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- Orešič, Matej, 1967-, et al.
(författare)
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Metabolome in progression to Alzheimer's disease
- 2011
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Ingår i: Translational Psychiatry. - New York : Nature Publishing Group. - 2158-3188. ; 1
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Tidskriftsartikel (refereegranskat)abstract
- Mild cognitive impairment (MCI) is considered as a transition phase between normal aging and Alzheimer's disease (AD). MCI confers an increased risk of developing AD, although the state is heterogeneous with several possible outcomes, including even improvement back to normal cognition. We sought to determine the serum metabolomic profiles associated with progression to and diagnosis of AD in a prospective study. At the baseline assessment, the subjects enrolled in the study were classified into three diagnostic groups: healthy controls (n=46), MCI (n=143) and AD (n=47). Among the MCI subjects, 52 progressed to AD in the follow-up. Comprehensive metabolomics approach was applied to analyze baseline serum samples and to associate the metabolite profiles with the diagnosis at baseline and in the follow-up. At baseline, AD patients were characterized by diminished ether phospholipids, phosphatidylcholines, sphingomyelins and sterols. A molecular signature comprising three metabolites was identified, which was predictive of progression to AD in the follow-up. The major contributor to the predictive model was 2,4-dihydroxybutanoic acid, which was upregulated in AD progressors (P=0.0048), indicating potential involvement of hypoxia in the early AD pathogenesis. This was supported by the pathway analysis of metabolomics data, which identified upregulation of pentose phosphate pathway in patients who later progressed to AD. Together, our findings primarily implicate hypoxia, oxidative stress, as well as membrane lipid remodeling in progression to AD. Establishment of pathogenic relevance of predictive biomarkers such as ours may not only facilitate early diagnosis, but may also help identify new therapeutic avenues.
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- Sindi, S., et al.
(författare)
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Midlife improvements in financial situation are associated with a reduced dementia risk later in life : the CAIDE 30-year study
- 2020
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Ingår i: International psychogeriatrics. - : Cambridge University Press. - 1041-6102 .- 1741-203X. ; 32:11, s. 1317-1324
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Perceived financial strain is associated with various health conditions, but it is unknown whether it is associated with an increased risk for dementia. The goal is to examine the associations between midlife perceptions of financial situation and dementia risk later in life.Methods: Participants were derived from the Cardiovascular Risk Factors, Aging, and Dementia population-based cohort study (n = 2000) (between 1972 and 1987, baseline mean age 50 years) in Finland. Participants returned for two re-examinations in late life (in 1998 and 2005–2008, mean age 71 and 78 years). In this study, 1442 subjects that participated in at least one re-examination (mean total follow-up 25 years) were included in analyses. Financial strain was measured using two questions in midlife on perceptions of financial situation and perceptions of changes in financial situation. For each question, participants were categorized into three groups reporting improvement, worsening, or stability, with the latter set as the reference group. Analyses were adjusted for potential confounding factors.Results: The group reporting better financial situation had a reduced risk for dementia (fully adjusted model: odds ratio (OR): 0.53, 95% confidence interval (CI): 0.33–0.86). In contrast, the group reporting worse financial situation did not have an increased risk for dementia (OR: 1.04, 95% CI: 0.53–2.02). Analyses on perceptions of current financial situation showed that the groups reporting satisfaction or dissatisfaction with financial situation did not differ in risk for dementia.Conclusion: This study is the first to show that midlife improvements in financial situation are associated with a reduced dementia risk later in life. Potential pathways related to stress reduction, improved lifestyle, and potential biological mechanisms are discussed.
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- Sindi, S., et al.
(författare)
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Sleep disturbances and later cognitive status: a multi-centre study
- 2018
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Ingår i: Sleep Medicine. - : Elsevier BV. - 1389-9457 .- 1878-5506. ; 52:December, s. 26-33
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the associations between sleep disturbances in mid-life and late-life and late-life cognitive status. Methods: In four population-based studies (three Swedish studies: H70 study, Kungsholmen Project (KP) and The Swedish Panel Study of Living Conditions of the Oldest Old (SWEOLD); and one Finnish study: Cardiovascular Risk Factors, Aging and Dementia (CAIDE)), participants provided self-reports on insomnia, nightmares and general sleep problems. Late-life cognitive status was measured by the Mini Mental State Exam (MMSE). The associations between late-life sleep disturbances and cognition 3-11 years later were investigated across all studies (n = 3210). Mean baseline ages were 70 (CAIDE, H70 and SWEOLD), and 84 years (KP). Additional analyses examined the association between midlife sleep and late-life cognition using CAIDE (21 and 31 years follow-up, n = 1306, mean age 50 years), and SWEOLD (20-24 years follow-up, n = 2068, mean age 58 years). Ordered logistic regressions, adjusted for potential baseline confounders, were used in the analyses. Results: Late-life sleep disturbances were associated with poorer cognition after 3-11 years (fully adjusted beta = -0.12, 95% CI = -0.24 to -0.01). Midlife nightmares and insomnia were also associated with lower MMSE scores (fully adjusted beta = -0.28, 95% CI = -0.49 to -0.07 and beta = -0.20, 95% CI = -0.39 to -0.01), although the latter association was attenuated after adjusting for lifestyle/health-related confounders. Midlife general sleep problems were not associated with late-life MMSE performance. Conclusions: Sleep disturbances and midlife nightmares were associated with lower MMSE scores, which suggests that sleep disturbances in earlier life stages can be associated with worse late-life cognition. (c) 2017 Published by Elsevier B.V.
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- Solomon, A, et al.
(författare)
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Lipid-lowering treatment is related to decreased risk of dementia : a population-based study (FINRISK)
- 2010
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Ingår i: Neurodegenerative diseases. - : S. Karger AG. - 1660-2862 .- 1660-2854. ; 7:1-3, s. 180-182
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Several lines of evidence have linked cholesterol to dementia.OBJECTIVE: To investigate lipid-lowering drug use and dementia development in a Finnish population.METHODS: FINRISK is a large population-based survey of cardiovascular risk factors carried out since 1972 every 5 years using independent, random and representative population samples from different parts of Finland. Several cohorts were part of the WHO-MONICA study. Data from cohorts 1972-2002 were linked to the Hospital Discharge Registry and Drug Reimbursement Registry (1995-2007) to ascertain dementia diagnoses and lipid-lowering treatment. Selection criteria for the study were: (1) alive and without dementia in 1995; (2) age > or = 60 years (in 1995 for earlier cohorts and in 1997 or 2002 for later cohorts; (3) treatment prescribed at least 1 year before dementia diagnosis.RESULTS: 17,597 persons were included in the study. Lipid-lowering treatment was related to decreased dementia risk. In Cox proportional hazards model, hazard ratio (95% CI) was 0.42 (0.37-0.49; controlled for age, sex, education, survey region, survey year, baseline cholesterol, body mass index and systolic blood pressure).CONCLUSION: Preliminary results from the FINRISK study indicate that lipid-lowering drugs may have a beneficial effect in dementia prevention. Further data linkage is ongoing in order to investigate the roles of different types of lipid-lowering drugs.
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- Sorensen, Charlotte, et al.
(författare)
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Daytime Sleepiness, Apnea, Neuroimaging Correlates and Cortisol Dysregulation in a Memory Clinic Cohort
- 2024
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Ingår i: The Journal of Prevention of Alzheimer's Disease. - : Springer. - 2274-5807 .- 2426-0266.
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSleep disturbances as well as cortisol hypersecretion are increasingly acknowledged as risk factors for Alzheimer's disease (AD). However, the mechanisms underlying the association, and the interplay with cortisol abnormalities, remain unclear.ObjectivesThis study aims to identify how self-reported sleep disturbances are associated with structural brain measures and diurnal cortisol dysregulation among memory clinic patients.DesignA cross-sectional study performed at Karolinska University Hospital Memory Clinic, Sweden.ParticipantsThe study was based on 146 memory clinic patients diagnosed with either subjective cognitive impairment or mild cognitive impairment.MeasurementsSelf-reported sleep was measured using the Karolinska Sleep Questionnaire. MRI or CT was used to quantify structural brain measures using four visual rating scales (Scheltens, Pasquier, Koedam, and Fazekas scales), and salivary cortisol was sampled to measure diurnal cortisol patterns through measures of cortisol immediately after awakening, cortisol awakening response, bedtime cortisol, total cortisol from awakening to bedtime, and the AM/PM cortisol ratio.ResultsIncreased sleep apnea index (OR=1.20, 95% CI=1.04:1.39, p=0.015) was associated with greater odds of posterior brain atrophy, measured by the Koedam visual rating scale, and reduced awakening Cortisol (beta=-0.03, 95% CI=- 0.07:0.00, p=0.045). Increased daytime sleepiness was associated with both reduced awakening cortisol (beta=-0.03, 95% CI=-0.06:0.00, p=0.025) and a reduced AM/PM cortisol ratio (beta=-0.04, CI=-0.08:-0.01, p= 0.021).ConclusionIn a memory clinic cohort self-reported sleep disturbances are associated with both worse structural brain tissue integrity and altered diurnal cortisol profiles. These findings may add insights into possible mechanisms behind sleep disturbances in aging with subjective and cognitive impairment.
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