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BACKGROUND/OBJECTIVES There are growing concerns about the safety and efficacy of psychotropic medications in Alzheimer's disease (AD). We sought to examine associations between psychotropic medication exposure and longitudinal change in cognitive, functional, and neuropsychiatric outcomes in a large clinical AD cohort. DESIGN Longitudinal observational study. SETTING National Alzheimer's Disease Coordinating Center combining data from 39 Alzheimer's disease centers. PARTICIPANTS 8,034 participants with AD dementia. MEASUREMENTS Mini‐Mental State Exam (MMSE), Clinical Dementia Rating Scale‐Sum of Boxes (CDR‐SB), and Neuropsychiatric Inventory Questionnaire (NPI‐Q) Total. Probability of exposure to medication (the propensity score, PS) calculated via logistic regression. Medication classes included all antipsychotics (atypical vs conventional), antidepressants (Selective Serotonin Reuptake Inhibitor [SSRI] vs non‐SSRI), and benzodiazepines. Participants treated with a medication class were matched with participants not treated with that class with the closest‐matched PS. The effect of medication treatment was assessed using linear mixed‐effects models. RESULTS: Participants had a mean (SD) age of 75.5 (9.8) years, and mean (SD) scores of MMSE 21.3 (5.7), CDR‐SB 5.5 (3.4), and NPI‐Q Total 4.5 (4.4). Mean duration of follow‐up was 2.9–3.3 years depending on medication class. Non‐SSRI antidepressant use was associated with better CDR‐SB (2‐year difference in change‐DIC: −0.38 [−0.61, −0.15], P =.001). Atypical antipsychotic use was associated with greater decline on MMSE (DIC: −0.91 [−1.54, −0.28] P =.005) and CDR‐SB scores (DIC: 0.50 [0.14, 0.86], P =.006). Notably, no drug class was associated with better NPI‐Q scores. CONCLUSIONS: Use of atypical antipsychotics was associated with poorer cognition and function, and no drug class was associated with improvement in neuropsychiatric symptoms. [ABSTRACT FROM AUTHOR]

Objectives: Postoperative delirium, associated with negative consequences including longer hospital stays and worse cognitive and physical outcomes, is frequently accompanied by sleep-wake disturbance. Our objective was to evaluate the efficacy and short-term safety of ramelteon, a melatonin receptor agonist, for the prevention of postoperative delirium in older patients undergoing orthopedic surgery.Design: A quadruple-masked randomized placebo-controlled trial (Clinical Trials.gov NCT02324153) conducted from March 2017 to June 2019.Setting: Tertiary academic medical center.Participants: Patients aged 65 years or older, undergoing elective primary or revision hip or knee replacement.Intervention: Ramelteon (8 mg) or placebo MEASUREMENTS: Eighty participants were randomized to an oral gel cap of ramelteon or placebo for 3 consecutive nights starting the night before surgery. Trained research staff conducted delirium assessments for 3 consecutive days starting on postoperative day (POD) 0, after recovery from anesthesia, and on to POD2. A delirium diagnosis was based upon DSM-5 criteria determined by expert panel consensus.Results: Of 80 participants, five withdrew consent (one placebo, four ramelteon) and four were excluded (four ramelteon) after randomization. Delirium incidence during the 2 days following surgery was 7% (5 of 71) with no difference between the ramelteon versus placebo: 9% (3 of 33) and 5% (2 of 38), respectively. The adjusted odds ratio for postoperative delirium as a function of assignment to the ramelteon treatment arm was 1.28 (95% confidence interval: 0.21-7.93; z-value 0.27; p-value = 0.79). Adverse events were similar between the two groups.Conclusion: In older patients undergoing elective primary or revision hip or knee replacement, ramelteon was not efficacious in preventing postoperative delirium. [ABSTRACT FROM AUTHOR]

BACKGROUND: There are few studies demonstrating how kidney function affects the risk of developing delirium in older adult surgical patients administered opioids. This study determined whether baseline kidney function influences the relationship between morphine equivalent dose and the development of delirium on postoperative day (POD) 2 in patients with hip fracture. METHODS: This retrospective study analyzed emergency department (ED) estimated glomerular filtration rate (eGFR), perioperative serum creatinine, intravenous morphine equivalents, and POD2 delirium assessment by the Confusion Assessment Method in 652 patients aged 65 years or older without preoperative delirium. ED eGFR was used to divide subjects into groups by presence or absence of chronic kidney disease (CKD), and associations of opioid dose with POD2 delirium were compared using multivariable logistic regression. RESULTS: POD2 delirium incidence was 29.8% (N = 194). Intraoperative and postanesthesia care unit (PACU) morphine equivalent dosage as well as ED eGFR were similar comparing patients with and without POD2 delirium. Age, American Society of Anesthesiologists status, and dementia were associated with delirium on POD2. The odds of POD2 delirium increased significantly with increase of intraoperative opioid in patients with CKD (odds ratio = 1.6; 95% confidence interval = 1.2–2.2), but not in patients without CKD (P‐interaction =.04). PACU or POD1 opioid doses were not associated with POD2 delirium after covariate adjustment. CONCLUSION: This study suggests that incremental increases in intraoperative opioids combined with CKD increase odds of POD2 delirium after hip fracture repair, compared with patients without CKD. [ABSTRACT FROM AUTHOR]

Introduction: The interaction between delirium and dementia is complex. We examined if Alzheimer’s disease (AD) biomarkers in patients without clinical dementia are associated with increased risk of postoperative delirium, and whether AD biomarkers demonstrate a graded association with delirium severity. Methods: Participants (n = 59) were free of clinical dementia, age ≥70 years, and scheduled for elective total knee or hip arthroplasties. Cerebrospinal fluid (CSF) was collected at the time of induction for spinal anesthesia. CSF AD biomarkers were measured by enzyme-linked immunosorbent assay (ELISA) (ADX/Euroimmun); cut points for amyloid, tau, and neurodegeneration (ATN) biomarker status wereA = amyloid beta (Aβ)42 <175 pg/mL or Aβ42/40 ratio <0.07; T = p-tau >80 pg/mL; and N = t-tau >700 pg/mL. Confusion Assessment Method (CAM) and CAM-Severity (CAM-S) were rated daily post-operatively for delirium and delirium severity, respectively. Results: Aβ42, tau, and p-tau mean pg/mL (SD) were 361.5 (326.1), 618.3 (237.1), and 97.1 (66.1), respectively, for those with delirium, and 550.4 (291.6), 518.3 (213.5), and 54.6 (34.5), respectively, for those without delirium. Thirteen participants (22%) were ATN positive. Delirium severity by peak CAM-S [mean difference (95% confidence interval)] was 1.48 points higher (0.29-2.67), P = 0.02 among the ATN positive. Delirium in the ATN-positive group trended toward but did not reach statistical significance (23% vs. 7%, p = 0.10). Peak CAM-S [mean (SD)] in the delirium group was 7 (2.8) compared to no delirium group 2.5 (1.3), but when groups were further classified by ATN status, an incremental effect on delirium severity was observed, such that patients who were both ATN and delirium negative had the lowest mean (SD) peak CAM-S scores of 2.5 (1.3) points, whereas those who were ATN and delirium positive had CAM-S scores of 8.7 (2.3) points; other groups (either ATN or delirium positive) had intermediate CAM-S scores. Discussion: The presence of AD biomarkers adds important information in predicting delirium severity. Future studies are needed to confirm this relationship and to better understand the role of AD biomarkers, even in pre-clinical phase, in delirium. [ABSTRACT FROM AUTHOR]

Background: This study determined whether the relationship between predicted propofol effect site concentration (Ce) and observer's assessment of alertness/sedation scale (OAA/S) or Bispectral Index (BIS) was similar comparing cognitively intact vs impaired patients undergoing hip fracture repair with spinal anesthesia and sedation. Methods: Following informed consent baseline mini-mental status exam (MMSE), Clinical Dementia Rating (CDR) and geriatric depression scale (GDS) were obtained. Intraoperatively OAA/S, BIS, and propofol (timing and exact amounts) administered were recorded. Cerebrospinal fluid was collected for Alzheimer's (AD) biomarkers. Mean Ce level (AvgCe) during surgery was calculated using the area under the Ce measurement series from incision to closure, divided by surgical time. Average OAA/S (AvgOAA/S), and BIS (AvgBIS) were similarly calculated. Pearson correlations of AvgCe with AvgOAA/S and AvgBIS were calculated overall and by CDR. Nonparametric locally weighted scatterplot smoothing (LOWESS) fits of AvgOAA/S and AvgBIS on AvgCe were produced, stratified by CDR. Multivariable regression incorporating baseline cognitive measurements or AD biomarkers assessed AvgOAA/S or AvgBIS associations with AvgCe. Results: In 186 participants AvgBIS and AvgOAA/S correlated with AvgCe (Pearson ρ = − 0.72; p < 0.0001 and Pearson ρ = − 0.81; p < 0.0001, respectively), and remained unchanged across CDR levels. Association patterns of AvgOAA/S or AvgBIS on AvgCe guided by LOWESS fits and modeled through regression, were similar when stratified by CDR (p = 0.16). Multivariable modeling found no independent effect on AvgBIS or AvgOAA/S by MMSE, CDR, GDS, or AD biomarkers after accounting for AvgCe. Conclusions: When administering sedation in conjunction with spinal anesthesia, cognitive impairment does not affect the relationship between predicted propofol AvgCe and AvgOAA/S or AvgBIS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]