The Effect of Pharmacist-Initiated Deprescribing Interventions in Older People: A Narrative Review of Randomized Controlled Trials.

Background Polypharmacy is common among older people and may be associated with adverse drug events (ADEs) and poor health outcomes. Pharmacists are well-positioned to reduce polypharmacy and potentially inappropriate medications. Objective The objective of this narrative review was to summarize the results from randomized-controlled trials that evaluated pharmacist-led interventions with the goal or effect to deprescribe medications in older individuals. Data Sources We searched Medline, Embase, CINAHL Complete, APA PsycInfo, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials. Data Synthesis Of the 25 studies included, the interventions were conducted in nursing facilities (n = 8), outpatient/community dwellings (n = 8), or community pharmacies (n = 9). Interventions were categorized as comprehensive medication reviews (n = 10), comprehensive medication reviews with pharmacist follow-up (n = 11), and educational interventions provided to patients and/or providers (n = 4). Pharmacist-led interventions had a beneficial effect on 22 out of 32 total medication-related outcomes (eg, number of medications, potentially inappropriate medications, or discontinuation). Most (n = 18) studies reported no evidence of an effect for other outcomes such as health care use, mortality, patient-centered outcomes (falls, cognition, function, quality of life), and ADEs. Discussion Interventions led to improvement in 69% of the medication-related outcomes examined across study settings. Five studies measured ADEs with none accounting for adverse drug-withdrawal events. Large well-designed studies that are powered to find an effect on patient-centered outcomes are needed. Conclusion Pharmacist-led interventions had a significant beneficial effect on medication-related outcomes. There was little evidence of benefit on other outcomes.

Medication use quality and safety in older adults: 2022 update.

Improving the quality of medication use and medication safety are important priorities for healthcare providers who care for older adults. The objective of this article was to identify four exemplary articles with this focus in 2022. We selected high-quality studies from an OVID search and hand searching of major high impact journals that advanced the field of research forward. The chosen articles cover domains related to deprescribing, medication safety, and optimizing medication use. The MedSafer Study, a cluster randomized clinical trial in Canada, evaluated whether patient specific deprescribing reports generated by electronic decision support software resulted in reduced adverse drug events in the 30 days post hospital discharge in older adults (domain: deprescribing). The second study, a retrospective cohort study using data from Premier Healthcare Database, examined in-hospital adverse clinical events associated with perioperative gabapentin use among older adults undergoing major surgery (domain: medication safety). The third study used an open-label parallel controlled trial in 39 Australian aged-care facilities to examine the effectiveness of a pharmacist-led intervention to reduce medication-induced deterioration and adverse reactions (domain: optimizing medication use). Lastly, the fourth study engaged experts in a Delphi method process to develop a consensus list of clinically important prescribing cascades that adversely affect older persons' health to aid clinicians to identify, prevent, and manage prescribing cascades (domain: optimizing medication use). Collectively, this review succinctly highlights pertinent topics related to promoting safe use of medications and promotes awareness of optimizing older adults' medication regimens.

Comparative safety of antimuscarinics versus mirabegron for overactive bladder in Parkinson disease.

BACKGROUND: Overactive bladder (OAB) is a common non-motor symptom of Parkinson disease (PD), often treated with antimuscarinics or beta-3 agonists. There is lack of evidence to guide OAB management in PD. OBJECTIVES: To assess the comparative safety of antimuscarinics versus beta-3 agonists for OAB treatment in PD. METHODS: We employed a new-user, active-comparator cohort study design. We included Medicare beneficiaries age ≥65 years with PD who were new users of either antimuscarinic or beta-3 agonist. The primary outcome was any acute care encounter (i.e., non-elective hospitalization or emergency department visit) within 90 days of OAB drug initiation. The main secondary outcome was a composite measure of acute care encounters for anticholinergic related adverse events (AEs). Matching on high-dimensional propensity score (hdPS) was used to address potential confounding. We used Cox proportional hazards models to examine the association between OAB drug category and outcomes. We repeated analyses for 30- and 180-day follow-up periods. RESULTS: We identified 27,091 individuals meeting inclusion criteria (mean age: 77.8 years). After hdPS matching, antimuscarinic users had increased risks for any acute care encounter (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.12-1.37) and encounters for anticholinergic related AEs (HR 1.18, 95% CI 1.04-1.34) compared to beta-3 agonist users. Similar associations were observed for sensitivity analyses. CONCLUSIONS: Among persons with PD, anticholinergic initiation was associated with a higher risk of acute care encounters compared with beta-3 agonist initiation. The long-term safety of anticholinergic vs. beta-3 agonist therapy in the PD population should be evaluated in a prospective study.

Systematic Review and Meta-analysis of Interventions to Reduce Adverse Drug Reactions in Older Adults: An Update.

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.

Potentially inappropriate medications in older adults with Parkinson disease before and after hospitalization for injury.

BACKGROUND: Parkinson disease (PD) patients are at increased risk of serious injury, such as fall-related fractures. Prescription medications are a modifiable factor for injury risk. OBJECTIVES: To determine the extent to which a serious injury requiring hospitalization affects prescribing of potentially inappropriate medications (PIMs) among older adults with PD. METHODS: We conducted a quasi-experimental difference-in-difference (DID) study using 2013-2017 Medicare data. The cohort consisted of beneficiaries with PD hospitalized for injury versus for other reasons. PIMs were classified into PD and injury-relevant categories (CNS-active PIMs, PD motor symptom PIMs, PD non-motor symptom PIMs, PIMs that reduce bone mineral density). We estimated mean standardized daily doses (SDDs) of medications within each PIM category before and at 3, 6, and 12 months after hospitalization. We used generalized linear regression models to compare changes in mean SDDs for each PIM category between the injury and non-injury group at each timepoint, adjusting for biological, clinical and social determinants of health variables. RESULTS: Both groups discontinued PIMs and/or reduced PIM doses after hospitalization. There were no between-group differences in mean SDD changes, after covariate adjustment, for any PIM category, except for the CNS-active PIMs category at 3 months (DID p-value = 0.00) and for the category of PIMs that reduce bone mineral density at all timepoints (DID p-values = 0.02, 0.04, 0.02 at 3, 6, and 12 months). CONCLUSIONS: Similar patterns of PIM among persons with PD after hospitalization for serious injury versus for other reasons may represent a missed opportunity to deprescribe high-risk medications during care transitions.

A health-system-embedded deprescribing intervention targeting patients and providers to prevent falls in older adults (STOP-FALLS trial): study protocol for a pragmatic cluster-randomized controlled trial.

BACKGROUND: Central nervous system (CNS) active medications have been consistently linked to falls in older people. However, few randomized trials have evaluated whether CNS-active medication reduction reduces falls and fall-related injuries. The objective of the Reducing CNS-active Medications to Prevent Falls and Injuries in Older Adults (STOP-FALLS) trial is to test the effectiveness of a health-system-embedded deprescribing intervention focused on CNS-active medications on the incidence of medically treated falls among community-dwelling older adults. METHODS: We will conduct a pragmatic, cluster-randomized, parallel-group, controlled clinical trial within Kaiser Permanente Washington to test the effectiveness of a 12-month deprescribing intervention consisting of (1) an educational brochure and self-care handouts mailed to older adults prescribed one or more CNS-active medications (aged 60 + : opioids, benzodiazepines and Z-drugs; aged 65 + : skeletal muscle relaxants, tricyclic antidepressants, and antihistamines) and (2) decision support for their primary health care providers. Outcomes are examined over 18-26 months post-intervention. The primary outcome is first incident (post-baseline) medically treated fall as determined from health plan data. Our sample size calculations ensure at least 80% power to detect a 20% reduction in the rate of medically treated falls for participants receiving care within the intervention (n = 9) versus usual care clinics (n = 9) assuming 18 months of follow-up. Secondary outcomes include medication discontinuation or dose reduction of any target medications. Safety outcomes include serious adverse drug withdrawal events, unintentional overdose, and death. We will also examine medication signetur fields for attempts to decrease medications. We will report factors affecting implementation of the intervention. DISCUSSION: The STOP-FALLS trial will provide new information about whether a health-system-embedded deprescribing intervention that targets older participants and their primary care providers reduces medically treated falls and CNS-active medication use. Insights into factors affecting implementation will inform future research and healthcare organizations that may be interested in replicating the intervention. TRIAL REGISTRATION: ClinicalTrial.gov NCT05689554. Registered on 18 January 2023, retrospectively registered.

Channeling of New Neuropsychiatric Drugs-Impact on Safety and Effectiveness Studies.

This study aimed to examine differential prescribing due to channeling and propensity score non-overlap over time in new versus established treatments for common neurological conditions. We conducted cross-sectional analyses on a national sample of US commercially insured adults using 2005-2019 data. We compared new users of recently approved versus established medications for management of diabetic peripheral neuropathy (pregabalin versus gabapentin), Parkinson disease psychosis (pimavanserin versus quetiapine), and epilepsy (brivaracetam versus levetiracetam). Within these drug pairs, we compared demographic, clinical, and healthcare utilization characteristics of recipients of each drug. In addition, we fit yearly propensity score models for each condition and assessed propensity score non-overlap over time. For all three drug pairs, users of the more recently approved medications more frequently had prior treatment (pregabalin = 73.9%, gabapentin = 38.7%; pimavanserin = 41.1%, quetiapine = 14.0%; brivaracetam = 93.4%, levetiracetam = 32.1%). Propensity score non-overlap and its resulting sample loss after trimming were the greatest in the first year that the more recently approved medication was available (diabetic peripheral neuropathy, 12.4% non-overlap; Parkinson disease psychosis, 6.1%; epilepsy, 43.2%) and subsequently improved. Newer neuropsychiatric therapies appear to be channeled to individuals with refractory disease or intolerance to other treatments, leading to potential confounding and biased comparative effectiveness and safety study findings when compared to established treatments. Propensity score non-overlap should be reported in comparative studies that include newer medications. When studies comparing newer and established treatments are critically needed as soon as new treatments enter the market, investigators should recognize the potential for channeling bias and implement methodological approaches like those demonstrated in this study to understand and improve this issue in such studies.

Provider knowledge, beliefs, and self-efficacy to deprescribe opioids and sedative-hypnotics.

BACKGROUND: While many studies have assessed and measured patient attitudes toward deprescribing, less quantitative research has addressed the provider perspective. We thus sought to describe provider knowledge, beliefs, and self-efficacy to deprescribe, with a focus on opioids and sedative-hypnotics. METHODS: An electronic anonymous survey was distributed to primary care providers at Kaiser Permanente Washington. Two reminder emails were sent. The survey included 10 questions on general deprescribing, and six questions each specific to opioid and sedative-hypnotic deprescribing. Knowledge questions used a multiple-choice response option format. Questions addressing beliefs and self-efficacy (i.e., confidence) used a 0-10 Likert scale. Scales were dichotomized at ≥7 to define agreement (belief questions) or confidence (self-efficacy questions). We calculated descriptive statistics to summarize the responses. RESULTS: Of 370 eligible primary care providers, 95 (26%) completed the survey. For general deprescribing questions, a majority believed that lack of patient willingness, withdrawal symptoms and fear of symptom return, and time constraints impeded deprescribing. Approximately half chose the correct answers about opioid deprescribing, 21% were confident that they could alleviate patient concerns about opioid tapering, and 32% were confident managing chronic non-cancer pain without opioids. For sedative-hypnotics, 64%-87% of respondents correctly answered questions about risks and the relative effectiveness of alternatives, but only one-third correctly answered a question about sedative-hypnotic tapering. Roughly half were confident in their ability to successfully engage patients in sedative deprescribing conversations and select alternatives. Only 54% and 34% were confident in writing a tapering protocol for opioids and sedative-hypnotics, respectively. CONCLUSION: Results suggest that raising provider awareness of patient willingness to deprescribe, addressing knowledge gaps, and increasing self-efficacy for deprescribing are important targets for improving deprescribing. Support for writing tapering protocols and prescribing evidence-based drug and non-drug alternatives may be important to improve care.

Overactive Bladder and Cognitive Impairment: The American Urogynecologic Society and Pelvic Floor Disorders Research Foundation State-of-the-Science Conference Summary Report.

IMPORTANCE: Overactive bladder (OAB) is prevalent in older adults in whom management is complicated by comorbidities and greater vulnerability to the cognitive effects of antimuscarinic medications. OBJECTIVES: The aim of this study is to provide a comprehensive evidence-based summary of the 2021 State-of-the-Science (SOS) conference and a multidisciplinary expert literature review on OAB and cognitive impairment. STUDY DESIGN: The American Urogynecologic Society and the Pelvic Floor Disorders Research Foundation convened a 3-day collaborative conference. Experts from multidisciplinary fields examined cognitive function, higher neural control of the OAB patient, risk factors for cognitive impairment in older patients, cognitive effects of antimuscarinic medications for OAB treatment, OAB phenotyping, conservative and advanced OAB therapies, and the need for a multidisciplinary approach to person-centered treatment. Translational topics included the blood-brain barrier, purine metabolome, mechanotransduction, and gene therapy for OAB targets. RESULTS: Research surrounding OAB treatment efficacy in cognitively impaired individuals is limited. Short- and long-term outcomes regarding antimuscarinic effects on cognition are mixed; however, greater anticholinergic burden and duration of use influence risk. Oxybutynin is most consistently associated with negative cognitive effects in short-term, prospective studies. Although data are limited, beta-adrenergic agonists do not appear to confer the same cognitive risk. CONCLUSIONS: The 2021 SOS summary report provides a comprehensive review of the fundamental, translational, and clinical research on OAB with emphasis on cognitive impairment risks to antimuscarinic medications. Duration of use and antimuscarinic type, specifically oxybutynin when examining OAB treatments, appears to have the most cognitive impact; however, conclusions are limited by the primarily cognitively intact population studied. Given current evidence, it appears prudent to minimize anticholinergic burden by emphasizing nonantimuscarinic therapeutic regimens in the older population and/or those with cognitive impairment.

Optimizing Medication Use in Older Adults With Rheumatic Musculoskeletal Diseases: Deprescribing as an Approach When Less May Be More.

The world population is aging, and the rheumatology workforce must be prepared to care for medically complex older adults. We can learn from our colleagues and experts in geriatrics about how to best manage multimorbidity, polypharmacy, geriatric syndromes, and shifting priorities of older adults in the context of delivering care for rheumatic and musculoskeletal diseases (RMDs). Polypharmacy, a common occurrence in an aging population with multimorbidity, affects half of older adults with RMDs and is associated with increased risk of morbidity and mortality. In addition, potentially inappropriate medications that should be avoided under most circumstances is common in the RMD population. In recent years, deprescribing, known as the process of tapering, stopping, discontinuing, or withdrawing drugs, has been introduced as an approach to improve appropriate medication use among older adults and the outcomes that are important to them. As the rheumatology patient population ages globally, it is imperative to understand the burden of polypharmacy and the potential of deprescribing to improve medication use in older adults with RMDs. We encourage the rheumatology community to implement geriatric principles, when possible, as we move toward becoming an age-friendly health care specialty.

Recommendations for outcome measurement for deprescribing intervention studies.

Interpreting results from deprescribing interventions to generate actionable evidence is challenging owing to inconsistent and heterogeneous outcome definitions between studies. We sought to characterize deprescribing intervention outcomes and recommend approaches to measure outcomes for future studies. A scoping literature review focused on deprescribing interventions for polypharmacy and informed a series of expert panel discussions and recommendations. Twelve experts in deprescribing research, policy, and clinical practice interventions participating in the Measures Workgroup of the US Deprescribing Research Network sought to characterize deprescribing outcomes and recommend approaches to measure outcomes for future studies. The scoping review identified 125 papers reflecting 107 deprescribing studies. Common outcomes included medication discontinuation, medication appropriateness, and a broad range of clinical outcomes potentially resulting from medication reduction. Panel recommendations included clearly defining clinically meaningful medication outcomes (e.g., number of chronic medications, dose reductions), ensuring adequate sample size and follow-up time to capture clinical outcomes resulting from medication discontinuation (e.g., quality of life [QOL]), and selecting appropriate and feasible data sources. A new conceptual model illustrates how downstream clinical outcomes (e.g., reduction in falls) should be interpreted in the context of initial changes in medication measures (e.g., reduction in mean total medications). Areas needing further development include implementation outcomes specific to deprescribing interventions and measures of adverse drug withdrawal events. Generating evidence to guide deprescribing is essential to address patient, caregiver, and clinician concerns about the benefits and harms of medication discontinuation. This article provides recommendations and an initial conceptual framework for selecting and applying appropriate intervention outcomes to support deprescribing research.

Association Between Informant-Reported Sleep Disturbance and Incident Dementia: An Analysis of the National Alzheimer's Coordinating Center Uniform Data Set.

Informants' reports can be useful in screening patients for future risk of dementia. We aimed to determine whether informant-reported sleep disturbance is associated with incident dementia, whether this association varies by baseline cognitive level and whether the severity of informant-reported sleep disturbance is associated with incident dementia among those with sleep disturbance. A longitudinal retrospective cohort study was conducted using the uniform data set collected by the National Alzheimer's Coordinating Center. Older adults without dementia at baseline living with informants were included in analysis. Cox proportional hazards models showed that participants with an informant-reported sleep disturbance were more likely to develop dementia, although this association may be specific for older adults with normal cognition. In addition, older adults with more severe sleep disturbance had a higher risk of incident dementia than those with mild sleep disturbance. Informant-reported information on sleep quality may be useful for prompting cognitive screening.

Association between having a family member with dementia and perceptions of dementia preventability.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Change in central nervous system-active medication use following fall-related injury in older adults.

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.

Barriers and enablers of older adults initiating a deprescribing conversation.

OBJECTIVE: To examine older adults' perceptions and identify barriers and enablers to initiating a conversation about stopping medication(s) with their healthcare provider. METHODS: We conducted one focus group (n = 3) and in-depth, face-to-face, individual interviews (n = 6) using an interview guide. Older adults aged ≥65 years in a retirement community who were taking ≥5 medications were recruited. Focus groups and interviews were audio-recorded and transcribed verbatim. Both a deductive analysis, informed by the Theoretical Domains Framework, and an inductive analysis were conducted. RESULTS: Five themes and fourteen sub-themes were identified. Theme 1, 'older adult-related barriers', discusses limited or varying self-efficacy, past unsuccessful deprescribing experiences and limited familiarity with medications/deprescribing. Theme 2, 'provider-related barriers', discusses trust, short office visits, lack of communication and multiple providers. Theme 3, 'environmental/social-related barriers', involves limited availability of resources and access to telehealth/internet. The remaining themes (Themes 4-5) identified enablers including strategies to promote older adults' self-efficacy and improved healthcare communication. CONCLUSION: Consumer-centric tools could improve older adults' self-efficacy to initiate deprescribing conversations. PRACTICE IMPLICATIONS: Removing barriers and implementing enablers may empower older adults to initiate deprescribing conversations with providers to take fewer medications. Ultimately, this could be a catalyst for increased translation of deprescribing in practice.

Medication use quality and safety in older adults: 2020 update.

Improving the quality of medication use and medication safety are important priorities for prescribers who care for older adults. The objective of this article was to identify four exemplary articles with this focus in 2020. We selected high-quality studies that moved the field of research forward and were not merely replication studies. The chosen articles cover domains related to deprescribing, medication safety, and optimizing medication use. The first study, a noninferiority randomized clinical trial in England, evaluated whether antihypertensive medication reduction is possible without significant changes in systolic blood pressure control or adverse events over the 12-week follow-up (domain: deprescribing). The second study, a prospective cohort study of women at Kaiser Permanente Southern, California, examined the association between bisphosphonate use and atypical femur fracture (domain: medication safety). The third study examined the effectiveness and safety of a multifaceted antimicrobial stewardship and quality improvement initiative in reducing unnecessary antimicrobial use for unlikely cystitis cases in noncatheterized residents in 25 nursing homes across the United States (domain: optimizing medication use). Lastly, the fourth study, a population-based cohort study in the United Kingdom, examined the association of tramadol use with risk of hip fracture (domain: medication safety). Collectively, this review succinctly highlights pertinent topics related to promoting safe use of medications and promotes awareness of optimizing older adults' medication regimens.

Alzheimer's Disease-Related Neuropathology Among Patients with Medication Treated Type 2 Diabetes in a Community-Based Autopsy Cohort.

BACKGROUND: Diabetes is a risk factor for Alzheimer's disease and related dementias (ADRD). Epidemiologic evidence shows an association between diabetes medications and ADRD risk; cell and mouse models show diabetes medication association with AD-related neuropathologic change (ADNC). OBJECTIVE: This hypothesis-generating analysis aimed to describe autopsy-measured ADNC for individuals who used diabetes medications. METHODS: Descriptive analysis of ADNC for Adult Changes in Thought (ACT) Study autopsy cohort who used diabetes medications, including sulfonylureas, insulin, and biguanides; total N = 118. ADNC included amyloid plaque distribution (Thal phasing), neurofibrillary tangle (NFT) distribution (Braak stage), and cortical neuritic plaque density (CERAD score). We also examined quantitative measures of ADNC using the means of standardized Histelide measures of cortical PHF-tau and Aß1-42. Adjusted analyses control for age at death, sex, education, APOE genotype, and diabetes complication severity index. RESULTS: Adjusted analyses showed no significant association between any drug class and traditional neuropathologic measures compared to nonusers of that class. In adjusted Histelide analyses, any insulin use was associated with lower mean levels of Aß1-42 (-0.57 (CI: -1.12, -0.02)) compared to nonusers. Five years of sulfonylureas and of biguanides use was associated with lower levels of Aß1-42 compared to nonusers (-0.15 (CI: -0.28, -0.02), -0.31 (CI: -0.54, -0.07), respectively). CONCLUSION: Some evidence exists that diabetes medications are associated with lower levels of Aß1-42, but not traditional measures of neuropathology. Future studies are needed in larger samples to build understanding of the mechanisms between diabetes, its medications, and ADRD, and to potentially repurpose existing medications for prevention or delay of ADRD.

Incident Dementia, Glycated Hemoglobin (HbA1c) Levels, and Potentially Preventable Hospitalizations in People Aged 65 and Older With Diabetes.

BACKGROUND: This study was aimed to determine whether incident dementia and HbA1c levels are associated with increased rates of potentially preventable hospitalizations (PPHs) in persons with diabetes. METHOD: A total of 565 adults aged 65+ ever treated for diabetes were enrolled from Adult Changes in Thought study. PPHs were from principal discharge diagnoses and included diabetes PPH (dPPH), respiratory PPH (rPPH), urinovolemic PPH (uPPH), cardiovascular PPH, and other PPH. Poisson generalized estimating equations estimated rate ratios (RRs) and 95% confidence intervals (CIs) for the associations between dementia or HbA1c measures and rate of PPHs. RESULTS: A total of 562 individuals contributed 3 602 dementia-free years, and 132 individuals contributed 511 dementia follow-up years. One hundred twenty-eight (23%) dementia-free individuals had 210 PPH admissions and a crude rate of 58 per 1 000 person-years, while 55 (42%) individuals with dementia had 93 PPH admissions and a crude rate of 182 per 1 000 person-years. The adjusted RR (95% CI) comparing rates between dementia and dementia-free groups were 2.27 (1.60, 3.21) for overall PPH; 5.90 (2.70, 12.88) for dPPH; 5.17 (2.49, 10.73) for uPPH; and 2.01 (1.06, 3.83) for rPPH. Compared with HbA1c of 7%-8% and adjusted for dementia, the RR (95% CI) for overall PPH was 1.43 (1.00, 2.06) for >8% HbA1c and 1.18 (0.85, 1.65) for <7% HbA1c. The uPPH RR was also increased, comparing >8% and <7% HbA1c levels. CONCLUSION: Incident dementia is associated with higher rates of PPHs among people with diabetes, especially PPHs due to diabetes, urinary tract infection (UTI), and dehydration. Potential evidence suggested that HbA1c levels of >8% versus lower levels are associated with higher rates of overall PPHs and UTI- and dehydration-related PPHs.

Glucose-Dementia Association Is Consistent Over Blood Pressure/Antihypertensive Groups.

BACKGROUND: Higher glucose levels are associated with dementia risk in people with and without diabetes. However, little is known about how this association might vary by hypertension status and antihypertensive treatment. Most studies on modifiable dementia risk factors consider each factor in isolation. OBJECTIVE: To test the hypothesis that hypertension and antihypertensive treatments may modify associations between glucose levels and dementia. METHODS: Analyses of data generated from a research study and clinical care of participants from a prospective cohort of dementia-free older adults, including glucose measures, diabetes and antihypertensive treatments, and blood pressure data. We defined groups based on blood pressure (hypertensive versus not, ≥140/90 mmHg versus <140/90 mmHg) and antihypertensive treatment intensity (0, 1, or ≥2 classes of antihypertensives). We used Bayesian joint models to jointly model longitudinal exposure and time to event data. RESULTS: A total of 3,056 participants without diabetes treatment and 480 with diabetes treatment were included (mean age at baseline, 75.1 years; mean 7.5 years of follow-up). Higher glucose levels were associated with greater dementia risk among people without and with treated diabetes. Hazard ratios for dementia were similar across all blood pressure/antihypertensive treatment groups (omnibus p = 0.82 for people without and p = 0.59 for people with treated diabetes). CONCLUSION: Hypertension and antihypertensive treatments do not appear to affect the association between glucose and dementia risk in this population-based longitudinal cohort study of community-dwelling older adults. Future studies are needed to examine this question in midlife and by specific antihypertensive treatments.