| 1. |
- Cui, Can, et al.
(författare)
-
Associations between autoimmune diseases and amyotrophic lateral sclerosis : a register-based study
- 2021
-
Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Informa Healthcare. - 2167-8421 .- 2167-9223. ; 22:3-4, s. 211-219
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the associations of 43 autoimmune diseases with the subsequent risk of ALS and further evaluate the contribution of familial confounding to these associations.Methods: We conducted a nationwide register-based nested case-control study including 3561 ALS patients diagnosed during 1990-2013 in Sweden and 35,610 controls that were randomly selected from the general population and individually matched to the cases on age, sex, and county of birth. To evaluate the contribution of familial factors on the studied association, we additionally studied the first-degree relatives (siblings and children) of ALS patients and their controls.Results: Patients with ALS had a 47% higher risk of being previously diagnosed with autoimmune disease (OR 1.47, 95% confidence interval [CI] 1.31-1.64), compared with controls. A positive association was noted for several autoimmune diseases, including myasthenia gravis, polymyositis or dermatomyositis, Guillain-Barre syndrome, type 1 diabetes diagnosed younger than 30 years, multiple sclerosis, and hypothyreosis. The increased risk of any autoimmune disease was greatest during the year before ALS diagnosis, likely due to misdiagnosis. A statistically significantly increased risk was also noted during 2-5 years, but not earlier, before ALS diagnosis. First-degree relatives of ALS patients had however no increased risk of autoimmune diseases compared with first-degree relatives of controls.Conclusions: Although it is difficult to completely remove the potential effects of misdiagnosis, there is likely a positive association between autoimmune disease (such as type 1 diabetes and multiple sclerosis) and ALS, which is not fully explained by shared familial confounding factors.
|
|
| 2. |
- Englund, Simon, et al.
(författare)
-
Predictors of patient-reported fatigue symptom severity in a nationwide multiple sclerosis cohort
- 2023
-
Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier. - 2211-0348 .- 2211-0356. ; 70
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Fatigue is a debilitating symptom of multiple sclerosis (MS), but its relation to sociodemographic and disease-related characteristics has not been investigated in larger studies. The objectives of this study were to evaluate predictors of self-reported fatigue in a Swedish nationwide register-based MS cohort.METHODS: Using a repeated cross-sectional design, we included 2,165 persons with relapsing- remitting and secondary progressive MS with one or multiple Fatigue Scale for Motor and Cognitive Functions (FSMC) scores, which was modelled using multivariable linear regressions for multiple predictors.RESULTS: Only associations to expanded disability status scale (EDSS) and Symbol Digit Modalities Test (SDMT) were considered clinically meaningful among MS-associated characteristics in our main model; compared to mild disability (EDSS 0-2.5), those with severe disability (EDSS ≥6) scored 17.6 (95% CI 13.1-22.2) FSMC points higher, while the difference was 10.7 (95% CI 8.0-13.4) points for the highest and lowest quartiles of SDMT. Differences between highest and lowest quartiles of health-related quality of life (HRQoL) instruments were even greater and considered clinically meaningful; EuroQoL Visual Analogue Scale (EQ-VAS) 31.9 (95% CI 29.9-33.8), Multiple Sclerosis Impact Scale (MSIS-29) psychological component 35.6 (95% CI 33.8-37.4) and MSIS-29 physical component 45.5 (95% CI 43.7-47.4).CONCLUSION: Higher self-reported fatigue is associated with higher disability level and worse cognitive processing speed, while associations to other MS-associated characteristics including MS type, line of disease modifying therapy (DMT), MS duration, relapse and new cerebral lesions are weak. Furthermore, we found a strong correlation between high fatigue rating and lower ratings on health-related quality of life instruments.
|
|
| 3. |
- Kläppe, Ulf, et al.
(författare)
-
Mortality among family members of patients with amyotrophic lateral sclerosis : a Swedish register-based study
- 2022
-
Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Informa Healthcare. - 2167-8421 .- 2167-9223. ; 23:3-4, s. 226-235
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To test two hypotheses: (1) partners of ALS patients have higher mortality due to outcomes related to psychological distress, and (2) parents and siblings of ALS patients have higher mortality due to diseases that co-occur with ALS.Methods: We performed a nationwide, register-based cohort study in Sweden. We included ALS-free partners, biological parents and full siblings (N = 11,704) of ALS patients, as well as ALS-free partners, biological parents and full siblings (N = 14,460,150) of ALS-free individuals, and followed them during 1961-2013. Hazard ratios (HRs) and 95% confidence intervals (CIs) of overall and cause-specific mortality were derived from Cox regression.Results: Partners of ALS patients, compared to partners of ALS-free individuals, displayed higher mortality due to external causes (HR 2.14; 95% CI 1.35-3.41), including suicide (HR 2.44; 95% CI 1.09-5.44) and accidents (HR 2.09; 95% CI 1.12-3.90), after diagnosis of the ALS patients. Parents of ALS patients had a slightly higher overall mortality (HR 1.03; 95% CI 1.00-1.07), compared with parents of ALS-free individuals. This was driven by mortality due to dementias and cardiovascular, respiratory, and skin diseases. Parents of ALS patients had, however, lower mortality than parents of ALS-free individuals due to neoplasms. Siblings of ALS patients had higher mortality due to dementias, and digestive and skin diseases.Conclusions: Increased mortality due to suicide and accidents among partners of ALS patients is likely attributable to severe psychological distress following the ALS diagnosis. Increased mortality due to dementias among parents and full siblings of ALS patients suggests shared mechanisms between neurodegenerative diseases.
|
|
| 4. |
- Longinetti, Elisa
(författare)
-
Amyotrophic lateral sclerosis and multiple sclerosis associated neuroinflammation : nationwide epidemiological studies on etiology, comorbidities, and treatment
- 2019
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Amyotrophic lateral sclerosis (ALS) is a relatively rare but fatal neurodegenerative disease characterized by progressive muscle paralysis, due to loss of upper and lower motor neurons. Signs of neuroinflammation have been reported in ALS, however it is still unknown whether neuroinflammation is a cause or a consequence of the motor neuron dysfunction. Neuroinflammation may also be one of the mechanisms underlying the overlap between ALS and other neurological, neuromuscular, and psychiatric disorders. Among neuromuscular disorders, the most studied disorder in association with ALS is multiple sclerosis (MS). MS is a complex disease of the central nervous system (CNS) characterized by chronic inflammation, demyelination, and neurodegeneration. A link between MS and psychiatric disorders has also been proposed. In this thesis we explored the associations of different correlates of neuroinflammation, including physical and cognitive fitness in early life (Study I), neurodegenerative and psychiatric disorders (Study II), neuromuscular diseases (Study III), depression and antidepressants use (Study IV) with the risks of either ALS or MS. In Study I, we investigated the association between physical and cognitive fitness in young adulthood with future risk of ALS. The study population included 1,838,376 Swedish men aged 17-20. Information on physical fitness, body mass index (BMI), intelligence quotient (IQ), and stress resilience was retrieved from the Swedish Conscription Register between 1968 and 2010. Information on subsequent ALS diagnosis was retrieved from the Swedish Patient Register. There were 439 incident cases of ALS during follow-up. Higher physical fitness was associated with an increased risk of ALS before age 45, while higher BMI tended to be associated with a lower risk of ALS at all ages. Higher IQ was associated with an increased risk of ALS at age 56 and onwards, whereas higher stress resilience was associated with a lower risk of ALS at age 55 and earlier. These results indicate that physical fitness, BMI, IQ, and stress resilience in young adulthood are associated with the development of early onset ALS. In Study II, we examined the risk of neurodegenerative and psychiatric disorders among individuals with ALS, compared to individuals free of the disease. The study population included 3,648 individuals with ALS and 36,480 age-, sex-, and county-of-birth-matched controls from the general population. In addition, we estimated the risk of neurodegenerative and psychiatric diseases among the relatives of ALS patients, compared to the relatives of the controls, to assess the potential contribution of familial factors. Individuals with previous neurodegenerative or psychiatric diseases had an increased risk of ALS, compared to individuals who did not have these diseases. After diagnosis, ALS patients had increased risks of neurodegenerative or psychiatric diseases, compared to individuals free of ALS. First-degree relatives of individuals with ALS had higher risk of neurodegenerative diseases compared to relatives of controls. Children of ALS patients had higher risk of psychiatric disorders, compared to children of controls. The increased risk of neurodegenerative disorders among relatives of ALS patients may be attributable to the overlapping etiopathogenesis of different neurodegenerative diseases. The increased risk of psychiatric disorders among ALS patients and their children may be due to non-motor symptoms of ALS or a severe stress response after the diagnosis of ALS. In Study III, we aimed at validating the co-occurrence of ALS and other neuromuscular diseases, investigating the temporal relationship between the diagnoses and clinical characteristics of patients with both ALS and other neuromuscular diseases. Using information from the Swedish Patient Register, we identified all patients diagnosed with ALS in Sweden between 1991 and 2014, who had also a concurrent MS, myasthenia gravis (MG), inflammatory polyneuropathies (IP), or dermatopolymyositis (DMPM). The group included 263 patients. We validated medical records for 92% of these patients to confirm the overlap. Then, we compared patients with a confirmed overlap (N=28) with an independent sample of patients with only ALS (N=271). Among the patients with a validated overlap, 12 had a confirmed diagnosis of MS, nine a confirmed diagnosis of MG, four a confirmed diagnosis of IP, and three a confirmed diagnosis of DMPM. Seventy-nine percent of the patients with a confirmed overlap had these diagnoses prior to ALS. Compared to patients with only ALS, patients with a confirmed overlap were older at symptoms onset, had higher prevalence of bulbar onset, but used riluzole and non-invasive ventilation less frequently. These results show that neuroinflammation around the motor unit might trigger ALS in a small subgroup of patients. In Study IV, we estimated the risk of depression and antidepressants prescription among patients with relapsing-remitting MS (RRMS) and explored the bi-directional relationship between different disease modulatory therapies (DMTs) and depression or antidepressants use. We included 4,867 patients with RRMS who were diagnosed in Sweden between January 2005 and September 2018 and did not have a diagnosis of depression or antidepressants prescription before initiation of their first DMT. We compared the risk of depression (defined by diagnosis or antidepressants prescription) in relation to different DMTs, using interferons as the reference and examined DMT discontinuation or relapse in relation to depression. RRMS patients treated with rituximab had a decreased risk of depression, compared to patients treated with interferons. No differences were found for other DMTs examined (dimethyl fumarate, fingolimod, and natalizumab), compared to interferons. Depression was not associated with the risk of DMT discontinuation or MS relapse. These results provide evidence for a lower risk of depression among RRMS patients treated with rituximab, compared to interferons. In conclusion, results from the studies included in this thesis support the notion that neuroinflammation might precede the onset of ALS. In addition, different neurodegenerative diseases might share common disease mechanisms including neuroinflammation. The reduced risk of depression in relation to treatment with rituximab among patients with RRMS also suggests that neuroinflammation might underlie the link between psychiatric disorders and neurodegenerative diseases because rituximab may modulate both the MS- and depression-related inflammation.
|
|
| 5. |
- Longinetti, Elisa, et al.
(författare)
-
Heart rate, intelligence in adolescence, and Parkinson's disease later in life
- 2021
-
Ingår i: European Journal of Epidemiology. - : Springer. - 0393-2990 .- 1573-7284. ; 36:10, s. 1055-1064
-
Tidskriftsartikel (refereegranskat)abstract
- To investigate whether physical and cognitive fitness measured in late adolescence was associated with future risk of Parkinson's disease (PD). The cohort included 1,259,485 Swedish men with physical fitness, body mass index (BMI), resting heart rate (RHR), blood pressure, intelligence quotient (IQ), and stress resilience measured at the age of 17-20 in relation to conscription. Incident cases of PD were ascertained from the Swedish Patient Register. Hazard ratios were estimated from Cox models, after controlling for multiple confounders. We further performed Mendelian randomization (MR) analyses to assess the causality of the associations, using GWAS summary statistics with > 800,000 individuals. During follow-up, we identified 1,034 cases of PD (mean age at diagnosis = 53). Men with an RHR > 100 beats per minute had a higher risk of PD compared to men with an RHR of 60-100 beats per minute (HR = 1.47; 95% CI = 1.08-1.99). Men with IQ above the highest tertile had a higher risk of PD compared to men with an IQ below the lowest tertile (HR = 1.46; 95% CI = 1.19-1.79). We found no association for physical fitness, BMI, blood pressure, or stress resilience. A causal relationship was suggested by the MR analysis between IQ and PD, but not between RHR and PD. RHR and IQ in late adolescence were associated with a higher risk of PD diagnosed at relatively young age. The association of IQ with PD is likely causal, whereas the association of RHR with PD suggests that altered cardiac autonomic function might start before 20 years of age in PD.
|
|
| 6. |
- Longinetti, Elisa, et al.
(författare)
-
Neurodegenerative and psychiatric diseases among families with amyotrophic lateral sclerosis
- 2017
-
Ingår i: Neurology. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0028-3878 .- 1526-632X. ; 89:6, s. 578-585
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objective: To estimate risks of neurodegenerative and psychiatric diseases among patients with amyotrophic lateral sclerosis (ALS) and their families. Methods: We conducted a register-based nested case-control study during 1990-2013 in Sweden to assess whether ALS patients had higher risks of other neurodegenerative and psychiatric diseases before diagnosis. We included 3,648 ALS patients and 36,480 age-, sex-, and county-of-birth matched population controls. We further conducted a follow-up study of the cases and controls to assess the risks of other neurodegenerative and psychiatric diseases after ALS diagnosis. To assess the potential contribution of familial factors, we conducted similar studies for the relatives of ALS patients and their controls. Results: Individuals with previous neurodegenerative or psychiatric diseases had a 49% increased risk of ALS (odds ratio=1.49, 95% confidence interval=1.35-1.66), compared to individuals without these diseases. After diagnosis, ALS patients had increased risks of other neurodegenerative or psychiatric diseases (hazard ratio=2.90, 95% confidence interval=2.46-3.43), compared to individuals without ALS. The strongest associations were noted for frontotemporal dementia, Parkinson’s disease, other dementia, Alzheimer’s disease, neurotic disorders, depression, stress-related disorders, and drug abuse/dependence. First-degree relatives of ALS patients had higher risk of neurodegenerative diseases, whereas only children of ALS patients had higher risk of psychiatric disorders, compared to relatives of the controls. Conclusions: Familial aggregation of ALS and other neurodegenerative diseases implies a shared etiopathogenesis among all neurodegenerative diseases. The increased risk of psychiatric disorders among ALS patients and their children might be attributable to non-motor symptoms of ALS and severe stress response toward the diagnosis.
|
|
| 7. |
- Longinetti, Elisa, et al.
(författare)
-
The Swedish motor neuron disease quality registry
- 2018
-
Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Taylor & Francis. - 2167-8421 .- 2167-9223. ; 19:7-8, s. 528-537
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: We set up the Swedish Motor Neuron Disease (MND) Quality Registry to assure early diagnosis and high-quality health care for all MND patients (mainly amyotrophic lateral sclerosis, ALS), and to create a research base by prospectively following the entire MND population in Sweden. Methods: Since 2015, the MND Quality Registry continuously collects information about a wide range of clinical measures, biological samples, and quality of life outcomes from all MND patients recruited at the time of MND diagnosis in Sweden and followed at each clinic visit approximately every 12 weeks. The Registry includes an Internet based patient own reporting portal that involves patients in the registration of their current symptoms and health status. Results: As of 20th January 2017, the MND Quality Registry included 99% of the MND patients of the Stockholm area (N = 194), consisting mostly of ALS patients (N = 153, 78.9%), followed by patients labeled as MND due to a neurophysiology finding but not fulfilling the criteria for ALS (N = 20, 10.3%), primary lateral sclerosis (N = 13, 6.7%), and progressive spinal muscular atrophy patients (N = 8, 4.1%). A higher proportion of these patients were women (N = 100, 52%), and women and men had a similar age at symptoms onset (59 years). Conclusions: Main strengths of the MND Quality Registry are its clinical, quantitative, qualitative, and prospective nature, providing the researchers potential means of identifying appropriate candidates for clinical trials and other research projects, as well as assuring to the patients an effective and adequate time spent on-site with the healthcare professionals.
|
|
| 8. |
- Longinetti, Elisa, et al.
(författare)
-
Trajectories of cognitive processing speed and physical disability over 11 years following initiation of a first multiple sclerosis disease-modulating therapy
- 2024
-
Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ Publishing Group Ltd. - 0022-3050 .- 1468-330X. ; 95:2, s. 134-141
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We analysed the COMparison Between All immunoTherapies for Multiple Sclerosis (NCT03193866), a Swedish nationwide observational study in relapsing-remitting multiple sclerosis (RRMS), to identify trajectories of processing speed and physical disability after disease-modulating therapy (DMT) start.METHODS: Using a group-modelling approach, we assessed trajectories of processing speed with oral Symbol Digit Modalities Test (SDMT) and physical disability with Expanded Disability Status Scale, from first DMT start among 1645 patients with RRMS followed during 2011-2022. We investigated predictors of trajectories using group membership as a multinomial outcome and calculated conditional probabilities linking membership across the trajectories.RESULTS: We identified 5 stable trajectories of processing speed: low SDMT scores (mean starting values=29.9; 5.4% of population), low/medium (44.3; 25.3%), medium (52.6; 37.9%), medium/high (63.1; 25.8%) and high (72.4; 5.6%). We identified 3 physical disability trajectories: no disability/stable (0.8; 26.8%), minimal disability/stable (1.6; 58.1%) and moderate disability (3.2; 15.1%), which increased to severe disability. Older patients starting interferons were more likely than younger patients starting rituximab to be on low processing speed trajectories. Older patients starting teriflunomide, with more than one comorbidity, and a history of pain treatment were more likely to belong to the moderate/severe physical disability trajectory, relative to the no disability one. There was a strong association between processing speed and physical disability trajectories.CONCLUSIONS: In this cohort of actively treated RRMS, patients' processing speed remained stable over the years following DMT start, whereas patients with moderate physical disability deteriorated in physical function. Nevertheless, there was a strong link between processing speed and disability after DMT start.
|
|
