Discussion
Our literature review demonstrates that few studies have examined modifiable risk factors for frontotemporal dementia (4, 5). It is important to note that early symptoms of frontotemporal dementia may include impulsive and disinhibited behaviour leading to, for example, hyperorality, with increased consumption of carbohydrate-rich foods in particular, or increased use of alcohol and tobacco (1, 3). Little is known about the length of the prodromal phase in frontotemporal dementia, but studies show that it may take up to five years from the initial examination for a diagnosis to be made (8).
The study showing that patients with frontotemporal dementia are younger and have higher educational levels than patients with Alzheimer's disease, used persons with other dementia disorders as controls. This may result in selection bias owing to differences in age of onset between the disorders (19). Another source of bias must also be considered: Higher education is more common among younger persons than among older generations, and frontotemporal dementia often affects younger individuals.
In terms of cardiovascular risk factors, a significant association was found between frontotemporal dementia and type 2 diabetes in one study (16), and between smoking, overweight and frontotemporal dementia in another (22). In case-control studies, overweight and smoking may be viewed as modifiable risk factors for frontotemporal dementia, but they may also form part of the prodromal phase.
There are conflicting findings in two studies regarding the status of hypertension as a risk factor: Kalkonde et al. found a fairly similar prevalence of hypertension in patients with frontotemporal dementia versus other forms of dementia (17), whereas Atkins et al., who included a cohort of individuals with early-stage frontotemporal dementia and a control group with early-stage Alzheimer's disease, found hypertension to be more common in Alzheimer's disease (22). One reason for the divergent findings may be that one of the studies used a younger disease cohort and a younger control group.
Three studies show that head injury increases the risk of developing frontotemporal dementia. One of these studies featured a markedly larger disease cohort than all of the other studies we identified, with 1 016 persons with frontotemporal dementia (21). Head injury is thus the most studied risk factor, but two of the studies have small sample sizes and all three use different definitions of head injury. One study found an association between autoimmune disease and the semantic variant of primary progressive aphasia (20). This study includes no control variables in terms of other diseases or lifestyle variables, which should be considered a weakness. It is unclear whether there is an association between systemic autoimmune disease and frontotemporal dementia.