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Objectives This study examines the gender-specific associations between a wide range of social activities and dementia risk. Methods A prospective cohort study was conducted involving community-dwelling older Australians (≥70 years) without significant cognitive impairment at enrolment. During the first year of enrolment, we assessed 25 self-reported social activities covering various aspects, including support from relatives and friends, community participation, social interactions with surroundings, and loneliness. Dementia diagnosis followed DSM-IV criteria, adjudicated by an international expert panel. To estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between social activities and dementia, we performed Cox proportional hazards models, adjusting for age, educational attainment, baseline global cognition, and depressive symptoms. Results Among 9,936 participants who completed all social activity questionnaires (median [IQR] age: 73.4 [71.6–77.1] years; 47.4% men), dementia was diagnosed in 3.8% of men (n  = 181/4,705) and 2.6% of women (n  = 138/5,231) over a median 6.4 years (IQR: 5.3–7.6, range: 0.2–10.1) follow-up. Gender-specific relationships emerged: caregiving for a person with illness/disability in women (HR: 0.65, 95% CI: 0.42–0.99), and having ≥9 relatives feeling close to call for help in men (HR: 0.56, 95% CI: 0.33–0.96; reference <9 relatives) were associated with reduced dementia risk. Unexpectedly, in women, having ≥5 friends with whom they felt comfortable discussing private matters were associated with a greater dementia risk (HR: 1.69, 95% CI: 1.10–2.59; reference ≤2 friends). Imputed models further identified that babysitting/childminding was associated with lower dementia risk in men (HR: 0.75, 95% CI: 0.56–0.99). No other social activities showed significant associations with dementia. Discussion This study provides evidence of social activities influencing dementia risk. Further investigations are required to uncover the mechanisms driving these observed relationships. [ABSTRACT FROM AUTHOR]

Background: This study examined the associations of body mass index (BMI) and waist circumference (WC), as well as their short‐ and long‐term changes over time, with incident dementia in older individuals. Methods: Data came from 18,837 community‐dwelling individuals aged 65+ years from Australia and the United States, who were relatively healthy without major cognitive impairment at enrolment. Anthropometric measures were prospectively assessed at baseline, as well as change and variability from baseline to year two (three time‐points). In a subgroup (n = 11,176), self‐reported weight at age 18 and 70+ years was investigated. Dementia cases satisfied DSM‐IV criteria. Cox regression was used to examine the associations between anthropometric measures and incident risk of dementia. Results: Compared to normal weight, an overweight (HR: 0.67, 95%CI: 0.57–0.79, p < 0.001) or obese BMI (HR: 0.73, 95%CI: 0.60–0.89, p = 0.002), or a larger WC (elevated, HR: 0.71, 95%CI: 0.58–0.86, p < 0.001; highly elevated, HR: 0.65, 95%CI: 0.55–0.78, p < 0.001; relative to low) at baseline was associated with lower dementia risk. In contrast, substantial increases in BMI (>5%) over 2 years after baseline were associated with higher dementia risk (HR: 1.49, 95% CI: 1.17–1.91, p = 0.001). Increased dementia risk was also seen with an underweight BMI at baseline and a 2‐year BMI decrease (>5%), but these associations appeared only in the first 4 years of follow‐up. Compared to normal weight at both age 18 and 70+ years, being obese at both times was associated with increased dementia risk (HR: 2.27, 95%CI: 1.22–4.24, p = 0.01), while obesity only at age 70+ years was associated with decreased risk (HR: 0.70, 95%CI: 0.51–0.95, p = 0.02). Conclusions: Our findings suggest that long‐term obesity and weight gain in later life may be risk factors for dementia. Being underweight or having substantial weight loss in old age may be early markers of pre‐clinical dementia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Surrogates and physicians may differ in their priorities and perspectives when making decisions for incapacitated, critically ill patients. Objectives: To determine the extent to which surrogate and physician decisions to sustain life support are associated with their expectations for patient outcomes. Setting/Subjects: Surrogates and physicians of 100 mechanically ventilated patients at an academic, tertiary care medical center in the United States were surveyed. Measurements: Linear regression was used to determine if participant expectations for patient survival, good quality of life, and confidence in these expectations were associated with their agreement that mechanical ventilation should be continued if required for patient survival. Results: Surrogates were more likely than physicians to expect that patients would be alive in three months (91% interquartile range [IQR 70–95%] vs. 65% [IQR 43–77%], p < 0.001) and have good quality of life in three months (71% [IQR 50–90%] vs. 40% [IQR 19–50%], p < 0.001). Surrogates who were most confident in their prognostic abilities were also the most optimistic for good patient outcomes. As such, expectations for patient survival and good quality of life were not associated with level agreement that mechanical ventilation should be continued among confident surrogates, (R2 = 0.03, p = 0.13) and (R2 = 0.01, p = 0.53), respectively. In contrast, among physicians, confidence was not synonymous with optimism. Instead, the significant associations between expectations for patient survival and good quality of life with the agreement that mechanical ventilation should be continued were strengthened when physicians were confident, (R2 = 0.34, p < 0.01) and (R2 = 0.47, p < 0.001), respectively. Conclusion: Surrogates and physicians have different approaches to incorporating their expectations for patient prognosis and their confidence in these expectations when they are making decisions for incapacitated critically ill patients. [ABSTRACT FROM AUTHOR]

Introduction: Teduglutide, a glucagon‐like peptide‐2 analog, is a novel therapy for intestinal failure that reduces need for parenteral support, especially in patients without a functional terminal ileum or colon. It can also predispose patients to accelerated progression of gastrointestinal (GI) malignancy and fluid overload. We demographically and clinically characterized American patients prescribed teduglutide. Methods: The Explorys database is an aggregate of deidentified patient data from dozens of US healthcare systems. We used SNOMED classification to identify patients prescribed teduglutide from 2015 to 2019. Through the browse cohort feature we determined the demographics, postsurgical anatomy, comorbidities, and indication for teduglutide use among these patients. Results: Of approximately 72 million patients, 170 were prescribed teduglutide. A large majority were female (70.6%). Most common etiologies of short‐bowel syndrome were intestinal obstruction (52.9%) and Crohn's disease (41.2%). Common postsurgical anatomy included total colectomy (41.2%) and ileostomy. Common incident symptoms included abdominal pain (41.2%) and nausea (23.5%). Thirty (17.6%) patients were prescribed teduglutide despite comorbid heart failure, and 5.9% despite prior GI malignancy. A total of 11.8% of patients had a history of benign GI neoplasms before starting teduglutide. A total of 5.9% of patients had posttreatment formation of colon polyps. Conclusion: In a large American database, the teduglutide prescription is rare. Only a minority have postsurgical anatomy associated with the most robust response to teduglutide. Serious adverse events appear rare, but a substantial number of patients are at risk for adverse effects because of the presence of comorbid heart failure or GI neoplasm. [ABSTRACT FROM AUTHOR]

Background: Anticholinergic medications may increase risk of dementia and stroke, but prospective studies in healthy older people are lacking.Objective: Compare risk of incident dementia and stroke by anticholinergic burden among initially healthy older people.Design: Prospective cohort study.Setting: Primary care (Australia and USA).Participants: 19,114 community-dwelling participants recruited for the ASPREE trial, aged 70+ years (65+ if US minorities) without major cardiovascular disease, dementia diagnosis, or Modified Mini-Mental State Examination score below 78/100.Measurements: Baseline anticholinergic exposure was calculated using the Anticholinergic Cognitive Burden (ACB) score. Dementia was adjudicated using Diagnostic and Statistical Manual of Mental Disorders volume IV criteria, and stroke using the World Health Organization definition.Results: At baseline, 15,000 participants (79%) had an ACB score of zero, 2930 (15%) a score of 1-2, and 1184 (6%) a score of ≥ 3 (indicating higher burden). After a median follow-up of 4.7 years and adjusting for baseline covariates, a baseline ACB score of ≥ 3 was associated with increased risk of ischemic stroke (adjusted HR 1.58, 95% CI 1.06, 2.35), or dementia (adjusted HR 1.36, 95% CI 1.01, 1.82), especially of mixed etiology (adjusted HR 1.53, 95% CI 1.06, 2.21). Results were similar for those exposed to moderate/highly anticholinergic medications.Limitations: Residual confounding and reverse causality are possible. Assessment of dose or duration was not possible.Conclusions: High anticholinergic burden in initially healthy older people was associated with increased risk of incident dementia and ischemic stroke. A vascular effect may underlie this association. These findings highlight the importance of minimizing anticholinergic exposure in healthy older people. [ABSTRACT FROM AUTHOR]

Importance: Depression is associated with increased inflammation, which may precede its onset, especially in older people. Some preclinical data suggest potential antidepressant effects of aspirin, supported by limited observational data suggesting lower rates of depression in individuals treated with aspirin. There currently appears to be no evidence-based pharmacotherapies for the primary prevention of depression.Objective: To determine whether low-dose aspirin (100 mg) reduces the risk of depression in healthy older adults.Design, Setting, and Participants: This double-blinded, placebo-controlled randomized clinical trial was a substudy of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, which examined if aspirin increased healthy life span, defined as survival free of dementia and disability. The prespecified secondary outcome was depression. Individuals of all races/ethnicities older than 70 years in Australia, as well as white individuals older than 70 years and black and Hispanic individuals older than 65 years in the United States, were included.Interventions: Participants were randomized to aspirin (100 mg daily) or placebo, with a median (interquartile range) follow-up of 4.7 (3.5-5.6) years.Main Outcomes and Measures: The primary outcome was a proxy measure of major depressive disorder defined as a score of 8 or more on the Center for Epidemiologic Studies Depression 10-item (CES-D-10) scale.Results: Of the 19 114 participants enrolled in the trial, 9525 received aspirin and 9589 received a placebo. The mean (SD) age was 75.2 (4.0) years in the aspirin group and 75.1 (4.5) years in the placebo group; 9531 (56.4%) were women. Participants' demographics and clinical characteristics at baseline were similar between groups. A total of 79 886 annual CES-D-10 measurements were taken, with a mean of 4.2 measurements per participant. There were no significant differences at annual visits in the proportions of CES-D-10 scores of 8 or more between the aspirin and placebo groups. The incidence rate of new CES-D-10 scores of 8 or more was 70.4 events per 1000 person-years in the aspirin group and 69.1 in the placebo group (hazard ratio, 1.02 [95% CI, 0.96-1.08]; P = .54).Conclusions and Relevance: Low-dose aspirin did not prevent depression in this large-scale study of otherwise healthy older adults.Trial Registration: ClinicalTrials.gov Identifier: NCT01038583. [ABSTRACT FROM AUTHOR]

ABSTRACT: Many informal caregivers of persons with dementia suffer adverse health consequences. Although established psychoeducation programs are known to benefit caregivers, attending in‐person programs is challenging for them. To address this challenge, the Savvy Caregiver Program, an evidence‐based psychoeducation program with demonstrated effectiveness for caregiving and disease‐related outcomes, was transformed into an on‐line program, Tele‐Savvy. This article describes the rationale for and design of a prospective longitudinal randomized controlled trial (targeted N = 215), currently underway. The trial aims to establish Tele‐Savvy's efficacy in (i) reducing the negative effects of caregiving on caregivers; (ii) promoting care recipients’ quality of life; (iii) improving caregiver mastery; and to explore (iv) Tele‐Savvy's efficacy among caregivers of different races/ethnicities. The mediating role of mastery will be assessed. Participants are randomized to the active condition (immediate Tele‐Savvy participation), attention control, or usual care. Participants in the two latter conditions will complete Tele‐Savvy 6 months post‐baseline. Multilevel mixed effects models will be used to examine changes in outcomes and to model group by time (months since baseline) interactions. The exploratory aim will be addressed using analysis of covariance and qualitative analysis. This trial's results may be used by healthcare and community organizations to implement Tele‐Savvy in dementia care, increasing caregivers’ access to this evidence‐based intervention. [ABSTRACT FROM AUTHOR]

Background: The human immunodeficiency virus (HIV) is associated with cognitive impairment, and loneliness is associated with cognitive decline in old age. Older Black adults with HIV may be at particular risk of loneliness due to stigma and lack of social resources.Objective: We tested the hypotheses that (1) older Black adults with HIV would show greater loneliness than older White adults with HIV, and (2) greater loneliness among older Black adults with HIV would be associated with poorer cognitive function.Methods: A total of 370 participants (177 with HIV, 193 without HIV; mean age 58.8 years, standard deviation 6.2 years; mean education 13.4 years, standard deviation 2.9 years; 73.9% male, 68.9% Black) in a community-based cross-sectional study of the Rush Center of Excellence on Disparities in HIV and Aging (CEDHA) completed a 5-item self-report scale used to measure emotional loneliness and a battery of cognitive measures.Results: Contrary to our expectations, older Black adults indicated less overall loneliness than White adults (β = -0.3893, SE = 0.1466, p = 0.0087) in models controlling for the effects of age, education, sex, global cognition, and income. However, in models with cognitive function as the outcome, an interaction between race and loneliness was observed, such that older Black adults who indicated greater loneliness showed poorer cognitive function relative to White adults (β = -0.2736, SE = 0.1138, p = 0.0174).Conclusion: Older Black adults with HIV reported less loneliness than older White adults; however, the inverse association between loneliness and cognitive function was stronger in Black than White older adults. Additional work is needed to elucidate the mechanisms underlying this interaction. [ABSTRACT FROM AUTHOR]

Background: Cancer and Alzheimer's disease (AD) are common diseases of aging and share many risk factors. Surprisingly, however, epidemiologic data from several recent independent cohort studies suggest that there may be an inverse association between these diseases.Objective: To determine the relationship between history of cancer and odds of dementia proximate to death and neuropathological indices of AD.Methods: Using data from two separate clinical-pathologic cohort studies of aging and AD, the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP), we compared odds of AD dementia proximate to death among participants with and without a history of cancer. We then examined the relation of history of cancer with measures of AD pathology at autopsy, i.e., paired helical filament tau (PHFtau) neurofibrillary tangles and amyloid-β load.Results: Participants reporting a history of cancer had significantly lower odds of AD (OR 0.70 [0.55-0.89], p = 0.0040) proximate to death as compared to participants reporting no prior history of cancer. The results remained significant after adjusting for multiple risk factors including age, sex, race, education, and presence of an APOEɛ4 allele. At autopsy, participants with a history of cancer had significantly fewer PHFtau tangles (p < 0.001) than participants without a history of cancer, but similar levels of amyloid-β.Conclusions: Cancer survivors have reduced odds of developing AD and a lower burden of neurofibrillary tangle deposition. [ABSTRACT FROM AUTHOR]

Background: Souvenaid® (uridine monophosphate, docosahexaenoic acid, eicosapentaenoic acid, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium), was developed to support the formation and function of neuronal membranes.Objective: To determine effect sizes observed in clinical trials of Souvenaid and to calculate the number needed to treat to show benefit or harm.Methods: Data from all three reported randomized controlled trials of Souvenaid in Alzheimer's disease (AD) dementia (Souvenir I, Souvenir II, and S-Connect) and an open-label extension study were included in analyses of effect size for cognitive, functional, and behavioral outcomes. Effect size was determined by calculating Cohen's d statistic (or Cramér's V method for nominal data), number needed to treat and number needed to harm. Statistical calculations were performed for the intent-to-treat populations.Results: In patients with mild AD, effect sizes were 0.21 (95% confidence intervals: -0.06, 0.49) for the primary outcome in Souvenir II (neuropsychological test battery memory z-score) and 0.20 (0.10, 0.34) for the co-primary outcome of Souvenir I (Wechsler memory scale delayed recall). No effect was shown on cognition in patients with mild-to-moderate AD (S-Connect). The number needed to treat (6 and 21 for Souvenir I and II, respectively) and high number needed to harm values indicate a favorable harm:benefit ratio for Souvenaid versus control in patients with mild AD.Conclusions: The favorable safety profile and impact on outcome measures converge to corroborate the putative mode of action and demonstrate that Souvenaid can achieve clinically detectable effects in patients with early AD. [ABSTRACT FROM AUTHOR]

Background: The neurocognitive effect of statins in older adults remain uncertain.Objectives: The aim of this study was to investigate the associations of statin use with cognitive decline and incident dementia among older adults.Methods: This analysis included 18,846 participants ≥65 years of age in a randomized trial of aspirin, who had no prior cardiovascular events, major physical disability, or dementia initially and were followed for 4.7 years. Outcome measures included incident dementia and its subclassifications (probable Alzheimer's disease, mixed presentations); mild cognitive impairment (MCI) and its subclassifications (MCI consistent with Alzheimer's disease, other MCI); and changes in domain-specific cognition, including global cognition, memory, language and executive function, psychomotor speed, and the composite of these domains. Associations of baseline statin use versus nonuse with dementia and MCI outcomes were examined using Cox proportional hazards models and with cognitive change using linear mixed-effects models, adjusting for potential confounders. The impact of statin lipophilicity on these associations was further examined, and effect modifiers were identified.Results: Statin use versus nonuse was not associated with dementia, MCI, or their subclassifications or with changes in cognitive function scores over time (p > 0.05 for all). No differences were found in any outcomes between hydrophilic and lipophilic statin users. Baseline neurocognitive ability was an effect modifier for the associations of statins with dementia (p for interaction < 0.001) and memory change (p for interaction = 0.02).Conclusions: In adults ≥65 years of age, statin therapy was not associated with incident dementia, MCI, or declines in individual cognition domains. These findings await confirmation from ongoing randomized trials. [ABSTRACT FROM AUTHOR]