Incidence and Prevalence of Early-Onset Dementia in Finland.

OBJECTIVES: Current epidemiologic data of early-onset dementia (EOD), characterized by the onset of the disease before the age of 65, are notably scarce. METHODS: We evaluated the incidence (from January 2010 to December 2021) and prevalence (on December 31, 2021) of EOD and its subtypes in 2 defined areas in Finland. All visits at the dementia outpatient clinics were manually retrospectively reviewed and reassessed (N = 12,490). RESULTS: In the population aged ≤65 years, crude incidence of EOD was 12.3/100,000 persons at risk/year based on 794 new cases from January 1, 2010, to December 31, 2021. Incidence rates for EOD were 20.5 and 33.7 per 100,000 person years in the age group of 30-64 and 45-64 years, respectively. The prevalence of EOD was 110.4 in the age group of 30-64 years and 190.3 in the age group 45-64. Alzheimer disease (AD) (48.2%) and behavioral variant frontotemporal dementia (12.7%) were the most frequent subtypes. The incidence of AD increased during the follow-up, whereas incidence of other forms of EOD remained stable. DISCUSSION: We found higher incidence rates of EOD than previously reported. Unlike other forms of EOD, the incidence of early-onset AD seems to be increasing.

Psychopharmacological Medication Use in Frontotemporal Dementia at the Time of Diagnosis: Comparison with Alzheimer's Disease.

BACKGROUND: Due to the significant presence of neuropsychiatric symptoms in patients with frontotemporal dementia (FTD) spectrum disorders, psychiatric misdiagnoses, diagnostic delay, and use of psychiatric treatments are common prior to the FTD diagnosis. Furthermore, treatment of diagnosed FTD patients mainly relies on off-label psychopharmacological approaches. Currently, limited real-world data are available regarding the actual use of psychopharmacological medications in FTD. OBJECTIVE: To evaluate psychopharmacological medication use at the time of FTD diagnosis. METHODS: Psychopharmacological medication use was evaluated in a Finnish FTD cohort containing 222 FTD patients, including the major clinical disease phenotypes (behavioral, language, and motor variants) and genetic patients carrying the C9orf72 repeat expansion. A cohort of 214 Alzheimer's disease (AD) patients was used as a neurodegenerative disease reference group. RESULTS: Active use of psychopharmacological medications at the time of diagnosis was significantly more common in FTD compared to AD, especially in the case of antidepressants (26.1% versus 15.0%, OR = 2.01, p = 0.008), antipsychotics (23.9% versus 9.3%, OR = 3.15, p < 0.001), and mood-stabilizers (6.3% versus 1.9%, OR = 2.93, p = 0.085; not statistically significant), whereas the use of cholinesterase inhibitors or memantine was nearly nonexistent in FTD patients. Female gender and behavioral variant of FTD phenotype alongside with depressive and psychotic symptoms were the most prominent factors associating with the use of these medications among the FTD spectrum patients. CONCLUSION: Use of off-label psychopharmacological medication and polypharmacy is substantially common at the time of FTD diagnosis. This likely reflects the challenges in using symptom-driven treatment approaches, especially prior to the eventual diagnosis.

Traumatic Brain Injury Associates with an Earlier Onset in Sporadic Frontotemporal Dementia.

BACKGROUND: Currently, there are few studies considering possible modifiable risk factors of frontotemporal dementia (FTD). OBJECTIVE: In this retrospective case-control study, we evaluated whether a history of traumatic brain injury (TBI) associates with a diagnosis of FTD or modulates the clinical phenotype or onset age in FTD patients. METHODS: We compared the prevalence of prior TBI between individuals with FTD (N = 218) and age and sex-matched AD patients (N = 214) or healthy controls (HC; N = 100). Based on the patient records, an individual was categorized to the TBI+ group if they were reported to have suffered from TBI during lifetime. The possible associations of TBI with age of onset and disease duration were also evaluated in the whole FTD patient group or separately in the sporadic and genetic FTD groups. RESULTS: The prevalence of previous TBI was the highest in the FTD group (19.3%) when compared to the AD group (13.1%, p = 0.050) or HC group (12%, p = 0.108, not significant). Preceding TBI was more often associated with the sporadic FTD cases than the C9orf72 repeat expansion-carrying FTD cases (p = 0.003). Furthermore, comparison of the TBI+ and TBI- FTD groups indicated that previous TBI was associated with an earlier onset age in the FTD patients (B = 3.066, p = 0.010). CONCLUSION: A preceding TBI associates especially with sporadic FTD and with earlier onset of symptoms. The results of this study suggest that TBI may be a triggering factor for the neurodegenerative processes in FTD. However, understanding the precise underlying mechanisms still needs further studies.

Modifiable potential risk factors in familial and sporadic frontotemporal dementia.

OBJECTIVE: Only a few studies have evaluated modifiable risk factors for frontotemporal dementia (FTD). Here, we evaluated several modifiable factors and their association with disease phenotype, genotype, and prognosis in a large study population including Finnish and Italian patients with FTD and control groups. METHODS: In this case-control study, we compared the presence of several cardiovascular and other lifestyle-related diseases and education between Finnish and Italian patients with familial (n = 376) and sporadic (n = 654) FTD, between different phenotypes of FTD, and between a subgroup of Finnish FTD patients (n = 221) and matched Finnish patients with Alzheimer's disease (AD) (n = 214) and cognitively healthy controls (HC) (n = 100). RESULTS: Patients with sporadic FTD were less educated (p = 0.042, B = -0.560, 95% CI -1.101 to -0.019) and had more heart diseases (p < 0.001, OR = 2.265, 95% CI 1.502-3.417) compared to patients with familial FTD. Finnish FTD patients were less educated (p = 0.032, B = 0.755, 95% CI 0.064-1.466) compared with AD patients. The Finnish FTD group showed lower prevalence of hypertension than the HC group (p = 0.003, OR = 2.162, 95% CI 1.304-3.583) and lower prevalence of hypercholesterolemia than in the HC group (p < 0.001, OR = 2.648, 95%CI 1.548-4.531) or in the AD group (p < 0.001, OR = 1.995, 95% CI 1.333-2.986). Within the FTD group, clinical phenotypes also differed regarding education and lifestyle-related factors. INTERPRETATION: Our study suggests distinct profiles of several modifiable factors in the FTD group depending on the phenotype and familial inheritance history and that especially sporadic FTD may be associated with modifiable risk factors.