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1.
  • Daniilidou, Makrina, et al. (författare)
  • Alzheimer's disease biomarker profiling in a memory clinic cohort without common comorbidities.
  • 2023
  • Ingår i: Brain communications. - 2632-1297. ; 5:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer's disease is a multifactorial disorder with large heterogeneity. Comorbidities such as hypertension, hypercholesterolaemia and diabetes are known contributors to disease progression. However, less is known about their mechanistic contribution to Alzheimer's pathology and neurodegeneration. The aim of this study was to investigate the relationship of several biomarkers related to risk mechanisms in Alzheimer's disease with the well-established Alzheimer's disease markers in a memory clinic population without common comorbidities. We investigated 13 molecular markers representing key mechanisms underlying Alzheimer's disease pathogenesis in CSF from memory clinic patients without diagnosed hypertension, hypercholesterolaemia or diabetes nor other neurodegenerative disorders. An analysis of covariance was used to compare biomarker levels between clinical groups. Associations were analysed by linear regression. Two-step cluster analysis was used to determine patient clusters. Two key markers were analysed by immunofluorescence staining in the hippocampus of non-demented control and Alzheimer's disease individuals. CSF samples from a total of 90 participants were included in this study: 30 from patients with subjective cognitive decline (age 62.4 ± 4.38, female 60%), 30 with mild cognitive impairment (age 65.6 ± 7.48, female 50%) and 30 with Alzheimer's disease (age 68.2 ± 7.86, female 50%). Angiotensinogen, thioredoxin-1 and interleukin-15 had the most prominent associations with Alzheimer's disease pathology, synaptic and axonal damage markers. Synaptosomal-associated protein 25kDa and neurofilament light chain were increased in mild cognitive impairment and Alzheimer's disease patients. Grouping biomarkers by biological function showed that inflammatory and survival components were associated with Alzheimer's disease pathology, synaptic dysfunction and axonal damage. Moreover, a vascular/metabolic component was associated with synaptic dysfunction. In the data-driven analysis, two patient clusters were identified: Cluster 1 had increased CSF markers of oxidative stress, vascular pathology and neuroinflammation and was characterized by elevated synaptic and axonal damage, compared with Cluster 2. Clinical groups were evenly distributed between the clusters. An analysis of post-mortem hippocampal tissue showed that compared with non-demented controls, angiotensinogen staining was higher in Alzheimer's disease and co-localized with phosphorylated-tau. The identification of biomarker-driven endophenotypes in cognitive disorder patients further highlights the biological heterogeneity of Alzheimer's disease and the importance of tailored prevention and treatment strategies.
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2.
  • Eriksson, D, et al. (författare)
  • Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
  • 2016
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 595-608
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
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3.
  • Gyllén, Jenny, 1968, et al. (författare)
  • Important sources of information to support self-management for families of children with pediatric cataracts – based on PECARE Sweden/Sahlgrenska University Hospital
  • 2015
  • Ingår i: International Journal of Ophthalmic Practice. - : Mark Allen Group. - 2044-5504 .- 2052-2851. ; 6:1, s. 23-29
  • Tidskriftsartikel (refereegranskat)abstract
    • ABSTRACT Purpose The aim of this study was to improve treatment concordance by investigating important sources of information on self-management for families of children with pediatric cataracts, from the perspective of parents and ophthalmologists. Methods This mixed-method study involved a deductive approach using a questionnaire administered to 69 families of children operated on and registered with the Swedish Pediatric Cataract Register (PECARE Sweden) in southern Sweden, as well as 30 pediatric ophthalmologists who monitored the patients upon their return to the local health care facility. An inductive approach was applied using analysis of open-ended questions about self-management. Both groups were asked about their perception of the value of strategies for providing information, and the timing of this. Results The response rate was 68% for families and 93% for ophthalmologists. Both groups agreed that ophthalmology visits were the most important source of information, followed by information in writing and online. Parents of children diagnosed before the age of 3 months were more likely to prefer written information. Content analysis revealed that a person-centred care is important. Conclusion Parents, particularly of the youngest children, requested more and directed information. By promoting self-management, a person-centred care may play a decisive role in treatment outcome.
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4.
  • Kindenberg, Björn, Doktorand, 1972-, et al. (författare)
  • Textuniversumkompetens hos yngre elever : [Transmedia competence among young students]
  • 2024
  • Ingår i: Forskning om undervisning och lärande. - 2000-9674 .- 2001-6131. ; 12:1, s. 7-26
  • Tidskriftsartikel (refereegranskat)abstract
    • Ungas erfarenheter av fiktion präglas alltmer av transmediering, i betydelsen att litterära element från det traditionella medieformatet, tryckt text, omskapas i andra medieformat (spel, filmer o.s.v.). Detta fenomen har i forskning begreppsliggjorts som textuniversum. I denna artikel diskuteras vilka typer av kompetenser som kan förknippas med textuniversumbaserad undervisning om skönlitteratur. Fyra dimensioner av kompetens ses som viktiga för textuniversumbaserad undervisning. Diskussionen utgår dels från tidigare forskning, dels från empiriska belägg hämtade från ett pågående forskningsprojekt i vilket nya former av läsning i skolan undersöks. Avslutningsvis i artikeln presenteras en didaktisk modell avsedd att hjälpa lärare i utformning av denna typ av undervisning.
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5.
  • Rosenberg, Anna, et al. (författare)
  • Multidomain lifestyle intervention benefits a large elderly population at risk for cognitive decline and dementia regardless of baseline characteristics : The FINGER trial
  • 2018
  • Ingår i: Alzheimer's & Dementia. - New York : Elsevier. - 1552-5260 .- 1552-5279. ; 14:3, s. 263-270
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The 2-year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) multidomain lifestyle intervention trial (NCT01041989) demonstrated beneficial effects on cognition. We investigated whether sociodemographics, socioeconomic status, baseline cognition, or cardiovascular factors influenced intervention effects on cognition.Methods: The FINGER recruited 1260 people from the general Finnish population (60-77 years, at risk for dementia). Participants were randomized 1: 1 to multidomain intervention (diet, exercise, cognition, and vascular risk management) and regular health advice. Primary outcome was change in cognition (Neuropsychological Test Battery z-score). Prespecified analyses to investigate whether participants' characteristics modified response to intervention were carried out using mixed-model repeated-measures analyses.Results: Sociodemographics (sex, age, and education), socioeconomic status (income), cognition (Mini-Mental State Examination), cardiovascular factors (body mass index, blood pressure, cholesterol, fasting glucose, and overall cardiovascular risk), and cardiovascular comorbidity did not modify response to intervention (P-values for interaction > .05). Conclusions: The FINGER intervention was beneficial regardless of participants' characteristics and can thus be implemented in a large elderly population at increased risk for dementia. 
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6.
  • Thunborg, Charlotta, 1965-, et al. (författare)
  • Integrating a multimodal lifestyle intervention with medical food in prodromal Alzheimer's disease : the MIND-ADmini randomized controlled trial.
  • 2024
  • Ingår i: Alzheimer's Research & Therapy. - : BioMed Central (BMC). - 1758-9193. ; 16:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed cognitive benefits from a multidomain lifestyle intervention in at-risk older people. The LipiDiDiet trial highlighted benefits of medical food in prodromal Alzheimer's disease (AD). However, the feasibility and impact of multimodal interventions combining lifestyle with medical food in prodromal AD is unclear.METHODS: MIND-ADmini was a 6-month multinational (Sweden, Finland, Germany, France) proof-of-concept randomized controlled trial (RCT). Participants were 60-85 years old, had prodromal AD (International Working Group-1 criteria), and vascular/lifestyle risk factors. The parallel-group RCT had three arms: multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); multimodal lifestyle intervention + medical food (Fortasyn Connect); and regular health advice/care (control). Participants were randomized 1:1:1 (computer-generated allocation at each site). Outcome evaluators were blinded to randomization. Primary outcome was feasibility of the multimodal intervention, evaluated by recruitment rate during a 6-month recruitment phase, overall adherence in each intervention arm, and 6-month retention rate. Successful adherence was pre-specified as attending ≥ 40% of sessions/domain in ≥ 2/4 domains (lifestyle intervention), and consuming ≥ 60% of the medical food (lifestyle intervention + medical food). The secondary outcomes included adherence/participation to each intervention component and overall adherence to healthy lifestyle changes, measured using a composite score for healthy lifestyle. Cognitive assessments were included as exploratory outcomes, e.g. Clinical Dementia Rating scale.RESULTS: During September 2017-May 2019, 93 individuals were randomized (32 lifestyle intervention, 31 lifestyle + medical food, and 30 control group). Overall recruitment rate was 76.2% (64.8% during the first 6 months). Overall 6-month retention rate was 91.4% (lifestyle intervention 87.5%; lifestyle + medical food 90.3%; control 96.7%). Domain-specific adherence in the lifestyle intervention group was 71.9% to cognitive training, 78.1% exercise, 68.8% nutritional guidance, and 81.3% vascular risk management; and in the lifestyle + medical food group, 90.3% to cognitive training, 87.1% exercise, 80.7% nutritional guidance, 87.1% vascular risk management, and 87.1% medical food. Compared with control, both intervention arms showed healthy diet improvements (βLifestyle×Time = 1.11, P = 0.038; βLifestyle+medical food×Time = 1.43, P = 0.007); the lifestyle + medical food group also showed vascular risk reduction (P = 0.043) and less cognitive-functional decline (P < 0.05, exploratory analysis). There were 5 serious adverse events (control group: 1; lifestyle intervention: 3; lifestyle + medical food: 1) unrelated to interventions.CONCLUSIONS: The multidomain lifestyle intervention, alone or combined with medical food, had good feasibility and adherence in prodromal AD. Longer-term cognitive and other health benefits should be further investigated in a larger-scale trial.TRIAL REGISTRATION: ClinicalTrials.gov NCT03249688.
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7.
  • Thunborg, Charlotta, 1965-, et al. (författare)
  • Integrating a multimodal lifestyle intervention with medical food in prodromal Alzheimer’s disease: the MIND-ADmini randomized controlled trial
  • 2024
  • Ingår i: Alzheimer's Research & Therapy. - : Springer. - 1758-9193. ; 16:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed cognitive benefits from a multidomain lifestyle intervention in at-risk older people. The LipiDiDiet trial highlighted benefits of medical food in prodromal Alzheimer’s disease (AD). However, the feasibility and impact of multimodal interventions combining lifestyle with medical food in prodromal AD is unclear.MethodsMIND-ADmini was a 6-month multinational (Sweden, Finland, Germany, France) proof-of-concept randomized controlled trial (RCT). Participants were 60–85 years old, had prodromal AD (International Working Group-1 criteria), and vascular/lifestyle risk factors. The parallel-group RCT had three arms: multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); multimodal lifestyle intervention + medical food (Fortasyn Connect); and regular health advice/care (control). Participants were randomized 1:1:1 (computer-generated allocation at each site). Outcome evaluators were blinded to randomization. Primary outcome was feasibility of the multimodal intervention, evaluated by recruitment rate during a 6-month recruitment phase, overall adherence in each intervention arm, and 6-month retention rate. Successful adherence was pre-specified as attending ≥ 40% of sessions/domain in ≥ 2/4 domains (lifestyle intervention), and consuming ≥ 60% of the medical food (lifestyle intervention + medical food). The secondary outcomes included adherence/participation to each intervention component and overall adherence to healthy lifestyle changes, measured using a composite score for healthy lifestyle. Cognitive assessments were included as exploratory outcomes, e.g. Clinical Dementia Rating scale.ResultsDuring September 2017-May 2019, 93 individuals were randomized (32 lifestyle intervention, 31 lifestyle + medical food, and 30 control group). Overall recruitment rate was 76.2% (64.8% during the first 6 months). Overall 6-month retention rate was 91.4% (lifestyle intervention 87.5%; lifestyle + medical food 90.3%; control 96.7%). Domain-specific adherence in the lifestyle intervention group was 71.9% to cognitive training, 78.1% exercise, 68.8% nutritional guidance, and 81.3% vascular risk management; and in the lifestyle + medical food group, 90.3% to cognitive training, 87.1% exercise, 80.7% nutritional guidance, 87.1% vascular risk management, and 87.1% medical food. Compared with control, both intervention arms showed healthy diet improvements (βLifestyle×Time = 1.11, P = 0.038; βLifestyle+medical food×Time = 1.43, P = 0.007); the lifestyle + medical food group also showed vascular risk reduction (P = 0.043) and less cognitive-functional decline (P < 0.05, exploratory analysis). There were 5 serious adverse events (control group: 1; lifestyle intervention: 3; lifestyle + medical food: 1) unrelated to interventions.ConclusionsThe multidomain lifestyle intervention, alone or combined with medical food, had good feasibility and adherence in prodromal AD. Longer-term cognitive and other health benefits should be further investigated in a larger-scale trial.Trial registrationClinicalTrials.gov NCT03249688.
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8.
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9.
  • Akenine, Ulrika, et al. (författare)
  • Attitudes of at-risk older adults about prevention of cardiovascular disease and dementia using eHealth : a qualitative study in a European context
  • 2020
  • Ingår i: BMJ Open. - 2044-6055. ; 10:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Prevention of cardiovascular disease (CVD) and dementia is a key health priority among older adults. Understanding individuals’ attitudes to, the prevention of these conditions, particularly when delivered through novel eHealth tools, could help in designing effective prevention programmes. The aim of the study was to explore the attitudes of older adults at increased risk of CVD and dementia regarding engagement in eHealth self-management prevention programmes, and to describe the facilitators and barriers.Design A qualitative research approach was used. Data were collected through eight focus groups in Finland, France and the Netherlands. Data were analysed following the principles of grounded theory.Setting and participants Forty-four community-dwellers aged 65+ at risk of CVD were recruited from a previous trial cohort in Finland, and through general practices in France and the Netherlands.Results The study identified three categories: access to reliable information, trust in the healthcare providers and burden and stigma of dementia. A core category was also identified: the interactive process of the three categories influencing engagement in self-management prevention programme. The categories were interconnected through an interactive process and influenced by the local healthcare culture and context which shaped them differently, becoming either facilitators or barriers to engage in eHealth self-management prevention programmes.Conclusions The study emphasises the importance of considering the interactions between the identified categories in this study, grounded in the local healthcare culture and context in further developments of eHealth self-management interventions that aim to prevent CVD and dementia.
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