The efficacy of real versus sham external Trigeminal Nerve Stimulation (eTNS) in youth with Attention-Deficit/Hyperactivity Disorder (ADHD) over 4 weeks: a protocol for a multi-centre, double-blind, randomized, parallel-group, phase IIb study (ATTENS).

BACKGROUND: Attention Deficit/Hyperactivity Disorder (ADHD), if severe, is usually treated with stimulant or non-stimulant medication. However, users prefer non-drug treatments due to side effects. Alternative non-medication treatments have so far only shown modest effects. External trigeminal nerve stimulation (eTNS) is a minimal risk, non-invasive neuromodulation device, targeting the trigeminal system. It was approved for ADHD in 2019 by the USA Food and Drug administration (FDA) based on a small proof of concept randomised controlled trial (RCT) in 62 children with ADHD showing improvement of ADHD symptoms after 4 weeks of nightly real versus sham eTNS with minimal side effects. We present here the protocol of a larger confirmatory phase IIb study testing efficacy, longer-term persistency of effects and underlying mechanisms of action. METHODS: A confirmatory, sham-controlled, double-blind, parallel-arm, multi-centre phase IIb RCT of 4 weeks of eTNS in 150 youth with ADHD, recruited in London, Portsmouth, and Southampton, UK. Youth with ADHD will be randomized to either real or sham eTNS, applied nightly for 4 weeks. Primary outcome is the change in the investigator-administered parent rated ADHD rating scale. Secondary outcomes are other clinical and cognitive measures, objective hyperactivity and pupillometry measures, side effects, and maintenance of effects over 6 months. The mechanisms of action will be tested in a subgroup of 56 participants using magnetic resonance imaging (MRI) before and after the 4-week treatment. DISCUSSION: This multi-centre phase IIb RCT will confirm whether eTNS is effective in a larger age range of children and adolescents with ADHD, whether it improves cognition and other clinical measures, whether efficacy persists at 6 months and it will test underlying brain mechanisms. The results will establish whether eTNS is effective and safe as a novel non-pharmacological treatment for ADHD. TRIAL REGISTRATION: ISRCTN82129325 on 02/08/2021, https://doi.org/10.1186/ISRCTN82129325 .

Genetic variants in the FOXO1 and ZNF469 genes are associated with keratoconus in Sweden: a case-control study.

BACKGROUND: Keratoconus (KC) is characterized by pathological thinning and bulging of the cornea that may lead to visual impairment. The etiology of sporadic KC remains enigmatic despite intensive research in recent decades. The purpose of this study was to examine the relationship between previously highlighted genetic variants associated with KC and sporadic KC in a Swedish cohort. METHODS: A total of 176 patients (age 16-70 years) with sporadic KC diagnosed by Scheimpflug-topography (Pentacam) were included. The control group (n = 418; age 70 years) was a subsample originating from the Gothenburg H70 Birth Cohort Studies of ageing. Extraction of DNA from blood samples was performed according to standard procedures, and genotyping was performed using competitive allele specific PCR (KASP) technology. A total of 11 single nucleotide polymorphisms (SNPs) were selected for analysis. RESULTS: Statistically significant associations (p = 0.005) were found between the SNPs rs2721051 and rs9938149 and sporadic KC. These results replicate earlier research that found associations between genetic variants in the FOXO1 and BANP-ZNF469 genes and sporadic KC in other populations. CONCLUSION: Genetic variations in the FOXO1 and BANP-ZNF469 genes may be involved in the pathogenesis of sporadic KC.

Randomised controlled trial of the short-term effects of osmotic-release oral system methylphenidate on symptoms and behavioural outcomes in young male prisoners with attention deficit hyperactivity disorder: CIAO-II study.

BACKGROUND: Research has shown that 20-30% of prisoners meet the diagnostic criteria for attention-deficit hyperactivity disorder (ADHD). Methylphenidate reduces ADHD symptoms, but effects in prisoners are uncertain because of comorbid mental health and substance use disorders. AIMS: To estimate the efficacy of an osmotic-release oral system methylphenidate (OROS-methylphenidate) in reducing ADHD symptoms in young adult prisoners with ADHD. METHOD: We conducted an 8-week parallel-arm, double-blind, randomised placebo-controlled trial of OROS-methylphenidate versus placebo in male prisoners (aged 16-25 years) meeting the DSM-5 criteria for ADHD. Primary outcome was ADHD symptoms at 8 weeks, using the investigator-rated Connors Adult ADHD Rating Scale (CAARS-O). Thirteen secondary outcomes were measured, including emotional dysregulation, mind wandering, violent attitudes, mental health symptoms, and prison officer and educational staff ratings of behaviour and aggression. RESULTS: In the OROS-methylphenidate arm, mean CAARS-O score at 8 weeks was estimated to be reduced by 0.57 points relative to the placebo arm (95% CI -2.41 to 3.56), and non-significant. The responder rate, defined as a 20% reduction in CAARS-O score, was 48.3% for the OROS-methylphenidate arm and 47.9% for the placebo arm. No statistically significant trial arm differences were detected for any of the secondary outcomes. Mean final titrated dose was 53.8 mg in the OROS-methylphenidate arm. CONCLUSIONS: ADHD symptoms did not respond to OROS-methylphenidate in young adult prisoners. The findings do not support routine treatment with OROS-methylphenidate in this population. Further research is needed to evaluate effects of higher average dosing and adherence to treatment, multi-modal treatments and preventative interventions in the community.

The effect of alcohol consumption on all-cause mortality in 70-year-olds in the context of other lifestyle risk factors: results from the Gothenburg H70 birth cohort study.

BACKGROUND: In this study, we examined the effect of alcohol, as well as the combined effect of seven lifestyle factors, on all-cause mortality in older adults (baseline age 70 years). METHODS: Data was derived from the population-based Gothenburg H70 Birth Cohort study, including 1124 participants from the 2014-16 examination. Risk consumption was defined as > 98 g alcohol per week, and hazardous drinking was based on the Alcohol Use Disorders Identification Test-Consumption questionnaire (AUDIT-C). Cox regression models were used to examine the individual effect of alcohol consumption, as well as the combined effect of seven lifestyle risk factors (high alcohol consumption, lifetime smoking, unhealthy Body Mass Index, insufficient physical activity, sedentary behavior, insufficient/prolonged sleep, unhealthy dietary pattern) on all-cause mortality. RESULTS: During a mean follow-up of 7.7 years, 81 (7.2%) participants died. Neither risk consumption nor hazardous drinking were associated with elevated mortality, but hazardous drinking was associated with an increased risk of mortality in those with insufficient physical activity. Those with at least five lifestyle risk factors had an increased all-cause mortality compared to those fulfilling criteria for a maximum of one lifestyle risk factor. High alcohol consumption showed a relatively minor impact on this risk, while physical activity and unhealthy dietary pattern had an independent effect on mortality. CONCLUSIONS: In this particular sample, there was no independent effect of alcohol on the risk of 8-year all-cause mortality. However, an interaction effect of physical activity was observed. It may be that high alcohol consumption per se is less important for mortality among older adults. However, a combination of several unhealthy lifestyle behaviors was linked to a substantial increase in the risk of mortality in Swedish older adults. Also, it has to be emphasized that high alcohol consumption may have other adverse health effects apart from mortality among older adults.

Six-year mortality associated with living alone and loneliness in Swedish men and women born in 1930.

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 2005 were 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.

Patient safety culture in home care settings in Sweden: a cross-sectional survey among home care professionals.

BACKGROUND: The connection between a weak patient safety culture and adverse patient events is well known, but although most long-term care is provided outside of hospitals, the focus of patient safety culture is most commonly on inpatient care. In Sweden, more than a third of people who receive care at home have been affected by adverse events, with the majority judged to be preventable. The aim of this study was to investigate the patient safety culture among care professionals working in care at home with older people. METHODS: This cross-sectional study used a purposive sample of 66 municipal care workers, health care professionals, and rehabilitation staff from five municipal care units in two districts in western Sweden who provided care at home for older people and had been employed for at least six months. The participants completed the Hospital Survey on Patient Safety Culture (HSOPSC) self-report questionnaire, which assessed aspects of patient safety culture-norms, beliefs, and attitudes. Logistic regression analysis was used to test how the global ratings of Patient safety grade in the care units and Reporting of patient safety events were related to the dimensions of safety culture according to the staff's professions and years of work experience. RESULTS: The most positively rated safety culture dimension was Teamwork within care units (82%), which indicates good cooperation with the closest co-workers. The least positively rated dimensions were Handoffs and transitions among care units (37%) and Management support (37%), which indicate weaknesses in the exchange of patient information across care units and limited support from top-level managers. The global rating of Patient safety grade was associated with Communication openness and Management support (p < 0.01 and p = 0.03, respectively). Staff with less work experience evaluated the Patient safety grade higher than those with more work experience. CONCLUSIONS: This study suggests that improvements are needed in care transitions and in support from top-level managers and that awareness of patient safety should be improved in staff with less work experience. The results also highlight that an open communication climate within the care unit is important for patient safety.

Successful rehabilitation after multiple severe complications following orthognathic surgery: a case report.

BACKGROUND: Complications of orthognathic surgery are quite rare, but they cause suffering in affected individuals. The range of complications is broad and includes both hard and soft tissue. CASE PRESENTATION: We here present a case of a fully healthy woman without signs of impaired healing capacity. The patient underwent bimaxillary orthognathic surgery and experienced multiple complications both peri- and post-operatively. During the post operative period, the patient also suffered from soft tissue complications after an orthopaedic injury. Therefore, we referred the patient to her general practitioner for further medical investigation. We also present the result after restorative surgery and endodontic and prosthodontic treatment resulting in a successful rehabilitation. CONCLUSION: This case report clearly shows the need for a good collaboration between different odontological and medical fields to achieve a good and predictable result. In situations where normal healing processes do not occur, in-depth analysis must be carried out. HIGHLIGHTS: Orthognathic surgery affects soft and hard tissue which can result in adverse healing and complications. It is of great importance to follow up performed surgery to see late complications. Be restrictive with early re-operations when there are signs of necrosis. Always use a multidisciplinary approach when handling complications after surgery.

Accuracy of 12 short versions of the Geriatric Depression Scale to detect depression in a prospective study of a high-risk population with different levels of cognition.

OBJECTIVES: To determine the accuracy of 12 previously validated short versions of the Geriatric Depression Scale (GDS) to detect major depressive disorder (MDD) in a high-risk population with and without global cognitive impairment. DESIGN: Cross-sectional study. SETTING: Five hospitals, Western Sweden. PARTICIPANTS: Older adults (age ≥70 years, n = 60) assessed at a home visit 1 year after hospital care in connection with suicide attempt. MEASUREMENTS: Depression symptoms were rated using the established 15-item GDS. Eleven short GDS versions identified by a recent systematic review were derived from this administered version. Receiver operating characteristic curves and area under the curve (AUC) for the identification of MDD diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were obtained for each version. The Youden Index optimal criterion was used to determine the appropriate cutoffs. Analyses were repeated after stratification by cognitive status (Mini Mental State Examination score ≤24 and >24) for the best performing GDS short versions and the established 15-item GDS. RESULTS: The 7-item GDS according to Broekman et al. (), with a cutoff 3, was the most accurate among the 12 short versions (AUC 0.90, 95% confidence interval 0.80-1.00), identifying MDD with sensitivity 88% and specificity 81%. The cutoff score remained consistent in the presence of global cognitive impairment, which was not the case for the standardized 15-item GDS. CONCLUSION: The Broekman 7-item GDS had high accuracy to detect MDD in this prospective clinical cohort at high risk for MDD. Further testing of GDS short versions in diverse settings is required.

Perceptions of providing safe care for frail older people at home: A qualitative study based on focus group interviews with home care staff.

BACKGROUND: Providing safe care is a core competence in healthcare. The concept usually refers to hospitals but, consistent with the increasing importance of integrated care, the provision of safe care needs to be extended to the context of home care, and more research is needed concerning home healthcare providers' perspectives in this context. AIM: The aim of this study was to describe care providers' perceptions of providing safe care for frail older persons living at home. METHOD: A qualitative methodology was chosen. In total, 30 care providers agreed to participate. Data were collected through five focus group interviews and analysed using a phenomenographic approach. RESULTS: Three themes regarding care providers' perceptions of providing safe care emerged from the data: 'safe care is created in the encounter and interaction with the older person', 'safe care requires responsibility from the caregiver' and 'safe care is threatened by insufficient organisational resources'. The findings show that providing safe care is an endeavour that requires a holistic view among the care providers as well as effective collaboration within the team, but insufficient competence or a lack of time can make it difficult to safeguard the psychological and existential needs of older persons. CONCLUSION: Providing safe care in home environments encompasses more than just risk reduction. The findings highlight the importance of establishing and integrating team-based and person-centred care into home care settings. Traditional communication structures for inpatient care also need to be adapted to the cross-disciplinary work in municipalities. Care providers should be given the opportunity to develop and maintain their competences and to prioritise relationship-oriented care.

Activities of daily living (ADL) and instrumental activities of daily living (IADL) disability in Swedish 85-year-olds born three decades apart-findings from the H70 study.

OBJECTIVE: Older adults make up the fastest growing segment of the population, and disability rates increase with age. There is much debate whether later born cohorts of 85-year-olds will face the same disability rates as earlier born cohorts. This study aimed to examine ADL and IADL disability in three birth cohorts of Swedish 85-year-olds born three decades apart, examined in 1986-87, 2008-10 and 2015-16, as well as potential factors associated with ADL and IADL disability in these birth-cohorts. METHODS: Systematically selected population-based birth cohorts of 85-year-olds (n = 1,551) from the Gothenburg H70 Birth Cohort studies, Sweden, born in 1901-02 (n = 494), 1923-24 (n = 571) and 1930 (n = 486) and examined with identical methods. Disability was defined as a need for assistance in any ADL/IADL activities. RESULTS: ADL/IADL disability decreased between cohorts in both men and women (from 76.7% in 1986-87, to 58.4% in 2008-10, and 48.4% in 2015-16, P-value trend <.001). Factors associated with ADL/IADL disability varied between cohorts, although dementia and depression increased the odds of disability in all three birth cohorts. CONCLUSION: Later born cohorts of 85-year-olds face less ADL/IADL disability compared to earlier born cohorts. As disability poses a significant financial burden on healthcare services, our findings might contribute to a more positive view on global ageing and the demographic challenges ahead. However, it might also be that in later born cohorts, ADL/IADL disability affects people at later ages, but due to increased longevity, the total number of years in late-life with a functional disability will remain the same.

Sex differences in dementia and response to a lifestyle intervention: Evidence from Nordic population-based studies and a prevention trial.

INTRODUCTION: Evidence on sex differences in the risk for dementia has been mixed. The goal was to assess sex differences in the development of dementia, and in the effects of a lifestyle intervention. METHODS: Two strategies were adopted, one using combined data from three large Nordic population-based cohort studies (n = 2289), adopting dementia as outcome, and 2-year multidomain lifestyle intervention (n = 1260), adopting cognitive change as outcome. RESULTS: There was higher risk for dementia after age 80 years in women. The positive effects of the lifestyle intervention on cognition did not significantly differ between men and women. Sex-specific analyses suggested that different vascular, lifestyle, and psychosocial risk factors are important for women and men in mid- and late-life. CONCLUSION: Women had higher risk for dementia among the oldest individuals. Lifestyle interventions may be effectively implemented among older men and women.

Sex differences in dementia: on the potentially mediating effects of educational attainment and experiences of psychological distress.

BACKGROUND: Old-age dementias are known to disproportionally affect women as well as individuals with low educational attainment. The higher lifetime risk of dementia among women is usually attributed to their longer life expectancy. However, the impact of sex, and subsequent gender inequity, is likely to be more multifaceted than this explanation implies. Not least because of historical inequities in access to education between the sexes and the gender and socio-economic gradients in risk factors such as stress, depression and social isolation. Consequently, the present study sought to test whether differences in educational attainment and experiences of general psychological distress mediate the association between female sex and dementia. METHODS: The study utilizes data obtained through the Gothenburg H70 Birth Cohort Study and the Prospective Populations Study on Women (n = 892). Data were analysed using Confirmatory Factor Analysis (CFA) and Structural Equation Modelling (SEM) with Weighted Least Squares Means and Variance adjusted (WLSMV) estimation. General psychological distress was indicated by a latent variable and constructed from five manifest items (previous depression, stress, self-esteem, chronic loneliness and satisfaction with social situation) that were all measured at baseline. RESULTS: While the results could not corroborate that education directly mediates the effect of sex on dementia, level of distress was predicted by both female sex (0.607, p < .001) and education (- 0.166, p < .01) and, in turn, shown to be significantly associated with dementia (0.167, p < .05), also after controlling for confounders. When time from baseline to diagnosis was increased through sequential exclusion of dementia cases, the effect of distress on dementia was no longer significant. CONCLUSION: The overall findings suggest that social (dis) advantage predicts general psychological distress, which thereby constitutes a potential, and rarely acknowledged, pathway between female sex, education, and dementia. They further underline the importance of attending to both education and distress as 'gendered' phenomena when considering the nature of their associations with dementia. However, the possibility of reverse causality bias must be acknowledged and the need for longitudinal studies with longer follow-up stressed.

Cardiovascular and all-cause mortality attributable to loneliness in older Swedish men and women.

BACKGROUND: This study examined whether loneliness predicts cardiovascular- and all-cause mortality in older men and women. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

In vivo measurement of pre-operational spallation source workers: baseline body burden levels and detection limits of relevant gamma emitters using high-resolution gamma spectrometry.

As a measure to prepare for long-term internal dose monitoring of workers at the European Spallation Source (ESS) in Lund, Sweden, operated by the European Research Infrastructure Consortium (ERIC), as well as to enhance emergency preparedness against accidental releases, a series of in vivo measurements were conducted using a high-resolution HPGe detector with a 123% relative efficiency (1.332 MeV). This study describes the whole-body counting set-up, calibration procedure, and subsequent validation measurements using conventional NaI(Tl)-scanning-bed geometry on a selection of workers from the ESS. Detection limits for the relevant gamma emitters 7Be, 172Hf, and 182Ta were determined to be 65 Bq, 130 Bq, and 22 Bq, respectively, using a 2400 s acquisition time. The baseline measurements suggest that care must be taken to ensure that the fluctuations in the presence of radon daughters 214Bi and 214Pb are minimised by, for example, ensuring a minimum air exchange between the measuring room and the ambient air, and by demanding that the measured subjects change clothes and shower before measurement. Furthermore, in a monitoring program for internal doses to spallation source workers, the presence of radionuclides originating from non-work-related sources (such as 226Ra from private water wells or 137Cs from intakes of Chernobyl contaminated foodstuffs), or radionuclides from previous work history (such as 60Co within the nuclear power industry), must be considered.

The Gothenburg H70 Birth cohort study 2014-16: design, methods and study population.

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.

Urate and risk of Alzheimer's disease and vascular dementia: A population-based study.

INTRODUCTION: Low serum urate (sU) has been suggested to increase the risk of dementia since a reduction might impair antioxidant capacity. On the other hand, high sU is associated with increased cardiovascular risk which might increase the risk of dementia, especially for vascular dementia. METHODS: In 1968-1969, a population-based sample of 1462 women aged 38 to 60 years was examined and were followed up over 44 years (mean 33.1 years). We examined whether sU (determined in 1968-1969 and 1992-1994) is associated with risk of late-life dementia. RESULTS: During 44 years of follow-up, a higher sU (per standard deviation of 76.5 µmol/L) was associated with lower risk for dementia (n = 320; hazard ratio [HR] 0.81; confidence interval [CI] 0.72-0.91), Alzheimer's disease (n = 152; HR 0.78; CI 0.66-0.91), and vascular dementia (n = 52; HR 0.66; CI 0.47-0.94). DISCUSSION: Our findings support the hypothesis that sU has a protective role in the development of dementia, regardless of dementia subtype. This may have important implications in the treatment of dementia and treatment goals for hyperuricemia in patients with gout.

Midlife Stress in Relation to Late-Life Cerebrospinal Fluid Biomarkers of Alzheimer's Disease: A 25-Year Follow-Up Study.

BACKGROUND/AIMS: Psychological stress has previously been associated with higher risk of developing late-life dementia, especially Alzheimer's disease (AD). This study tested whether longstanding midlife stress is related to cerebrospinal fluid (CSF) biomarkers of late-life AD, such as tau protein and amyloid beta (Aß). METHODS: The study included 79 nondemented females from the Prospective Population Study of Women in Gothenburg, Sweden, who responded to a standardized stress question at baseline (mean age 49 years) and underwent a lumbar puncture at follow-up 25 years later. Multiple linear regression models analyzed the relationships between midlife psychological stress and late-life CSF measures of total tau (t-tau), phosphorylated tau (p-tau), Aß40, and Aß42. RESULTS: Longstanding stress in midlife was associated with higher levels of CSF t-tau (ß = 0.64, p = 0.01) and Aß40 (ß = 0.60, p = 0.02) in late life. No associations were found between midlife stress and levels of p-tau or Aß42. CONCLUSION: The findings suggest that longstanding stress stimulates unspecific neurodegenerative processes, but not the core processes of AD, at least not in the early phase of the disease. The association with higher concentration of CSF t-tau may reflect neural degeneration and the association with higher Aß40 may be an early sign of Aß overproduction or cerebrovascular processes in the brain.

Increased risk for dementia both before and after stroke: A population-based study in women followed over 44 years.

INTRODUCTION: Longitudinal studies are needed to understand the long-term associations between stroke and dementia. METHODS: A population sample of 1460 women without stroke or dementia at baseline was followed over 44 years, from 1968 to 2012. Information on stroke and dementia was obtained from neuropsychiatric examinations, key-informant interviews, hospital registry, and medical records. RESULTS: During 44 years follow-up, 362 women developed stroke and 325, dementia. The age-specific incidence of the two disorders was similar. The incidence of dementia was higher in those with stroke than among those without (33.7% vs. 18.5%; age-adjusted hazard ratio 1.44, 95% confidence interval 1.15-1.81). The increased risk of dementia started already 5 years before stroke, was highest 1 year after stroke, and continued more than 11 years after stroke. DISCUSSION: There is an increased risk for dementia both before and after stroke. This has implications for understanding the relation between the two disorders and for prevention of dementia and stroke.

Sleep disturbances and dementia risk: A multicenter study.

INTRODUCTION: Few longitudinal studies assessed whether sleep disturbances are associated with dementia risk. METHODS: Sleep disturbances were assessed in three population-based studies (H70 study and Kungsholmen Project [Sweden]; Cardiovascular Risk Factors, Aging and Dementia study [Finland]). Late-life baseline analyses (3-10 years follow-up) used all three studies (N = 1446). Baseline ages ≈ 70 years (Cardiovascular Risk Factors, Aging and Dementia, H70), and ≈84 years (Kungsholmen Project). Midlife baseline (age ≈ 50 years) analyses used Cardiovascular Risk Factors, Aging and Dementia (21 and 32 years follow-up) (N = 1407). RESULTS: Midlife insomnia (fully adjusted hazard ratio = 1.24, 95% confidence interval = 1.02-1.50) and late-life terminal insomnia (fully adjusted odds ratio = 1.94, 95% confidence interval = 1.08-3.49) were associated with a higher dementia risk. Late-life long sleep duration (>9 hours) was also associated with an increased dementia risk (adjusted odds ratio = 3.98, 95% confidence interval = 1.87-8.48). DISCUSSION: Midlife insomnia and late-life terminal insomnia or long sleep duration were associated with a higher late-life dementia risk.

Self-rated health and its association with mortality in older adults in China, India and Latin America-a 10/66 Dementia Research Group study.

Background: empirical evidence from high-income countries suggests that self-rated health (SRH) is useful as a brief and simple outcome measure in public health research. However, in many low- and middle-income countries (LMIC) there is a lack of evaluation and the cross-cultural validity of SRH remains largely untested. This study aims to explore the prevalence of SRH and its association with mortality in older adults in LMIC in order to cross-culturally validate the construct of SRH. Methods: population-based cohort studies including 16,940 persons aged ≥65 years in China, India, Cuba, Dominican Republic, Peru, Venezuela, Mexico and Puerto Rico in 2003. SRH was assessed by asking 'how do you rate your overall health in the past 30 days' with responses ranging from excellent to poor. Covariates included socio-demographic characteristics, use of health services and health factors. Mortality was ascertained through a screening of all respondents until 2007. Results: the prevalence of good SRH was higher in urban compared to rural sites, except in China. Men reported higher SRH than women, and depression had the largest negative impact on SRH in all sites. Without adjustment, those with poor SRH showed a 142% increase risk of dying within 4 years compared to those with moderate SRH. After adjusting for all covariates, those with poor SRH still showed a 43% increased risk. Conclusion: our findings support the use of SRH as a simple measure in survey settings to identify vulnerable groups and evaluate health interventions in resource-scares settings.