Publications

BACKGROUND: Older surgical patients with Alzheimer's disease (AD) dementia and delirium are at increased risk for accelerated long-term cognitive decline.

OBJECTIVE: Investigate associations between a probabilistic marker of preclinical AD, delirium, and long-term cognitive decline.

METHODS: The Successful Aging after Elective Surgery cohort includes older adults (≥70 years) without dementia who underwent elective surgery. 140 patients underwent preoperative magnetic resonance imaging and had≥6 months cognitive follow-up. Cortical thickness was measured in 'AD-Signature' regions. Delirium was evaluated each postoperative day by the Confusion Assessment Method. Cognitive performance was assessed using a detailed neuropsychological battery at baseline; months 1, 2, and 6; and every 6 months thereafter until 36 months. Using either a General Cognitive Performance composite (GCP) or individual test scores as outcomes, we performed linear mixed effects models to examine main effects of AD-signature atrophy and the interaction of AD-signature atrophy and delirium on slopes of cognitive change from post-operative months 2-36.

RESULTS: Reduced baseline AD-signature cortical thickness was associated with greater 36-month cognitive decline in GCP (standardized beta coefficient, β = -0.030, 95% confidence interval [-0.060, -0.001]). Patients who developed delirium who also had thinner AD signature cortex showed greater decline on a verbal learning test (β = -0.100 [-0.192, -0.007]).

CONCLUSION: Patients with the greatest baseline AD-related cortical atrophy who develop delirium after elective surgery appear to experience the greatest long-term cognitive decline. Thus, atrophy suggestive of preclinical AD and the development of delirium may be high-risk indicators for long-term cognitive decline following surgery.

OBJECTIVES: We examined the association between delirium severity and outcomes of delirium among persons with and without Alzheimer's disease and related dementias (ADRD).

DESIGN: Prospective cohort study.

SETTING: Academic tertiary medical center.

PARTICIPANTS: A total of 352 medical and surgical patients.

MEASUREMENTS: Delirium incidence and severity were rated daily using the Confusion Assessment Method (CAM) and CAM-Severity (CAM-S) score during hospitalization. Severe delirium was defined as a CAM-S Short Form score in the highest tertile (3-7 points out of 7). ADRD status was determined by a clinical consensus process. Clinical outcomes included prolonged length of stay (>6 d), discharge to post-acute nursing facility, any decline in activities of daily living (ADLs) at 1 month from prehospital baseline, ongoing nursing facility stay, and mortality.

RESULTS: Patients with ADRD (n = 85 [24%]) had a significantly higher relative risk (RR) for incident delirium (RR = 2.31; 95% confidence interval [CI] = 1.64-3.28) and higher peak CAM-S scores (mean difference = 1.24 points; CI = .83-1.65; P < .001). Among patients with ADRD, severe delirium significantly increased the RR for nursing facility stay (RR = 2.22; CI = 1.05-4.69; P = .04) and increased the RR for mortality (RR = 2.10; CI = .89-4.98; P = .09). Among patients without ADRD, severe delirium was associated with a significantly increased risk for all poor outcomes except mortality including prolonged length of stay in the hospital (RR = 1.47; CI = 1.18-1.82) and discharge to a post-acute nursing facility (RR = 2.17; CI = 1.58-2.98) plus decline in ADLs (RR = 1.30; CI = 1.05-1.60) and nursing facility stay at 1 month (RR = 1.93; CI = 1.31-2.83).

CONCLUSION: Severe delirium is associated with increased risk for poor clinical outcomes in patients with and without ADRD. In both groups, severe delirium increased risk of nursing home placement. In patients with ADRD, delirium was more severe and associated with a trend toward increased mortality at 1 month. Although the increased risk remains substantial by RR, the study had limited power to examine the rarer outcome of death. J Am Geriatr Soc 68:1722-1730, 2020.

Delirium is an acute disorder of attention and cognition. It occurs across the life span, yet it is particularly common among older adults, and is closely linked with underlying neurocognitive disorders. Evidence is mounting that intervening on delirium may represent an important opportunity for delaying the onset or progression of dementia. To accelerate the current understanding of delirium, the Network for Investigation of Delirium: Unifying Scientists (NIDUS) held a conference "Advancing Delirium Research: A Scientific Think Tank" in June 2019. This White Paper encompasses the major knowledge and research gaps identified at the conference: advancing delirium definition and measurement, understanding delirium pathophysiology, and prevention and treatment of delirium. A roadmap of research priorities is proposed to advance the field in a systematic, interdisciplinary, and coordinated fashion. A call is made for an international consortium and biobank targeted to delirium, as well as a public health campaign to advance the field.

IMPORTANCE: Guidelines recommend that women 75 years and older be informed of the benefits and harms of mammography before screening.

OBJECTIVE: To test the effects of receipt of a paper-based mammography screening decision aid (DA) for women 75 years and older on their screening decisions.

DESIGN, SETTING, AND PARTICIPANTS: A cluster randomized clinical trial with clinician as the unit of randomization. All analyses were completed on an intent-to-treat basis. The setting was 11 primary care practices in Massachusetts or North Carolina. Of 1247 eligible women reached, 546 aged 75 to 89 years without breast cancer or dementia who had a mammogram within 24 months but not within 6 months and saw 1 of 137 clinicians (herein referred to as PCPs) from November 3, 2014, to January 26, 2017, participated. A research assistant (RA) administered a previsit questionnaire on each participant's health, breast cancer risk factors, sociodemographic characteristics, and screening intentions. After the visit, the RA administered a postvisit questionnaire on screening intentions and knowledge.

INTERVENTIONS: Receipt of the DA (DA arm) or a home safety (HS) pamphlet (control arm) before a PCP visit.

MAIN OUTCOMES AND MEASURES: Participants were followed up for 18 months for receipt of mammography screening (primary outcome). To examine the effects of the DA, marginal logistic regression models were fit using generalized estimating equations to allow for clustering by PCP. Adjusted probabilities and risk differences were estimated to account for clustering by PCP.

RESULTS: Of 546 women in the study, 283 (51.8%) received the DA. Patients in each arm were well matched; their mean (SD) age was 79.8 (3.7) years, 428 (78.4%) were non-Hispanic white, 321 (of 543 [59.1%]) had completed college, and 192 (35.2%) had less than a 10-year life expectancy. After 18 months, 9.1% (95% CI, 1.2%-16.9%) fewer women in the DA arm than in the control arm had undergone mammography screening (51.3% vs 60.4%; adjusted risk ratio, 0.84; 95% CI, 0.75-0.95; P = .006). Women in the DA arm were more likely than those in the control arm to rate their screening intentions lower from previsit to postvisit (69 of 283 [adjusted %, 24.5%] vs 47 of 263 [adjusted %, 15.3%]), to be more knowledgeable about the benefits and harms of screening (86 [adjusted %, 25.5%] vs 32 [adjusted %, 11.7%]), and to have a documented discussion about mammography with their PCP (146 [adjusted %, 47.4%] vs 111 [adjusted %, 38.9%]). Almost all women in the DA arm (94.9%) would recommend the DA.

CONCLUSIONS AND RELEVANCE: Providing women 75 years and older with a mammography screening DA before a PCP visit helps them make more informed screening decisions and leads to fewer women choosing to be screened, suggesting that the DA may help reduce overscreening.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02198690.

BACKGROUND: Postoperative delirium is associated with adverse postoperative outcomes. However, whether intravenous and inhalation anesthetics are associated with different risks of postoperative delirium remains unknown.

OBJECTIVE: We set up to determine the incidence and duration of postoperative delirium in older patients who had surgery under the intravenous anesthetic propofol or the inhalational anesthetic sevoflurane.

METHODS: Participants were patients who had total hip/knee replacements and were randomized to propofol (N = 106) or sevoflurane (N = 103) anesthesia group. The Confusion Assessment Method was employed by investigators who were blinded to the anesthesia regimen to assess the incidence and duration (days of postoperative delirium per person) of postoperative delirium on postoperative days 1, 2, and 3.

RESULTS: A total of 209 participants (71.2±6.7 years old, 29.2% male) were included in the final data analysis. The incidence of postoperative delirium was 33.0% with propofol anesthesia and 23.3% with sevoflurane anesthesia (p = 0.119, Chi-square test), and we estimated that we would need 316 participants in each arm to detect a potential statistically significant difference. Days of postoperative delirium per person were higher in the propofol (0.5±0.8) anesthesia group compared to the sevoflurane anesthesia group (0.3±0.5, p = 0.049, Student's t-test).

CONCLUSION: This pilot study established a system to compare effects of different anesthetics and generated a hypothesis that propofol trended to have a higher incidence and had longer duration of postoperative delirium than sevoflurane. Additional studies with a larger sample size are needed to test this hypothesis.

BACKGROUND: Delirium is a common and preventable geriatric syndrome. Moving beyond the binary classification of delirium present/absent, delirium severity represents a potentially important outcome for evaluating preventive and treatment interventions and tracking the course of patients. Although several delirium severity assessment tools currently exist, most have been developed in the absence of advanced measurement methodology and have not been evaluated with rigorous validation studies.

OBJECTIVE: We aimed to report our development of new delirium severity items and the results of item reduction and selection activities guided by psychometric analysis of data derived from a field study.

METHODS: Building on our literature review of delirium instruments and expert panel process to identify domains of delirium severity, we adapted items from existing delirium severity instruments and generated new items. We then fielded these items among a sample of 352 older hospitalized patients.

RESULTS: We used an expert panel process and psychometric data analysis techniques to narrow a set of 303 potential items to 17 items for use in a new delirium severity instrument. The 17-item set demonstrated good internal validity and favorable psychometric characteristics relative to comparator instruments, including the Confusion Assessment Method - Severity (CAM-S) score, the Delirium Rating Scale Revised 98, and the Memorial Delirium Assessment Scale.

CONCLUSION: We more fully conceptualized delirium severity and identified characteristics of an ideal delirium severity instrument. These characteristics include an instrument that is relatively quick to administer, is easy to use by raters with minimal training, and provides a severity rating with good content validity, high internal consistency reliability, and broad domain coverage across delirium symptoms. We anticipate these characteristics to be represented in the subsequent development of our final delirium severity instrument.

BACKGROUND/OBJECTIVES: Dementia is associated with higher healthcare expenditures, in large part due to increased hospitalization rates relative to patients without dementia. Data on contemporary trends in the incidence and outcomes of potentially preventable hospitalizations of patients with dementia are lacking.

DESIGN: Retrospective cohort study using the National Inpatient Sample from 2012 to 2016.

SETTING: U.S. acute care hospitals.

PARTICIPANTS: A total of 1,843,632 unique hospitalizations of older adults (aged ≥65 years) with diagnosed dementia.

MEASUREMENTS: Annual trends in the incidence of hospitalizations for all causes and for potentially preventable conditions including acute ambulatory care sensitive conditions (ACSCs), chronic ACSCs, and injuries. In-hospital outcomes including mortality, discharge disposition, and hospital costs.

RESULTS: The survey weighted sample represented an estimated 9.27 million hospitalizations for patients with diagnosed dementia (mean [standard deviation] age = 82.6 [6.7] years; 61.4% female). In total, 3.72 million hospitalizations were for potentially preventable conditions (40.1%), 2.07 million for acute ACSCs, .76 million for chronic ACSCs, and .89 million for injuries. Between 2012 and 2016, the incidence of all-cause hospitalizations declined from 1.87 million to 1.85 million per year (P = .04) while the incidence of potentially preventable hospitalizations increased from .75 million to .87 million per year (P < .001), driven by an increased number of hospitalizations of community-dwelling older adults. Among patients with dementia hospitalized for potentially preventable conditions, inpatient mortality declined from 6.4% to 6.1% (P < .001), inflation-adjusted median costs increased from $7,319 to $7,543 (P < .001), and total annual costs increased from $7.4 to $9.3 billion. Although 86.0% of hospitalized patients were admitted from the community, only 32.7% were discharged to the community.

CONCLUSION: The number of potentially preventable hospitalizations of older adults with dementia is increasing, driven by hospitalizations of community-dwelling older adults. Improved strategies for early detection and goal-directed treatment of potentially preventable conditions in patients with dementia are urgently needed. J Am Geriatr Soc 68:2240-2248, 2020.

Major surgery is associated with a systemic inflammatory cascade that is thought, in some cases, to contribute to transient and/or sustained cognitive decline, possibly through neuroinflammatory mechanisms. However, the relationship between surgery, peripheral and central nervous system inflammation, and post-operative cognitive outcomes remains unclear in humans, primarily owing to limitations of in vivo biomarkers of neuroinflammation which vary in sensitivity, specificity, validity, and reliability. In the present study, [11C]PBR28 positron emission tomography, cerebrospinal fluid (CSF), and blood plasma biomarkers of inflammation were assessed pre-operatively and 1-month post-operatively in a cohort of patients (N = 36; 30 females; ≥70 years old) undergoing major orthopedic surgery under spinal anesthesia. Delirium incidence and severity were evaluated daily during hospitalization. Whole-brain voxel-wise and regions-of-interest analyses were performed to determine the magnitude and spatial extent of changes in [11C]PBR28 uptake following surgery. Results demonstrated that, compared with pre-operative baseline, [11C]PBR28 binding in the brain was globally downregulated at 1 month following major orthopedic surgery, possibly suggesting downregulation of the immune system of the brain. No significant relationship was identified between post-operative delirium and [11C]PBR28 binding, possibly due to a small number (n = 6) of delirium cases in the sample. Additionally, no significant relationships were identified between [11C]PBR28 binding and CSF/plasma biomarkers of inflammation. Collectively, these results contribute to the literature by demonstrating in a sizeable sample the effect of major surgery on neuroimmune activation and preliminary evidence identifying no apparent associations between [11C]PBR28 binding and fluid inflammatory markers or post-operative delirium.