We report sex-related differences in the clinical diagnosis of the bvFTD in a large sample of FTD patients from a referral center of neurodegenerative dementias in Catalonia. Importantly, the observed sex-related differences were restricted to the bvFTD. In the bvFTD, women showed a higher frequency of previous psychiatric diagnosis when compared to men. This finding may suggest that women that are diagnosed of bvFTD in our environment receive a previous psychiatric diagnosis more frequently than men. Furthermore, we found lower MMSE at diagnosis in women diagnosed of bvFTD when compared to men. This finding may suggest that women that are finally diagnosed of bvFTD may be referred to our centre at a later disease stage than men. These results underscore a possible bias towards the misdiagnosis of psychiatric illness in the bvFTD, as suggested by a previous study in the United States of America (15).
In our cohort, we found a male predominance restricted to the bvFTD. Then, we analyzed that group using biomarkers classification according to Rascovsky criteria. The proportion of possible bvFTD and highly probable bvFTD was similar to the observed in previous well-characterized cohorts (30).
In booth subgroups (possible and highly probable bvFTD) we found a male predominance. Finally, we found a similar behavioural profile in men and women. Thus, we did not find sex-related differences in the phenotype of the bvFTD in our center. Taken together, these findings suggest a sex-related bias in the identification of bvFTD before the referral of the patients to our center.
It is worth noting that bvFTD symptoms may mimic psychiatric symptoms, leading to psychiatric misdiagnosis (3,4). Family members and doctors that are not familiar with the diagnosis of the bvFTD may overlook the typical change in personality of patients with the bvFTD and misdiagnose bvFTD patients with psychiatric diagnoses. This is a key factor that may contribute to delay the diagnosis of a neurodegenerative disease (31). As mentioned before, our findings regarding a higher frequency of psychiatric misdiagnosis in women with bvFTD agree with those described in other well-characterized cohorts in the United States of America (15). However, it should be noted that unlike previous studies,
14
our study has been carried out in a European population with a public healthcare system and universal access. This is an important difference because in a public system the time from the onset of symptoms to the consultation, the access to the health system and the quality of care received are independent of the patient's socioeconomic level and may decrease healthcare access bias (32).
The MMSE is a useful tool to measure the cognitive impairment in bvFTD, as it has been shown in previous studies (20). The MMSE score was lower in female patients with bvFTD but not in the other presentations. We found higher impairment restricted to highly probable bvFTD subgroup. The time from the estimated symptom onset to diagnosis varied between syndromes. Concretely, we found a higher time to diagnosis in the bvFTD. This finding may suggest a delay in the diagnosis of the bvFTD.
However, this difference was not significant when comparing women and men. We found that the MMSE impairment was not associated with more time to diagnosis in women. Although one might initially presume that MMSE impairment implies a longer time from onset to diagnosis, this hypothesis is contradicted by our data. However, it should be noted that the time from symptom onset to the diagnosis is an estimation that can be influenced by the caregivers’ ability to identify the earliest changes in the patient’s personality. Thus, this estimation can be influenced by several factors escaping out of our control. By the contrary, the MMSE is an objective score widely used by neurologists.
Not all the studies support the existence of sex-related differences in the bvFTD (24). This may be due to socio-cultural factors (many family members do not consider personality change as a disease), factors in the differential diagnosis (diagnosing FTD syndromes may be difficult for physicians and general neurologists), or factors from the patient's neurological study (the lack of use of biomarkers to support the diagnosis). Another possibility is that women may display more aggressive phenotypes of FTD. However, there is no evidence to support this hypothesis in the literature. Taken together, our results highlight the importance of identifying diagnosis biases of FTD. Further studies should specifically address the factors contributing to sex-related differences in the diagnosis of FTD among general neurologist and psychiatrists.
15
The main strength of this study is the deep phenotyping of the patients included. CSF biomarkers ruled out AD in the patients included in this study. Thus, we have low probability of AD misdiagnosis.
Furthermore, in our cohort we considered the wide range of FTD-related syndromes. Finally, our study is the first to assess sex-related differences in the diagnosis of FTD in European population with a public healthcare system.
This study has also some limitations. Although we think that a cross-sectional design is the most feasible way to study sex-related differences in the clinical presentation of FTD, our cohort is made up of patients from a single center. Thus we cannot exclude the possibility of a selection bias (33).
Further multicenter studies are needed to improve our understanding of potential sex-related differences in the diagnosis of FTD in our environment.
In conclusion, the bvFTD is more frequently diagnosed in men in our environment, and women are diagnosed at a more advanced stage with a higher frequency of previous psychiatric diagnosis. In sum, our results suggest that women diagnosed with the bvFTD may be more frequently misdiagnosed with psychiatric conditions in our environment.This work highlights the importance of sex-related biases for the diagnosis of the bvFTD and the need of educational activities to improve the knowledge about FTD among general practitioners and the population in our environment. Further multicenter studies are needed to confirm our observations and disentangle the underpinnings of sex-related biases in the diagnosis of the bvFTD.
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