| 1. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 2. |
- Jones, Lesley, et al.
(författare)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Tidskriftsartikel (refereegranskat)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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| 3. |
- Ferreira, Daniel, et al.
(författare)
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The interactive effect of demographic and clinical factors on hippocampal volume : A multicohort study on 1958 cognitively normal individuals
- 2017
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Ingår i: Hippocampus. - : Wiley. - 1050-9631 .- 1098-1063. ; 27:6, s. 653-667
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease is characterized by hippocampal atrophy. Other factors also influence the hippocampal volume, but their interactive effect has not been investigated before in cognitively healthy individuals. The aim of this study is to evaluate the interactive effect of key demographic and clinical factors on hippocampal volume, in contrast to previous studies frequently investigating these factors in a separate manner. Also, to investigate how comparable the control groups from ADNI, AIBL, and AddNeuroMed are with five population-based cohorts. In this study, 1958 participants were included (100 AddNeuroMed, 226 ADNI, 155 AIBL, 59 BRC, 295 GENIC, 279 BioFiNDER, 398 PIVUS, and 446 SNAC-K). ANOVA and random forest were used for testing between-cohort differences in demographic-clinical variables. Multiple regression was used to study the influence of demographic-clinical variables on hippocampal volume. ANCOVA was used to analyze whether between-cohort differences in demographic-clinical variables explained between-cohort differences in hippocampal volume. Age and global brain atrophy were the most important variables in explaining variability in hippocampal volume. These variables were not only important themselves but also in interaction with gender, education, MMSE, and total intracranial volume. AddNeuroMed, ADNI, and AIBL differed from the population-based cohorts in several demographic-clinical variables that had a significant effect on hippocampal volume. Variability in hippocampal volume in individuals with normal cognition is high. Differences that previously tended to be related to disease mechanisms could also be partly explained by demographic and clinical factors independent from the disease. Furthermore, cognitively normal individuals especially from ADNI and AIBL are not representative of the general population. These findings may have important implications for future research and clinical trials, translating imaging biomarkers to the general population, and validating current diagnostic criteria for Alzheimer's disease and predementia stages.
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| 4. |
- Heiland, Emerald G, et al.
(författare)
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Association of mobility limitations with incident disability among older adults : a population-based study.
- 2016
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Ingår i: Age and Ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 45:6, s. 812-819
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: mobility-related limitations predict future disability; however, the extent to which individual and combined mobility tests may predict disability remains unclear.OBJECTIVES: to estimate the odds of developing disability in activities of daily living (ADL) according to limitations in walking speed, balance or both; and explore the role of chronic diseases and cognitive function.DESIGN: a prospective cohort study.SETTING: urban area of Stockholm, Sweden.SUBJECTS: one thousand nine hundred and seventy-one disability-free persons (age ≥60 years, 63% women) from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K), who underwent baseline examination in 2001-04 and follow-up assessments for 6 years.MEASUREMENTS: mobility limitation was defined as a one-leg balance stand <5 s or walking speed <0.8 m/s. ADL disability was defined as the inability to complete one or more ADL: bathing, dressing, using the toilet, transferring and eating.RESULTS: during a total of 11,404 person-years (mean per person 5.8 years, SD 0.30) of follow-up, 119 (incidence 1.5/100 person-years) participants developed ADL disability. The demographic adjusted odds ratios (OR) (95% confidence intervals, CI) of incident ADL disability related to balance stand and walking speed limitations were 3.8 (2.3-6.3) and 8.4 (5.2-13.3), respectively. The associations remained statistically significant after controlling for number of chronic diseases and cognitive status. People with limitations in both balance and walking speed had an OR of 12.9 (95% CI 7.0-23.7) for incident disability compared with no limitation.CONCLUSION: balance and walking speed tests are simple clinical procedures that can indicate hierarchical risk of ADL dependence in older adults.
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| 5. |
- Heiland, Emerald G, et al.
(författare)
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Cardiovascular Risk Burden and Future Risk of Walking Speed Limitation in Older Adults
- 2017
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Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 65:11, s. 2418-2424
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To explore the association between cardiovascular risk factor (CRF) burden and limitation in walking speed, balance, and chair stand and to verify whether these associations vary according to age and cognitive status.DESIGN: Longitudinal population-based study.SETTING: Urban area of Stockholm, Sweden.PARTICIPANTS: Individuals aged 60 and older who participated in the Swedish National Study on Aging and Care in Kungsholmen and were free of limitations in walking speed (n = 1,441), balance (n = 1,154), or chair stands (n = 1,496) at baseline (2001-04).MEASUREMENTS: At baseline, data on demographic characteristics, CRFs, other lifestyle factors, C-reactive protein, and cognitive function were collected. CRF burden was measured using the Framingham general cardiovascular risk score (FRS). Limitations in walking speed (<0.8 m/s), balance (<5 seconds), and chair stand (inability to rise 5 times) were determined at 3-, 6-, and 9-year follow-up. Data were analyzed using Cox proportional hazards models stratified according to age (<78, >= 78).RESULTS: During follow-up, 326 persons developed limitations in walking speed, 303 in balance, and 374 in chair stands. An association between the FRS and walking speed limitation was evident only in adults younger than 78 (for each 1-point increase in FRS: hazard ratio (HR) = 1.09, 95% confidence interval (CI) = 1.02-1.17) after controlling for potential confounders including cognitive function (correspondingly, in adults aged >= 78: HR = 0.98, 95% CI = 0.92-1.03). Also, higher FRS was significantly associated with faster decline in walking speed (P<.001).CONCLUSION: A higher FRS is associated with greater risk of subsequent development of walking speed limitation in adults younger than 78, independent of cognitive function. Interventions targeting multiple CRFs in younger-old people may help in maintaining mobility function.
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| 6. |
- Heiland, Emerald G, et al.
(författare)
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Cardiovascular Risk Factors and the Risk of Disability in Older Adults : Variation by Age and Functional Status.
- 2019
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Ingår i: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610 .- 1538-9375. ; 20:2, s. 208-212.e3
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: We aimed to quantify the increased risk of disability associated with cardiovascular risk factors among older adults, and to verify whether this risk may vary by age and functional status.DESIGN: Longitudinal population-based cohort study.SETTING: Urban area of Stockholm, Sweden.PARTICIPANTS: Community-dwelling and institutionalized adults ≥60 years in the Swedish National study on Aging and Care in Kungsholmen free of cardiovascular diseases and disability (n = 1756) at baseline (2001-2004).MEASURES: Incident disability in activities of daily living (ADL) was ascertained over 9 years. Cardiovascular risk factors (physical inactivity, alcohol consumption, smoking, high blood pressure, diabetes, high body mass index, high levels of total cholesterol, and high C-reactive protein) and walking speed were assessed at baseline. Data were analyzed using Cox proportional hazards models, stratifying by younger-old (age 60-72 years) and older-old (≥78 years).RESULTS: During the follow-up, 23 and 148 persons developed ADL-disability among the younger- and older-old, respectively. In the younger-old, the adjusted hazard ratio (HR) of developing ADL-disability was 4.10 (95% confidence interval [CI] 1.22-13.76) for physical inactivity and 5.61 (95% CI 1.17-26.82) for diabetes. In the older-old, physical inactivity was associated with incident ADL-disability (HR 1.99, 95% CI 1.36-2.93), and there was a significant interaction between physical inactivity and walking speed limitation (<0.8 m/s), showing a 6-fold higher risk of ADL-disability in those who were both physically inactive and had walking speed limitation than being active with no limitation, accounting for a population-attributable risk of 42.7%.CONCLUSIONS/IMPLICATIONS: Interventions targeting cardiovascular risk factors may be more important for the younger-old in decreasing the risk of disability, whereas improving physical function and maintaining physical activity may be more beneficial for the older-old.
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| 7. |
- Rönnemaa, Elina, 1975-
(författare)
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Predictors of Dementia : Insulin, Fatty Acids and Vascular Risk Factors
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Identification of modifiable risk factors for Alzheimer’s disease (AD) is crucial in order to diminish suffering from this devastating disease. The aim of this thesis was to investigate if different aspects of glucose metabolism, insulin, fatty-acid composition or other vascular risk factors predict the future development of AD and dementia. This thesis is based on the Uppsala Longitudinal Study of Adult Men (ULSAM) cohort, which started in 1970. A total of 2322 men at age 50 were examined with focus on vascular risk factors. The cohort was re-examined at ages 60, 71, 77, 82 and 88. Incident diagnoses of AD, vascular dementia, other dementias and cognitive impairment were assessed in 2005–2010. The risk of AD was increased in subjects with lower early insulin response measured with both an intravenous glucose tolerance test at 50 years and an oral glucose tolerance test at 71 years of age. The presence of vascular risk factors such as hypertension, obesity, hypercholesterolemia and smoking increased the risk of future vascular dementia but not of AD. Furthermore, saturated fatty acids at midlife were inversely associated with risk of AD. No evidence of a protective effect of omega-3 fatty acids against dementia was found. The susceptibility allele, APOE ε4, was the strongest individual risk factor. APOE ε4 carriers with vascular risk factors had the greatest risk of developing dementia. Low insulin response was a risk factor for AD mainly in APOE ε4 non-carriers. Disturbances in insulin and glucose metabolism, vascular risk factors and fatty acids are linked differentially to the pathogenesis of AD and vascular dementia. These observations should be considered when future clinical approaches are planned to prevent and postpone the onset of dementia.
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| 8. |
- Santoni, Giola, et al.
(författare)
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Temporal trends in impairments of physical function among older adults during 2001–16 in Sweden : towards a healthier ageing
- 2018
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Ingår i: Age and Ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 47:5, s. 698-704
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Tidskriftsartikel (refereegranskat)abstract
- Background: a trend towards decline in disability has been reported in older adults, but less is known about corresponding temporal trends in measured physical functions.Objective: to verify these trends during 2001-16 in an older Swedish population.Methods: functional status was assessed at three occasions: 2001-04 (n = 2,266), 2007-10 (n = 2,033) and 2013-16 (n = 1,476), using objectively measured balance, chair stands and walking speed. Point prevalence was calculated and trajectories of change in impairment/vital status were assessed and were sex-adjusted and age-stratified: 66; 72; 78; 81 and 84; 87 and 90.Results: point prevalence of impairment was significantly lower at the 2013-16 assessment than the 2001-04 in chair stand amongst age cohorts 78-90 years, and in walking speed amongst age cohorts 72-84 years (P < 0.05), but not significantly different for balance. The prevalence remained stable between 2001-04 and 2007-10, while the decrease in chair stands and walking speed primarily occurred between 2007-10 and 2013-16. Among persons unimpaired in 2007-10, the proportion of persons who remained unimpaired in 2013-16 tended to be higher, and both the proportion of persons who became impaired and the proportion of persons who died within 6 years tended to be lower, relative to corresponding proportions for persons unimpaired in 2001-04. Overall, there were no corresponding changes for those starting with impairment.Conclusions: our results suggest a trend towards less functional impairment in older adults in recent years. The improvements appear to be driven by improved prognosis amongst those without impairments rather than substantial changes in prognosis for those with impairments.
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| 9. |
- Santoni, Giola, et al.
(författare)
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Using an Integrated Clinical and Functional Assessment Tool to Describe the Use of Social and Medical Care in an Urban Community-Dwelling Swedish Older Population
- 2019
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Ingår i: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610 .- 1538-9375. ; 20:8, s. 988-
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To describe the use of social and medical care services in a community-dwelling older population from Stockholm, Sweden, using an integrated clinical and functional assessment tool. Design: Study based on data from the longitudinal community-based Swedish National Study on Aging and Care in Kungsholmen. Setting and Participants: Random sample of people >65 years of age living in the community in central Stockholm between March 2001 and June 2004 (N = 2368). Measures: Health status was measured with a health assessment tool (HAT), which combines 5 indicators (gait speed, cognitive function, chronic multimorbidity, mild disability, severe disability) collected during Swedish National Study on Aging and Care in Kungsholmen clinical examinations. The amount of formal and informal social care was self-reported in hours per month and recorded by trained nurses at baseline and the 3-year follow-up for those >= 78 years of age at baseline. Data on hospital admissions, 30-day readmissions, days spent in the hospital, primary care visits, and specialist visits were obtained from Stockholm County Council registers (2001-2007). Results: At baseline, 10% of the sample received formal social care and 11% received informal care. Annually between baseline and the 3-year follow-up, 15% were admitted to the hospital, 5% were readmitted, 78% visited a specialist, and 89% visited primary care. Those with the best HAT scores received 0.02 hours/month of formal care; those with the worst, 34 h/mo. The corresponding numbers for other variables were 0.02 vs 73 h/mo of informal care, 2 vs 11 hospital admissions per 10 persons/year, 44 vs 226 hospital days per 10 persons/y, 0.4 vs 2 30-day readmissions per 10 persons/y, 37 vs 78 specialist visits per 10 persons/y, and 50 vs 327 primary care visits per 10 persons/y. Conclusions/Implications: Because of its high discriminative power, the easy-to-use HAT index could help decision makers to plan medical and social care services. (C) 2018 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
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| 10. |
- Shakersain, Behnaz, et al.
(författare)
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Prudent diet may attenuate the adverse effects of Western diet on cognitive decline
- 2016
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 12:2, s. 100-109
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The influence of mixed dietary patterns on cognitive changes is unknown. Methods: A total of 2223 dementia-free participants aged >= 60 were followed up for 6 years to examine the impact of dietary patterns on cognitive decline. Mini-mental state examination (MMSE) was administered. Diet was assessed by a food frequency questionnaire. By factor analysis, Western and prudent dietary patterns emerged. Mixed-effect models for longitudinal data with repeated measurements were used. Results: Compared with the lowest adherence to each pattern, the highest adherence to prudent pattern was related to less MMSE decline (beta = 0.106, P = .011), whereas the highest adherence to Western pattern was associated with more MMSE decline (beta = -0.156, P < .001). The decline associated withWestern diet was attenuated when accompanied by high adherence to prudent pattern. Discussion: High adherence to prudent diet may diminish the adverse effects of high adherence to Western diet on cognitive decline.
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