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BackgroundThe immune and blood coagulation systems have been implicated in the pathophysiology of the geriatric syndrome of frailty, but limited prospective data examining the relationship of clotting/inflammation biomarkers to risk of incident frailty exist.MethodsThis prospective analysis was derived from a nested case-control study within the Women's Health Initiative. Among women 65 to 79 years free of frailty at enrollment, we randomly selected 900 incident cases from those developing frailty within 3 years; 900 non-frail controls were individually matched on age, ethnicity, and blood collection date. Biomarkers assessed for risk of incident frailty included fibrinogen, factor VIII, D-dimer, C-reactive protein, interleukin-6, and tissue plasminogen activator (t-PA).ResultsWhen examined by quartiles in multivariable adjusted models, higher D-dimer and t-PA levels were each associated with increased risk of frailty (P trend = .04). Relative to the lowest quartile, the odds ratios for frailty compared with the upper quartile were 1.52 (95% confidence interval, 1.05-2.22) for t-PA and 1.57 (95% confidence interval, 1.11-2.22) for D-dimer. For women having high t-PA and high D-dimer compared with women having lower levels of both biomarkers, the odds of frailty was 2.20 (1.29-3.75). There was little evidence for association between coagulation factor VIII, fibrinogen, C-reactive protein, or interleukin-6 levels and incident frailty.ConclusionThis prospective analysis supports the role of markers of fibrin turnover and fibrinolysis as independent predictors of incident frailty in postmenopausal women.

Background: We previously reported that interventions to optimize medication use reduced adverse drug reactions (ADRs) by 21% and serious ADRs by 36% in older adults. With new evidence, we sought to update the systematic review and meta-analysis. Method: We searched OVID, Cochrane Library, ClinicalTrials.gov and Google Scholar from 30 April 2017–30 April 2023. Included studies had to be randomized controlled trials of older adults (mean age ≥65 years) taking medications that examined the outcome of ADRs. Two authors independently reviewed all citations, extracted relevant data, and assessed studies for potential bias. The outcomes were any and serious ADRs. We performed subgroup analyses by intervention type and setting. Random-effects models were used to combine the results from multiple studies and create summary estimates. Results: Six studies are new to the update, resulting in 19 total studies (15,675 participants). Interventions were pharmacist-led (10 studies), other healthcare professional-led (5 studies), technology based (3 studies), and educational (1 study). The interventions were implemented in various clinical settings, including hospitals, outpatient clinics, long-term care facilities/rehabilitation wards, and community pharmacies. In the pooled analysis, the intervention group participants were 19% less likely to experience an ADR (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.68–0.96) and 32% less likely to experience a serious ADR (OR 0.68, 95% CI 0.48–0.96). We also found that pharmacist-led interventions reduced the risk of any ADR by 35%, compared with 8% for other types of interventions. Conclusion: Interventions significantly and substantially reduced the risk of ADRs and serious ADRs in older adults. Future research should examine whether effectiveness of interventions vary across health care settings to identify those most likely to benefit. Implementation of successful interventions in health care systems may improve medication safety in older patients. [ABSTRACT FROM AUTHOR]

One's experience with dementia may affect their perceptions about dementia preventability, which in turn could influence preventive health behaviors. We aimed to examine how having a family history of dementia and caregiving experience are associated with perceptions about and self-efficacy for dementia preventability. Cross-sectional, self-administered survey. Participants reported whether they have had a family member with dementia and, among those who reported having a family member with dementia, whether they served as a caregiver. Outcomes were perceptions about the likelihood of dementia preventability, self-efficacy for dementia prevention, and benefits of specific dementia prevention strategies. Associations were assessed via partial proportional odds model for ordinal outcome variables and logistic regression for binary outcome variables. Of 1,575 respondents, 71% had a family member with dementia, of which 42% served as a caregiver. People with a family member with dementia were less likely to believe that dementia is preventable (aOR = 0.75, 95% CI: 0.58, 0.96) and had lower self-efficacy for dementia prevention (aOR = 0.71, 95% CI: 0.56, 0.90). The subgroup analysis among those with caregiving experience was consistent with the primary findings, showing less belief in the likelihood of dementia preventability (aOR = 0.69, 95% CI: 0.46, 1.03) and self-efficacy (aOR = 0.75, 95% CI: 0.56, 1.00). Having a family member with dementia is associated with unfavorable perceptions about dementia preventability. Incorporating family history of dementia into communication efforts about dementia risk reduction may help address potential barriers to preventive health behaviors. [ABSTRACT FROM AUTHOR]

Background: Central nervous system (CNS)‐active medication use is an important modifiable risk factor for falls in older adults. A fall‐related injury should prompt providers to evaluate and reduce CNS‐active medications to prevent recurrent falls. We evaluated change in CNS‐active medications up to 12 months following a fall‐related injury in community‐dwelling older adults compared with a matched cohort without fall‐related injury. Methods: Participants were from the Adult Changes in Thought study conducted at Kaiser Permanente Washington. Fall‐related injury codes between 1994 and 2014 defined index encounters in participants with no evidence of such injuries in the preceding year. We matched each fall‐related injury index encounter with up to five randomly selected clinical encounters from participants without injury. Using automated pharmacy data, we estimated the average change in CNS‐active medication use at 3, 6, and 12 months post‐index according to the presence or absence of CNS‐active medication use before index. Results: One thousand five hundred sixteen participants with fall‐related injury index encounters (449 CNS‐active users, 1067 nonusers) were matched to 7014 index encounters from people without fall‐related injuries (1751 users, 5236 nonusers). Among CNS‐active users at the index encounter, those with fall‐related injury had an average decrease in standard daily doses (SDDs) at 12 months (−0.43; 95% CI: −0.63 to −0.23), and those without injury had a greater (p = 0.047) average decrease (−0.66; 95% CI: −0.78 to −0.55). Among nonusers at index, those with fall‐related injury had a smaller increase than those without injury (+0.17, 95% CI: +0.13 to +0.21, vs. +0.24, 95% CI: +0.20 to +0.28, p = 0.005). Conclusions: The differences in CNS‐active medication use change over 12 months between those with and without fall‐related injury were small and unlikely to be clinically significant. These results suggest that fall risk‐increasing drug use is not reduced following a fall‐related injury, thus opportunities exist to reduce CNS‐active medications, a potentially modifiable risk factor for falls. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To determine whether antidepressant use is associated with dementia risk. DESIGN: Prospective cohort study. SETTING: Kaiser Permanente Washington (KPWA), an integrated healthcare delivery system. PARTICIPANTS: Community‐dwelling individuals aged 65 and older without dementia and with 10 years or more of KPWA enrollment at baseline (N=3,059). MEASUREMENTS: Primary exposures were selective serotonin reuptake inhibitors (paroxetine vs other), tricyclic antidepressants, and serotonin antagonist and reuptake inhibitors. Using health plan pharmacy data, we calculated cumulative medication exposure, defined as total standardized daily doses (TSDDs), over rolling 10‐year windows. Exposure in the most recent year was excluded to avoid use related to prodromal symptoms. The Cognitive Abilities Screening Instrument was administered every 2 years; low scores triggered clinical evaluation and consensus diagnosis procedures. Dementia risk was estimated according to medication use using Cox proportional hazards models. RESULTS: During a mean follow‐up of 7.7 years, 775 participants (25%) developed dementia; 659 (22%) developed possible or probable Alzheimer's disease. Individual antidepressant classes were not associated with differences in dementia risk, although paroxetine use was associated with higher risk of dementia for all TSDD categories than no use (0–90 TSDDs: hazard ratio (HR)=1.69, 95% confidence interval (CI)=1.18–2.42; 91–365 TSDDs: HR=1.40, 95% CI=0.88–2.23; 366–1095 TSDDs: HR=2.13, 95% CI=1.32–3.43; ≥1095 TSDDs: HR=1.42, 95% CI=0.82–2.46). CONCLUSION: Most commonly prescribed nonanticholinergic depression medications used in late life do not appear to be associated with dementia risk. Paroxetine and other anticholinergic antidepressants may be exceptions in older individuals. Future studies are warranted to improve scientific understanding of potential associations in other settings and populations. [ABSTRACT FROM AUTHOR]

Objectives: To examine the effect of interventions to optimize medication use on adverse drug reactions (ADRs) in older adults. Design: Systematic review and meta‐analysis. EMBASE, PubMed, OVID, Cochrane Library, Clinicaltrials.gov, and Google Scholar were searched through April 30, 2017. Setting: Randomized controlled trials. Participants: Older adults (mean age ≥65) taking medications. Measurements: Two authors independently extracted relevant information and assessed studies for risk of bias. Discrepancies were resolved in consensus meetings. The outcomes were any and serious ADRs. Random‐effects models were used to combine the results of multiple studies and create summary estimates. Results: Thirteen randomized controlled trials involving 6,198 older adults were included. The studies employed a number of different interventions that were categorized as pharmacist‐led interventions (8 studies), other health professional‐led interventions (3 studies), a brief educational session (1 study), and a technology intervention (1 study). The intervention group was 21% less likely than the control group to experience any ADR (odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.62–0.99). In the six studies that examined serious ADRs, the intervention group was 36% less likely than the control group to experience a serious ADR (OR = 0.64, 95% CI = 0.42–0.98). Conclusion: Interventions designed to optimize medication use reduced the risk of any and serious ADRs in older adults. Implementation of these successful interventions in healthcare systems may improve medication safety in older adults. [ABSTRACT FROM AUTHOR]

Objectives To compare the ability of the commonly used Women's Health Initiative ( WHI) and Cardiovascular Health Study ( CHS) frailty phenotypes to predict falls, hip fracture, and death in WHI Clinical Trial participants aged 65 and older. Design Longitudinal cohort study. Setting WHI Clinical Trial. Participants Participants with data for WHI and CHS frailty phenotypes (N = 3,558). Measurements Frailty was operationally defined in the CHS as the presence of three or more of weight loss, poor energy, weakness, slowness, and low physical activity. WHI operationalized frailty similarly but with the RAND-36 physical function scale substituted for slowness and weakness ( RAND-36 physical function scale score <13 = 2 points, 13-78 = 1 point, >78 = 0 points). Frailty was defined as a summary score of 3 or greater, prefrailty as a score of 2 or 1, and nonfrailty as a score of 0. Outcomes were modeled using Cox regression. Harrell C-statistics were compared for models containing alternative instruments. Results Approximately 5% of participants were frail based on the CHS or WHI phenotype. The WHI frailty phenotype was associated with higher rates of falls (hazard ratio ( HR) = 1.48, P = .003), hip fracture ( HR = 1.87, P = .04), and death ( HR = 2.32, P < .001). Comparable HRs in CHS-phenotype frail women were 1.32 ( P = .04), 1.08 ( P = .83), and 1.91 ( P < .001), respectively. Harrell C-statistics revealed marked but insignificant differences in predicting abilities between CHS and WHI phenotype models ( P > .50 for all). Conclusion The WHI phenotype, which does not require direct measurements of physical performance, might offer a practical advantage for epidemiological and clinical needs. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the associations between anesthesia and dementia or Alzheimer's disease ( AD) risk using prospectively collected data. Design Cohort study. Participants Community-dwelling members of the Adult Changes in Thought cohort aged 65 and older and free of dementia at baseline (N = 3,988). Measurements Participants self-reported all prior surgical procedures with general or neuraxial (spinal or epidural) anesthesia at baseline and reported new procedures every 2 years. People undergoing high-risk surgery with general anesthesia, other surgery with general anesthesia, and other surgery with neuraxial anesthesia exposures were compared with those with no surgery and no anesthesia. Cox proportional hazards models were used to estimate hazard ratios ( HRs) and 95% confidence intervals ( CIs) for dementia and AD associated with time-varying lifetime and recent (past 5 years) anesthesia exposures. Results At baseline, 254 (6%) people reported never having anesthesia; 248 (6%) had had one or more high-risk surgeries with general anesthesia, 3,363 (84%) had had one or more other surgeries with general anesthesia, and 123 (3%) had had one or more surgeries with neuraxial anesthesia. High-risk surgery with general anesthesia was not associated with greater risk of dementia (HR = 0.86, 95% CI = 0.58-1.28) or AD (HR = 0.95, 95% CI = 0.61-1.49) than no history of anesthesia. People with any history of other surgery with general anesthesia had a lower risk of dementia (HR = 0.63, 95% CI = 0.46-0.85) and AD (HR = 0.65, 95% CI = 0.46-0.93) than people with no history of anesthesia. There was no association between recent anesthesia exposure and dementia or AD. Conclusion Anesthesia exposure was not associated with of dementia or AD in older adults. [ABSTRACT FROM AUTHOR]

Purpose of the Study: Postmenopausal osteoporosis can impact quality-of-life even prefracture. To determine whether osteoporosis should be a greater concern in women Veterans versus non-Veterans, we compared fracture rates and bone mineral density (BMD) for Veterans and non-Veterans using Women's Health Initiative data. Design and Methods: In this cohort study, participants were women aged 50-79 years. Outcomes were hip, central body, and limb fractures occurring during up to 19 years of follow-up and hip, spine, and whole body BMD collected three times over a 6-year period in a participant subsample. Covariates comprised risk factors for fracture, including fall history and other components of the World Health Organization Fracture Risk Assessment Tool (FRAX). Cox Proportional Hazards models were used to examine fracture rates for Veterans compared with non-Veterans. Results: Of 161,808 women, 145,521 self-identified as Veteran (n = 3,719) or non-Veteran (n = 141,802). Baseline FRAX scores showed that Veterans had higher 10-year probabilities for any major fracture (13.3 vs 10.2; p < .01) and hip fracture (4.1 vs 2.2; p < .01) compared with non-Veterans. The age-adjusted rate of hip fracture per 1,000 person-years for Veterans was 3.3 versus 2.4 for non-Veterans (p < .01). After adjustment, the hazards ratio for hip fracture was 1.24 (95% confidence interval 1.03-1.49) for Veterans versus non-Veterans. Hazards ratios at other anatomic sites did not differ by Veteran status. Mean BMD at baseline and at Years 3 and 6 also did not differ by Veteran status at any site. Implications: Women Veterans had an increased hip fracture rate not explained by differences in well-recognized fracture risk factors. [ABSTRACT FROM AUTHOR]

Purpose of the Study: To compare the prevalence and cardiometabolic health impact of sleep disturbance among postmenopausal Veteran and non-Veteran participants in the Women's Health Initiative (WHI). Design and Methods: The prevalence of five categories of sleep disturbance--medication/alcohol use for sleep; risk for insomnia; risk for sleep disordered breathing [SDB]; risk for comorbid insomnia and SDB (insomnia + SDB); and aberrant sleep duration [SLD]--was compared in 3,707 Veterans and 141,354 non-Veterans using logistic or multinomial regression. Cox proportional hazards models were used to evaluate the association of sleep disturbance and incident cardiovascular disease (CVD) and Type 2 diabetes in Veterans and non-Veterans. Results: Women Veterans were more likely to have high risk for insomnia + SDB relative to non-Veteran participants. However, prevalence of other forms of sleep disturbance was similar across groups. Baseline sleep disturbance was not differentially associated with cardiometabolic health outcomes in Veteran versus non-Veteran women. Risks for SDB and insomnia + SDB were both linked to heightened risk of CVD and diabetes; SLD was consistently linked with greater risk of CVD and diabetes in non-Veterans but less strongly and consistently in Veterans. Implications: Efforts to identify and treat sleep disturbances in postmenopausal women are needed and may positively contribute to the attenuation of cardiometabolic morbidity risk. Increased awareness of women Veterans' vulnerability to postmenopausal insomnia + SDB may be particularly important for health care providers who treat this population. [ABSTRACT FROM AUTHOR]

Objectives To determine whether prescription opioid use is associated with higher dementia risk or greater cognitive decline. Design Prospective cohort study. Setting Group Health, an integrated healthcare delivery system. Participants Community-dwelling individuals aged 65 and older without dementia with at least 10 years of Group Health enrollment at baseline (N = 3,434; median age 74). Measurements The Cognitive Abilities Screening Instrument (CASI) was administered every 2 years. Low scores triggered detailed evaluation, and a multidisciplinary committee assigned dementia diagnoses. From computerized pharmacy data, cumulative opioid exposure was defined as total standardized doses (TSDs) dispensed over 10 years (excluding the most recent year because of possible prodromal symptoms). For comparison, use of nonsteroidal anti-inflammatory drugs (NSAIDs), characterized similarly, was examined. Dementia risk was analyzed using Cox proportional hazards models and CASI trajectory using linear regression models and generalized estimating equations. Results Seven hundred ninety-seven participants (23%) developed dementia over a mean follow-up of 7.3 years; 637 (19%) had possible or probable Alzheimer's disease. For cumulative opioid use, the hazard ratios (HRs) for dementia were 1.06 (95% confidence interval (CI) = 0.88-1.26) for 11 to 30 TSDs, 0.88 (95% CI = 0.70-1.09) for 31 to 90 TSDs, and 1.29 (95% CI = 1.02-1.62) for 91 or more TSDs, versus 0 to 10 TSDs. A similar pattern was seen for NSAID use. Heavier opioid use was not associated with more-rapid cognitive decline. Conclusion People with the heaviest opioid or NSAID use had slightly higher dementia risk than people with little or no use. These results may reflect an effect of chronic pain on cognition or residual confounding. Although opioids have other risks, little evidence of long-term cognitive harm specific to opioids was found. [ABSTRACT FROM AUTHOR]

Objectives To examine the association between statin use and objectively assessed decline in gait speed in community-dwelling older adults. Design Longitudinal cohort study. Setting Health, Aging and Body Composition (Health ABC) Study. Participants Two thousand five participants aged 70-79 at baseline with medication and gait speed data at 1998-99, 1999-2000, 2001-02, and 2002-03. Measurements The independent variables were any statin use and their standardized daily doses (low, moderate, high) and lipophilicity. The primary outcome measure was decline in gait speed of 0.1 m/s or more in the following year of statin use. Multivariable generalized estimating equations were used, adjusting for demographic characteristics, health-related behaviors, health status, and access to health care. Results Statin use increased from 16.2% in 1998-99 to 25.6% in 2002-03. The overall proportions of those with decline in gait speed of 0.1 m/s or more increased from 22.2% in 1998 to 23.9% in 2003. Statin use was not associated with decline in gait speed of 0.1 m/s or more (adjusted odds ratio ( AOR) = 0.90, 95% confidence interval ( CI) = 0.77-1.06). Similar nonsignificant trends were also seen with the use of hydrophilic or lipophilic statins. Users of low-dose statins were found to have a 22% lower risk of decline in gait speed than nonusers ( AOR = 0.78, 95% CI = 0.61-0.99), which was mainly driven by the results from 1999-2000 follow-up. Conclusion These results suggest that statin use did not increase decline in gait speed in community-dwelling older adults. [ABSTRACT FROM AUTHOR]

Objectives To examine associations between angiotensin-converting enzyme ( ACE) inhibitor and statin medications and baseline and mean annual change in physical performance measures and muscle strength in older women. Design Prospective cohort study. Participants Participants from the Women's Health Initiative Clinical Trials aged 65 to 79 at baseline who had physical performance measures, self-report of health insurance, and no prior history of stroke or congestive heart failure were included (N = 5,777). Women were recruited between 1993 and 1998. Measurements Medication use was ascertained through a baseline inventory. Physical performance measures (timed 6-m walk, repeated chair stands in 15 seconds) and grip strength were assessed at baseline and follow-up Years 1, 3, and 6. Multivariable-adjusted linear repeated-measures models were adjusted for demographic and health characteristics. Results ACE inhibitor use was associated with lower mean grip strength at baseline (22.40 kg, 95% confidence interval ( CI) = 21.89-22.91 vs 23.18 kg, 95% CI 23.02-23.34; P = .005) and greater mean annual change in number of chair stands (−0.182, 95% CI −0.217 to −0.147 vs −0.145, 95% CI −0.156 to −0.133; P = .05) than nonuse. Statin use was not significantly associated with baseline measures or mean annual change for any outcome. A subgroup analysis suggested that statin use was associated with less mean annual change in chair stands ( P = .006) in the oldest women. Conclusion These results do not support an association between statin or ACE inhibitor use and slower decline in physical performance or muscle strength and thus do not support the use of these medications for preserving functional status in older adults. [ABSTRACT FROM AUTHOR]

Objectives To examine the associations between depressive symptoms, antidepressant use, and duration of use with incident frailty 3 years later in nonfrail women aged 65 and older. Design Secondary analysis of the Women's Health Initiative Observational Study ( WHI- OS), a prospective cohort study. Setting WHI- OS was conducted in 40 U. S. clinical centers. Participants Women aged 65 to 79, not frail at baseline. Measurements Antidepressant use was assessed through medication container inspection at baseline. Four groups were created according to baseline use and Burnam depression screen (range 0-1, 0.06 cutoff): antidepressant nonusers without depressive symptoms (reference group), antidepressant nonusers with depressive symptoms, antidepressant users without depressive symptoms, and antidepressant users with depressive symptoms. Frailty components included slowness or weakness, exhaustion, low physical activity, and unintended weight loss, ascertained through self-report and physical measurements at baseline and Year 3. Results Of 27,652 women at baseline, 1,350 (4.9%) were antidepressant users and 1,794 (6.5%) were categorized as depressed. At Year 3, 4,125 (14.9%) were frail. All groups had a greater risk of incident frailty than the reference group. Odds ratios ( ORs) ranged from 1.73 (95% confidence interval ( CI) = 1.41-2.12) in antidepressant users who were not depressed to 3.63 in antidepressant users who were depressed (95% CI = 2.37-5.55). All durations of use were associated with incident frailty (<1 year OR = 1.95, 95% CI = 1.41-2.68; 1-3 years OR = 1.99, 95% CI = 1.45-2.74; >3 years OR = 1.60, 95% CI = 1.20-2.14). Conclusion In older adult women, depressive symptoms and antidepressant use were associated with frailty after 3 years of follow-up. [ABSTRACT FROM AUTHOR]

Objectives To evaluate whether the use of angiotensin-converting enzyme ( ACE) inhibitors and statins is associated with a lower risk of incident mobility limitation in older community dwelling adults. Design Longitudinal cohort study. Setting Health, Aging and Body Composition (Health ABC) study. Participants Three thousand fifty-five participants who were well functioning at baseline (no mobility limitations). Measurements Summated standardized daily doses (low, medium, high) and duration of ACE inhibitor and statin use were computed. Mobility limitation (two consecutive self-reports of having any difficulty walking one-quarter of a mile or climbing 10 steps without resting) was assessed every 6 months after baseline. Multivariable Cox proportional hazards analyses were conducted, adjusting for demographics, health status, and health behaviors. Results At baseline, 15.2% used ACE inhibitors and 12.9% used statins; use of both was greater than 25% by Year 6. Over 6.5 years of follow-up, 49.8% had developed mobility limitation. In separate multivariable models, neither ACE inhibitor (multivariate hazard ratio ( HR) = 0.95, 95% confidence interval ( CI) = 0.82-1.09) nor statin use (multivariate HR = 1.02, 95% CI = 0.87-1.17) was associated with lower risk of mobility limitation. Similar findings were seen in analyses examining dose-response and duration-response relationships and a sensitivity analysis restricted to those with hypertension. Conclusion ACE inhibitors and statins widely prescribed to treat hypertension and hypercholesterolemia, respectively, do not lower risk of mobility limitation, an important indicator of quality of life. [ABSTRACT FROM AUTHOR]

Objectives To determine the extent of concomitant use of cholinesterase inhibitor ( ChI) and anticholinergic ( ACh) medications and the clinical consequences of dual use in a population-based setting. Design Retrospective cohort study. Setting Group Health Cooperative and Kaiser Permanente Colorado. Participants Five thousand six hundred twenty-five adults aged 50 and older who began new use of a ChI between 2000 and 2007. Measurements Rates and characteristics of concomitant ChI and ACh use and the association between dual use and the outcomes of death and nursing home placement (claim from a nursing home with no prior claims used as a proxy). Results Thirty-seven percent of ChI users also received AChs. Eleven percent of ChI users were concomitantly using two or more moderate to potent AChs. Median duration of this concomitant use was approximately 4 months, but a substantial proportion (25%) continued to use both medication classes simultaneously for longer than 12 months. In 23% of ChI users, AChs were being used at the time ChI therapy was initiated. The majority of this ACh use (77%) was not stopped once ChIs were started. No association was observed between concomitant use and risk of death or nursing home placement. Conclusion These results should raise awareness about the prevalence and potential inappropriateness of concomitant use of ChIs and AChs and promote evaluations of practices intended to improve care standards. [ABSTRACT FROM AUTHOR]