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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]

Introduction: Neuroimaging-based 'brain age' can identify individuals with 'advanced' or 'resilient' brain aging. Brain-predicted age difference (brain-PAD) is predictive of cognitive and physical health outcomes. However, it is unknown how individual health and lifestyle factors may modify the relationship between brain-PAD and future cognitive or functional performance. We aimed to identify health-related subgroups of older individuals with resilient or advanced brain- PAD, and determine if membership in these subgroups is differentially associated with changes in cognition and frailty over three to five years. Methods: Brain-PAD was predicted from T1-weighted images acquired from 326 community-dwelling older adults (73.8 ± 3.6 years, 42.3% female), recruited from the larger ASPREE (ASPirin in Reducing Events in the Elderly) trial. Participants were grouped as having resilient (n=159) or advanced (n=167) brain-PAD, and latent class analysis (LCA) was performed using a set of cognitive, lifestyle, and health measures. We examined associations of class membership with longitudinal change in cognitive function and frailty deficit accumulation index (FI) using linear mixed models adjusted for age, sex and education. Results: Subgroups of resilient and advanced brain aging were comparable in all characteristics before LCA. Two typically similar latent classes were identified for both subgroups of brain agers: class 1 were characterized by low prevalence of obesity and better physical health and class 2 by poor cardiometabolic, physical and cognitive health. Among resilient brain agers, class 1 was associated with a decrease in cognition, and class 2 with an increase over 5 years, though was a small effect that was equivalent to a 0.04 standard deviation difference per year. No significant class distinctions were evident with FI. For advanced brain agers, there was no evidence of an association between class membership and changes in cognition or FI. Conclusion: These results demonstrate that the relationship between brain age and cognitive trajectories may be influenced by other health-related factors. In particular, people with age-resilient brains had different trajectories of cognitive change depending on their cognitive and physical health status at baseline. Future predictive models of aging outcomes will likely be aided by considering the mediating or synergistic influence of multiple lifestyle and health indices alongside brain age. [ABSTRACT FROM AUTHOR]

Background: Cognitive test-retest reliability measures can be used to evaluate meaningful changes in scores.Objective: This analysis aimed to develop a comprehensive set of test-retest reliability values and minimal detectable change (MDC) values for a cognitive battery for community-dwelling older individuals in Australia and the U.S., for use in clinical practice.Methods: Cognitive scores collected at baseline and year 1, in the ASPirin in Reducing Events in the Elderly clinical trial were used to calculate intraclass correlation coefficients (ICC) for four tests: Modified Mini-Mental State examination (3MS), Hopkins Verbal Learning Test-Revised (HVLT-R), single-letter Controlled Oral Word Association Test (COWAT-F), and Symbol Digit Modalities Test (SDMT). 16,956 participants aged 70 years and over (65 years and over for U.S. minorities) were included. ICCs were used to calculate MDC values for eight education and ethno-racial subgroups.Results: All four cognitive tests had moderate (ICC > 0.5) to good (ICC > 0.7) test-retest reliability. ICCs ranged from 0.53 to 0.63 (3MS), 0.68 to 0.77 (SDMT), 0.56 to 0.64 (COWAT-F), 0.57 to 0.69 (HVLT-R total recall), and 0.57 to 0.70 (HVLT-R delayed recall) across the subgroups. MDC values ranged from 6.60 to 9.95 (3MS), 12.42 to 15.61 (SDMT), 6.34 to 8.34 (COWAT-F), 8.13 to 10.85 (HVLT-R total recall), and 4.00 to 5.62 (HVLT-R delayed recall).Conclusion: This large cohort of older individuals provides test-retest reliability and MDC values for four widely employed tests of cognitive function. These results can aid interpretation of cognitive scores and decline instead of relying on cross-sectional normative data alone. [ABSTRACT FROM AUTHOR]

I Background: i The ASPREE (ASPirin in Reducing Events in the Elderly) trial was a randomized, double-blind, placebo-controlled primary prevention trial of aspirin in 19 114 community-dwelling persons aged 70 years and older (>=65 years in U.S. racial minorities). I Objective: i To investigate the effect of aspirin cessation versus continuation on disability-free survival and other clinical outcomes in a post hoc analysis of ASPREE participants who were regularly taking aspirin before trial enrollment. [Extracted from the article]

Frailty is a state of heightened vulnerability and susceptibility to physiologic stressors that increases with age. It has shown increasing utility in predicting a range of adverse health outcomes. Here, we characterize a 67-item deficit-accumulation frailty index (FI) in 19 110 community-dwelling individuals in the ASPirin in Reducing Events in the Elderly clinical trial. Participants aged 65-98 years were recruited from the United States and Australia and were without diagnosed dementia and cardiovascular disease, and major physical disability. The median FI score was .10 (interquartile range: .07-.14) at baseline, and the prevalence of frailty (FI > .21) increased from 8.1% to 17.4% after 6 years. FI was positively associated with age, and women had significantly higher scores than men at all ages. The FI was negatively correlated with gait speed (r = -.31) and grip strength (r = -.46), and strongly associated with a modified Fried's frailty phenotype (p < .0001, for all comparisons). Frailty was associated with the primary composite outcome capturing independent life lived free of major disability and dementia, and increased the rate of persistent physical disability (hazard ratio: 21.3, 95% confidence interval: 15.6-28.9). It added significantly to the predictive capacity of these outcomes above age, sex, and ethnicity alone. The FI is thus a useful biomarker of aging even among relatively healthy older individuals and provides important information about an individual's vulnerability to and risk of disease. [ABSTRACT FROM AUTHOR]

Background: Cerebrovascular events, dementia, and cancer can contribute to physical disability with activities of daily living (ADL). It is unclear whether low-dose aspirin reduces this burden in aging populations. In a secondary analysis, we now examine aspirin's effects on incident and persistent ADL disability within a primary prevention aspirin trial in community-dwelling older adults.Methods: The ASPREE (ASPirin in Reducing Events in the Elderly) trial of daily 100 mg aspirin versus placebo recruited 19 114 healthy adults aged 70+ years (65+ years if U.S. minority) in Australia and the United States. Six basic ADLs were assessed every 6 months. Incident ADL disability was defined as inability or severe difficulty with ≥1 ADL; persistence was confirmed if the same ADL disability remained after 6 months. Proportional hazards modeling compared time to incident or persistent ADL disability for aspirin versus placebo; death without prior disability was a competing risk.Results: Over a median of 4.7 years, incident ADL disability was similar in those receiving aspirin (776/9525) and placebo (787/9589) with walking, bathing, dressing, and transferring the most commonly reported. Only 24% of incident ADL disability progressed to persistent. Persistent ADL disability was lower in the aspirin group (4.3 vs 5.3 events/1000 py; hazard ratio [HR] = 0.81, 95% confidence interval [CI]: 0.66-1.00), with bathing and dressing the most common ADL disabilities in both groups. Following persistent ADL disability, there were more deaths in the aspirin group (24 vs 12).Discussion: Low-dose aspirin in initially healthy older people did not reduce the risk of incident ADL disability, although there was evidence of reduced persistent ADL disability. [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]

Background: Health-related quality of life (HRQoL) has been shown to predict adverse health outcome in the general population.Objective: We examined the cross-sectional association between HRQoL and cognitive performance at baseline. Next, we explored whether baseline HRQoL predicted 5-year incident cognitive decline and dementia and whether there were gender differences.Methods: 19,106 community-dwelling participants from the ASPirin in Reducing Events in the Elderly (ASPREE) trial, aged 65-98 years, free of major cognitive impairments, and completed the HRQoL 12-item short-form (SF-12) at baseline (2010-2014), were followed until June 2017. The physical (PCS) and mental component scores (MCS) of SF-12 were calculated. The cognitive tests were assessed at baseline, year 1, 3, 5, and 7 or close-out visit. Cognitive decline was defined as > 1.5 SD drop from baseline on any of the cognitive tests. Dementia was adjudicated according to DSM-IV criteria. Linear and Cox proportional-hazards regressions were used to examine the cross-sectional and longitudinal associations respectively.Results: At baseline, higher PCS and MCS were associated with better cognition. Over a median 4.7-year follow-up, higher MCS was associated with a reduced risk of cognitive decline and dementia (12% and 15% respectively, per 10-unit increase) and a 10-unit higher PCS was associated with a 6% decreased risk of cognitive decline. PCS did not predict dementia incidence. Findings were not different by gender.Conclusion: Our study found that higher HRQoL, in particular MCS, predicted a reduced risk of cognitive decline and dementia over time in community-dwelling 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]

Background: Despite the importance of persons with dementia (PWDs) engaging in advance care planning (ACP) at a time when they are still competent to appoint a surrogate decision maker and meaningfully participate in ACP discussions, studies of ACP in PWDs are rare. Objective: We conducted an intervention development study to adapt an efficacious ACP intervention, SPIRIT (sharing patient's illness representations to increase trust), for PWDs in early stages (recent Montreal Cognitive Assessment [MoCA] score ≥13) and their surrogates and assess whether SPIRIT could help PWDs engage in ACP. Design: A formative expert panel review of the adapted SPIRIT, followed by a randomized trial with qualitative interviews, was conducted. Patient–surrogate dyads were randomized to SPIRIT in person (in a private room in a memory clinic) or SPIRIT remote (via videoconferencing from home). Setting/Subjects: Twenty-three dyads of PWDs and their surrogates were recruited from an outpatient brain health center. Participants completed preparedness outcome measures (dyad congruence on goals of care, patient decisional conflict, and surrogate decision-making confidence) at baseline and two to three days post-intervention, plus a semistructured interview. Levels of articulation of end-of-life wishes of PWDs during SPIRIT sessions were rated (3 = expressed wishes very coherently, 2 = somewhat coherently, and 1 = unable to express coherently). Results: All 23 were able to articulate their end-of-life wishes very or somewhat coherently during the SPIRIT session; of those, 14 PWDs had moderate dementia. While decision-making capacity was higher in PWDs who articulated their wishes very coherently, MoCA scores did not differ by articulation levels. PWDs and surrogates perceived SPIRIT as beneficial, but the preparedness outcomes did not change pre–post. Conclusions: SPIRIT engaged PWDs and surrogates in meaningful ACP discussions, but requires testing of efficacy and long-term outcomes. [ABSTRACT FROM AUTHOR]

Importance: Worldwide, 47 million people live with dementia and, by 2050, the number is expected to increase to 131 million.Observations: Dementia is an acquired loss of cognition in multiple cognitive domains sufficiently severe to affect social or occupational function. In the United States, Alzheimer disease, one cause of dementia, affects 5.8 million people. Dementia is commonly associated with more than 1 neuropathology, usually Alzheimer disease with cerebrovascular pathology. Diagnosing dementia requires a history evaluating for cognitive decline and impairment in daily activities, with corroboration from a close friend or family member, in addition to a thorough mental status examination by a clinician to delineate impairments in memory, language, attention, visuospatial cognition such as spatial orientation, executive function, and mood. Brief cognitive impairment screening questionnaires can assist in initiating and organizing the cognitive assessment. However, if the assessment is inconclusive (eg, symptoms present, but normal examination findings), neuropsychological testing can help determine whether dementia is present. Physical examination may help identify the etiology of dementia. For example, focal neurologic abnormalities suggest stroke. Brain neuroimaging may demonstrate structural changes including, but not limited to, focal atrophy, infarcts, and tumor, that may not be identified on physical examination. Additional evaluation with cerebrospinal fluid assays or genetic testing may be considered in atypical dementia cases, such as age of onset younger than 65 years, rapid symptom onset, and/or impairment in multiple cognitive domains but not episodic memory. For treatment, patients may benefit from nonpharmacologic approaches, including cognitively engaging activities such as reading, physical exercise such as walking, and socialization such as family gatherings. Pharmacologic approaches can provide modest symptomatic relief. For Alzheimer disease, this includes an acetylcholinesterase inhibitor such as donepezil for mild to severe dementia, and memantine (used alone or as an add-on therapy) for moderate to severe dementia. Rivastigmine can be used to treat symptomatic Parkinson disease dementia.Conclusions and Relevance: Alzheimer disease currently affects 5.8 million persons in the United States and is a common cause of dementia, which is usually accompanied by other neuropathology, often cerebrovascular disease such as brain infarcts. Causes of dementia can be diagnosed by medical history, cognitive and physical examination, laboratory testing, and brain imaging. Management should include both nonpharmacologic and pharmacologic approaches, although efficacy of available treatments remains limited. [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]

We examined the association between racial/ethnic minority segregation and low birth weight (LBW) in Chicago and Toronto communities. While previous work has documented the importance of contextual effects on LBW, these studies have usually been conducted within a single city. We used Pearson correlation coefficients and OLS regression models to examine potential variability in the association between racial/ethnic minority segregation and LBW in Chicago (N = 77 communities) and Toronto (N = 140 communities). Results indicate that racial/ethnic minority segregation, unemployment, and low educational attainment are not associated with LBW in Toronto, while these indicators have strong and significant associations with LBW in Chicago. In a combined model with data from both cities, a 10% increase in minority composition is associated with a 0.5% increase in LBW, controlling for the effects of unemployment and low educational attainment. Stratified models show that this effect is only significant in Chicago, and subsequent models revealed opposite effects for percentage non-Hispanic Black and percentage Hispanic. Future research should consider additional cities for comparative analysis. Such work could test the notion that Chicago and Toronto represent opposite sides of a spectrum, reflecting variability in how social determinants map on to public health outcomes. Future research should also examine the significant heterogeneity observed in highly segregated communities, particularly in Chicago. [ABSTRACT FROM PUBLISHER]

Background: There are no primary prevention trials of aspirin with relevant geriatric outcomes in elderly people. ASPirin in Reducing Events in the Elderly (ASPREE) is a placebo-controlled trial of low-dose aspirin that will determine whether 5 years of daily 100-mg enteric-coated aspirin extends disability-free and dementia-free life in a healthy elderly population and whether these benefits outweigh the risks.Methods: Set in primary care, this randomized double-blind placebo-controlled trial has a composite primary endpoint of death, incident dementia or persistent physical disability. Participants aged 70+ years (non-minorities) or 65+ years (U.S. minorities) were free of cardiovascular disease, dementia, or physical disability and without a contraindication to, or indication for, aspirin. Baseline data include physical and lifestyle, personal and family medical history, hemoglobin, fasting glucose, creatinine, lipid panel, urinary albumin:creatinine ratio, cognition (3MS, HVLT-R, COWAT, SDMT), mood (CES-D-10), physical function (gait speed, grip strength), Katz activities of daily living and quality of life (SF-12).Results: Recruitment ended in December 2014 with 16,703 Australian and 2,411 U.S. participants, a median age of 74 (range 65-98) years and 56% women. Approximately 55% of the U.S. cohort were from minority groups; 9% of the total cohort. Proportions with hypertension, overweight, and chronic kidney disease were similar to age-matched populations from both countries although lower percentages had diabetes, dyslipidemia, and osteoarthritis.Discussion: Findings from ASPREE will be generalizable to a healthier older population in both countries and will assess whether the broad benefits of daily low-dose aspirin in prolonging independent life outweigh the risks. [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]

Objectives To investigate whether the use of antihypertensive and statin medication in very old adults is associated with the level of motor performance. Design Cross-sectional study. Settings A community-based study recruited from over 40 residential facilities across the metropolitan Chicago area. Participants Community-dwelling very old adults (n = 1520; mean age 80.2; standard deviation 7.7). Measurements Eleven motor performances were summarized using a composite motor score. All prescription and over the counter medications taken by participants were inspected and coded using the Medi-Span Data Base System. Demographic characteristics and medical history were obtained by means of detailed interview and medical examinations. Results In multiple linear regression models, antihypertensive medications were associated with global motor score [β = −0.075, standard error (SE) 0.011, P < .001]. Thus, motor function in an individual with antihypertensive medication, was on average, about 7.5% lower than an age-, sex-, and education-matched individual without antihypertensive medication. The number of antihypertensive medications, which were being used had an additive effect, such that a reduction in the level of motor function was observed with each additional medication, and receiving 3 or more antihypertensive medications was associated with about a 15% reduction in the level of motor function. The association between antihypertensive medications and motor function was robust, and remained unchanged after adjusting for confounding by indication using several potentially confounding variables: smoking, hypertension, diabetes, stroke, congestive heart failure, myocardial infarction, and intermittent claudication (β = −0.05, SE 0.015, P = .001). In contrast, the use of statin medications was not related to motor function (unadjusted: β = 0.003, SE 0.015, P = .826; fully adjusted: β = 0.018, SE 0.014, P = .216). Conclusions The use of antihypertensive medications is associated with a lower level of motor function in very old adults. The nature of this association warrants further investigation. [ABSTRACT FROM AUTHOR]

The article discusses a study focused on how surrogate characteristics impact clinical decision making for critically ill patients. Topics discussed include patient-surrogate decision maker relationship, surrogate's understanding of condition of the patient, and physicians' strategies to discuss end-of-life decision making for critically ill patients with surrogate decision makers.

Background: we previously demonstrated that patients with mild Alzheimer's disease and parkinsonian features (AD + PF) are at a higher risk of having daytime sleepiness than mild AD patients without PF (AD − PF).Objective: to determine whether AD + PF patients demonstrate a known a consequence of daytime sleepiness, reduced performance-based sustained attention, compared with AD − PF patients.Methods: a nocturnal polysomnogram and a next-day multiple sleep latency test (MSLT) were performed. Between MSLT nap opportunities, a 10-min psychomotor vigilance test (PVT) was administered and analysed for reciprocal mean response times (IMEAN), number of lapses (LAPSE) and reciprocal mean slowest 10% (ISLOW).Results: a total of 35 patients met criteria (AD + PF, n = 16; AD − PF, n = 19). Comparatively, the AD + PF group had slower IMEAN results [F(1,28) = 6.64, P < 0.05] and higher LAPSE rates [F(1,27) = 7.57, P < 0.05]. ISLOW measures were not different between groups. When accounting for MSLT results, IMEAN and LAPSE results were no longer significantly different between groups during morning tests, but remained significantly different on afternoon tests.Conclusion: PFs in mild AD are associated with decreased sustained attention as measured by the PVT. Sleepiness did not fully account for the impairment in sustained attention, suggesting that the presence of PFs has an independent negative association with sustained attention in mild AD. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative condition associated with cognitive loss, behavioural changes, functional ability decline and caregiver burden. Given the worldwide public health impact of AD, novel interventions to reduce suffering experienced by AD patients need to be developed. Foods may offer a mechanism for intervention complementary to drugs, devices, biologicals and vaccines. Apart from foods with health claims (including dietary supplements), medical foods are also being explored as an intervention option. The purpose of this article is to describe how medical foods may complement other interventions for AD patients by: (i) defining what a medical food is; (ii) discussing whether AD is a condition amenable to medical food intervention; (iii) reviewing current clinical trial data on medical foods used in participants with AD; and (iv) highlighting steps needed to establish a more comprehensive framework for developing medical foods for AD. While medical foods may be defined differently in other countries, the US Orphan Drug Act of 1998 defined a medical food as a food formulated for enteral intake, taken under physician supervision, and intended to meet the distinctive nutritional requirements identified for a disease or condition. For AD to be amenable to medical food intervention, it must: (i) result in limited or impaired capacity to ingest, digest, absorb or metabolize ordinary food- stuff or certain nutrients; or (ii) have unique, medically determined nutrient requirements; and (iii) require dietary management that cannot be achieved by modification of the normal diet alone. While these criteria are most likely met in advanced AD, identifying unique nutritional requirements in early AD that cannot be met by normal diet modification requires a better under- standing of AD pathophysiology. A PubMed search using the terms 'medical food' and 'Alzheimer', limited to clinical trials published in English with human participants with AD aged >65 years and supplemented by other articles known to meet the inclusion criteria, revealed that only two medical foods, AC-1202 and Souvenaid® with Fortasyn Connect™, have clinical trial results available for discussion. As medical food development for AD is a relatively new endeavour, a window of opportunity exists for all stakeholders to develop a comprehensive framework for assuring that medical food interventions for AD achieve the highest possible scientific and ethical standards to warrant commercialization. [ABSTRACT FROM AUTHOR]

Objective: To perform a systematic review of randomized trials comparing oral vs intravenous (IV) iron therapy to treat postpartum anemia.Data Sources: Data sources were as follows: PubMed (1972-2017); Cochrane Central Register of Controlled Trials, CENTRAL (1972-2017); CINAHL (1972-2017); Web of Science; Excerpta Medica Database, and EMBASE (1972-2017).Study Eligibility Criteria: We included randomized trials comparing oral vs IV iron monotherapy to treat postpartum anemia (classified as a hemoglobin <12 g/dL).Study Appraisal and Synthesis Methods: Study quality was assessed with the Cochrane risk of bias assessment tool. The primary outcome was hemoglobin concentration at 6 weeks postpartum. Secondary outcomes included hemoglobin concentration at 1-5 weeks postpartum, ferritin concentration at 1-6 weeks postpartum, and maternal adverse outcomes. For meta-analysis, mean differences and odds ratios using a random effects model were calculated. Risk of heterogeneity was reported as I2.Results: A total of 15 randomized trials met our inclusion criteria (n = 1001 and 1 181 women receiving oral iron and IV iron, respectively); 4 studies reported data for our primary outcome. We observed higher postpartum week 6 hemoglobin concentrations in the IV iron group compared to the oral iron group (mean difference, 0.9 g/dL; 95% confidence interval (CI), 0.4-1.3; P = .0003). Compared to oral iron, women receiving IV iron had higher hemoglobin concentrations at postpartum weeks 1, 2, and 3; higher ferritin concentrations at postpartum weeks 1, 2, 4, and 6; an increased likelihood of skin flushing (odds ratio [OR], 6.95; 95% CI, 1.56-31.03; P = .01; I2 = 0%); and a decreased likelihood of constipation (OR, 0.08; 95% CI, 0.03-0.21; P < .00001, I2 = 27%) and dyspepsia (OR, 0.07; 95% confidence interval, 0.01-0.42; P = .004; I2 = 0%). The reported event rate for anaphylaxis among women receiving IV iron was 0.6%.Conclusion: In this systematic review, among women with postpartum anemia, hemoglobin concentrations at 6 weeks postpartum were almost 1 g/dL higher in women who received IV iron compared to oral iron. The safety profile of IV iron was also reassuring. Given the weaker hemoglobin response and higher risk of gastrointestinal side effects with oral iron use, our findings suggest that IV iron be considered as a viable treatment option for postpartum iron deficiency anemia. [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]

Keywords: aging; aspirin; body weight EN aging aspirin body weight 1110 1112 3 04/20/20 20200331 NES 200331 A recent meta-analysis[1] of individual patient data from several randomized, controlled trials evaluating aspirin for the prevention of primary or secondary cardiovascular events found that the protective effect of low-dose aspirin (<=100 mg) was limited to individuals weighing <70 kg, driven by lean body mass (LBM) but not body mass index (BMI).[1] Given the limited number of people >=70 years of age who were included in the meta-analysis[1] and calls for validation of these findings,[2],[3] we investigated whether body habitus modulated the efficacy of aspirin in a post hoc analysis of the ASPREE trial (Aspirin in Reducing Events in the Elderly).[4] ASPREE randomized 19 114 older participants to daily 100-mg enteric-coated aspirin (9525) or matched placebo (9589) and followed them up for a median of 4.7 years for disability-free survival and other clinical outcomes.[4] Trial participants were community-dwelling Australian (16 703) and US (2411) men and women who were >=70 years of age at enrollment or >=65 years of age for US blacks and Hispanics. At baseline, anthropometric indexes (mean±SD) of body weight, BMI, waist circumference, and LBM in the aspirin versus placebo groups were 77.0±15.1 kg versus 77.0±14.8 kg, 28.1±4.8 kg/m SP 2 sp versus 28.1±4.7 kg/m SP 2 sp , 97±13 cm versus 97±13 cm, and 49.8±8.3 kg versus 49.9±8.2 kg, respectively. Larger BMI or waist circumference or LBM also did not alter the effect of aspirin on the risk of cardiovascular disease or major hemorrhage (Figure). [Extracted from the article]

The identification of a gain-of-function mutation in CACNA1C as the cause of Timothy Syndrome (TS), a rare disorder characterized by cardiac arrhythmias and syndactyly, highlighted unexpected roles for the L-type voltage-gated Ca2+ channel CaV1.2 in nonexcitable cells. How abnormal Ca2+ influx through CaV1.2 underlies phenotypes such as the accompanying syndactyly or craniofacial abnormalities in the majority of affected individuals is not readily explained by established CaV1.2 roles. Here, we show that CaV1.2 is expressed in the first and second pharyngeal arches within the subset of cells that give rise to jaw primordia. Gain-of-function and loss-of-function studies in mouse, in concert with knockdown/rescue and pharmacological approaches in zebrafish, demonstrated that Ca2+ influx through CaV1.2 regulates jaw development. Cranial neural crest migration was unaffected by CaV1.2 knockdown, suggesting a role for CaV1.2 later in development. Focusing on the mandible, we observed that cellular hypertrophy and hyperplasia depended upon Ca2+ signals through CaV1.2, including those that activated the calcineurin signaling pathway. Together, these results provide new insights into the role of voltage-gated Ca2+ channels in nonexcitable cells during development. [ABSTRACT FROM AUTHOR]