTD was 52.8 years and there was a striking male preponderance (14:3).
This rate is notably higher than that found in the Dutch study, and it has been suggested that the reason is ethnicity -- the Dutch study, as mentioned, had a significant proportion of non-Caucasians, while the British (Cambridge) study explicitly mentioned that minorities were under-represented.
It has been estimated that frontotemporal dementia accounts for approximately 8% of patients with dementia, but this is now thought to be an underestimation.
Genes as a factor
There is a high level of genetic involvement in this type of dementia.
As mentioned, the Dutch study found a family history of dementia in 43% of FTD patients. Another large Dutch study3 found 38% of FTD patients had one or more first-degree relatives with dementia before age 80 compared to 15% of age-matched controls; 10% had two or more first-degree relatives with dementia compared with 0.9% of the controls. FTD patients were also three times more likely to have 2 "Alzheimer's genes" (2 e4 alleles of the ApoE gene) than the controls: 7% vs 2.3%.
This study also supports findings with other dementias that earlier-onset is more likely to have genetic causes. First-degree relatives of FTD patients (who had twice the risk of dementia before age 80 compared with relatives of controls) were much more likely to develop dementia early: age of onset of dementia in affected first-degree relatives of FTD patients averaged was just under 61, compared to 72.3 for affected first-degree relatives of controls.
The genes implicated in familial cases of FTD are on chromosome 17, in the gene for the tau protein, and in the gene for the progranulin protein. Research4 has now confirmed that people with these hereditable defects produce only half of the normal amount of progranulin, and recently a simple test for measuring the quantity of progranulin in the blood was developed. The test reveals whether someone has the mutations that carry an increased risk of FTD.
A recent study5 involving 225 FTD patients found 41.8% of patients had some family history, although only 10.2% had a clear autosomal dominant history (at least 3 cases within the last 2 generations). However, the importance of genes varied across the different clinical subtypes of the disease, with the behavioral variant being the most heritable and FTD–motor neuron disease and the language syndromes (particularly semantic dementia) the least heritable.
For more information:
- Rosso, S.M. et al. 2003. Frontotemporal dementia in The Netherlands: Patient characteristics and prevalence estimates from a population-based study. Brain, 126, 2016-22. Full text available at http://brain.oxfordjournals.org/cgi/content/full/126/9/2016
- Ratnavalli, E., Brayne, C., Dawson, K. & Hodges, J.R. 2002. The prevalence of frontotemporal dementia. Neurology, 58, 1615-1621.
- Stevens, M. et al. 1998. Familial aggregation in frontotemporal dementia. Neurology, 50(6), 1541-5.
- Sleegers, K. et al. 2009. Serum biomarker for progranulin-associated frontotemporal lobar degeneration. Annals of Neurology, Published online March 13.
- Rohrer, J.D. et al. 2009. The heritability and genetics of frontotemporal lobar degeneration. Neurology, 73(18), 1451-1456.