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BACKGROUND & AIMS: Prior studies have suggested that proton pump inhibitor (PPI) use is associated with increased risk of dementia; however, these have been limited by incomplete assessment of medication use and failure to account for confounders. Furthermore, prior studies have relied on claims-based diagnoses for dementia, which can lead to misclassification. We investigated the associations of PPI and histamine-2 receptor antagonist (H2RA) use with dementia and cognitive decline. METHODS: We conducted a post hoc analysis of ASPirin in Reducing Events in the Elderly (ASPREE), a randomized trial of aspirin in the United States and Australia, including 18,934 community-based adults ≥65 years of all races/ethnicities. Baseline and recent PPI and H2RA use were determined according to review of medications during annual in-person study visits. Incident dementia was defined according to Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, criteria. Secondary endpoints include cognitive impairment, no dementia (CIND) and changes in cognition. Associations of medication use with dementia and CIND outcomes were examined using Cox proportional hazards models. Changes in cognitive test scores were examined using linear mixed-effects models. RESULTS: Baseline PPI use vs nonuse was not associated with incident dementia (multivariable hazard ratio, 0.88; 95% confidence interval, 0.72-1.08), CIND (multivariable hazard ratio, 1.00; 95% confidence interval, 0.92-1.09), or with changes in overall cognitive test scores over time (multivariable B, -0.002; standard error, 0.01; P = .85). Similarly, no associations were observed between H2RA use and all cognitive endpoints. CONCLUSIONS: In adults ≥65 years of age, PPI and H2RA use were not associated with incident dementia, CIND, or decline in cognition over time. These data provide reassurance about the safety of long-term use of PPIs among older adults.
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Disfunção Cognitiva , Inibidores da Bomba de Prótons , Idoso , Humanos , Aspirina , Cognição , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Estudos Prospectivos , Inibidores da Bomba de Prótons/efeitos adversos , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
BACKGROUND & AIMS: The burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is growing rapidly, as is the number of older adults globally. However, relatively few studies have been performed evaluating the prevalence and risk factors for MASLD in older adults. As such, we aimed to identify the prevalence of MASLD in older adults, as well as sociodemographic, clinical, functional and biochemical associations. METHODS: The study population included older adults without a history of cardiovascular disease, dementia or independence-limiting functional impairment who had participated in the ASPirin in Reducing Events in the Elderly (ASPREE) randomised trial. MASLD was defined using the Fatty Liver Index (FLI). Associations were identified using Poisson regression with robust variance for FLI ≥ 60 vs FLI < 30. RESULTS: 9097 Australian participants aged ≥70 years had complete biochemical and anthropometric data to identify MASLD. The study population had a mean age of 75.1 ± 4.3 years and was 45.0% male. Almost one-third (33.0%) had prevalent MASLD, and the prevalence decreased with increasing age (adjusted RR [aRR] 0.96, 95% CI: 0.96-0.97). MASLD was also negatively associated with social advantage (aRR 0.94, 95% CI: 0.90-0.99) and exercise tolerance and was positively associated with diabetes mellitus (aRR: 1.22, 95% CI: 1.16-1.29), hypertension (aRR: 1.31, 95% CI: 1.22-1.41), male sex (aRR: 1.66, 95% CI: 1.57-1.74), pre-frailty (aRR: 1.99, 95% CI: 1.82-2.12) and frailty (aRR: 2.36, 95% CI: 2.16-2.56). MASLD and nonalcoholic fatty liver disease (NAFLD) results were 100% concordant. CONCLUSION: This study in a large cohort of relatively healthy community-dwelling older adults shows that MASLD is common, decreases with age and is associated with poorer metabolic health, social disadvantage and frailty.
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Fragilidade , Doenças Metabólicas , Hepatopatia Gordurosa não Alcoólica , Idoso , Feminino , Humanos , Masculino , Antropometria , Austrália/epidemiologia , Fragilidade/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Estudos TransversaisRESUMO
BACKGROUND: We examine precursors of child emotional distress during the COVID-19 pandemic in a prospective intergenerational Australian cohort study. METHODS: Parents (N = 549, 60% mothers) of 934 1-9-year-old children completed a COVID-19 specific module in 2020 and/or 2021. Decades prior, a broad range of individual, relational and contextual factors were assessed during parents' own childhood, adolescence and young adulthood (7-8 to 27-28 years old; 1990-2010) and again when their children were 1 year old (2012-2019). RESULTS: After controlling for pre-pandemic socio-emotional behaviour problems, COVID-19 child emotional distress was associated with a range of pre-pandemic parental life course factors including internalising difficulties, lower conscientiousness, social skills problems, poorer relational health and lower trust and tolerance. Additionally, in the postpartum period, pre-pandemic parental internalising difficulties, lower parental warmth, lower cooperation and fewer behavioural competencies predicted child COVID-19 emotional distress. CONCLUSIONS: Findings highlight the importance of taking a larger, intergenerational perspective to better equip young populations for future adversities. This involves not only investing in child, adolescent, and young adult emotional and relational health, but also in parents raising young families.
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BACKGROUND: Epigenetic ageing is among the most promising ageing biomarkers and may be a useful marker of physical function decline, beyond chronological age. This study investigated whether epigenetic age acceleration (AA) is associated with the change in frailty scores over 7 years and the 7-year risk of incident frailty and persistent Activities of Daily Living (ADL) disability among 560 Australians (50.7% females) aged ≥70 years. METHODS: Seven AA indices, including GrimAge, GrimAge2, FitAge and DunedinPACE, were estimated from baseline peripheral-blood DNA-methylation. Frailty was assessed using both the 67-item deficit-accumulation frailty index (FI) and Fried phenotype (Fried). Persistent ADL disability was defined as loss of ability to perform one or more basic ADLs for at least 6 months. Linear mixed models and Cox proportional-hazard regression models were used as appropriate. RESULTS: Accelerated GrimAge, GrimAge2, FitAge and DunedinPACE at baseline were associated with increasing FI scores per year (adjusted-Beta ranged from 0.0015 to 0.0021, P < 0.05), and accelerated GrimAge and GrimAge2 were associated with an increased risk of incident FI-defined frailty (adjusted-HRs 1.43 and 1.39, respectively, P < 0.05). The association between DunedinPACE and the change in FI scores was stronger in females (adjusted-Beta 0.0029, P 0.001 than in males (adjusted-Beta 0.0002, P 0.81). DunedinPACE, but not the other AA measures, was also associated with worsening Fried scores (adjusted-Beta 0.0175, P 0.04). No associations were observed with persistent ADL disability. CONCLUSION: Epigenetic AA in later life is associated with increasing frailty scores per year and the risk of incident FI-defined frailty.
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Atividades Cotidianas , Envelhecimento , Epigênese Genética , Idoso Fragilizado , Fragilidade , Avaliação Geriátrica , Humanos , Feminino , Masculino , Idoso , Fragilidade/genética , Fragilidade/epidemiologia , Fragilidade/diagnóstico , Idoso Fragilizado/estatística & dados numéricos , Avaliação Geriátrica/métodos , Envelhecimento/genética , Fatores de Risco , Idoso de 80 Anos ou mais , Avaliação da Deficiência , Metilação de DNA , Fatores Etários , Medição de Risco , Fatores de Tempo , Estado FuncionalRESUMO
INTRODUCTION: Risk factors for cardiovascular disease (CVD) also increase the risk of dementia. However, whether commonly used CVD risk scores are associated with dementia risk in older adults who do not have a history of CVD, and potential gender differences in this association, remains unclear. The aim of this study was to determine whether CVD risk scores are prospectively associated with cognitive decline and dementia in initially healthy older men and women. METHODS: A total of19,114 participants from a prospective cohort of individuals aged 65+ years without known CVD or dementia were recruited. The atherosclerotic cardiovascular disease risk score (ASCVDRS), Systematic Coronary Risk Evaluation 2-Older Persons (SCORE2-OP), and the Framingham risk score (FRS) were calculated at baseline. Risk of dementia (according to DSM-IV criteria) and cognitive decline (defined as a >1.5 standard deviation decline in global cognition, episodic memory, psychomotor speed, or verbal fluency from the previous year) were assessed using hazard ratio. RESULTS: Over a median follow-up of 6.4 years, 850 individuals developed dementia and 4,352 cognitive decline. Men and women in the highest ASCVDRS tertile had a 41% (95% CI 1.08, 1.85) and 45% (1.11, 1.89) increased risk of dementia compared to the lowest tertile, respectively. Likewise, men and women in the highest SCORE2-OP tertile had a 64% (1.24, 2.16) and 60% (1.22, 2.11) increased risk of dementia compared to the lowest tertile, respectively. Findings were similar, but the risk was slightly lesser when examining risk of cognitive decline for both ASCVDRS and SCORE2-OP. However, FRS was only associated with the risk of cognitive decline among women (highest vs. lowest tertiles: 1.13 [1.01-1.26]). CONCLUSION: These findings suggest the utility of the ASCVDRS and SCORE2-OP in clinical practice, to not only assess future risk of CVD, but also as potential early indicators of cognitive impairment, even in relatively healthy older men and women.
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Doenças Cardiovasculares , Disfunção Cognitiva , Demência , Masculino , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Demência/diagnóstico , Demência/epidemiologia , Demência/etiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos Prospectivos , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Fatores de Risco , Fatores de Risco de Doenças CardíacasRESUMO
OBJECTIVES: Few studies have examined the impact of late-life depression trajectories on specific domains of cognitive function. This study aims to delineate how different depressive symptom trajectories specifically affect cognitive function in older adults. DESIGN: Prospective longitudinal cohort study. SETTING: Australia and the United States of America. PARTICIPANTS: In total, 11,035 community-dwelling older adults with a mean age of 75 years. MEASUREMENTS: Depressive trajectories were modelled from depressive symptoms according to annual Centre for Epidemiological Studies Depression Scale 10 (CES-D-10) surveys. Four trajectories of depressive symptoms were identified: low ("nondepressed"), consistently mild ("subthreshold depression"), consistently moderate ("persistent depression"), and initially low but increasing ("emerging depression"). Global cognition (Modified Mini-Mental State Examination [3MS]), verbal fluency (Controlled Oral Word Association Test [COWAT]), processing speed (Symbol Digit Modalities Test [SDMT]), episodic memory (Hopkins Verbal Learning Test - Revised [HVLT-R]), and a composite z-score were assessed over a subsequent median 2 years. RESULTS: Subthreshold depression predicted impaired performance on the SDMT (Cohen's d -0.04) and composite score (-0.03); emerging depression predicted impaired performance on the SDMT (-0.13), HVLT-R (-0.09), 3 MS (-0.08) and composite score (-0.09); and persistent depression predicted impaired performance on the SDMT (-0.08), 3 MS (-0.11), and composite score (-0.09). CONCLUSIONS: Depressive symptoms are associated with later impaired processing speed. These effects are small. Diverse depression trajectories have different impacts on cognitive function.
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INTRODUCTION: Poor social connection is considered a risk factor for dementia. Since socializing behaviors may cluster together or act compensatorily, we aimed to investigate social connection patterns and their association with dementia, for men and women separately. METHODS: A total of 12,896 community-dwelling older adults (mean ± SD age: 75.2 ± 4.3 years, 54% women) without major cognitive impairment were included. Latent class analysis was conducted using 24 baseline social connection indicators. Cox proportional hazards regression was used to estimate the association between latent classes and incident dementia over 12 (median: 8.4) years follow-up. RESULTS: Three distinct classes were identified in both genders: strong social connections with an intermediate friend-relative network (Class 1: men, 43.8%; women, 37.9%), weak social connections (Class 2: men, 29.6%; women, 27.4%), and strong social connections with a larger friend-relative network (Class 3: men, 26.6%; women, 34.7%). Compared to Class 1, men in Class 2 (HR: 1.38, 95% CI: 1.08-1.77) and women in Class 3 (HR: 1.27, 95% CI: 1.01-1.60) had an increased risk of dementia. DISCUSSION: Dementia risk varies with different social connection patterns among older men and women. HIGHLIGHTS: Three distinct social connection patterns were identified based on 24 indicators. These patterns were related to dementia risk differently in men and women. In men, a weak social connection pattern was associated with a higher dementia risk. In women, a strong social connection with a relatively larger friend-relative network was associated with a greater dementia risk.
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Demência , Vida Independente , Humanos , Masculino , Feminino , Demência/epidemiologia , Idoso , Fatores de Risco , Fatores Sexuais , Apoio Social , Idoso de 80 Anos ou maisRESUMO
Women who have experienced conflict-related sexual violence report significant long-term effects, including posttraumatic stress disorder (PTSD), depression and relationship difficulties. Research has demonstrated that maternal trauma is associated with children's behavioural difficulties and challenges in family functioning, such as impaired communication and harsh parenting. This pilot study is aimed at evaluating the preliminary effectiveness of family therapy for Kosovar mothers who experienced conflict-related sexual violence in 1998-1999 and later developed PTSD and their children in improving family functioning and reducing behavioural difficulties in postwar times. Sixty-four mothers were randomised to an intervention group or a waitlist control group. Data was collected during a screening phase, at baseline before intervention initiation, after the intervention group completed family therapy and once the waitlist control group received the intervention. Generalised linear mixed models were used to analyse group differences in family functioning and children's behaviours over time. At follow-up, mothers in the intervention group reported improved family functioning. However, mothers in the waitlist control group reported significantly fewer behavioural difficulties than mothers in the intervention group before the control group had started family therapy. There was no significant interaction between group condition and time for child-rated family functioning. Overall, this pilot study suggests that family therapy could be effective in reducing the effects of intergenerational trauma related to PTSD and conflict-related sexual violence. Future research should evaluate the long-term effects of family therapy to assess if immediate effects were maintained.
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Terapia Familiar , Mães , Transtornos de Estresse Pós-Traumáticos , Humanos , Feminino , Projetos Piloto , Terapia Familiar/métodos , Adulto , Transtornos de Estresse Pós-Traumáticos/psicologia , Transtornos de Estresse Pós-Traumáticos/terapia , Mães/psicologia , Criança , Delitos Sexuais/psicologia , Relações Mãe-Filho/psicologia , Masculino , Kosovo , Resultado do Tratamento , Filho de Pais com Deficiência/psicologia , Filho de Pais com Deficiência/estatística & dados numéricosRESUMO
BACKGROUND: Talazoparib is a poly (adenosine diphosphate-ribose) polymerase inhibitor approved for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), HER2-negative, locally advanced or metastatic breast cancer (LA/mBC), with approval based on the EMBRACA trial. To date, there are no published data on talazoparib use in the real-world United States (USA) setting. PATIENTS AND METHODS: Characteristics, treatment patterns, and clinical outcomes of real-world US patients with gBRCAm HER2-negative LA/mBC treated with talazoparib monotherapy were collected via retrospective chart review and summarized using descriptive statistics. RESULTS: Among 84 eligible patients, 35.7% had hormone receptor-positive tumors and 64.3% had triple-negative LA/mBC (TNBC). At talazoparib initiation, 29.8% had ECOG PS of ≥2 and 19.0% had brain metastasis. Mutations in gBRCA1 or 2 were detected among 64.3% and 35.7% of patients, respectively. Talazoparib was given as 1st-line therapy in 14.3% of patients, 2nd-line in 40.5%, and 3rd- or 4th-line in 45.2%. Median time to talazoparib treatment failure was 8.5 months (95% CI, 8.0-9.7), median progression-free survival was 8.7 months (95% CI, 8.0-9.9), the median time from initiation to chemotherapy was 12.2 months (95% CI, 10.5-20.1), and the overall response rate was 63.1%. No differences in clinical outcomes were observed between patients with HR-positive/HER2-negative LA/mBC and patients with TNBC by using unadjusted statistical comparisons. Brain metastasis and ECOG PS ≥2 at talazoparib initiation were associated with treatment failure and progression or mortality. CONCLUSION: Overall, talazoparib clinical outcomes in this real-world population are consistent with findings from EMBRACA.
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Neoplasias Encefálicas , Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Adulto , Humanos , Estados Unidos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Estudos RetrospectivosRESUMO
OBJECTIVE: The role of circulating sex hormones on structural brain ageing is yet to be established. This study explored whether concentrations of circulating sex hormones in older women are associated with the baseline and longitudinal changes in structural brain ageing, defined by the brain-predicted age difference (brain-PAD). DESIGN: Prospective cohort study using data from NEURO and Sex Hormones in Older Women; substudies of the ASPirin in Reducing Events in the Elderly clinical trial. PATIENTS: Community-dwelling older women (aged 70+ years). MEASUREMENTS: Oestrone, testosterone, dehydroepiandrosterone (DHEA), and sex-hormone binding globulin (SHBG) were quantified from plasma samples collected at baseline. T1-weighted magnetic resonance imaging was performed at baseline, 1 and 3 years. Brain age was derived from whole brain volume using a validated algorithm. RESULTS: The sample comprised of 207 women not taking medications known to influence sex hormone concentrations. A statistically higher baseline brain-PAD (older brain age relative to chronological age) was seen for women in the highest DHEA tertile compared with the lowest in the unadjusted analysis (p = .04). This was not significant when adjusted for chronological age, and potential confounding health and behavioural factors. Oestrone, testosterone and SHBG were not associated with brain-PAD cross-sectionally, nor were any of the examined sex hormones or SHBG associated with brain-PAD longitudinally. CONCLUSION: No strong evidence of an association between circulating sex hormones and brain-PAD. Given there is prior evidence to suggests sex hormones may be important for brain ageing, further studies of circulating sex hormones and brain health in postmenopausal women are warranted.
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Estradiol , Estrona , Idoso , Humanos , Feminino , Estudos Prospectivos , Pós-Menopausa , Hormônios Esteroides Gonadais , Testosterona , Encéfalo/metabolismo , Desidroepiandrosterona , Globulina de Ligação a Hormônio Sexual/metabolismoRESUMO
Brain-derived neurotrophic factor (BDNF) is important for sleep physiology. This study investigates whether BDNF variants and promoter I methylation may be implicated in sleep disturbances in older adults. Genotyping was performed for seven BDNF single nucleotide polymorphisms (SNPs) in 355 community-dwelling older adults (aged ≥65 years) and BDNF exon 1 promoter methylation was measured in blood samples at baseline (n = 153). Self-reported daytime sleepiness and insomnia, ambulatory polysomnography measures of sleep continuity and architecture, and psychotropic drug intake were assayed during follow-up. Logistic regression adjusted for age, sex, comorbidities, body mass index, and psychotropic drug intake. Associations were found specifically between wake time after sleep onset (WASO) and four SNPs in the participants not taking psychotropic drugs, whereas in those taking drugs, the associations were either not significant (rs6265 and rs7103411) or in the reverse direction (rs11030101 and rs28722151). Higher BDNF methylation levels were found at most CpG units in those with long WASO and this varied according to psychotropic drug use. The reference group with short WASO not taking drugs showed the lowest methylation levels and the group with long WASO taking treatment, the highest levels. Some SNPs also modified the associations, the participants carrying the low-risk genotype having the lower methylation levels. This genetic and epigenetic study demonstrated blood BDNF promoter methylation to be a potential biomarker of prolonged nocturnal awakenings in older people. Our results suggest the modifying effect of psychotropic drugs and BDNF genetic variants in the associations between methylation and WASO.
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Metilação de DNA , Distúrbios do Início e da Manutenção do Sono , Idoso , Humanos , Fator Neurotrófico Derivado do Encéfalo/genética , Metilação de DNA/genética , Genótipo , Polimorfismo de Nucleotídeo Único , Distúrbios do Início e da Manutenção do Sono/genéticaRESUMO
BACKGROUND: Gerontology and ageing research are increasingly focussing on healthy life span (healthspan), the period of life lived free of serious disease and disability. Late-life depression (LLD) is believed to impact adversely on physical health. However, no studies have examined its effect on healthspan. This study investigated the effect of LLD and subthreshold depression on disability-free survival, a widely accepted measure of healthspan. METHODS: This prospective cohort study used data from the ASPirin in Reducing Events in the Elderly study. Participants were aged ≥70 years (or ≥65 years for African-American and Hispanic participants) and free of dementia, physical disability and cardiovascular disease. Depressive symptoms were measured using the 10-item Centre for Epidemiological Studies Depression Scale (CES-D-10). LLD and subthreshold depression were defined as CES-D-10 scores ≥8 and 3-7, respectively. Disability-free survival was defined as survival free of dementia and persistent physical disability. RESULTS: A total of 19,110 participants were followed up for a maximum of 7.3 years. In female participants, LLD was associated with lower disability-free survival adjusting for sociodemographic and lifestyle factors, medical comorbidities, polypharmacy, physical function and antidepressant use (HR, 1.50; 95% CI, 1.23-1.82). In male participants, LLD was associated with lower disability-free survival adjusting for sociodemographic and lifestyle factors (HR, 1.30; 95% CI, 1.03-1.64). Subthreshold depression was also associated with lower disability-free survival in both sexes. CONCLUSIONS: LLD may be a common and important risk factor for shortened healthspan.
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Demência , Pessoas com Deficiência , Idoso , Humanos , Masculino , Feminino , Depressão/diagnóstico , Estudos Prospectivos , Antidepressivos/uso terapêutico , Demência/tratamento farmacológicoRESUMO
OBJECTIVES: The importance of trauma-informed care (TIC) within residential aged care (RAC) settings has been increasingly recognised. TIC would ensure that older people who have experienced trauma over their lifetime have their needs better understood and accommodated. This scoping review examined the extent to which TIC has been applied within RAC settings. METHODS: A scoping review was conducted according to Cochrane recommendations and the PRISMA-ScR checklist. A systematic search of six databases (Embase, Emcare, CENTRAL, CINAHL, PsychInfo and Medline) was performed in July 2022 and March 2023 and peer-reviewed primary research, in English and involved RAC staff or residents (aged 65 years and over) providing or receiving TIC were eligible for inclusion. Studies focused on trauma intervention, assessment, screening, or treatment were excluded. Thematic synthesis was performed to extract themes relating to trauma-informed practice, barriers and enablers to TIC, and outcomes from the application of TIC approaches. RESULTS: Five articles were included. There was little evidence of the implementation of TIC interventions in RAC settings. Only one study examined the application of a TIC framework in a RAC setting. However, there was some evidence that approaches that consider resident's experience of trauma have emerged from practice experience and been used in RAC as an extension of person-centred care. CONCLUSIONS: Whilst trauma-informed approaches to resident care are emerging through practice experience, and despite policy recommendations to do so, there is little evidence that formal TIC interventions or frameworks have been applied to RAC internationally. This study highlights a gap in research and practice and makes several recommendations for further research and implementation of TIC in RAC.
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Instituição de Longa Permanência para Idosos , Ferimentos e Lesões , Idoso , Humanos , Ferimentos e Lesões/terapiaRESUMO
BACKGROUND: Evidence for the prognostic implications of hyperglycaemia in older adults is inconsistent. OBJECTIVE: To evaluate disability-free survival (DFS) in older individuals by glycaemic status. METHODS: This analysis used data from a randomised trial recruiting 19,114 community-based participants aged ≥70 years, who had no prior cardiovascular events, dementia and physical disability. Participants with sufficient information to ascertain their baseline diabetes status were categorised as having normoglycaemia (fasting plasma glucose [FPG] < 5.6 mmol/l, 64%), prediabetes (FPG 5.6 to <7.0 mmol/l, 26%) and diabetes (self-report or FPG ≥ 7.0 mmol/l or use of glucose-lowering agents, 11%). The primary outcome was loss of disability-free survival (DFS), a composite of all-cause mortality, persistent physical disability or dementia. Other outcomes included the three individual components of the DFS loss, as well as cognitive impairment-no dementia (CIND), major adverse cardiovascular events (MACE) and any cardiovascular event. Cox models were used for outcome analyses, with covariate adjustment using inverse-probability weighting. RESULTS: We included 18,816 participants (median follow-up: 6.9 years). Compared to normoglycaemia, participants with diabetes had greater risks of DFS loss (weighted HR: 1.39, 95% CI 1.21-1.60), all-cause mortality (1.45, 1.23-1.72), persistent physical disability (1.73, 1.35-2.22), CIND (1.22, 1.08-1.38), MACE (1.30, 1.04-1.63) and cardiovascular events (1.25, 1.02-1.54) but not dementia (1.13, 0.87-1.47). The prediabetes group did not have an excess risk for DFS loss (1.02, 0.93-1.12) or other outcomes. CONCLUSIONS: Among older people, diabetes was associated with reduced DFS, and higher risk of CIND and cardiovascular outcomes, whereas prediabetes was not. The impact of preventing or treating diabetes in this age group deserves closer attention.
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Doenças Cardiovasculares , Diabetes Mellitus , Estado Pré-Diabético , Idoso , Humanos , Aspirina , Diabetes Mellitus/diagnóstico , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/tratamento farmacológico , Prognóstico , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/prevenção & controleRESUMO
BACKGROUND: Posttraumatic Stress Disorder (PTSD) could potentially increase the risk of mortality, and there is a need for a meta-analysis to quantify this association. This study aims to determine the extent to which PTSD is a predictor of mortality. METHODS: EMBASE, MEDLINE, and PsycINFO were searched systematically on 12th February 2020, with updated searches conducted in July 2021, and December 2022 (PROSPERO CRD42019142971). Studies involving community-dwelling participants with a diagnosis of PTSD or PTSD symptoms, and a comparator group of individuals without PTSD, and which assessed mortality risk, were included. A random-effects meta-analysis was conducted on studies reporting Odds Ratio (OR), Hazard Ratio (HR), and Risk Ratio (RR), and subgroup analysis was also performed by age, sex, type of trauma experienced, PTSD diagnosis, and cause of death. RESULTS: A total of 30 eligible studies of mostly good methodological quality were identified, with a total of more than 2.1 million participants with PTSD. The majority of studies involved male-dominated, veteran populations. PTSD was associated with a 47% (95% CI: 1.06-2.04) greater risk of mortality across six studies that reported OR/RR, and a 32% increased risk across 18 studies which reported time to death (HR: 1.32, 95% CI: 1.10-1.59). There was very high study heterogeneity (I2 > 94%) and this was not explained by the prespecified subgroup analysis. CONCLUSION: PTSD is associated with increased mortality risk, however further research is required amongst civilians, involving women, and in individuals from underdeveloped countries.
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Terapia Cognitivo-Comportamental , Transtornos de Estresse Pós-Traumáticos , Masculino , Humanos , Feminino , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Listas de Espera , Países em DesenvolvimentoRESUMO
INTRODUCTION: Frailty is a common geriatric syndrome that adversely impacts health outcomes. This study examined correlates of physical frailty in healthy community-dwelling older adults and studied the effect of frailty on disability-free survival (DFS), defined as survival free of independence-limiting physical disability or dementia. METHODS: This is a post hoc analysis of 19,114 community-dwelling older adults (median age: 74.0 years, interquartile range or IQR: 6.1 years) from Australia and the USA enrolled in the "ASPirin in Reducing Events in the Elderly (ASPREE)" clinical trial. Frailty was assessed using a modified Fried phenotype and a deficit accumulation frailty index (FI) utilizing a ratio score derived from 66 items. Multinomial logistic regression was used to examine the correlates of frailty and Cox regression to analyze the association between frailty and DFS (and its components). RESULTS: At study enrollment, 39.0% were prefrail, and 2.2% of participants were frail, according to Fried phenotype. Older age, higher waist circumference, lower education, ethnoracial origin, current smoking, depression, and polypharmacy were associated with prefrailty and frailty according to Fried phenotype and FI. Fried phenotype defined prefrailty and frailty predicted reduced DFS (prefrail: HR: 1.67; 95% CI: 1.50-1.86 and frail: HR: 2.80; 95% CI: 2.27-3.46), affecting each component of DFS including dementia, physical disability, and mortality. Effect sizes were larger, according to FI. CONCLUSION: Our study showed that prefrailty is common in community-dwelling older adults initially free of cardiovascular disease, dementia, or independence-limiting physical disability. Prefrailty and frailty significantly reduced disability-free survival. Addressing modifiable correlates, like depression and polypharmacy, might reduce the adverse impact of frailty on dementia-free and physical disability-free survival.
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Fragilidade , Humanos , Idoso , Vida Independente , Austrália/epidemiologia , Idoso Fragilizado , Avaliação GeriátricaRESUMO
Frailty and chronic kidney disease (CKD) both increase with age and are prevalent in older adults. However, studies in older adults examining the relationship between frailty and milder impairments of kidney function are relatively sparse. We examined the cross-sectional association of baseline estimated glomerular filtration rate (eGFR), albuminuria and CKD ([eGFR <60 ml/min/1.73 m2 ] and/or albuminuria [>3.0 mg/mmol]) with prefrailty and frailty in the ASPirin in Reducing Events in the Elderly (ASPREE) trial cohort of healthy older participants. Univariate logistic regression models measured the unadjusted odds ratios (OR) and 95% confidence intervals (CI) for prevalent combined prefrailty and frailty (respectively defined as presence of 1-2 or 3+ of 5 modified fried criteria) for the association between CKD, eGFR, albuminuria and other potential risk factors. Multivariable models calculated OR for prefrailty-frailty adjusted for potential confounders and either CKD, (i) eGFR and albuminuria measured as either continuous variables; (ii) or categorical variables; (iii). Of 17 759 eligible participants, 6934 were classified as prefrail, 389 were frail. CKD, eGFR and albuminuria were all associated with combined prefrailty-frailty on univariate analysis. In the multivariable modelling, neither CKD (reduced eGFR and/or albuminuria), nor eGFR (either continuous or categorical variables) were associated with prefrailty-frailty. However, albuminuria, either as a continuous variable (OR [95% CI] 1.07 [1.04-1.10]; p < .001), or categorical variable (OR 1.21 [1.08-1.36]; p = .001) was consistently associated with prefrailty-frailty. The complex relationship between albuminuria (which may be a biomarker for vascular inflammation), ageing, progressive CKD and frailty requires further investigation.
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Fragilidade , Insuficiência Renal Crônica , Humanos , Idoso , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Albuminúria/diagnóstico , Albuminúria/epidemiologia , Aspirina/efeitos adversos , Estudos Transversais , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Taxa de Filtração Glomerular , Fatores de RiscoRESUMO
INTRODUCTION: Cardiovascular disease (CVD) is a recognized risk factor for dementia. Here we determined the extent to which an incident CVD event modifies the trajectory of cognitive function and risk of dementia. METHODS: 19,114 adults (65+) without CVD or dementia were followed prospectively over 9 years. Incident CVD (fatal coronary heart disease, nonfatal myocardial infarction [MI], stroke, hospitalization for heart failure) and dementia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) were adjudicated by experts. RESULTS: Nine hundred twenty-two participants had incident CVD, and 44 developed dementia after CVD (4.9% vs. 4.4% for participants without CVD). Following a CVD event there was a short-term drop in processing speed (-1.97, 95% confidence interval [CI]: -2.57 to -1.41), but there was no significant association with longer-term processing speed. In contrast, faster declines in trajectories of global function (-0.56, 95% CI: -0.76 to -0.36), episodic memory (-0.10, 95% CI: -0.16 to -0.04), and verbal fluency (-0.19, 95% CI: -0.30 to -0.01) were observed. DISCUSSION: Findings highlight the importance of monitoring cognition after a CVD event.
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Doenças Cardiovasculares , Doença das Coronárias , Demência , Humanos , Idoso , Doenças Cardiovasculares/epidemiologia , Fatores de Risco , Cognição , Demência/epidemiologiaRESUMO
INTRODUCTION: Recent genome-wide association studies identified new dementia-associated variants. We assessed the performance of updated polygenic risk scores (PRSs) using these variants in an independent cohort. METHODS: We used Cox models and area under the curve (AUC) to validate new PRSs (PRS-83SNP, PRS-SBayesR, and PRS-CS) compared with an older PRS-23SNP in 12,031 initially-healthy participants ≥70 years of age. Dementia was rigorously adjudicated according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. RESULTS: PRS-83SNP, PRS-SBayesR, and PRS-CS were associated with incident dementia, with fully adjusted (including apolipoprotein E [APOE] ε4) hazard ratios per standard deviation (SD) of 1.35 (1.23-1.47), 1.37 (1.25-1.50), and 1.42 (1.30-1.56), respectively. The AUC of a model containing conventional/non-genetic factors and APOE was 74.7%. This was improved to 75.7% (p = 0.007), 76% (p = 0.004), and 76.1% (p = 0.003) with addition of PRS-83SNP, PRS-SBayesR, and PRS-CS, respectively. The PRS-23SNP did not improve AUC (74.7%, p = 0.95). CONCLUSION: New PRSs for dementia significantly improve risk-prediction performance, but still account for less risk than APOE genotype overall.
Assuntos
Demência , Estratificação de Risco Genético , Humanos , Estudos Prospectivos , Estudo de Associação Genômica Ampla , Apolipoproteínas E/genética , Demência/genética , Fatores de RiscoRESUMO
BACKGROUND: We sought to determine the association between heart failure (HF) and cognitive change and dementia. METHODS AND RESULTS: Systematic search of three electronic databases was performed and 29 eligible studies involving approximately 3 million participants were identified. Twelve studies examined dementia and 20 cognitive change, but only a subset of studies could be included in the meta-analysis. These findings indicated that HF was not significantly associated with dementia (nâ¯=â¯8, hazard ratio 1.18, 95% confidence interval 0.93-1.50), but increased the risk of cognitive impairment (nâ¯=â¯3, hazard ratio 1.80, 95% confidence interval 1.14-2.86) . Additionally, HF was associated with poorer mean cognitive performance in global cognition (Hedges' g -0.73, 95% confidence interval -1.12 to -0.35), memory (Hedges' g -0.57, 95% confidence interval -0.72 to -0.42), executive function (Hedges' g -0.58, 95% confidence interval -0.72 to -0.43), attention/speed (Hedges' g -0.50, 95% confidence interval -0.63 to -0.37) and language (Hedges' g -0.61, 95% confidence interval -1.05 to -0.17). CONCLUSIONS: Patients with HF perform worse on all cognitive tests and have an increased risk of cognitive impairment. These findings highlight the need for clinicians to consider cognition as part of routine care for patients with HF.