Search

Alzheimer’s disease (AD) and frontotemporal dementia (FTD) are the most common causes of early-onset dementia (EOD). The epidemiology and genetic etiology of EOD are rather unknown. The main genetic causes of AD and FTD are mutations in the APP, PSEN1, PSEN2, MAPT and GRN genes and the hexanucleotide repeat expansion of C9orf72, which is the main genetic cause of FTD in Finland. However, autosomal dominant mutations explain only a minority of familial EOD cases, whereas rare and low-frequency gene variants related to neurodegenerative diseases increase the risk of EOD and may be involved in the etiology of EOD. The epidemiology of FTD in Northern Ostrobothnia, Finland, was determined using the hospital discharge register from Oulu University Hospital and the population statistics for 2006–2010. The genes previously associated with AD, FTD and PD were screened from the EOD patients (n=39) with familial dementia, atypical onset or rapidly progressive disease using next-generation sequencing. The presence of C9orf72 repeat expansion was excluded. The rare and low-frequency variants of genes related to PD were screened in an additional large EOD cohort (n=279). The five-year incidence of FTD was 5.5/100000 in 2006–2010, with a prevalence of 20.5/100000 (age group of 45–65 years). Two pathogenic mutations, PSEN1 p.His163Arg and MAPT p.Arg406Trp, were identified from the selected EOD cohort (n=39). The possible risk-increasing variants of PSEN1, PSEN2, TREM2, BIN1, APP, UBQLN2, GRN, MAPT, TMEM106B, LRRK2, SNCAIP, PARK2 and GBA were identified. After excluding two patients with pathogenic PSEN1 and MAPT mutations, 24% (n=9) of the remaining cohort (n=37) and 15% (n=47) of all screened EOD patients (n=316) carried rare, low-frequency variants of PD-related genes. This research adds to the literature on the epidemiology of FTD and the genetics of EOD. The incidence and prevalence of FTD in Finland are high compared to other countries worldwide. Screening for pathoge, Tiivistelmä Alzheimerin tauti (AT) ja otsa-ohimolohkorappeuma (frontotemporal dementia, FTD) ovat kaksi yleisintä varhain (alle 65-vuotiaana) alkavaa muistisairautta. Näiden epidemiologiaa on tutkittu vähän. Suomessa otsa-ohimolohkorappeuman yleisin tunnettu geneettinen syy on C9orf72 toistojakson laajentuma. Autosomissa dominantisti periytyvien tekijöiden lisäksi lukuisien väestössä harvinaisten geenivarianttien on viime vuosina osoitettu lisäävän muistisairauksien riskiä. Kuitenkin yhä merkittävä osa sairastuneista jää ilman geneettistä selitystä, vaikka sukuhistoriakin puoltaisi perinnöllistä sairautta. Otsa-ohimolohkorappeumien ilmaantuvuus ja esiintyvyys tutkittiin käyttäen Oulun yliopistollisen sairaalan hoidonpäättämisrekisteriä vuosilta 2006–2010. Tunnetut AT:iin, otsa-ohimolohkorappeumiin sekä Parkinsonin tautiin (PT) liitetyt geenit tutkittiin tarkkaan valikoidusta varhain alkavaa muistisairautta sairastavien potilaiden kohortista (n=39) käyttäen uuden sukupolven sekvensointia (next generation sequencing, NGS). C9orf72 toistojaksomutaation kantajat oli poissuljettu. Kohortista löydetyt PT:iin liitettyjen geenien variantit seulottiin lisäksi valikoimattomilta varhain alkavaa muistisairautta sairastavilta potilailta (n=279). Otsa-ohimolohkorappeumien viiden vuoden ilmaantuvuus 45–65-vuotiaiden ikäryhmässä oli 5.5/100000 ja esiintyvyys 20.5/100000. Valikoidusta kohortista löydettiin kaksi tautia aiheuttavaa mutaatiota (PSEN1 p.His163Arg ja MAPT p.Arg406Trp). Harvinaisia variantteja todettiin geeneissä PSEN1, PSEN2, TREM2, BIN1, APP, UBQLN2, GRN, MAPT, TMEM106B, LRRK2, SNCAIP, PARK2 ja GBA. PT:iin liitettyjen geenien variantteja ilmeni enemmän valikoiduilla kuin kaikilla seulotuilla potilailla (24 % vs. 15 %). Otsa-ohimolohkorappeumien ilmaantuvuus ja esiintyvyys Pohjois-Pohjanmaalla ovat korkeita verrattuna aiemmin maailmalla kuvattuihin tuloksiin. Tautia aiheuttavia mutaatioita löytyy nuorilta, valikoiduilta potilailta. Patogeeniset PSEN1 ja MAPT mutaatiot l

Background: Fatigue is a prominent and disabling symptom of multiple sclerosis (MS), impairing quality of life. The disease course of relapsing remitting MS (RRMS) is individual. Objectives: We aimed to study the effects of demographic and clinical characteristics, as well as lifestyle risk factors on experienced fatigue and health-related quality of life (HRQoL) among RRMS patients, comparing benign and severe disease types. Methods: Altogether 198 Finnish RRMS patients were recruited for this real-life cross-sectional study. Self-reported questionnaires were used to evaluate fatigue and HRQoL by using Fatigue Scale for Motor and Cognitive Functions and 15D health-related quality of life questionnaires. Patients were categorized into subgroups based on the current disability status measured by the Expanded Disability Status Scale (EDSS) cut-off value of 4.5, and by retrospective clinical course divided into benign and aggressive RRMS. Results: All in all, 73% of the RRMS patients suffered from fatigue. Lower HRQoL had a strong correlation with more prominent fatigue (r = -0.719). Higher EDSS was associated with more prominent fatigue and lower HRQoL in the whole RRMS cohort. Older age at the disease onset was associated with more prominent fatigue and decreased HRQoL in the groups of aggressive RRMS and EDSS > 4.5. In the groups of EDSS ≤ 4.5 and benign RRMS, a higher number of used disease-modifying treatments (DMTs) was associated with more pronounced fatigue and reduced HRQoL. In addition, higher BMI was associated with lower HRQoL in patients with benign RRMS. Side effects (45 %) and lack of efficacy (26 %) were the most common reasons for discontinuing a DMT. Cessation due to side effects was the only reason that was significantly associated with more prominent fatigue and lower HRQoL. Use of nicotine products, gender, or disease duration were not associated with fatigue or HRQoL. Conclusions: Individuals with severe RRMS and higher EDSS scores are

Tiivistelmä Väestön vanhetessa muistisairauksien varhaiseen tunnistamiseen perusterveydenhuollossa tarvitaan paljon lisää resursseja. Kognitiivinen tehtäväsarja CERAD on osoittautunut hyvin toimivaksi välineeksi Alzheimerin taudin ensivaiheen arvioinnissa. Koulutus ja ikä vaikuttavat kognitiivisissa testeissä suoriutumiseen, joten ne on tärkeää huomioida tulosten tulkinnassa. Tehtäväsarjaan on päivitetty koulutustason huomioivat katkaisurajat sekä uutena kokonaispistemäärän käyttö.

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. Conclusions: 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.

Background: Currently, there are few studies considering possible modifiable risk factors of frontotemporal dementia (FTD). Objectives: 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). Conclusions: 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.