| 1. |
- Skoog, Ingmar, 1954, et al.
(författare)
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Association between APOE Genotype and Change in Physical Function in a Population-Based Swedish Cohort of Older Individuals Followed Over Four Years
- 2016
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The association between decline in physical function and age-related conditions, such as reduced cognitive performance and vascular disease, may be explained by genetic influence on shared biological pathways of importance for aging. The apolipoprotein F (APOE) gene is well-known for its association with Alzheimer's disease, but has also been related to other disorders of importance for aging. The aim of this study was to investigate possible associations between APOE allele status and physical function in a population-based longitudinal study of older individuals. In 2005, at the age of 75, 622 individuals underwent neuropsychiatric and physical examinations, including tests of physical function, and APOE-genotyping. Follow-up examinations were performed at age 79. A significantly larger decline in grip strength (p = 0.015) between age 75 and 79 was found when comparing APOE epsilon 4 allele carriers with non carriers [10.3 (+/- 10.8) kg versus 7.8 (+/- 10.1) kg]. No association was seen with decline in gait speed, chair-stand, or balance. The association with grip strength remained after correction for cognitive and educational level, depression, cardiovascular disease, stroke, and BMI.
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| 2. |
- Rydberg Sterner, Therese, et al.
(författare)
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Depression and neuroticism decrease among women but not among men between 1976-2016 in Swedish septuagenarians
- 2019
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Ingår i: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 139:4, s. 381-394
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: We evaluated birth cohort differences in depressive symptom burden, prevalence of depression diagnoses, and neuroticism, among Swedish 70-year-olds examined between 1976 and 2016. Methods: We used a repeated cross-sectional design examining four representative population samples of Swedish 70-year-olds (total n=2279) with identical methods in 1976-77 (n=392), 1992-93 (n=226), 2000-02 (n=487), and 2014-16 (n=1166). Depressive symptom burden was rated with the Montgomery Åsberg Depression Rating Scale. Major depression was diagnosed according to DSM-5, and minor depression according to DSM-IV-TR research criteria. Neuroticism was rated with the Eysenck Personality Inventory. Results: For women in 2014-16, MADRS score (4.4 vs. 6.1 vs. 5.8; p<0.05) and neuroticism (6.6 vs. 7.7 vs. 9.2; p<0.05) were lower compared to 1992-93 and 1976-77, and the prevalence of any depression was lower compared to 2000-02 and 1992-93 (10.9% vs. 16.9% vs. 18.1%; p<0.05). For men, we observed no birth cohort differences in depression, while neuroticism was found to be lower in 2014-16 compared to 1976-77 among men without depression (5.1 vs. 5.9; p<0.01). The sex difference for MADRS and neuroticism declined between 1976-77 and 2014-16 (cohort*sex p<0.05). Conclusions: Depressive burden and neuroticism decreased in 70-year-old women between 1976 and 2016.
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| 3. |
- Zettergren, Anna, 1978, et al.
(författare)
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Proteomic analyses of limbic regions in neonatal male, female and androgen receptor knockout mice
- 2017
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Ingår i: Bmc Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is well-established that organizational effects of sex steroids during early development are fundamental for sex-typical displays of, for example, mating and aggressive behaviors in rodents and other species. Male and female brains are known to differ with respect to neuronal morphology in particular regions of the brain, including the number and size of neurons, and the density and length of dendrites in nuclei of hypothalamus and amygdala. The aim of the present study was to use global proteomics to identify proteins differentially expressed in hypothalamus/amygdala during early development (postnatal day 8) of male, female and conditional androgen receptor knockout (AR(NesDel)) male mice, lacking androgen receptors specifically in the brain. Furthermore, verification of selected sexually dimorphic proteins was performed using targeted proteomics. Results: Our proteomic approach, iTRAQ, allowed us to investigate expression differences in the 2998 most abundantly expressed proteins in our dissected tissues. Approximately 170 proteins differed between the sexes, and 38 proteins between AR(NesDel) and control males (p < 0.05). In line with previous explorative studies of sexually dimorphic gene expression we mainly detected subtle protein expression differences (fold changes < 1.3). The protein MARCKS (myristoylated alanine rich C kinase substrate), having the largest fold change of the proteins selected from the iTRAQ analyses and of known importance for synaptic transmission and dendritic branching, was confirmed by targeted proteomics as differentially expressed between the sexes. Conclusions: Overall, our results provide solid evidence that a large number of proteins show sex differences in their brain expression and could potentially be involved in brain sexual differentiation. Furthermore, our finding of a sexually dimorphic expression of MARCKS in the brain during development warrants further investigation on the involvement in sexual differentiation of this protein.
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| 4. |
- Zettergren, Anna, 1978, et al.
(författare)
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The ACE Gene Is Associated with Late-Life Major Depression and Age at Dementia Onset in a Population-Based Cohort.
- 2017
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Ingår i: The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. - : Elsevier BV. - 1064-7481 .- 1545-7214. ; 25:2, s. 170-177
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Tidskriftsartikel (refereegranskat)abstract
- Depression and dementia in the elderly have been suggested to share similar risk factors and pathogenetic background, and recently the authors reported that the APOEɛ4 allele is a risk factor for both disorders in the general population. The aim of the present study was to examine the influence of the well-known polymorphisms rs1799752 in the angiotensin-converting enzyme (ACE) and rs5186 in the angiotensin receptor II type 1 (AGTR1) on late-life depression and dementia in a population-based Swedish cohort of older individuals followed over 12 years.In 2000-2001, 900 individuals underwent neuropsychiatric and neuropsychological examinations. Follow-up evaluations were performed in 2005-2006 and 2009-2010, and register data on dementia to 2012 were included. Cross-sectional associations between genotypes/alleles and depression and dementia at baseline and between genotypes/alleles and depression on at least one occasion during the study period and dementia onset to 2012 were investigated.As previously found for rs1799752 in ACE, rs5186 in AGTR1 was associated with dementia at baseline (OR: 3.25 [CI: 1.42-7.06], z = 2.90, p = 0.004). These associations became substantially weaker, or disappeared, when dementia onset to 2012 was included. For rs1799752 this could be explained by a significant association with age at onset (mean: 79.5 [SD: 6.45] years for risk-genotype carriers and 81.7 [SD: 7.12] years for carriers of other genotypes, b = -2.43, t = -2.38, df = 192, p = 0.02). When individuals with major depression on at least one occasion were analyzed, a significant association (OR: 2.14 [95% CI: 1.13-4.20], z = 2.28, p = 0.02), remaining after exclusion of dementia, with rs1799752 in ACE was found.In this population-based sample of older individuals, genetic variations in ACE seem to be important both for late-life major depression and dementia.
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| 5. |
- Chibnik, L. B., et al.
(författare)
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Trends in the incidence of dementia: design and methods in the Alzheimer Cohorts Consortium
- 2017
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 32:10, s. 931-938
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have reported a decline in incidence of dementia which may have large implications for the projected burden of disease, and provide important guidance to preventive efforts. However, reports are conflicting or inconclusive with regard to the impact of gender and education with underlying causes of a presumed declining trend remaining largely unidentified. The Alzheimer Cohorts Consortium aggregates data from nine international population-based cohorts to determine changes in the incidence of dementia since 1990. We will employ Poisson regression models to calculate incidence rates in each cohort and Cox proportional hazard regression to compare 5-year cumulative hazards across study-specific epochs. Finally, we will meta-analyse changes per decade across cohorts, and repeat all analysis stratified by sex, education and APOE genotype. In all cohorts combined, there are data on almost 69,000 people at risk of dementia with the range of follow-up years between 2 and 27. The average age at baseline is similar across cohorts ranging between 72 and 77. Uniting a wide range of disease-specific and methodological expertise in research teams, the first analyses within the Alzheimer Cohorts Consortium are underway to tackle outstanding challenges in the assessment of time-trends in dementia occurrence.
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| 6. |
- Fardell, Camilla, et al.
(författare)
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S100B polymorphisms are associated with age of onset of Parkinson's disease
- 2018
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Ingår i: Bmc Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 19:42
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Tidskriftsartikel (refereegranskat)abstract
- Background: In this study we investigated the association between SNPs in the S100B gene and Parkinson's disease (PD) in two independent Swedish cohorts. The SNP rs9722 has previously been shown to be associated with higher S100B concentrations in serum and frontal cortex in humans. S100B is widely expressed in the central nervous system and has many functions such as regulating calcium homeostasis, inflammatory processes, cytoskeleton assembly/disassembly, protein phosphorylation and degradation, and cell proliferation and differentiation. Several of these functions have been suggested to be of importance for the pathophysiology of PD. Methods: The SNPs rs9722, rs2239574, rs881827, rs9984765, and rs1051169 of the S100B gene were genotyped using the KASPar (R) PCR SNP genotyping system in a case-control study of two populations (431 PD patients and 465 controls, 195 PD patients and 378 controls, respectively). The association between the genotype and allelic distributions and PD risk was evaluated using Chi-Square and Cox proportional hazards test, as well as logistic regression. Linear regression and Cox proportional hazards tests were applied to assess the effect of the rs9722 genotypes on age of disease onset. Results: The S100B SNPs tested were not associated with the risk of PD. However, in both cohorts, the T allele of rs9722 was significantly more common in early onset PD patients compared to late onset PD patients. The SNP rs9722 was significantly related to age of onset, and each T allele lowered disease onset with 4.9 years. In addition, allelic variants of rs881827, rs9984765, and rs1051169, were significantly more common in early-onset PD compared to late-onset PD in the pooled population. Conclusions: rs9722, a functional SNP in the 3'-UTR of the S100B gene, was strongly associated with age of onset of PD.
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| 7. |
- Göthberg, Hanna, 1973, et al.
(författare)
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Cross-sectional assessment of hearing acuity of an unscreened 85-year-old cohort - Including a 10-year longitudinal study of a sub-sample.
- 2019
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Ingår i: Hearing research. - : Elsevier BV. - 1878-5891 .- 0378-5955. ; 382
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Tidskriftsartikel (refereegranskat)abstract
- As the proportion of older people increases, it is important to investigate hearing acuity in older individuals and to calculate hearing decline for older ages, using standardised test protocols. The main aim of this study was to determine pure-tone hearing thresholds in an unscreened birth cohort of 85-year-olds born in 1930, living in an industrial Swedish city. A further aim was to describe hearing decline in men and women from 75 to 85 years of age with the aid of longitudinal data. The study was part of the Gothenburg H70 Birth Cohort Studies in Sweden. Hearing thresholds (0.25-8 kHz) were measured using automated pure-tone audiometry for 286 85-year-old participants. A subsample (n = 182) was hearing examined at 75 years of age and studied longitudinally from 75 to 85 years. At age 85 years, men had better hearing at low frequencies but poorer hearing at high frequencies than women. The longitudinal study showed a considerable decline between 75 and 85 years at mid-high frequencies (>1 kHz) and the amount of decline was similar between sexes. The results contribute to the estimation of the future need for hearing health services.
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| 8. |
- Hasselgren, Caroline, 1987, et al.
(författare)
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APOE ε4 and the long arm of social inequity: estimated effects of socio-economic status and sex on the timing of dementia onset
- 2019
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Ingår i: Ageing & Society. - 0144-686X .- 1469-1779. ; 39:9, s. 1951-1975
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Tidskriftsartikel (refereegranskat)abstract
- It is well established that carriers of the apolipoprotein E (APOE) ε4 allele run a greater risk of developing Alzheimer's disease, the most common form of dementia and a strongly age-related condition known to disproportionally affect women. Low educational attainment also stands out as a prominent risk factor, and it has been suggested that occupational class plays a similar role in disease susceptibility. Not yet fully explored, however, is the question of whether socio-economic status (SES) could moderate the effect of APOE ε4. In the present paper, we address this issue. As substantial inequities in workforce participation and educational opportunities have existed between men and women in previous generations, we further examine whether SES-related moderations of the relationship between dementia and APOE ε4 are sex-specific. Our analyses are based on a sample of 580 individuals from the H70 Birth Cohort Study and the Prospective Population Study on Women in Gothenburg, Sweden. Data were analysed using Cox proportional hazards regression, and the results suggest that while high SES postpones dementia onset among male APOE ε4 carriers, this is not the case for women. These findings underscore the long-term impact of social inequity on health as well as the importance of considering potential interactions between social and genetic risk factors if we are to understand better the complex aetiology of dementia.
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