To improve health care for older persons, we need to learn more about ageing, e.g. identify protective factors and early markers for diseases. The Gothenburg H70 Birth Cohort Studies (the H70 studies) are multidisciplinary epidemiological studies examining representative birth cohorts of older populations in Gothenburg, Sweden. So far, six birth cohorts of 70-year-olds have been examined over time, and examinations have been virtually identical between studies. This paper describes the study procedures for the baseline examination of the Birth cohort 1944, conducted in 2014–16. In this study, all men and women born 1944 on specific dates, and registered as residents in Gothenburg, were eligible for participation (n = 1839). A total of 1203 (response rate 72.2%; 559 men and 644 women; mean age 70.5 years) agreed to participate in the study. The study comprised sampling of blood and cerebrospinal fluid, psychiatric, cognitive, and physical health examinations, examinations of genetics and family history, use of medications, social factors, functional ability and disability, physical fitness and activity, body composition, lung function, audiological and ophthalmological examinations, diet, brain imaging, as well as a close informant interview, and qualitative studies. As in previous examinations, data collection serves as a basis for future longitudinal follow-up examinations. The research gained from the H70 studies has clinical relevance in relation to prevention, early diagnosis, clinical course, experience of illness, understanding pathogenesis and prognosis. Results will increase our understanding of ageing and inform service development, which may lead to enhanced quality of care for older persons. Electronic supplementary material The online version of this article (10.1007/s10654-018-0459-8) contains supplementary material, which is available to authorized users.

The number of people with dementia has increased dramatically with global ageing. Nevertheless, the pathogeneses of these diseases are not sufficiently understood. The present study aims to analyse the relationship between psychological stress in midlife and the development of dementia in late-life. A representative sample of females (n = 1462) aged 38-60 years were examined in 1968-69 and re-examined in 1974-75, 1980-81, 1992-93 and 2000-03. Psychological stress was rated according to a standardized question in 1968, 1974 and 1980. Dementia was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders criteria based on information from neuropsychiatric examinations, informant interviews, hospital records and registry data. During the 35-year follow-up, 161 females developed dementia (105 Alzheimer's disease, 40 vascular dementia and 16 other dementias). We found that the risk of dementia (hazard ratios, 95% confidence intervals) was increased in females reporting frequent/constant stress in 1968 (1.60, 1.10-2.34), in 1974 (1.65, 1.12-2.41) and in 1980 (1.60, 1.01-2.52). Frequent/constant stress reported in 1968 and 1974 was associated with Alzheimer's disease. Reporting stress at one, two or three examinations was related to a sequentially higher dementia risk. Compared to females reporting no stress, hazard ratios (95% confidence intervals) for incident dementia were 1.10 (0.71-1.71) for females reporting frequent/constant stress at one examination, 1.73 (1.01-2.95) for those reporting stress at two examinations and 2.51 (1.33-4.77) at three examinations. To conclude, we found an association between psychological stress in middle-aged women and development of dementia, especially Alzheimer's disease. More studies are needed to confirm our findings and to study potential neurobiological mechanisms of these associations.

In this study we show that embryonic neurite growth-promoting protein amphoterin binds to carboxylated N-glycans previously identified on mammalian endothelial cells. Since amphoterin is a ligand for the receptor for advanced glycation end products (RAGE), and the ligand-binding V-domain of the receptor contains two potential N-glycosylation sites, we hypothesized that N-glycans on RAGE may mediate its interactions with amphoterin. In support of this, anti-carboxylate antibody mAbGB3.1 immunoprecipitates bovine RAGE, and PNGase F treatment reduces its molecular mass by 4.5 kDa, suggesting that the native receptor is a glycoprotein. The binding potential of amphoterin to RAGE decreases significantly in presence of soluble carboxylated glycans or when the receptor is deglycosylated. Oligosaccharide analysis shows that RAGE contains complex type anionic N-glycans with non-sialic acid carboxylate groups, but not the HNK-1 (3-sulfoglucuronyl b1-3 galactoside) epitope. Consistent with the functional localization of RAGE and amphoterin at the leading edges of developing neurons, mAbGB3.1 stains axons and growth cones of mouse embryonic cortical neurons, and inhibits neurite outgrowth on amphoterin matrix. The carboxylated glycans themselves promote neurite outgrowth in embryonic neurons and RAGE-transfected neuroblastoma cells. This outgrowth requires full-length, signalling-competent RAGE, as cells expressing cytoplasmic domain-deleted RAGE are unresponsive. These results indicate that carboxylated N-glycans on RAGE play an important functional role in amphoterin-RAGE-mediated signalling.

ObjectiveTo investigate whether cognitive and physical activities in midlife are associated with reduced risk of dementia and dementia subtypes in women followed for 44 years.MethodsA population-based sample of 800 women aged 38–54 years (mean age 47 years) was followed from 1968 to 2012. Cognitive (artistic, intellectual, manual, religious, and club) and physical activity were assessed at baseline. During follow-up, dementia (n = 194), Alzheimer disease (n = 102), vascular dementia (n = 27), mixed dementia (n = 41), and dementia with cerebrovascular disease (n = 81) were diagnosed according to established criteria based on information from neuropsychiatric examinations, informant interviews, hospital records, and registry data. Cox regression models were used with adjustment for age, education, socioeconomic status, hypertension, body mass index, cigarette smoking, diabetes mellitus, angina pectoris, stress, and major depression.ResultsWe found that cognitive activity in midlife was associated with a reduced risk of total dementia (hazard ratio [HR] 0.66; 95% confidence interval [CI] 0.49–0.89) and Alzheimer disease (HR 0.54; 95% CI 0.36–0.82) during follow-up. Physical activity in midlife was associated with a reduced risk of mixed dementia (HR 0.43; 95% CI 0.22–0.86) and dementia with cerebrovascular disease (HR 0.47; 95% CI 0.28–0.78). The results were similar after excluding those who developed dementia before 1990 (n = 21), except that physical activity was then also associated with reduced risk of total dementia (HR 0.67; 95% CI 0.46–0.99).ConclusionOur findings suggests that midlife cognitive and physical activities are independently associated with reduced risk of dementia and dementia subtypes. The results indicate that these midlife activities may have a role in preserving cognitive health in old age.

Individuals aged 80 years and older constitute the fastest growing segment of the population worldwide, leading to an expected increase in dementia cases. Education level and treatment of vascular risk factors has increased during the last decades. We examined whether this has influenced the prevalence of dementia according to DSM-III-R using population-based samples of 85-year-olds (N = 1065) examined with identical methods 1986–87 and 2008–10. The prevalence of dementia was 29.8% in 1986–87 and 21.7% in 2008–10 (OR 0.66; 95%-CI: 0.50–0.86). The decline was mainly observed for vascular dementia. The proportion with more than basic education (25.2% and 57.7%), and the prevalence of stroke (20% and 30%) increased, but the odds ratio for dementia with stroke decreased from 4.3 to 1.8 (interaction stroke*birth cohort; p = 0.008). In a logistic regression, education (OR 0.70; 95%-CI 0.51–0.96), stroke (OR 3.78; 95%-CI 2.28–6.29), interaction stroke*birth cohort (OR 0.50; 95%-CI 0.26–0.97), but not birth cohort (OR 0.98; 95%-CI 0.68–1.41), were related to prevalence of dementia. Thus, the decline in dementia prevalence was mainly explained by higher education and lower odds for dementia with stroke in later born birth cohorts. The findings may be related to an increased cognitive reserve and better treatment of stroke in later-born cohorts.

Our study suggests that midlife neuroticism is associated with increased risk of AD dementia, and that distress mediates this association. The results have clinical implications because a group of women at risk of AD dementia is identified.

ObjectiveTo study the relation among psychosocial stressors, long-standing distress and incidence of dementia, in a sample of women followed from midlife to late life.DesignProspective longitudinal population study.SettingThe analyses originate from the prospective population study of women in Gothenburg, Sweden, a representative sample of women examined in 1968 (participation rate 90%) and re-examined in 1974, 1980, 1992, 2000 and 2005.Participants800 women born in 1914, 1918, 1922 and 1930 who were systematically selected for a psychiatric examination at baseline, in 1968.Primary and secondary outcome measures18 psychosocial stressors (eg, divorce, widowhood, work problems and illness in relative) were obtained at baseline. Symptoms of distress were measured according to a standardised question at each study wave. Dementia was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) criteria based on information from neuropsychiatric examinations, informant interviews, hospital records, and registry data, and measured through the whole study period.ResultsDuring the 37 years of follow-up, 153 women developed dementia (104 of those had Alzheimer's disease (AD)). Number of psychosocial stressors in 1968 was associated (HR, 95% CI) with higher incidence of dementia (1.15, 1.04 to 1.27) and AD (1.20, 1.07 to 1.35) between 1968 and 2005, in multivariate Cox regressions. Number of psychosocial stressors in 1968 was also associated (OR, 95% CI) with distress in 1968 (1.48, 1.32 to 1.67), 1974 (1.31, 1.17 to 1.46), 1980 (1.27, 1.11 to 1.45), 2000 (1.39, 1.14 to 1.70) and 2005 (1.35, 1.02 to 1.79), in multivariate logistic regressions. Number of psychosocial stressors (HR 1.17, 95% CI 1.03 to 1.33) and long-standing distress (1968–1974–1980) (HR 1.58, 95% CI 1.03 to 2.45) were independently associated with AD.ConclusionsOur study shows that common psychosocial stressors may have severe and long-standing physiological and psychological consequences. However, more studies are needed to confirm these results and investigate whether more interventions such as stress management and behavioural therapy should be initiated in individuals who have experienced psychosocial stressors.

Midlife insomnia and late-life terminal insomnia or long sleep duration were associated with a higher late-life dementia risk.