Risk factors of transition from mild cognitive impairment to Alzheimer's disease and death: A cohort study

BackgroundKnowledge of risk factors is essential for developing strategies that prevent or minimise transitions from mild cognitive impairment (MCI) to Alzheimer's disease (AD) and death. The aim of this study was to assess risk factors for progression to AD and death among Chinese individuals with cognitive impairment.MethodsWe conducted a multisite, population-based cohort study on 437 community-dwelling elderly MCI residents in Taiyuan, China from 2010 to 2014. MCI, AD, death from AD and death from a cause other than AD were specified as disease states during the natural history of dementia. Transition-specific Cox model was fitted and hazard ratio (HR) with 95% confidence intervals (CIs) was estimated.ResultsAnalyses showed that risk factors played different roles in affecting transitions to AD and death. Risk factors for transition from MCI to AD were being female (HR: 1.82; 95%CI: 1.20–2.77), older age (HR: 3.09; 95%CI: 1.81–5.25), reading occasionally (HR: 1.79; 95%CI: 1.11–2.89), current smoking (HR: 1.74; 95%CI: 1.15–2.65), light–moderate alcohol drinker (HR: 2.24; 95%CI: 1.42–3.53), cerebrovascular disease (HR: 2.70; 95%CI: 1.68–4.34), hyperlipidemia (HR: 1.87; 95%CI: 1.16–3.02) and diabetes (HR: 1.81; 95%CI: 1.18–2.77). Only cerebrovascular disease (HR: 3.04; 95%CI: 1.22–7.58) was a significant risk factor for transition from MCI to death from a cause other than AD. Older age (HR: 10.68; 95%CI: 1.16–97.93) and low level education (HR: 0.14; 95%CI: 0.05–0.44) were significant predictors for transition from AD to death from a cause other than AD.ConclusionsParticipants with advanced age, low-level education, history of harmful alcohol consumption or smoking, cerebrovascular disease, hyperlipidemia, diabetes or who were female were at increased risk of transitioning to AD or death. Strategies to control modifiable risk factors in specific disease stage should be implemented to decrease the conversion to AD or death among Chinese patients with MCI.     

Do Acetylcholinesterase Inhibitors Prevent or Delay Psychotropic Prescribing in People With Dementia? Analyses of the Swedish Dementia Registry

ObjectivesTo investigate whether acetylcholinesterase inhibitor (AChEI) use prevents or delays subsequent initiation of psychotropic medications in people with Alzheimer's disease (AD) and Lewy body dementia (LBD).MethodsCohort study of 17,763 people with AD and LBD, without prior psychotropic use at time of dementia diagnosis, registered in the Swedish Dementia Registry from 2007 to 2015. Propensity score-matched regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between time-dependent AChEI use and risk of psychotropic initiation.ResultsCompared with matched comparators, AChEI users had a lower risk of antipsychotic (HR: 0.85, 95%CI: 0.75–0.95) and anxiolytic (HR: 0.76, 95%CI: 0.72–0.80) initiation. In subanalyses, this association remained significant at higher AChEI doses, and in AD but not LBD. There were no associations between AChEI use and initiation of antidepressants or hypnotics.ConclusionAChEI use may be associated with lower risk of antipsychotic and anxiolytic initiation in AD, particularly at higher doses. Further investigation into aceytylcholinesterase inhibitors in behavioral and psychological symptoms of dementia management in LBD is warranted.     

Association of Depressive Symptoms With Postoperative Delirium and CSF Biomarkers for Alzheimer's Disease Among Hip Fracture Patients

ObjectivesWhile there is growing evidence of an association between depressive symptoms and postoperative delirium, the underlying pathophysiological mechanisms remain unknown. The goal of this study was to explore the association between depression and postoperative delirium in hip fracture patients, and to examine Alzheimer's disease (AD) pathology as a potential underlying mechanism linking depressive symptoms and delirium.MethodsPatients 65 years old or older (N = 199) who were undergoing hip fracture repair and enrolled in the study “A Strategy to Reduce the Incidence of Postoperative Delirium in Elderly Patients” completed the 15-item Geriatric Depression Scale (GDS-15) preoperatively. Cerebrospinal fluid (CSF) was obtained during spinal anesthesia and assayed for amyloid-beta (Aβ) 40, 42, total tau (t-tau), and phosphorylated tau (p-tau)₁₈₁.ResultsFor every one point increase in GDS-15, there was a 13% increase in odds of postoperative delirium, adjusted for baseline cognition (MMSE), age, sex, race, education and CSF AD biomarkers (OR = 1.13, 95%CI = 1.02–1.25). Both CSF Aβ42/t-tau (β = −1.52, 95%CI = −2.1 to −0.05) and Aβ42/p-tau₁₈₁ (β = −0.29, 95%CI = −0.48 to −0.09) were inversely associated with higher GDS-15 scores, where lower ratios indicate greater AD pathology. In an analysis to identify the strongest predictors of delirium out of 18 variables, GDS-15 had the highest classification accuracy for postoperative delirium and was a stronger predictor of delirium than both cognition and AD biomarkers.ConclusionsIn older adults undergoing hip fracture repair, depressive symptoms were associated with underlying AD pathology and postoperative delirium. Mild baseline depressive symptoms were the strongest predictor of postoperative delirium, and may represent a dementia prodrome.     

The Roles of Apathy and Depression in Predicting Alzheimer Disease: A Longitudinal Analysis in Older Adults With Mild Cognitive Impairment

ObjectiveApathy and depression have each been associated with an increased risk of conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD).These symptoms often co-occur and the contribution of each to risk of AD is not clear.MethodsNational Alzheimer's Coordinating Center participants diagnosed with MCI at baseline and followed until development of AD or loss to follow-up (n = 4,932) were included. The risks of developing AD in MCI patients with neuropsychiatric symptoms (NPS) (apathy only, depression only, or both) were compared to that in those without NPS in a multivariate Cox regression survival analysis adjusting for baseline cognitive impairment, years of smoking, antidepressant use, and AD medication use.ResultsThirty-seven percent (N = 1713) of MCI patients developed AD (median follow-up 23 months). MCI patients with both apathy and depression had the greatest risk (hazard ratio [HR] = 1.37; 95% confidence interval [CI]: 1.17–1.61; p < 0.0001; Wald χ² = 14.70; df = 1). Those with apathy only also had a greater risk (HR = 1.24; 95% CI: 1.05–1.47; p = 0.01; Wald χ² = 6.22; df = 1), but not those with depression only (HR = 1.08; 95% CI: 0.95–1.22; p=0.25; Wald χ² = 1.30; df = 1). Post-hoc analyses suggested depression may exacerbate cognitive decline in MCI patients with apathy (odds ratio = 0.70; 95% CI 0.52–0.95; p = 0.02; Wald χ² = 5.28; df = 1), compared to those without apathy.ConclusionMCI patients with apathy alone or both apathy and depression are at a greater risk of developing AD compared to those with no NPS. Interventions targeting apathy and depression may reduce risk of AD.     

Estrogen receptor polymorphisms and incident dementia: The prospective 3C study

BackgroundGenetic variation in the estrogen receptor (ESR) may be associated with the incidence of Alzheimer's disease (AD), but this association could be modified by genetic and environmental factors.MethodsThe association between five ESR α (ESR1) and β (ESR2) polymorphisms with 7-year dementia incidence was examined among 6959 older men and women from the Three City Study using multivariate-adjusted Cox regression models with delayed entry. Gender, the apolipoprotein E (APOE) ε4 allele, and hormone treatment were considered as potential effect modifiers of this association.ResultsAmong women, the CC genotype of ESR1 rs2234693 was specifically associated with a small increased risk of AD (adjusted hazard ratio [HR]: 1.54, 95% confidence interval [CI]: 1.03–2.28, P = .03). However, women with this genotype had a substantially increased risk of AD associated with the APOE ε4 allele (adjusted HR: 3.24, 95% CI: 1.81–5.79 for women rs2234693 CC; compared with HR: 1.87, 95% CI: 1.37–2.56 for all women). There was also evidence of a nominally significant interaction between the ESR1 and ESR2 polymorphisms on the risk of all dementias (P = .04). Hormone treatment did not modify these associations, and there were no significant associations in men.ConclusionsAlthough there was only weak support for a gender-specific association between the common ESR1 rs2234693 polymorphism and AD, this polymorphism may act as an effect modifier, modifying the association between an ESR2 polymorphism and dementia, as well as the risk of AD associated with the APOE ε4 allele.     

Depressive symptoms and 10-year risk for cardiovascular morbidity and mortality

Abstract

Objectives. Depression is associated with increased physical morbidity and overall mortality. As less is known about how much depression increases the 10-year risk for fatal and nonfatal cardiovascular (CV) events, we evaluated the cross-sectional risk with two well-characterized risk functions measuring CV mortality and total CV event risk. Methods. The prevalence of increased depressive symptoms was measured with the Beck Depression Inventory (BDI), and the SCORE and Framingham risk functions were calculated in a middle-aged population-based sample (N=923). For metabolic syndrome (MetS), the modified National Cholesterol Education Program – Adult Treatment Panel III criteria were employed. Results. Depressive symptoms were associated with increased CV mortality and morbidity risk in men: OR for SCORE 2.9; 95%CI 1.4–5.7 and OR for Framingham function 2.2 (95%CI 1.1–4.2). In women, the corresponding figures were 1.4 (95%CI 0.3–6.9) and 1.3 (95%CI 0.7–2.6). The BDI scores showed significant correlations with SCORE (r=0.18 for men, P < 0.001; and r=0.14 for women, P=0.002), and Framingham function (for men r=0.16, P < 0.001; and for women r=0.13, P=0.005). Conclusions. Our results suggest that screening and effective treatment of depression are important in the primary and secondary prevention of cardiovascular events, especially in males.     

Life-Weariness,Wish to Die,Active Suicidal Ideation,and All-Cause Mortality in Population-Based Samples of Older Adults

ObjectivesTo investigate potential differences in the strength of associations between different levels of passive and active suicidal ideation and all-cause mortality in older adults.DesignProspective cohort study.SettingPopulation-based samples of older adults in Gothenburg, Sweden.ParticipantsOlder adults aged 79 and above who participated in any wave of the Gothenburg H70 Birth Cohort Studies or the Prospective Population Study of Women between 1986 and 2015 (n = 2,438; 1,737 women, 701 men; mean age 86.6).MeasurementsMost intense level of passive or active suicidal ideation during the past month: life-weariness, wish to die, or active suicidal ideation. The outcome was all-cause mortality over 3 years.ResultsDuring follow-up, 672 participants (27.6%) died. After adjustments for sex, age, and year of examination, participants who reported a wish to die (HR 2.01; 95% CI 1.55–2.60) as the most intense level of ideation, but not participants who reported life-weariness (HR 1.40; 95% CI 0.88–2.21) or active suicidal ideation (HR 1.10; 95% CI 0.69–1.76) were at increased risk of all-cause mortality. Reporting a wish to die remained associated with mortality in a fully adjusted model, including somatic conditions, dementia, depression, and loneliness (HR 1.70; 95% CI 1.27–2.26).ConclusionIn older adults, reporting a wish to die appears to be more strongly associated with all-cause mortality than either life-weariness or active suicidal ideation     

Brain arterial dilatation and the risk of Alzheimer's disease

IntroductionWe tested the hypothesis that brain arterial dilatation increases the risk of Alzheimer's dementia (AD).MethodsWe studied dementia-free participants in the Washington Heights-Inwood Columbia Aging Project who had a brain MRI and post-MRI dementia adjudication. We measured the axial T2-proton density diameters of the intracranial carotids and basilar diameters and used Cox models to obtain AD hazard ratios and 95% intervals.ResultsOf 953 participants (mean age 77 ± 7 y, women 64%, 71% nonwhite) followed on average for 3 ± 3 years, 76 (8%) developed AD. In a model adjusted for demographics, vascular risks, apolipoprotein E (APOE)-ε4, and white matter hyperintensities, larger carotid diameters increased the risk of AD, defined categorically as ≥ 90th percentile (HR 4.34, 1.70–11.11) or continuously (HR 1.44 per SD, 1.07–1.94).DiscussionUnderstanding the pathophysiology of the association between AD and brain arterial dilatation may reveal new clues to the vascular contributions to AD.     

Results of a follow-up study to the randomized Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT)

ObjectivesThe Alzheimer's Disease Anti-inflammatory Prevention Trial Follow-up Study (ADAPT-FS) was designed to evaluate the efficacy of naproxen and celecoxib for the primary prevention of Alzheimer's disease (AD) several years after cessation of treatment in ADAPT.MethodsADAPT was a randomized, double-masked, multicenter clinical trial of naproxen or celecoxib vs placebo (1:1:1.5 assignment ratio) at six U.S.-based clinics. The trial enrolled 2528 people between 2001 and 2004. Treatments were discontinued in December 2004 and participants were monitored regularly until 2007. In 2010 and 2011, ADAPT-FS screened 1537 participants by telephone and, if indicated, examined them in person using standardized clinical assessments. The primary outcome was time to diagnosis of AD. Death index searches were performed for participants not located.ResultsEighty-nine additional AD events were identified (24 celecoxib, 25 naproxen, and 40 placebo) yielding a total of 161 events (48 [6.6% of randomized participants] celecoxib, 43 [6.0%] naproxen, and 70 [6.5%] placebo) across ADAPT and ADAPT-FS. Adjusted hazard ratios (HRs) comparing each treatment with placebo showed no overall reduction in risk of AD: HR celecoxib vs placebo, 1.03 (95% confidence interval [CI], 0.72–1.50; P = .86); HR naproxen vs placebo, 0.92 (95% CI, 0.62–1.35; P = .66). There were 349 deaths (110 [15.2%] celecoxib, 96 [13.4%] naproxen, and 143 [13.2%] placebo). Risk of death was similar for the naproxen- and placebo-assigned groups (HR, 0.99; 95% CI, 0.76–1.28; P = .93) and slightly higher for celecoxib compared with the placebo-assigned group (HR, 1.15; 95% CI, 0.90–1.48; P = .27).ConclusionsThese results acquired during a follow-up of approximately 7 years (which included a median of less than 1.5 years of treatment) do not support the hypothesis that celecoxib or naproxen prevent AD in adults with a family history of dementia.     

Obesity and the Risk of Cryptogenic Ischemic Stroke in Young Adults

ObjectivesWe examined the association between obesity and early-onset cryptogenic ischemic stroke (CIS) and whether fat distribution or sex altered this association.Materials and MethodsThis prospective, multi-center, case-control study included 345 patients, aged 18-49 years, with first-ever, acute CIS. The control group included 345 age- and sex-matched stroke-free individuals. We measured height, weight, waist circumference, and hip circumference. Obesity metrics analyzed included body mass index (BMI), waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), and a body shape index (ABSI). Models were adjusted for age, level of education, vascular risk factors, and migraine with aura.ResultsAfter adjusting for demographics, vascular risk factors, and migraine with aura, the highest tertile of WHR was associated with CIS (OR for highest versus lowest WHR tertile 2.81, 95%CI 1.43-5.51; P=0.003). In sex-specific analyses, WHR tertiles were not associated with CIS. However, using WHO WHR cutoff values (>0.85 for women, >0.90 for men), abdominally obese women were at increased risk of CIS (OR 2.09, 95%CI 1.02-4.27; P=0.045). After adjusting for confounders, WC, BMI, WSR, or ABSI were not associated with CIS.ConclusionsAbdominal obesity measured with WHR was an independent risk factor for CIS in young adults after rigorous adjustment for concomitant risk factors.     

Risk and prognostic factors for pneumonia and choking amongst Parkinson’s disease patients with dysphagia

ObjectiveTo evaluate the time to hospitalisation and baseline factors associated with pneumonia/choking in Parkinson’s Disease (PD) patients.BackgroundAlthough dysphagia and pneumonia are common problems in PD, scarce research has been performed.MethodsA total of 194 PD patients who underwent a VFS evaluation were retrospectively selected. The mode of feeding and admissions for pneumonia/choking were analyzed. Baseline clinical and demographic variables were compared between feeding groups. Kaplan-Meier survival analysis was performed to estimate time to pneumonia/choking. Clinical variables significantly associated with pneumonia/choking free survival were identified using Cox regression.ResultsHospitalisation for pneumonia/choking occurred in 89 out of 194 patients, with the highest admission rate in rejected enteral feeding group (66.7%), followed by enteral feeding (61.8%) and oral feeding (38.8%) groups. The estimates of median time to event were 11, 14, and 47 months for rejected enteral feeding, enteral and oral feeding groups respectively (log-rank test p < 0.001). The rejected enteral feeding group had the highest risk of pneumonia/choking (HR 4.61, 95%CI:2.33–9.08, p < 0.001), followed by enteral feeding group (HR 2.29, 95%CI:1.25–4.19, p = 0.007), when compared to oral feeding group after adjusting for possible confounders. A stepwise Cox regression showed that the rejected enteral feeding (HR 4.89, 95%CI:2.19–10.88, p < 0.001), enteral mode of feeding (HR 2.43, 95%CI:1.11–5.32, p = 0.026), and Charlson weighted index of co-morbidity (HR 1.27, 95%CI:1.03–1.58, p = 0.028) were independently associated with higher hazard of pneumonia/choking.ConclusionsCompliance to feeding recommendations is important to reduce the risk of hospitalisation for pneumonia/choking. The recommended mode of feeding and comorbidity index was significantly associated with pneumonia/choking risk.     

Sex Differences in Post-Stroke Depression in the Elderly

ObjectivePost-stroke depression (PSD) occurs in approximately one-third of ischemic stroke patients. However, there is conflicting evidence on sex differences in PSD. We sought to assess sex differences in risk and time course of PSD in US ischemic stroke (IS) patients. We hypothesized that women are at greater risk of PSD than men, and that a greater proportion of women experience PSD in the acute post-stroke phase.Materials and MethodsWe conducted a retrospective cohort study of 100% de-identified data for US Medicare beneficiaries admitted for ischemic stroke from July 1, 2016 to December 31, 2017. We calculated Kaplan-Meier unadjusted cumulative risk of depression, stratified by sex, up to 1.5 years following index admission. We performed Cox regression to report the hazard ratio (HR) for diagnosis of depression up to 1.5 years post-stroke in females vs. males, adjusting for patient demographics, comorbidities, length of stay, and acute stroke interventions.ResultsIn elderly stroke patients, females (n=90,474) were 20% more likely to develop PSD than males (n=84,427) in adjusted models. Cumulative risk of depression was consistently elevated for females throughout 1.5 years of follow-up (0.2055 [95% CI 0.2013–0.2097] vs. 0.1690 [95% CI 0.1639–0.1741] (log-rank p < 0.0001). HR for PSD in females vs. males remained significant in fully adjusted analysis at 1.20 (95% CI 1.17-1.23, p < 0.0001).ConclusionsOver 1.5 years of follow-up, female stroke patients had significantly greater hazard of developing PSD, highlighting the need for long-term depression screening in this population and further investigation of underlying reasons for sex differences.     

An Analysis of Stroke Risk Factors by HIV Serostatus in Uganda: Implications for Stroke Prevention in Sub-Saharan Africa

ObjectiveHIV infection is an important stroke risk factor in sub-Saharan Africa.  However, data on stroke risk factors in the era of antiretroviral therapy (ART) are sparse. We aimed to determine if stroke risk factors differed by HIV serostatus in Uganda.MethodsWe conducted a matched cohort study, enrolling persons living with HIV (PWH) with acute stroke, matched by sex and stroke type to HIV uninfected (HIV-) individuals. We collected data on stroke risk factors and fitted logistic regression models for analysis.ResultsWe enrolled 262 participants:105 PWH and 157 HIV-. The median ART duration was 5 years, and the median CD4 cell count was 214 cells/uL. PWH with ischemic stroke had higher odds of hypertriglyceridemia (AOR 1.63; 95% CI 1.04, 2.55, p=0.03), alcohol consumption (AOR 2.84; 95% CI 1.32, 6.14, p=0.008), and depression (AOR 5.64; 95%CI 1.32, 24.02, p=0.02) while HIV- persons with ischemic stroke were more likely to be > 55 years of age (AOR 0.43; 95%CI 0.20-0.95, p=0.037), have an irregular heart rhythm (AOR 0.31; 95%CI 0.10-0.98, p=0.047) and report low fruit consumption (AOR 0.39; 95%CI 0.18-0.83, p=0.014).  Among all participants with hemorrhagic stroke (n=78) we found no differences in the prevalence of risk factors between PWH and HIV-.ConclusionsPWH with ischemic stroke in Uganda present at a younger age, and with a combination of traditional and psychosocial risk factors. By contrast, HIV- persons more commonly present with arrhythmia. A differential approach to stroke prevention might be needed in these populations.     

Preeclampsia and the longitudinal risk of hospitalization for depression at 28 years

Purpose

The association between pregnancy characteristics and risk of depression in women is poorly understood. We investigated the relationship between preeclampsia and risk of hospitalization for depression over three decades.

Methods

We carried out a longitudinal cohort study of 1,210,963 women who delivered an infant in any hospital in Quebec, Canada, between 1989 and 2016. The exposure was preeclampsia at the first or in subsequent pregnancies, including preeclampsia onset time (early < 34 weeks vs. late ≥ 34 weeks of gestation) and severity (mild, severe, superimposed). The outcome was hospitalization for depression any time after pregnancy. We used Cox proportional hazards regression models adjusted for maternal characteristics to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of preeclampsia with depression hospitalization.

Results

Women with preeclampsia had a higher incidence of hospitalization for depression compared with no preeclampsia (1.43 vs. 1.14 per 1000 person-years). Preeclampsia was associated with 1.16 times the risk of depression hospitalization after 28 years of follow-up (95% CI 1.09–1.23). Associations were present for mild (HR 1.15, 95% CI 1.07–1.24), severe (HR 1.16, 95% CI 1.04–1.29) and late onset preeclampsia (HR 1.17, 95% CI 1.10–1.25). Risks were more pronounced after the first year postpartum.

Conclusion

Preeclampsia appears to be associated with the risk of depression hospitalization several decades after pregnancy. Clinicians who care for women with mental health disorders should be aware that a history of preeclampsia increases the risk of severe depression.

     

Personality and risk of Alzheimer's disease: New data and meta-analysis

BackgroundWe examine whether broad factors and specific facets of personality are associated with increased risk of incident Alzheimer's disease (AD) in a long-run longitudinal study and a meta-analysis of published studies.MethodsParticipants (n = 1671) were monitored for up to 22 years from a baseline personality assessment. The meta-analysis pooled results from up to five prospective studies (n = 5054).ResultsIndividuals with scores in the top quartile of neuroticism (hazard ratio = 3.1; 95% confidence interval = 1.6–6.0) or the lowest quartile of conscientiousness (hazard ratio = 3.3; 95% confidence interval = 1.4–7.4) had a threefold increased risk of incident AD. Among the components of these traits, self-discipline and depression had the strongest associations with incident AD. The meta-analysis confirmed the associations of neuroticism (P = 2 × 10⁻⁹) and conscientiousness (P = 2 × 10⁻⁶), along with weaker effects for openness and agreeableness (P < .05).ConclusionsThe current study and meta-analysis indicate that personality traits are associated with increased risk of AD, with effect sizes similar to those of well-established clinical and lifestyle risk factors.     

Off-label use of antipsychotics and associated factors in community living older adults*

Background: Given the common off-label use of antipsychotics (AP), we aimed to assess the factors associated with this use in community living older adults.

Methods: The study sample consisted of a large representative sample of older adults (n = 4108), covered under a public drug insurance plan in Canada. Off-label use of antipsychotics was defined by the absence of an approved indication for this use, according to Health Canada's drug product database. Multinomial logistic regression was used to assess the factors associated with off-label use.

Results: The prevalence of antipsychotics use was 2.5%, of which 78% was off-label. Compared to non-use, off-label antipsychotics use was negatively associated with advanced age (≥75 vs. 65–74 years old) (OR: 0.46; 95%CI: 0.27–0.78); and positively associated with higher education level (OR: 2.68; 95% CI: 1.64–4.40), higher number of outpatient visits (≥6) (OR: 2.39; 95%CI: 1.34–4.25), antidepressant or benzodiazepine use (OR: 5.81; 95%CI: 3.31–10.21), and the presence of an organic brain syndrome & Alzheimer's (OR: 5.73; 95%CI: 1.74–18.89). Compared to labeled use, off-label use was less likely in those with major depression (OR: 0.02; 95%CI: <0.01–0.11) and with insomnia (OR: 0.13; 95%CI: 0.02–0.91).

Conclusions: The majority of antipsychotics prescribed to community living older adults were off-label. This off-label use was more likely in complex clinical cases with multiple outpatient visits and other psychotropic drugs use. Further research should focus on the long-term effects associated with off-label use of antipsychotics.     

Risk of self-harm in physically ill patients in UK primary care

ObjectiveTo examine self-harm risk across the adult age range in patients diagnosed with various physical illnesses using the General Practice Research Database — a broadly representative sample of all people registered with a family practice in the United Kingdom.MethodsWe conducted a large nested case–control study sampled from the whole primary care cohort. During 2001–2008 we studied 2306 cases of self-harm and 46,120 age and gender-matched controls without such an episode recorded. Relative risks were estimated against reference patients with none of the examined physical illnesses. Additionally, we assessed confounding by recorded depression, effect modification by gender and multi-morbidity effects.ResultsRisk was significantly elevated in relation to any of the physical illnesses (male OR 1.35, 95% CI 1.18–1.54; female OR 1.62, 95% CI 1.40–1.86). For both genders combined, risk was raised with each specific illness. Effects sizes were consistently larger in women. Adjustment for recorded depression explained much of the elevated risk, but not so in women with asthma, back pain, diabetes, epilepsy or hypertension. Raised risk was seen in younger adults and during middle age, but not among older people. There was a dose–response relationship with increasing number of physical illnesses, and in women this was independent of depression.ConclusionHeightened risk was seen with a variety of physical illnesses. The findings indicate a need for tackling psychological distress and reducing self-harm risk in physically ill patients who attend primary healthcare services for non-psychiatric reasons, particularly so for women and younger and middle aged adults.     

Liver Fibrosis is Associated with Ischemic Stroke Risk in Women but not Men: The REGARDS Study

BackgroundNonalcoholic fatty liver disease is inconsistently associated with ischemic stroke, with one study suggesting an association in women and not men. The relative importance of liver fibrosis, as opposed to fatty liver, for cardiovascular risk is increasingly appreciated. We hypothesized that advanced liver fibrosis is associated with incident ischemic stroke risk, and especially in women.MethodsWe performed a case-cohort study in the REasons for Geographic and Racial Differences in Stroke cohort. Black and white individuals aged 45 and older were recruited between 2003 and 2007 and followed for ischemic stroke. The Fibrosis-4 (FIB-4) score and Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS) were calculated using baseline data for stroke cases and a cohort random sample; advanced liver fibrosis was classified using validated cutoffs. Cox proportional hazards models were used to estimate hazard ratios (HR) of stroke after adjusting for potential confounders. Sex differences were assessed.ResultsThere were 572 incident ischemic strokes (285 in women) over 5.4 (SD, 2.2) years. Advanced liver fibrosis was not significantly associated with ischemic stroke overall using the FIB-4 (HR 1.44; 95% CI 0.49–4.28) or NFS (HR 1.76; 95% CI 0.67–4.61). However, liver fibrosis was associated with stroke in women (HR 3.51; 95% CI 1.00–12.34) but not men (HR 0.70, 95% CI 0.16–3.16) (P = 0.098 for interaction) when using FIB-4. A similar but non-significant sex difference was seen for NFS.ConclusionAdvanced liver fibrosis may be associated with a higher risk of ischemic stroke in women but not men.     

Low Mood and Risk of Dementia: The Role of Marital Status and Living Situation

ObjectiveThis study aims to explore whether low mood is related to an increased dementia risk in two cohorts of older adults of different generations, and whether marital status and living situation modify this association.MethodsParticipants (≥70 years), free from dementia and living at home, were identified from two population-based studies: the Kungsholmen Project (KP; n = 1,197) and the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K; n = 1,402). Low mood was obtained by self-report (KP and SNAC-K) at baseline in 1987–89 (KP) and 2001–04 (SNAC-K). Incident dementia cases were ascertained over 9 years, using the same diagnostic procedures and comparable criteria for the two cohorts (DSM-III-R in KP and DSM-IV-TR in SNAC-K). Hazard ratios (HR) were derived from Cox proportional hazards models.ResultsThose having low mood at baseline were at higher risk of dementia in both cohorts combined (HR: 1.2, 95% confidence interval (CI): 1.0–1.4) than those without low mood. However, an increased risk was detected only in those who did not have a partner (HR: 1.5, 95% CI: 1.2–1.9), or lived alone (HR: 1.5, 95% CI: 1.2–1.9), but not among those who had a partner or lived with someone (HR: 0.8, 95% CI: 0.5–1.2).ConclusionMarital status and living situation have the potential to buffer the detrimental effects of low mood on dementia onset. Thus, specific attention from health care should target individuals having low mood and who do not have a partner or live alone.     

Current and past leisure time physical activity in relation to risk of Alzheimer's disease in older adults

IntroductionThe associations between self-reported current and past leisure time physical activity (LTPA) and Alzheimer's disease (AD) incidence were determined using data from the multiethnic Washington/Hamilton Heights-Inwood Columbia Aging Project (WHICAP) study.MethodsThe metabolic equivalent of LTPA energy expenditure was calculated for self-reported current and past LTPA for 1345 older adults. A Cox proportional hazard model was conducted to estimate the association between LTPA (low, middle, and high) and incident AD risk.ResultsComparing high to low level, current and past LTPA were both associated with reduced AD risk, with hazard ratio (95% confidence interval) = 0.39 (0.20–0.75) and 0.37 (0.18–0.75), respectively. Compared with “always low,” “increased” and “always high” LTPA throughout life were associated with reduced AD risk, with hazard ratio (95% confidence interval) = 0.60 (0.36–0.99) and 0.28 (0.08–0.94), respectively. Light- and moderate-intensity LTPA were associated with lower AD risk.DiscussionLTPA both throughout life and later in life are associated with lower risk of AD.