Patient and caregiver perspectives on a tool to increase recognition of undiagnosed dementia: a qualitative study.

BACKGROUND: Early detection of dementia may improve patient care and quality of life, yet up to half of people with dementia are undiagnosed. Electronic health record (EHR) data could be used to help identify individuals at risk of having undiagnosed dementia for outreach and assessment, but acceptability to people with dementia and caregivers is unknown. METHODS: We conducted five focus groups at Kaiser Permanente Washington (KPWA), an integrated healthcare system in Washington State, to explore people's feelings about timing of dementia diagnosis, use of EHR-based tools to predict risk of undiagnosed dementia, and communication about risk. We recruited people enrolled in KPWA who had dementia or mild cognitive impairment, people enrolled in KPWA who had neither diagnosis, and caregivers (i.e., loved ones of people with dementia who assist with various tasks of daily life). People who were non-white or Hispanic were oversampled. Two team members analyzed transcripts using thematic coding. RESULTS: Forty people (63% women; 59% non-white or Hispanic) participated in the focus groups. Themes that arose included: perceived pros and cons of early dementia diagnosis; questions and concerns about a potential tool to assess risk of undiagnosed dementia; and preferences related to patient-provider conversations disclosing that a person was at high risk to have undiagnosed dementia. Participants supported early diagnosis, describing benefits such as time to adjust to the disease, plan, involve caregivers, and identify resources. They also acknowledged the possible psychosocial toll of receiving the diagnosis. Participants supported use of an EHR-based tool, but some people worried about accuracy and privacy. Participants emphasized that information about risk of undiagnosed dementia should be communicated thoughtfully by a trusted provider and that the conversation should include advice about prognosis, treatment options and other resources when a new dementia diagnosis was made. CONCLUSION: People with dementia or mild cognitive impairment, people with neither diagnosis, and caregivers of people with dementia supported using EHR-based tools to help identify individuals at risk of having undiagnosed dementia. Such tools must be implemented carefully to address concerns and ensure that people living with dementia and their caregivers are adequately supported.

Association of Lifetime TBI and Military Employment with Late Life ADL Functioning: A Population-Based Prospective Cohort Study.

OBJECTIVE: To determine associations of traumatic brain injury (TBI) and military employment with activities of daily living (ADL) in late life. DESIGN: Population-based prospective cohort study with biennial follow-up and censoring at the time of dementia diagnosis. SETTING: Community-based integrated health care delivery system. PARTICIPANTS: Participants (N=4953) were men (n=2066) and women (n=2887) aged ≥65 years who were dementia free. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: ADL difficulties at baseline and accumulation during follow-up. RESULTS: TBI with loss of consciousness (LOC) before the age of 40 years was associated with slightly higher ADL difficulty at baseline for women (rate ratio [RR], 1.44; 95% confidence interval [CI], 1.08-1.93; P=.01). For men, TBI with LOC at any age was associated with greater ADL difficulty at baseline (age <40y: RR, 1.58; 95% CI, 1.20-2.08; P=.001; age ≥40y: RR, 2.14; 95% CI, 1.24-3.68; P=.006). TBI with LOC was not associated with the rate of accumulation of ADL difficulties over time in men or women. There was no evidence of an association between military employment and either outcome, nor of an interaction between military employment and TBI with LOC. Findings were consistent across a variety of sensitivity analyses. CONCLUSIONS: Further investigation into factors underlying greater late life functional impairment among survivors of TBI is warranted.

Beliefs about benefits and harms of medications and supplements for brain health.

The role of medications and supplements for brain health is a fast-changing and growing field, making it difficult for patients to receive updated and accurate information. The objective of this study was to assess patients' beliefs about the helpfulness or harmfulness of various medications and supplements on brain health. A convenience sample of adults from an integrated healthcare system completed a web-based survey. Descriptive statistics were used for this hypothesis-generating study. A total of 1661 respondents completed the survey. The majority of respondents were female (77%), between the ages of 51-70 (64%), and white (89%). Across the selected medications and supplements purported to improve a person's brain health (vitamin E, ginkgo biloba, hormones such as estrogen or testosterone, fish oil, and statins), 46-64% of respondents reported not knowing or skipped the item regarding their helpfulness to improve brain health. One out of four respondents reported benefits of vitamin E and nearly half reported benefits of fish oil on brain health; neither benefit is supported by current evidence. For the two medication classes evaluated for increasing dementia risk (proton pump inhibitors and anticholinergics used as sleep aids), 63-77% of respondents reported not knowing or skipped the item regarding their harmfulness to brain health. Survey respondents largely reported not knowing the potential benefits and harms of different medications and supplements for brain health. Improved health communication on pharmaceutical effects on dementia risk is greatly needed, and its development and dissemination should involve healthcare providers, patients, and media outlets.

Development and Validation of eRADAR: A Tool Using EHR Data to Detect Unrecognized Dementia.

OBJECTIVES: Early recognition of dementia would allow patients and their families to receive care earlier in the disease process, potentially improving care management and patient outcomes, yet nearly half of patients with dementia are undiagnosed. Our aim was to develop and validate an electronic health record (EHR)-based tool to help detect patients with unrecognized dementia (EHR Risk of Alzheimer's and Dementia Assessment Rule [eRADAR]). DESIGN: Retrospective cohort study. SETTING: Kaiser Permanente Washington (KPWA), an integrated healthcare delivery system. PARTICIPANTS: A total of 16 665 visits among 4330 participants in the Adult Changes in Thought (ACT) study, who undergo a comprehensive process to detect and diagnose dementia every 2 years and have linked KPWA EHR data, divided into development (70%) and validation (30%) samples. MEASUREMENTS: EHR predictors included demographics, medical diagnoses, vital signs, healthcare utilization, and medications within the previous 2 years. Unrecognized dementia was defined as detection in ACT before documentation in the KPWA EHR (ie, lack of dementia or memory loss diagnosis codes or dementia medication fills). RESULTS: Overall, 1015 ACT visits resulted in a diagnosis of incident dementia, of which 498 (49%) were unrecognized in the KPWA EHR. The final 31-predictor model included markers of dementia-related symptoms (eg, psychosis diagnoses, antidepressant fills), healthcare utilization pattern (eg, emergency department visits), and dementia risk factors (eg, cerebrovascular disease, diabetes). Discrimination was good in the development (C statistic = .78; 95% confidence interval [CI] = .76-.81) and validation (C statistic = .81; 95% CI = .78-.84) samples, and calibration was good based on plots of predicted vs observed risk. If patients with scores in the top 5% were flagged for additional evaluation, we estimate that 1 in 6 would have dementia. CONCLUSION: The eRADAR tool uses existing EHR data to detect patients with good accuracy who may have unrecognized dementia. J Am Geriatr Soc 68:103-111, 2019.

"It would be so much easier": health system-led genetic risk notification-feasibility and acceptability of cascade screening in an integrated system.

Assess the feasibility and acceptability of health system-led genetic risk notification in a US integrated health system. We conducted semi-structured phone interviews with individuals age 40-64 years who had undergone genetic sequencing, but had not yet received their results, assessing attitudes to direct outreach to relatives. During each interview, we collected contact information for adult relatives identified as members of the same system and attempted to identify each relative in administrative data. We conducted 20 interviews. Most participants expressed support for Kaiser Permanente Washington involvement in familial risk notification. Direct outreach to relatives received the most unqualified support; outreach to the relatives' physician or interaction with the relatives' electronic medical record received more tempered support. Support was motivated by the desire to have risk communicated accurately and quickly. The most common caveat was a desire to alert relatives before the health system contacted them. Of 57 named relatives who were members of the same health system, we retrieved a single match for 40 (70.2%) based on name or birthdate. Health system involvement in familial risk notification received support in a sample of patients in a US integrated health system, and identification of relatives is feasible.

Brain Health and Dementia Prevention: A Mixed-method Analysis.

Objective: In this study, we assessed patient knowledge, beliefs, and attitudes about brain health and strategies for Alzheimer's disease and related dementias (ADRD) prevention. Methods: We administered a Web-based survey consisting of 17 questions about brain health and strategies for ADRD prevention in a convenience sample of 1661 patients in an integrated healthcare delivery system in Washington state between February and March 2018. We calculated frequency distributions of the quantitative data and conducted inductive content analysis of qualitative data. Results: Most respondents were female (77%), 51-70 years of age (64%), and white (89%). Although most agreed it is possible to improve brain health and reduce personal ADRD risk, one- third lacked confidence that they could take action to reduce personal ADRD risk. Participants' responses to open-ended questions revealed 10 themes grouped into 3 organizing categories regarding their perceptions about how to prevent ADRD onset: (1) understand ADRD; (2) stay engaged; and (3) manage one's own health and healthcare. Conclusions: Survey respondents were engaged and aware of dementia prevention, but they lacked access to personally action- able evidence..

Patterns of antihypertensive and statin adherence prior to dementia: findings from the adult changes in thought study.

BACKGROUND: Detecting patients with undiagnosed dementia is an important clinical challenge. Changes in medication adherence might represent an early sign of cognitive impairment. We sought to examine antihypertensive and statin adherence trajectories in community-dwelling older adults, comparing people who went on to develop dementia to those who did not. METHODS: We analyzed data from Adult Changes in Thought (ACT), a population-based cohort study embedded within an integrated healthcare delivery system. Analyses included 4368 participants aged ≥65 years who had at least one follow-up visit. Research-quality dementia diagnoses were used to identify cases. We selected non-dementia control visits matched on age, sex, and study cohort that occurred at similar ACT follow-up time as the case's dementia onset; we treated this as the index date. Participants were included if they were prevalent users of either a statin or antihypertensive medication on the first day of follow up - 3 years prior to the index date. Using prescription fill dates and days supply, we calculated daily binary medication availability measures for each participant ('days covered') over 3 years leading up to the index date. We used group-based trajectory models to identify patterns of antihypertensive and statin adherence, and used conditional logistic regression to examine associations between adherence trajectories and dementia. RESULTS: Four trajectories were identified for antihypertensive users (292 cases, 3890 control visits), including near perfect (n = 1877, 36.6% cases, 45.5% controls), high (n = 1840, 43.2% cases, 44.1% controls), moderate (n = 365, 18.5% cases, 8.0% controls) and early poor adherence (n = 100, 1.7% cases, 2.4% controls). Odds of dementia was 3 times greater for those with moderate antihypertensive adherence compared to those with near perfect adherence (adjusted OR 3.0, 95% CI 2.0, 4.3). Four trajectories were identified for statin users (148 cases, 1131 control visits), including high (n = 1004, 75.0% cases, 79.0% controls), moderate (n = 192, 19.6% cases, 14.4% controls), early poor (n = 43, 2.0% cases, 3.5% controls), and delayed poor adherence (n = 40, 3.4% cases, 3.1% controls). No association was detected between statin adherence trajectories and dementia. CONCLUSIONS: Patterns of medication adherence may be useful to identify a subset of people at higher likelihood of developing dementia.

Systematic Multi-Domain Alzheimer's Risk Reduction Trial (SMARRT): Study Protocol.

This article describes the protocol for the Systematic Multi-domain Alzheimer's Risk Reduction Trial (SMARRT), a single-blind randomized pilot trial to test a personalized, pragmatic, multi-domain Alzheimer's disease (AD) risk reduction intervention in a US integrated healthcare delivery system. Study participants will be 200 higher-risk older adults (age 70-89 years with subjective cognitive complaints, low normal performance on cognitive screen, and ≥ two modifiable risk factors targeted by our intervention) who will be recruited from selected primary care clinics of Kaiser Permanente Washington, oversampling people with non-white race or Hispanic ethnicity. Study participants will be randomly assigned to a two-year Alzheimer's risk reduction intervention (SMARRT) or a Health Education (HE) control. Randomization will be stratified by clinic, race/ethnicity (non-Hispanic white versus non-white or Hispanic), and age (70-79, 80-89). Participants randomized to the SMARRT group will work with a behavioral coach and nurse to develop a personalized plan related to their risk factors (poorly controlled hypertension, diabetes with evidence of hyper or hypoglycemia, depressive symptoms, poor sleep quality, contraindicated medications, physical inactivity, low cognitive stimulation, social isolation, poor diet, smoking). Participants in the HE control group will be mailed general health education information about these risk factors for AD. The primary outcome is two-year cognitive change on a cognitive test composite score. Secondary outcomes include: 1) improvement in targeted risk factors, 2) individual cognitive domain composite scores, 3) physical performance, 4) functional ability, 5) quality of life, and 6) incidence of mild cognitive impairment, AD, and dementia. Primary and secondary outcomes will be assessed in both groups at baseline and 6, 12, 18, and 24 months.

A study paradigm integrating prospective epidemiologic cohorts and electronic health records to identify disease biomarkers.

Defining the full spectrum of human disease associated with a biomarker is necessary to advance the biomarker into clinical practice. We hypothesize that associating biomarker measurements with electronic health record (EHR) populations based on shared genetic architectures would establish the clinical epidemiology of the biomarker. We use Bayesian sparse linear mixed modeling to calculate SNP weightings for 53 biomarkers from the Atherosclerosis Risk in Communities study. We use the SNP weightings to computed predicted biomarker values in an EHR population and test associations with 1139 diagnoses. Here we report 116 associations meeting a Bonferroni level of significance. A false discovery rate (FDR)-based significance threshold reveals more known and undescribed associations across a broad range of biomarkers, including biometric measures, plasma proteins and metabolites, functional assays, and behaviors. We confirm an inverse association between LDL-cholesterol level and septicemia risk in an independent epidemiological cohort. This approach efficiently discovers biomarker-disease associations.

Cumulative Antidepressant Use and Risk of Dementia in a Prospective Cohort Study.

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.

Proton pump inhibitor use and the risk of fractures among an older adult cohort.

PURPOSE: The purpose of the study is to determine if the use of a proton pump inhibitor (PPI) is associated with an increased fracture risk, as some prior studies have suggested. METHODS: This retrospective cohort study included data on 4438 participants aged 65 and older who had no fracture in the year prior to baseline and had ≥5 years of enrollment history in Kaiser Permanente Washington, an integrated healthcare delivery system in Seattle, WA, during 1994 to 2014. Time-varying cumulative exposure to PPIs was determined from automated pharmacy data by summing standard daily doses (SDDs) across fills, and patients were categorized as no use (reference group, ≤30 SDD), light use (31-540 SDD), moderate use (541-1080 SDD), and heavy use (≥1081 SDD). Incident fractures were assessed using International Classification of Diseases, Ninth Revision codes from electronic medical records. Potential confounders, chosen a priori, were assessed at baseline and at each 2-year follow-up visit. Fracture risk was analyzed using a Cox proportional hazards model. RESULTS: Over a mean follow-up of 6.1 years, 802 (18.1%) participants experienced a fracture. No overall association was found between PPI use and fracture risk. Adjusted hazard ratios comparing users to the referent category were 1.08 (95% CI 0.83-1.40) for light users, 1.31 (95% CI 0.86-1.95) for moderate users, and 0.95 (95% CI 0.68-1.34) for heavy users. Among patients with SSD > 30, no appreciable increase in fracture risk was present in persons with recent versus distant use (adjusted hazard ratio of 1.14 [95% CI 0.91-1.42]). CONCLUSIONS: No association was observed between PPI use and fracture risk among older adults.

Proton Pump Inhibitor Use and Dementia Risk: Prospective Population-Based Study.

OBJECTIVES: To determine whether higher cumulative proton pump inhibitor (PPI) exposure is associated with greater dementia risk. DESIGN: Prospective population-based cohort study. SETTING: Kaiser Permanente Washington, an integrated healthcare delivery system in Seattle, Washington. PARTICIPANTS: Individuals aged 65 and older without dementia at study entry (N = 3,484). MEASUREMENTS: Participants were screened for dementia every 2 years, and those who screened positive underwent extensive evaluation. Dementia outcomes were determined using standard diagnostic criteria. Time-varying PPI exposure was determined from computerized pharmacy data and consisted of total standardized daily doses (TSDDs) dispensed to an individual in the prior 10 years. We also assessed duration of use. Multivariable Cox regression was used to estimate the association between PPI exposure and time to dementia or Alzheimer's disease (AD). RESULTS: Over a mean follow-up of 7.5 years, 827 participants (23.7%) developed dementia (670 with possible or probable AD). PPI exposure was not associated with risk of dementia (P = .66) or AD (P = .77). For dementia, the risk for specific levels of cumulative exposure compared to no use was: 365 TSDDs (HR 0.87, 95% CI 0.65-1.18), 1,095 TSDDs (HR 0.99, CI 0.75-1.30) and 1,825 TSDDs (HR 1.13, CI 0.82-1.56). These TSDD levels represent approximately 1, 3 and 5 years of daily use respectively. Duration of PPI use was not associated with dementia outcomes either. CONCLUSION: Proton pump inhibitor use was not associated with dementia risk, even for people with high cumulative exposure. Although there are other safety concerns with long-term PPI use, results from our study do not support that these medications should be avoided out of concern about dementia risk.

Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study.

OBJECTIVE: To determine whether higher cumulative use of benzodiazepines is associated with a higher risk of dementia or more rapid cognitive decline. DESIGN: Prospective population based cohort. SETTING: Integrated healthcare delivery system, Seattle, Washington. PARTICIPANTS: 3434 participants aged ≥ 65 without dementia at study entry. There were two rounds of recruitment (1994-96 and 2000-03) followed by continuous enrollment beginning in 2004. MAIN OUTCOMES MEASURES: The cognitive abilities screening instrument (CASI) was administered every two years to screen for dementia and was used to examine cognitive trajectory. Incident dementia and Alzheimer's disease were determined with standard diagnostic criteria. Benzodiazepine exposure was defined from computerized pharmacy data and consisted of the total standardized daily doses (TSDDs) dispensed over a 10 year period (a rolling window that moved forward in time during follow-up). The most recent year was excluded because of possible use for prodromal symptoms. Multivariable Cox proportional hazard models were used to examine time varying use of benzodiazepine and dementia risk. Analyses of cognitive trajectory used linear regression models with generalized estimating equations. RESULTS: Over a mean follow-up of 7.3 years, 797 participants (23.2%) developed dementia, of whom 637 developed Alzheimer's disease. For dementia, the adjusted hazard ratios associated with cumulative benzodiazepine use compared with non-use were 1.25 (95% confidence interval 1.03 to 1.51) for 1-30 TSDDs; 1.31 (1.00 to 1.71) for 31-120 TSDDs; and 1.07 (0.82 to 1.39) for ≥ 121 TSDDs. Results were similar for Alzheimer's disease. Higher benzodiazepine use was not associated with more rapid cognitive decline. CONCLUSION: The risk of dementia is slightly higher in people with minimal exposure to benzodiazepines but not with the highest level of exposure. These results do not support a causal association between benzodiazepine use and dementia.

Anesthesia Exposure and Risk of Dementia and Alzheimer's Disease: A Prospective Study.

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.

Prescription Opioids and Risk of Dementia or Cognitive Decline: A Prospective Cohort Study.

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.

Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study.

IMPORTANCE: Many medications have anticholinergic effects. In general, anticholinergic-induced cognitive impairment is considered reversible on discontinuation of anticholinergic therapy. However, a few studies suggest that anticholinergics may be associated with an increased risk for dementia. OBJECTIVE: To examine whether cumulative anticholinergic use is associated with a higher risk for incident dementia. DESIGN, SETTING, AND PARTICIPANTS: Prospective population-based cohort study using data from the Adult Changes in Thought study in Group Health, an integrated health care delivery system in Seattle, Washington. We included 3434 participants 65 years or older with no dementia at study entry. Initial recruitment occurred from 1994 through 1996 and from 2000 through 2003. Beginning in 2004, continuous replacement for deaths occurred. All participants were followed up every 2 years. Data through September 30, 2012, were included in these analyses. EXPOSURES: Computerized pharmacy dispensing data were used to ascertain cumulative anticholinergic exposure, which was defined as the total standardized daily doses (TSDDs) dispensed in the past 10 years. The most recent 12 months of use was excluded to avoid use related to prodromal symptoms. Cumulative exposure was updated as participants were followed up over time. MAIN OUTCOMES AND MEASURES: Incident dementia and Alzheimer disease using standard diagnostic criteria. Statistical analysis used Cox proportional hazards regression models adjusted for demographic characteristics, health behaviors, and health status, including comorbidities. RESULTS: The most common anticholinergic classes used were tricyclic antidepressants, first-generation antihistamines, and bladder antimuscarinics. During a mean follow-up of 7.3 years, 797 participants (23.2%) developed dementia (637 of these [79.9%] developed Alzheimer disease). A 10-year cumulative dose-response relationship was observed for dementia and Alzheimer disease (test for trend, P < .001). For dementia, adjusted hazard ratios for cumulative anticholinergic use compared with nonuse were 0.92 (95% CI, 0.74-1.16) for TSDDs of 1 to 90; 1.19 (95% CI, 0.94-1.51) for TSDDs of 91 to 365; 1.23 (95% CI, 0.94-1.62) for TSDDs of 366 to 1095; and 1.54 (95% CI, 1.21-1.96) for TSDDs greater than 1095. A similar pattern of results was noted for Alzheimer disease. Results were robust in secondary, sensitivity, and post hoc analyses. CONCLUSIONS AND RELEVANCE: Higher cumulative anticholinergic use is associated with an increased risk for dementia. Efforts to increase awareness among health care professionals and older adults about this potential medication-related risk are important to minimize anticholinergic use over time.

Association of living alone and hospitalization among community-dwelling elders with and without dementia.

BACKGROUND: Older persons account for the majority of hospitalizations in the United States.1 Identifying risk factors for hospitalization among elders, especially potentially preventable hospitalization, may suggest opportunities to improve primary care. Certain factors-for example, living alone-may increase the risk for hospitalization, and their effect may be greater among persons with dementia and the old-old (aged 85+). OBJECTIVES: To determine the association of living alone and risk for hospitalization, and see if the observed effect is greater among persons with dementia or the old-old. DESIGN: Retrospective longitudinal cohort study. PARTICIPANTS: 2,636 participants in the Adult Changes in Thought (ACT) study, a longitudinal cohort study of dementia incidence. Participants were adults aged 65+ enrolled in an integrated health care system who completed biennial follow-up visits to assess for dementia and living situation. MAIN MEASURES: Hospitalization for all causes and for ambulatory care sensitive conditions (ACSCs) were identified using automated data. KEY RESULTS: At baseline, the mean age of participants was 75.5 years, 59 % were female and 36 % lived alone. Follow-up time averaged 8.4 years (SD 3.5), yielding 10,431 approximately 2-year periods for analysis. Living alone was positively associated with being aged 85+, female, and having lower reported social support and better physical function, and negatively associated with having dementia. In a regression model adjusted for age, sex, comorbidity burden, physical function and length of follow-up, living alone was not associated with all-cause (OR = 0.93; 95 % CI 0.84, 1.03) or ambulatory care sensitive condition (ACSC) hospitalization (OR = 0.88; 95 % CI 0.73, 1.07). Among participants aged 85+, living alone was associated with a lower risk for all-cause (OR = 0.76; 95 % CI 0.61, 0.94), but not ACSC hospitalization. Dementia did not modify any observed associations. CONCLUSION: Living alone in later life did not increase hospitalization risk, and in this population may be a marker of healthy aging in the old-old.

Sustaining Research Networks: the Twenty-Year Experience of the HMO Research Network.

PURPOSE: As multi-institutional research networks assume a central role in clinical research, they must address the challenge of sustainability. Despite its importance, the concept of network sustainability has received little attention in the literature, and the sustainability strategies of durable scientific networks have not been described. INNOVATION: The Health Maintenance Organization Research Network (HMORN) is a consortium of 18 research departments in integrated health care delivery systems with over 15 million members in the United States and Israel. The HMORN has coordinated federally funded scientific networks and studies since 1994. This case study describes the HMORN approach to sustainability, proposes an operational definition of network sustainability, and identifies 10 essential elements that can enhance sustainability. CREDIBILITY: The sustainability framework proposed here is drawn from prior publications on organizational issues by HMORN investigators and from the experience of recent HMORN leaders and senior staff. CONCLUSION AND DISCUSSION: Network sustainability can be defined as (1) the development and enhancement of shared research assets to facilitate a sequence of research studies in a specific content area or multiple areas, and (2) a community of researchers and other stakeholders who reuse and develop those assets. Essential elements needed to develop the shared assets of a network include: network governance; trustworthy data and processes for sharing data; shared knowledge about research tools; administrative efficiency; physical infrastructure; and infrastructure funding. The community of researchers within a network is enhanced by: a clearly defined mission, vision and values; protection of human subjects; a culture of collaboration; and strong relationships with host organizations. While the importance of these elements varies based on the membership and goals of a network, this framework for sustainability can enhance strategic planning within the network and can guide relationships with external stakeholders.

Neuropathologic changes associated with atrial fibrillation in a population-based autopsy cohort.

BACKGROUND: Atrial fibrillation (AF) is associated with higher risk of dementia and Alzheimer's disease. To better understand the mechanism, we examined neuropathologic changes seen with AF. METHODS: We analyzed data from an autopsy series arising from a population-based, prospective cohort study set within Group Health, an integrated health care delivery system. Participants were people aged 65 and older, community-dwelling, and nondemented at study enrollment, who died during follow-up and underwent autopsy. AF was defined from medical records. Permanent AF was defined as having two or more electrocardiograms showing AF between 6 and 36 months apart with no evidence of sinus rhythm in between. The primary study outcomes were gross infarcts, neuritic plaques, and neurofibrillary tangles, ascertained using consensus guidelines. Adjusted relative risks and 95% CIs were calculated using modified Poisson regression, weighted to account for selection into the autopsy cohort. RESULTS: Three hundred and twenty-eight participants underwent autopsy; 134 (41%) had AF. People with AF were more likely to have gross infarcts than those without AF (45% vs 31%; relative risk 1.82, 95% CI 1.23-2.71); in 30%, these infarcts were not clinically recognized before death. Alzheimer's disease neuropathologic changes were not associated with ever having AF but were more common in people with permanent AF. Adjusted relative risks for frequent neuritic plaques and neurofibrillary tangles were 1.47 (0.96-2.28) and 1.40 (0.79-2.49), respectively, for people with permanent AF versus no AF. CONCLUSIONS: AF is associated with gross infarcts. Permanent AF may contribute to Alzheimer's disease neuropathologic changes, but more study is needed.