SwePub - search: WFRF:(Zettergren Anna 1978)

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1.	Skoog, Ingmar, 1954, et al. (author) Association between APOE Genotype and Change in Physical Function in a Population-Based Swedish Cohort of Older Individuals Followed Over Four Years 2016 In: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 8 Journal article (peer-reviewed)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.
2.	Dittrich, Anna, 1972, et al. (author) Association of Chronic Kidney Disease With Plasma NfL and Other Biomarkers of Neurodegeneration: The H70 Birth Cohort Study in Gothenburg. 2023 In: Neurology. - 1526-632X. ; 101:3 Journal article (peer-reviewed)abstract Studies associate chronic kidney disease (CKD) with neurodegeneration. This study investigated the relationship between kidney function, blood, CSF, and structural brain MRI markers of neurodegeneration in a sample including individuals with and without CKD.Participants from the Gothenburg H70 Birth Cohort Study, with data on plasma neurofilament light (P-NfL), estimated glomerular filtration rate (eGFR), and structural brain MRI were included. Participants were invited to also have the CSF collected. The primary endpoint of this study was to determine any association between CKD and P-NfL. Secondary endpoints included cross-sectional associations between CKD, eGFR, and CSF-derived and MRI-derived markers of neurodegeneration and Alzheimer disease (AD) pathology (MRI: cortical thickness, hippocampal volume, lateral ventricle volume, and white matter lesion volume; CSF: β-amyloid (Aβ) 42, Aβ42/40, Aβ42/p-tau, t-tau, p-tau, and NfL). Participants with P-NfL and eGFR at baseline were re-examined on eGFR, 5.5 (5.3-6.1) years (median; IQR) after the first visit, and the predictive value of P-NfL levels on incident CKD was estimated longitudinally, using a Cox proportional hazards model.We included 744 participants, 668 without CKD (age 71 [70-71] years, 50% males) and 76 with CKD (age 71 [70-71] years, 39% males). Biomarkers from the CSF were analyzed in 313 participants. A total of 558 individuals returned for a re-examination of eGFR (75% response rate, age 76 [76; 77] years, 48% males, 76 new cases of CKD). Participants with CKD had higher P-NfL levels than those with normal kidney function (median; 18.8 vs 14.1 pg/mL, p < 0.001), while MRI and CSF markers were similar between the groups. P-NfL was independently associated with CKD after adjustment for confounding variables, including hypertension and diabetes (OR; 3.231, p < 0.001), in a logistic regression model. eGFR and CSF Aβ 42/40: R = 0.23, p = 0.004 correlated in participants with Aβ42 pathology. P-NfL levels in the highest quartile were associated with incident CKD at follow-up (HR; 2.39 [1.21: 4.72]).In a community-based cohort of 70-year olds, P-NfL was associated with both prevalent and incident CKD, while CSF and/or imaging measures did not differ by CKD status. Participants with CKD and dementia presented similar levels of P-NfL.
3.	Dittrich, Anna, 1972, et al. (author) Plasma and CSF NfL are differentially associated with biomarker evidence of neurodegeneration in a community-based sample of 70-year-olds 2022 In: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. - : Wiley. - 2352-8729. ; 14:1 Journal article (peer-reviewed)abstract Neurofilament light protein (NfL) in cerebrospinal fluid (CSF) and plasma (P) are suggested to be interchangeable markers of neurodegeneration. However, evidence is scarce from community-based samples. NfL was examined in a small-scale sample of 287 individuals from the Gothenburg H70 Birth cohort 1944 study, using linear models in relation to CSF and magnetic resonance imaging (MRI) biomarker evidence of neurodegeneration. CSF-NfL and P-NfL present distinct associations with biomarker evidence of Alzheimer's disease (AD) pathology and neurodegeneration. P-NfL was associated with several markers that are characteristic of AD, including smaller hippocampal volumes, amyloid beta (A beta)(42), A beta(42/40), and A beta(42)/t-tau (total tau). CSF-NfL demonstrated associations with measures of synaptic and neurodegeneration, including t-tau, phosphorylated tau (p-tau), and neurogranin. Our findings suggest that P-NfL and CSF-NfL may exert different effects on markers of neurodegeneration in a small-scale community-based sample of 70-year-olds.
4.	Dittrich, Anna, 1972, et al. (author) Proportion of Community-Dwelling Individuals Older Than 70 Years Eligible for Lecanemab Initiation: The Gothenburg H70 Birth Cohort Study. 2024 In: Neurology. - 0028-3878 .- 1526-632X. ; 102:9 Journal article (peer-reviewed)abstract To determine the prevalence of individuals with Alzheimer disease (AD) eligible for treatment with the recently FDA-approved lecanemab based on data from a population-based sample of 70-year-olds and extrapolate an estimation of individuals eligible in Europe and the United States.Participants from the Gothenburg H70 Birth Cohort Study with clinical data, CSF-amyloid beta 42, and brain MRI analysis were evaluated for eligibility to receive lecanemab treatment according to FDA-approved recommendations, noting factors requiring special consideration. Results were used to extrapolate the number of eligible individuals in Europe and the United States using public demographic data.Thirty (10.3%) of 290 participants met the indication for treatment of whom 18 (6.2%) were eligible and did not present factors requiring special consideration. Our estimate that 6.2% of all 70-year-olds in the full cohort are eligible for treatment extrapolates to an approximation that around 5.9 million Europeans and 2.2 million US residents could be eligible.Information on proportion of individuals eligible for AD treatment with lecanemab in the general public is limited. We provide information on 70-year-olds in Sweden and extrapolate these data to Europe and the United States. This study opens for larger studies on this proportion and implementation of lecanemab treatment.
5.	Jeppsson, Anna, et al. (author) Plasma and cerebrospinal fluid concentrations of neurofilament light protein correlate in patients with idiopathic normal pressure hydrocephalus 2023 In: Fluids and Barriers of the CNS. - 2045-8118. ; 20:1 Journal article (peer-reviewed)abstract Background Neurofilament light chain protein (NFL), a marker of neuronal axonal degeneration, is increased in cerebrospinal fluid (CSF) of patients with idiopathic normal pressure hydrocephalus (iNPH). Assays for analysis of NFL in plasma are now widely available but plasma NFL has not been reported in iNPH patients. Our aim was to examine plasma NFL in iNPH patients and to evaluate the correlation between plasma and CSF levels, and whether NFL levels are associated with clinical symptoms and outcome after shunt surgery. Methods Fifty iNPH patients with median age 73 who had their symptoms assessed with the iNPH scale and plasma and CSF NFL sampled pre- and median 9 months post-operatively. CSF plasma was compared with 50 healthy controls (HC) matched for age and gender. Concentrations of NFL were determined in plasma using an in-house Simoa method and in CSF using a commercially available ELISA method. Results Plasma NFL was elevated in patients with iNPH compared to HC (iNPH: 45 (30-64) pg/mL; HC: 33 (26-50) (median; Q1-Q3), p = 0.029). Plasma and CSF NFL concentrations correlated in iNPH patients both pre- and postoperatively (r = 0.67 and 0.72, p < 0.001). We found only weak correlations between plasma or CSF NFL and clinical symptoms and no associations with outcome. A postoperative NFL increase was seen in CSF but not in plasma. Conclusions Plasma NFL is increased in iNPH patients and concentrations correlate with CSF NFL implying that plasma NFL can be used to assess evidence of axonal degeneration in iNPH. This finding opens a window for plasma samples to be used in future studies of other biomarkers in iNPH. NFL is probably not a very useful marker of symptomatology or for prediction of outcome in iNPH.
6.	Marseglia, Anna, et al. (author) Metabolic Syndrome Is Associated With Poor Cognition : A Population-Based Study of 70-Year-Old Adults Without Dementia 2021 In: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 76:12, s. 2275-2283 Journal article (peer-reviewed)abstract Background: Individual conditions of metabolic syndrome (MetS) have been related to dementia; however, their combined impact on the preclinical stage is unknown. We investigated the associations between MetS and domain-specific cognitive function as well as the role of sociodemographic, cardiovascular, and genetic factors.Methods: Within the Gothenburg H70 Birth Cohort Study-Birth cohort 1944, 1131 dementia-free participants (aged 70 years) were examined during 2014-2016. MetS (central obesity plus at least 2 factors [reduced HD11.-cholesterol, elevated triglycerides, blood pressure, or blood glucose]) was identified according to the International Diabetes Federation criteria. Five cognitive domains (memory, attention/perceptual speed, executive function, verbal fluency, visuospatial abilities) were generated after z-standardizing raw scores from 10 neuropsychological tests. Education, heart disease, claudication (indicating peripheral atherosclerosis), and apolipoprotein genotype were ascertained by trained staff. Data were analyzed with linear regression models.Results: Overall, 618 participants (55%) had MetS. In multiadjusted linear regressions, MetS was related to poorer performance in attention/ perceptual speed (beta -0.14 [95% CI -0.25, -0.02]), executive function (beta -0.12 [95% CI -0.23, -0.01]), and verbal fluency (beta -0.19 [95% CI -0.30, -0.08]). These associations were present only among individuals who did not carry any APOE-epsilon 4 allele or were highly educated. However, among those with MetS, high education was related to better cognitive performance. MetS together with comorbid heart disease or claudication was associated with even worse cognitive performance than each alone.Conclusions: MetS is associated with poor attention/perceptual speed, executive function, and verbal fluency performance. Education, apolipoprotein E-epsilon 4 allele, and comorbid cardiovascular disease influenced the observed associations.
7.	Novak, Masuma, 1969, et al. (author) Cardiovascular and all-cause mortality attributable to loneliness in older Swedish men and women. 2020 In: BMC geriatrics. - : Springer Science and Business Media LLC. - 1471-2318. ; 20:1 Journal article (peer-reviewed)abstract This study examined whether loneliness predicts cardiovascular- and all-cause mortality in older men and women.Baseline data from the Gothenburg H70 Birth Cohort Studies, collected during 2000 on 70-year-olds born 1930 and living in Gothenburg were used for analysis (n=524). Mortality data were analyzed until 2012 through Swedish national registers.Perceived loneliness was reported by 17.1% of the men and 30.9% of the women in a face-to-face interview with mental health professional. A total of 142 participants died during the 12-year follow-up period, with 5334 person-years at risk, corresponding to 26.6 deaths/1000 person-years. Cardiovascular disease accounted for 59.2% of all deaths. The cumulative rates/1000 person-years for cardiovascular mortality were 20.8 (men) and 11.5 (women), and for all-cause mortality 33.8 (men) and 20.5 (women), respectively. In Cox regression models, no significant increased risk of mortality was seen for men with loneliness compared to men without loneliness (cardiovascular mortality HR 1.52, 95% CI 0.78-2.96; all-cause HR 1.32, 95% CI 0.77-2.28). Increased risk of cardiovascular mortality was observed in women with loneliness compared to those without (HR 2.25 95% CI 1.14-4.45), and the risk remained significant in a multivariable-adjusted model (HR 2.42 95% CI 1.04-5.65).Loneliness was shown to be an independent predictor of cardiovascular mortality in women. We found no evidence to indicate that loneliness was associated with an increased risk of either cardiovascular- or all-cause mortality in men.
8.	Novak, Masuma, 1969, et al. (author) Six-year mortality associated with living alone and loneliness in Swedish men and women born in 1930 2023 In: BMC Geriatrics. - 1471-2318. ; 23:1 Journal article (peer-reviewed)abstract Background: This study examined how living alone and loneliness associate with all-cause mortality in older men and women. Methods: Baseline data from the Gothenburg H70 Birth Cohort Studies, including 70-year-olds interviewed in 2000 and 75-year-olds (new recruits) interviewed in 2005were used for analyses (N = 778, 353 men, 425 women). Six-year mortality was based on national register data. Results: At baseline, 36.6% lived alone and 31.9% reported feelings of loneliness. A total of 72 (9.3%) participants died during the 6-year follow-up period. Cumulative mortality rates per 1000 person-years were 23.9 for men and 9.6 for women. Mortality was increased more than twofold among men who lived alone compared to men living with someone (HR 2.40, 95% CI 1.34–4.30). Elevated risk remained after multivariable adjustment including loneliness and depression (HR 2.56, 95% CI 1.27–5.16). Stratification revealed that mortality risk in the group of men who lived alone and felt lonely was twice that of their peers who lived with someone and did not experience loneliness (HR 2.52, 95% CI 1.26–5.05). In women, a more than fourfold increased risk of mortality was observed in those who experienced loneliness despite living with others (HR 4.52, 95% CI 1.43–14.23). Conclusions: Living alone was an independent risk factor for death in men but not in women. Mortality was doubled in men who lived alone and felt lonely. In contrast, mortality was particularly elevated in women who felt lonely despite living with others. In the multivariable adjusted models these associations were attenuated and were no longer significant after adjusting for mainly depression in men and physical inactivity in women. Gender needs to be taken into account when considering the health consequences of living situation and loneliness.
9.	Remnestål, Julia, et al. (author) Association of CSF proteins with tau and amyloid β levels in asymptomatic 70-year-olds. 2021 In: Alzheimer's research & therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 13:1 Journal article (peer-reviewed)abstract Increased knowledge of the evolution of molecular changes in neurodegenerative disorders such as Alzheimer's disease (AD) is important for the understanding of disease pathophysiology and also crucial to be able to identify and validate disease biomarkers. While several biological changes that occur early in the disease development have already been recognized, the need for further characterization of the pathophysiological mechanisms behind AD still remains.In this study, we investigated cerebrospinal fluid (CSF) levels of 104 proteins in 307 asymptomatic 70-year-olds from the H70 Gothenburg Birth Cohort Studies using a multiplexed antibody- and bead-based technology.The protein levels were first correlated with the core AD CSF biomarker concentrations of total tau, phospho-tau and amyloid beta (Aβ42) in all individuals. Sixty-three proteins showed significant correlations to either total tau, phospho-tau or Aβ42. Thereafter, individuals were divided based on CSF Aβ42/Aβ40 ratio and Clinical Dementia Rating (CDR) score to determine if early changes in pathology and cognition had an effect on the correlations. We compared the associations of the analysed proteins with CSF markers between groups and found 33 proteins displaying significantly different associations for amyloid-positive individuals and amyloid-negative individuals, as defined by the CSF Aβ42/Aβ40 ratio. No differences in the associations could be seen for individuals divided by CDR score.We identified a series of transmembrane proteins, proteins associated with or anchored to the plasma membrane, and proteins involved in or connected to synaptic vesicle transport to be associated with CSF biomarkers of amyloid and tau pathology in AD. Further studies are needed to explore these proteins' role in AD pathophysiology.
10.	Rydberg Sterner, Therese, et al. (author) Depression and neuroticism decrease among women but not among men between 1976-2016 in Swedish septuagenarians 2019 In: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 139:4, s. 381-394 Journal article (peer-reviewed)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.
11.	Rydberg Sterner, Therese, et al. (author) Depression in relation to sex and gender expression among Swedish septuagenarians-Results from the H70 study 2020 In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 15:9 Journal article (peer-reviewed)abstract Objective Little is known about the role of gender expression (femininity, masculinity, or androgyny) in relation to sex differences in depression. This study tested if gender expression was associated with depression and burden of depressive symptoms in a 70-year-old population. Methods A cross-sectional population-based sample of 70-year-olds from The Gothenburg H70 Birth Cohort Study (n = 1203) was examined in 2014-16. Data were collected using psychiatric examinations and structured questionnaires, including the Positive-Negative Sex-Role Inventory to assess gender expression. Depression was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders criteria, and symptom burden was assessed with Montgomery angstrom sberg Depression Rating Scale (MADRS). Results Gender expression was related to MADRS score and depression diagnosis. In fully adjusted models, feminine traits with low social desirability (FEM-) were associated with a higher MADRS score (R(2)0.16; B 0.16; CI 0.1-0.2), while androgyny (t ratio) (R(2)0.12; B 0.42; CI 0.1-0.7) and masculine traits with high social desirability (MAS+) (R(2)0.13; B -0.06; CI -0.1--0.01) were associated with a lower MADRS score. Also, feminine traits with low social desirability (FEM-) were positively associated with depression (OR 1.04; CI 1.01-1.1). No associations between depression and masculinity or androgyny were observed in adjusted models. There were no interactions between sex and gender expression in relation to depression or MADRS score, indicating that the effects of gender expression were similar in men and women. Conclusions We found that gender expression was associated to both depression and burden of depressive symptoms. More specifically, we found that femininity was associated to higher levels of depression, irrespective of biological sex. In addition, masculinity and androgyny were associated with lower levels of depression. These results highlight the importance of taking gender expression into consideration when studying sex differences in depression among older populations in future studies.
12.	Rydén, Lina, 1982, et al. (author) Attrition in the Gothenburg H70 birth cohort studies, an 18-year follow-up of the 1930 cohort 2023 In: Frontiers in Epidemiology. - 2674-1199. ; 3 Journal article (peer-reviewed)abstract Background: Longitudinal studies are essential to understand the ageing process, and risk factors and consequences for disorders, but attrition may cause selection bias and impact generalizability. We describe the 1930 cohort of the Gothenburg H70 Birth Cohort Studies, followed from age 70 to 88, and compare baseline characteristics for those who continue participation with those who die, refuse, and drop out for any reason during follow-up. Methods: A population-based sample born 1930 was examined with comprehensive assessments at age 70 (N = 524). The sample was followed up and extended to increase sample size at age 75 (N = 767). Subsequent follow-ups were conducted at ages 79, 85, and 88. Logistic regression was used to analyze baseline characteristics in relation to participation status at follow-up. Results: Refusal to participate in subsequent examinations was related to lower educational level, higher blood pressure, and lower scores on cognitive tests. Both attrition due to death and total attrition were associated with male sex, lower educational level, smoking, ADL dependency, several diseases, poorer lung function, slower gait speed, lower scores on cognitive tests, depressive symptoms, and a larger number of medications. Attrition due to death was also associated with not having a partner. Conclusions: It is important to consider different types of attrition when interpreting results from longitudinal studies, as representativeness and results may be differently affected by different types of attrition. Besides reducing barriers to participation, methods such as imputation and weighted analyses can be used to handle selection bias.
13.	Samuelsson, Jessica, et al. (author) Associations between dietary patterns and dementia-related neuroimaging markers 2023 In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:10, s. 4629-4640 Journal article (peer-reviewed)abstract BACKGROUNDThe exploration of associations between dietary patterns and dementia-related neuroimaging markers can provide insights on food combinations that may impact brain integrity. METHODSData were derived from the Swedish Gothenburg H70 Birth Cohort Study (n = 610). Three dietary patterns were obtained using principal component analysis. Magnetic resonance imaging markers included cortical thickness, an Alzheimer's disease (AD) signature score, small vessel disease, and white matter microstructural integrity. Adjusted linear/ordinal regression analyses were performed. RESULTSA high-protein and alcohol dietary pattern was negatively associated with cortical thickness in the whole brain (Beta: -0.011; 95% confidence interval [CI]: -0.018 to -0.003), and with an Alzheimer's disease cortical thickness signature score (Beta: -0.013; 95% CI: -0.024 to -0.001). A positive association was found between a Mediterranean-like dietary pattern and white matter microstructural integrity (Beta: 0.078; 95% CI: 0.002-0.154). No associations were found with a Western-like dietary pattern. DISCUSSIONDietary patterns may impact brain integrity through neurodegenerative and vascular pathways. HighlightsCertain dietary patterns were associated with dementia-related neuroimaging markers.A Mediterranean dietary pattern was positively associated with white matter microstructure.A high-protein and alcohol pattern was negatively associated with cortical thickness.
14.	Westerlund, Marie, et al. (author) Altered enzymatic activity and allele frequency of OMI/HTRA2 in Alzheimer's disease. 2011 In: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - : Wiley. - 1530-6860. ; 25:4, s. 1345-52 Journal article (peer-reviewed)abstract The serine-protease OMI/HTRA2, required for several cellular processes, including mitochondrial function, autophagy, chaperone activity, and apoptosis, has been implicated in the pathogenesis of both Alzheimer's disease (AD) and Parkinson's disease (PD). Western blot quantification of OMI/HTRA2 in frontal cortex of patients with AD (n=10) and control subjects (n=10) in two separate materials indicated reduced processed (active, 35 kDa) OMI/HTRA2 levels, whereas unprocessed (50 kDa) enzyme levels were not significantly different between the groups. Interestingly, the specific protease activity of OMI/HTRA2 was found to be significantly increased in patients with AD (n=10) compared to matched control subjects (n=10) in frontal cortex in two separate materials. Comparison of OMI/HTRA2 mRNA levels in frontal cortex and hippocampus, two brain areas particularly affected by AD, indicated similar levels in patients with AD (n=10) and matched control subjects (n=10). In addition, we analyzed the occurrence of the OMI/HTRA2 variants A141S and G399S in Swedish case-control materials for AD and PD and found a weak association of A141S with AD, but not with PD. In conclusion, our genetic, histological, and biochemical findings give further support to an involvement of OMI/HTRA2 in the pathology of AD; however, further studies are needed to clarify the role of this gene in neurodegeneration.
15.	Wetterberg, Hanna, et al. (author) Representativeness in population-based studies of older adults: five waves of cross-sectional examinations in the Gothenburg H70 Birth Cohort Study 2022 In: Bmj Open. - : BMJ. - 2044-6055. ; 12:12 Journal article (peer-reviewed)abstract ObjectivesTo describe representativeness in the Gothenburg H70 1930 Birth Cohort Study.DesignRepeated cross-sectional examinations of a population-based study.SettingGothenburg, Sweden.ParticipantsAll residents of Gothenburg, Sweden, born on specific birth dates in 1930 were invited to a comprehensive health examination at ages 70, 75, 79, 85 and 88. The number of participants at each examination was 524 at age 70, 767 at age 75, 580 at age 79, 416 at age 85, and 258 at age 88.Primary outcome measuresWe compared register data on sociodemographic characteristics and hospital discharge diagnoses between participants and (1) refusals, (2) all same-aged individuals in Gothenburg and (3) all same-aged individuals in Sweden. We also compared mortality rates between participants and refusals.ResultsRefusal rate increased with age. At two or more examination waves, participants compared with refusals had higher educational level, more often had osteoarthritis, had lower mortality rates, had lower prevalence of neuropsychiatric, alcohol-related and cardiovascular disorders, and were more often married. At two examination waves, participants compared with same-aged individuals in Gothenburg had higher education and were more often born in Sweden. At two examination waves or more, participants compared with same-aged individuals in Sweden had higher education, had higher average income, less often had ischaemic heart disease, were less often born in Sweden and were more often divorced.ConclusionsParticipants were more similar to the target population in Gothenburg than to refusals and same-aged individuals in Sweden. Our study shows the importance of having different comparison groups when assessing representativeness of population studies, which is important in evaluating generalisability of results. The study also contributes unique and up-to-date knowledge about participation bias in these high age groups.
16.	Zettergren, Anna, 1978, et al. (author) Proteomic analyses of limbic regions in neonatal male, female and androgen receptor knockout mice 2017 In: Bmc Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 18 Journal article (peer-reviewed)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.
17.	Zettergren, Anna, 1978, et al. (author) The ACE Gene Is Associated with Late-Life Major Depression and Age at Dementia Onset in a Population-Based Cohort. 2017 In: 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 Journal article (peer-reviewed)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.
18.	Ahlner, Felicia, 1987, et al. (author) Patterns of Alcohol Consumption and Associated Factors in a Population-Based Sample of 70-Year-Olds: Data from the Gothenburg H70 Birth Cohort Study 2014-16 2022 In: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1660-4601 .- 1661-7827. ; 19:14 Journal article (peer-reviewed)abstract Older adults of today consume more alcohol, yet knowledge about the factors associated with different consumption levels is limited in this age group. Based on the data from a population-based sample (n = 1156, 539 men and 617 women) in The Gothenburg H70 Birth Cohort Study 2014-16, we examined sociodemographic, social, and health-related factors associated with alcohol consumption levels in 70-year-olds, using logistic regression. Total weekly alcohol intake was calculated based on the self-reported amount of alcohol consumed. Alcohol consumption was categorized as lifetime abstention, former drinking, moderate consumption (<= 98 g/week), and at-risk consumption (>98 g/week). At-risk consumption was further categorized into lower at-risk (98-196 g/week), medium at-risk (196-350 g/week), and higher at-risk (>= 350 g/week). We found that among the 1156 participants, 3% were lifetime abstainers, 3% were former drinkers, 64% were moderate drinkers, and 30% were at-risk drinkers (20% lower, 8% medium, 2% higher). Among several factors, former drinking was associated with worse general self-rated health (OR 1.65, 95% CI 1.08-2.51) and lower health-related quality of life (measured by physical component score) (OR 0.94, 95% CI 0.91-0.97), higher illness burden (OR 1.16, 95% CI 1.07-1.27), and weaker grip strength (OR 0.96, 95% CI 0.94-0.98). Higher at-risk drinkers more often had liver disease (OR 11.41, 95% CI 3.48-37.37) and minor depression (OR 4.57, 95% CI 1.40-14.95), but less contacts with health care (OR 0.32, 95% CI 0.11-0.92). Our findings demonstrate the importance of classifications beyond abstinence and at-risk consumption, with implications for both the prevention and clinical management of unhealthy consumption patterns in older adults.
19.	Arvidsson Rådestig, Maya, et al. (author) Cerebrospinal fluid biomarkers of axonal and synaptic degeneration in a population-based sample 2023 In: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 15:1 Journal article (peer-reviewed)abstract BackgroundNeurofilament light (NfL) and neurogranin (Ng) are promising candidate AD biomarkers, reflecting axonal and synaptic damage, respectively. Since there is a need to understand the synaptic and axonal damage in preclinical Alzheimer's disease (AD), we aimed to determine the cerebrospinal fluid (CSF) levels of NfL and Ng in cognitively unimpaired elderly from the Gothenburg H70 Birth Cohort Studies classified according to the amyloid/tau/neurodegeneration (A/T/N) system.MethodsThe sample consisted of 258 cognitively unimpaired older adults (age 70, 129 women and 129 men) from the Gothenburg Birth Cohort Studies. We compared CSF NfL and Ng concentrations in A/T/N groups using Student's T-test and ANCOVA.ResultsCSF NfL concentration was higher in the A-T-N+ group (p=0.001) and the A-T+N+ group (p=0.006) compared with A-T-N-. CSF Ng concentration was higher in the A-T-N+, A-T+N+, A+T-N+, and A+T+N+ groups (p<0.0001) compared with A-T-N-. We found no difference in NfL or Ng concentration in A+ compared with A- (disregarding T- and N- status), whereas those with N+ had higher concentrations of NfL and Ng compared with N- (p<0.0001) (disregarding A- and T- status).ConclusionsCSF NfL and Ng concentrations are increased in cognitively normal older adults with biomarker evidence of tau pathology and neurodegeneration.
20.	Arvidsson Rådestig, Maya, et al. (author) Cognitive Performance and Cerebrospinal Fluid Markers in Preclinical Alzheimer's Disease: Results from the Gothenburg H70 Birth Cohort Studies. 2021 In: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 79:1, s. 225-235 Journal article (peer-reviewed)abstract We have previously shown that older adults with preclinical Alzheimer's disease (AD) pathology in cerebrospinal fluid (CSF) had slightly worse performance in Mini-Mental State Examination (MMSE) than participants without preclinical AD pathology.We therefore aimed to compare performance on neurocognitive tests in a population-based sample of 70-year-olds with and without CSF AD pathology.The sample was derived from the population-based Gothenburg H70 Birth Cohort Studies in Sweden. Participants (n=316, 70 years old) underwent comprehensive cognitive examinations, and CSF Aβ-42, Aβ-40, T-tau, and P-tau concentrations were measured. Participants were classified according to the ATN system, and according to their Clinical Dementia Rating (CDR) score. Cognitive performance was examined in the CSF amyloid, tau, and neurodegeneration (ATN) categories.Among participants with CDR 0 (n=259), those with amyloid (A+) and/or tau pathology (T+, N+) showed similar performance on most cognitive tests compared to participants with A-T-N-. Participants with A-T-N+ performed worse in memory (Supra span (p=0.003), object Delayed (p=0.042) and Immediate recall (p=0.033)). Among participants with CDR 0.5 (n=57), those with amyloid pathology (A+) scored worse in category fluency (p=0.003).Cognitively normal participants with amyloid and/or tau pathology performed similarly to those without any biomarker evidence of preclinical AD in most cognitive domains, with the exception of slightly poorer memory performance in A-T-N+. Our study suggests that preclinical AD biomarkers are altered before cognitive decline.
21.	Arvidsson Rådestig, Maya, et al. (author) Subtle Differences in Cognition in 70-Year-Olds with Elevated Cerebrospinal Fluid Neurofilament Light and Neurogranin: A H70 Cross-Sectional Study 2023 In: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 91:1, s. 291-303 Journal article (peer-reviewed)abstract Background: Most research on cerebrospinal fluid (CSF) neurofilament light protein (NfL) as a marker for neurodegeneration and neurogranin (Ng) for synaptic dysfunction has largely focused on clinical cohorts rather than population-based samples. Objective: We hypothesized that increased CSF levels of NfL and Ng are associated with subtle cognitive deficits in cognitively unimpaired (CU) older adults. Methods: The sample was derived from the Gothenburg H70 Birth Cohort Studies and comprised 258 CU 70-year-olds, with a Clinical Dementia Rating score of zero. All participants underwent extensive cognitive testing. CSF levels of NfL and Ng, as well as amyloid beta(1-42), total tau, and phosphorylated tau, were measured. Results: Participants with high CSF NfL performed worse in one memory-based test (Immediate recall, p = 0.013) and a language test (FAS, p = 0.016). Individuals with high CSF Ng performed worse on the memory-based test Supra Span (p = 0.035). When stratified according to CSF tau and A beta(42) concentrations, participants with high NfL and increased tau performed worse on a memory test than participants normal tau concentrations (Delayed recall, p = 0.003). In participants with high NfL, those with pathologic A beta(42) concentrations performed worse on the Delayed recall memory (p = 0.044). In the high Ng group, participants with pathological A beta(42) concentrations had lower MMSE scores (p = 0.027). However, in regression analysis we found no linear correlations between CSF NfL or CSF Ng in relation to cognitive tests when controlled for important co-variates. Conclusion: Markers of neurodegeneration and synaptic pathology might be associated with subtle signs of cognitive decline in a population-based sample of 70-year-olds.
22.	Ayala, Marcelo, 1965, et al. (author) Association of Single Nucleotide Polymorphisms Located in LOXL1 with Exfoliation Glaucoma in Southwestern Sweden 2021 In: Genes. - : MDPI AG. - 2073-4425. ; 12:9 Journal article (peer-reviewed)abstract Introduction: Glaucoma is an optic neuropathy that leads to visual field defects. Genetic mechanisms seem to be involved in glaucoma development. Lysyl Oxidase Like 1 (LOXL1) has been described in previous studies as a predictor factor for exfoliation glaucoma. The present article studied the association between three single nucleotide polymorphisms (SNPs) in the LOXL1 gene and the presence of exfoliation glaucoma in Southwestern Sweden. Methods: Case-control study for genetic association. In total, 136 patients and 1011 controls were included in the study. Patients with exfoliation glaucoma were recruited at the Eye Department of Sahlgrenska University Hospital and Skaraborgs Hospital, Sweden. Controls were recruited from the Gothenburg H70 Birth Cohort Study. Three different SNPs were genotyped: LOXL1_rs3825942, LOXL1_rs2165241 and LOXL1_rs1048661. Results: The distribution of allele frequencies was significantly different between controls and glaucoma patients; for rs3825942 (p = 2 x 10(-12)), for rs2165241 (p = 3 x 10(-16)) and for rs1048661 (p = 2 x 10(-6)). Logistic regression analyses using an additive genetic model, adjusted for sex and age, also showed associations between the studied SNPs and glaucoma (p = 9 x 10(-6); p = 2 x 10(-14); p = 1 x 10(-4)). Conclusion: A strong association was found between allele frequencies of three different SNPs (LOXL1_rs3825942, LOXL1_rs2165241, and LOXL1_rs1048661) and the presence of exfoliation glaucoma in a Southwestern Swedish population.
23.	Ayala, Marcelo, 1965, et al. (author) Single nucleotide polymorphisms in LOXL1 as biomarkers for progression of exfoliation glaucoma in Sweden 2023 In: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 101:5, s. 521-529 Journal article (peer-reviewed)abstract Purpose: Exfoliation glaucoma is a common and aggressive type of glaucoma with high prevalence in Scandinavia. The aim of this study was to elucidate whether the allele frequencies of two single nucleotide polymorphisms (SNPs) located in LOXL1 were associated with the progression of exfoliation glaucoma in Swedish patients. Methods: In this non-randomised cohort study, we enrolled patients with exfoliation glaucoma, and they performed at least five reliable visual field tests. Blood samples were collected, and genotyping was performed using competitive allele-specific PCR genotyping. Glaucoma progression was evaluated using the guided glaucoma progression analysis (GPA), mean deviation (MD) difference and rate of progression (ROP). In addition, associations between allele frequencies and glaucoma progression were tested using logistic regression for GPA and linear regression for MD and ROP. Results: We enrolled a total of 130 patients in the study. The general genetic model showed statistical significance for LOXL1_rs2165241 (p=8 × 10−7, Fisher's exact test) and LOXL1_rs1048661 (p=2 × 10−6, Fisher's exact test). Regression analyses using an additive genetic model showed significant values for LOXL1_rs2165241SNP in relation to GPA, MD and ROP as outcomes (p=1.8 × 10−4, 4 × 10−2, 6 × 10−4) and for LOXL1_rs1048661 SNP in relation to GPA, MD and ROP (p=7 × 10−5, 8 × 10−3, 2 × 10−4). Conclusions: This was the first study to show an association of the SNPs LOXL1_rs2165241 and LOXL1_rs1048661 with the progression of exfoliation glaucoma. Further large-scale studies are required to verify these findings.
24.	Badji, A., et al. (author) Cerebrospinal Fluid Biomarkers, Brain Structural and Cognitive Performances Between Normotensive and Hypertensive Controlled, Uncontrolled and Untreated 70-Year-Old Adults 2022 In: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 13 Journal article (peer-reviewed)abstract Background: Hypertension is an important risk factor for Alzheimer's disease (AD). The pathophysiological mechanisms underlying the relationship between AD and hypertension are not fully understood, but they most likely involve microvascular dysfunction and cerebrovascular pathology. Although previous studies have assessed the impact of hypertension on different markers of brain integrity, no study has yet provided a comprehensive comparison of cerebrospinal fluid (CSF) biomarkers and structural brain differences between normotensive and hypertensive groups in a single and large cohort of older adults in relationship to cognitive performances.Objective: The aim of the present work was to investigate the differences in cognitive performances, CSF biomarkers and magnetic resonance imaging (MRI) of brain structure between normotensive, controlled hypertensive, uncontrolled hypertensive, and untreated hypertensive older adults from the Gothenburg H70 Birth Cohort Studies.Methods: As an indicator of vascular brain pathology, we measured white matter hyperintensities (WMHs), lacunes, cerebral microbleeds, enlarged perivascular space (epvs), and fractional anisotropy (FA). To assess markers of AD pathology/neurodegeneration, we measured hippocampal volume, temporal cortical thickness on MRI, and amyloid-beta(42), phosphorylated tau, and neurofilament light protein (NfL) in cerebrospinal fluid. Various neuropsychological tests were used to assess performances in memory, attention/processing speed, executive function, verbal fluency, and visuospatial abilities.Results: We found more white matter pathology in hypertensive compared to normotensive participants, with the highest vascular burden in uncontrolled participants (e.g., lower FA, more WMHs, and epvs). No significant difference was found in any MRI or CSF markers of AD pathology/neurodegeneration when comparing normotensive and hypertensive participants, nor among hypertensive groups. No significant difference was found in most cognitive functions between groups.Conclusion: Our results suggest that good blood pressure control may help prevent cerebrovascular pathology. In addition, hypertension may contribute to cognitive decline through its effect on cerebrovascular pathology rather than AD-related pathology. These findings suggest that hypertension is associated with MRI markers of vascular pathology in the absence of a significant decline in cognitive functions.
25.	Borda, Miguel German, et al. (author) Nutrient Intake and Its Association with Appendicular Total Lean Mass and Muscle Function and Strength in Older Adults: A Population-Based Study 2024 In: NUTRIENTS. - : MDPI. - 2072-6643. ; 16:4 Journal article (peer-reviewed)abstract Treatment options for sarcopenia are currently limited, and primarily rely on two main therapeutic approaches: resistance-based physical activity and dietary interventions. However, details about specific nutrients in the diet or supplementation are unclear. We aim to investigate the relationship between nutrient intake and lean mass, function, and strength. Data were derived from the Gothenburg H70 birth cohort study in Sweden, including 719,70-year-olds born in 1944 (54.1% females). For independent variables, the diet history method (face-to-face interviews) was used to estimate habitual food intake during the preceding three months. Dependent variables were gait speed (muscle performance), hand grip strength (muscle strength), and the appendicular lean soft tissue index (ALSTI). Linear regression analyses were performed to analyze the relationship between the dependent variables and each of the covariates. Several nutrients were positively associated with ALSTI, such as polyunsaturated fatty acids (DHA, EPA), selenium, zinc, riboflavin, niacin equivalent, vitamin B12, vitamin D, iron, and protein. After correction for multiple comparisons, there were no remaining correlations with handgrip and gait speed. Findings of positive correlations for some nutrients with lean mass suggest a role for these nutrients in maintaining muscle volume. These results can be used to inform clinical trials to expand the preventive strategies and treatment options for individuals at risk of muscle loss and sarcopenia.

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