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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., (© 2021 The American Geriatrics Society.)

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., (© 2019 The American Geriatrics Society.)

Objectives: To evaluate associations between high-density lipoprotein cholesterol (HDL) and non-HDL-C levels at specific ages and subsequent Alzheimer's disease (AD) risk., Design: Prospective population-based cohort study., Setting: Adult Changes in Thought (ACT) Study., Participants: Individuals aged 65 and older with no dementia at ACT Study entry. We identified separate, partially overlapping subcohorts of ACT participants who were eligible for each age band-specific analysis (50-59, n = 1,088; 60-69, n = 2,852; 70-79, n = 2,344; 80-89, n = 537)., Measurements: Exposure consisted of clinical measures of total cholesterol (TC) and HDL-C from laboratory data during a given age band. Outcomes of incident AD were assessed post-age band using standard research diagnostic criteria. Statistical analyses used adjusted Cox proportional hazards regression models for each exposure and outcome pair within an age band. Cholesterol exposures were modeled using cubic splines., Results: For non-HDL-C, we found a statistically significant association with AD risk in the 60 to 69 (omnibus p = .005) and 70 to 79 (omnibus p = .04) age bands, suggesting a potential U-shaped relationship (greater risk at low and high levels). For example, in people aged 60 to 69, those with an average non-HDL-C level of 120 mg/DL had a 29% greater AD hazard (hazard ratio (HR)=1.29, 95% confidence interval (CI)=1.04-1.61) than those with an average non-HDL-C level of 160 mg/dL, whereas those with an average non-HDL-C level of 210 mg/dL had a 16% greater hazard (HR=1.16, 95% CI=1.01-1.33). We did not find a statistically significant association between HDL-C and AD risk., Conclusion: People with low (120 mg/dL) and high (210 mg/dL) non-HDL-C levels during their 60s and 70s had modestly higher risk of AD than those with intermediate (160 mg/dL) levels. The extreme age bands (50s and 80s) had small sample sizes. J Am Geriatr Soc 66:2344-2352, 2018., (© 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.)

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., (© 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.)

Objectives: To develop three prognostic indices of varying degree of required detail for 2-year pneumonia risk in older adults., Design: Retrospective cohort study., Setting: Group Health (GH), an integrated healthcare delivery system., Participants: Community-dwelling dementia-free individuals aged 65 and older who had been GH members for at least 2 years before start of follow-up and were enrolled in the Adult Changes in Thought study (N = 3,375; development cohort, n = 2,250; validation cohort, n = 1,125., Measurements: Potential pneumonia risk factors were identified from questionnaire data and interviewer assessments of functional status, medical history, smoking and alcohol use, cognitive function, personal care, and problem solving. Risk factors were also identified based on physical measures such as grip strength and gait speed and administrative database information on comorbid illnesses, laboratory tests, and prescriptions dispensed. Incident community-acquired pneumonia was defined presumptively from administrative data and validated using medical record review., Results: Participants (59% female) contributed 12,998 visits at which risk factors were assessed; 642 pneumonia events were observed during follow-up. Age, sex, chronic obstructive pulmonary disease, congestive heart failure, body mass index, and use of inhaled or oral corticosteroids were critical predictors in all prognostic indices. A risk score based on these seven variables, information on which is commonly available in electronic medical records (EMRs), had equal or better performance (c-index = 0.69 in the validation cohort) than scores including more-detailed data such as functional status., Conclusion: Data commonly available in EMRs can stratify older adults into groups with varying subsequent 2-year pneumonia risk., (© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.)

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., (© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.)

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., (© 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.)

Objectives: To determine whether use of anticholinergics is associated with risk of community-acquired pneumonia in older adults., Design: Population-based case-control study., Setting: An integrated healthcare delivery system in Washington State., Participants: Data from a nested case-control study of community-dwelling immunocompetent adults aged 65 to 94 were analyzed. Pneumonia cases (n=1,039) were ascertained according to International Classification of Diseases, Ninth Revision, codes from 2000 to 2003 and validated using chart review. Controls (n=2,022) were matched 2:1 to cases according to age, sex, and year., Measurements: Anticholinergic medication exposure was ascertained using prescription data; acute use was defined as one or more prescription fills 90 days or less before the index date (date of pneumonia diagnosis), past use was defined as one or more prescription fills within the prior year but none within 90 days, and chronic use was defined as three or more prescription fills within the prior year. The reference group was those with no fills in the prior year. Conditional logistic regression was used to analyze the association between anticholinergic use and pneumonia, adjusted for comorbidities., Results: Acute use of anticholinergics was observed in 59% of cases and 35% of controls (adjusted odds ratio (aOR)=2.55, 95% confidence interval (CI)=2.08-3.13) and past use in 17% of cases and 23% of controls (aOR=1.19, 95% CI=0.92-1.53). Chronic use of anticholinergics was observed in 53% of cases and 36% of controls (aOR 2.07, 95% CI=1.68-2.54). Results were not different for high- and low-potency anticholinergic medications., Conclusion: In older adults, anticholinergic medication use is associated with pneumonia risk, adding to substantial evidence suggesting that these medications are high risk., (© 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.)

Objectives: To evaluate the association between dynamic measures of renal function ascertained over time and onset of dementia., Design: Prospective community cohort study., Setting: Group Health, Seattle, Washington., Participants: Two thousand nine hundred sixty-eight adults aged 65 and older followed for the development of dementia over a median of 6.0 years (interquartile range 3.1-10.1 years)., Measurements: Time-varying measures of renal function were constructed based on 49,340 serum creatinine measurements and included average estimated glomerular filtration rate (eGFR), eGFR trajectory, and variability in eGFR around this trajectory over 5-year exposure windows. The association between these three eGFR exposure measures and risk of dementia was estimated using a Cox regression model adjusted for other participant characteristics. Time-varying measures of urine protein by dipstick were also adjusted for in sensitivity analyses., Results: Participants with a lower eGFR had a higher incidence of dementia, but this did not reach statistical significance in adjusted analyses (omnibus P = .14). There were trends toward a higher adjusted incidence of dementia in participants with positive eGFR trajectories (omnibus P = .07) and greater variability in eGFR (omnibus P = .04) over time. The results of sensitivity analyses, including those in which time-varying measures of proteinuria were included, were consistent with those of the primary analysis., Conclusion: In a community cohort of older adults followed for a median of 6 years, strong associations were not found between measures of kidney disease severity and progression and incident dementia., (© 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.)

Objectives: To examine whether use of opioids or benzodiazepines is associated with risk of community-acquired pneumonia in older adults., Design: Population-based case-control study., Setting: An integrated healthcare delivery system., Participants: Community-dwelling, immunocompetent adults aged 65 to 94 from 2000 to 2003. Presumptive pneumonia cases were identified from health plan automated data and validated through medical record review. Two controls were selected for each case with pneumonia, matched on age, sex, and calendar year., Measurements: Information about opioid and benzodiazepine use came from computerized pharmacy data. Information on covariates including comorbid illnesses and functional and cognitive status came from medical record review and electronic health data., Results: One thousand thirty-nine validated cases of pneumonia and 2,022 matched controls were identified. One hundred forty-four (13.9%) cases and 161 (8.0%) controls used prescription opioids (adjusted odds ratio (OR) = 1.38, 95% confidence interval (CI) = 1.08-1.76 vs nonuse). Risk was highest for opioids categorized as immunosuppressive based on immunological studies (OR = 1.88, 95% CI = 1.26-1.79 vs nonuse), whereas for nonimmunosuppressive opioids the OR was 1.23 (95% CI = 0.89-1.69). Risk was highest in the first 14 days of use (OR = 3.24, 95% CI = 1.64-6.39 vs nonuse). For long-acting opioids, the OR was 3.43 (95% CI = 1.44-8.21) versus nonuse, whereas for short-acting opioids, it was 1.27 (95% CI = 0.98-1.64). No greater risk was seen for current benzodiazepine use compared to nonuse (OR = 1.08, 95% CI = 0.80-1.47)., Conclusion: Use of opioids but not benzodiazepines was associated with pneumonia risk. The differences in risk seen for different opioid regimens warrant further study., (© 2011, Copyright the Authors Journal compilation © 2011, The American Geriatrics Society.)

Objectives: To examine whether histamine-2 receptor antagonist medications (H2RAs) are associated with a lower incidence of all-cause dementia or Alzheimer's disease (AD), as some studies have suggested., Design: Prospective population-based cohort, Setting: Group Health, an integrated health maintenance organization, Seattle, Washington., Participants: Two thousand nine hundred twenty-three participants aged 65 and older without dementia at baseline, with initial recruitment between 1994 and 1996., Measurements: Follow-up occurred every 2 years to identify incident dementia and AD using standard criteria. Exposure to H2RAs was determined based on automated pharmacy data. Three aspects of exposure (time-varying) were examined based on standard daily dose (SDD): cumulative use, intensity of use (highest SDD in any prior 2-year window), and cumulative use stratified according to recency (1-3 years vs >3 years before)., Results: Over a mean follow-up of 6.7 years, 585 subjects developed dementia (453 developed AD). Total cumulative exposure was not associated with dementia (P=.35; omnibus test) or AD (P=.23). The adjusted hazard ratios for the highest exposure category (>1,080 SDDs) compared with light or no use were 1.28 (95% confidence interval (CI)=0.95-1.72) for dementia and 1.41 (95% CI=1.00-1.97) for AD. Intensity of use was not associated with dementia (P=.39) or AD (P=.63). Examining exposure according to recent and distant cumulative use also showed no association with dementia (P=.11) or AD (P=.30)., Conclusion: No association was found between H2RA use and risk of all-cause dementia or AD using more-detailed and -extensive information about past H2RA use than any prior study., (© 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.)