PURPOSE:(1) To describe cognitive trajectory patterns over 6 years after major surgery in older adults, and (2) To identify patient characteristics associated with severe cognitive decline. METHODS:Group-based semiparametric trajectory modeling was performed on longitudinal cognitive data from the SAGES study, which enrolled patients aged ≥ 70 years undergoing major elective noncardiac surgery. Participants received comprehensive neuropsychological testing prior to surgery and postoperatively every 6-12 months up to 72 months. The primary outcome was change in general cognitive performance score, a composite of neuropsychological tests, at each of 11 follow-up timepoints relative to baseline. Generalized linear models were used to assess the associations of pre-surgical patient characteristics and incidence of postoperative delirium with cognitive trajectory. RESULTS:Of 560 participants, 326 were women (58%) and the average age was 76.7 (standard deviation 5.2) years. They underwent orthopedic (81%), gastrointestinal (13%), and vascular surgeries (6%), and 24% experienced postoperative delirium. We found the 3-group cognitive trajectory model to be optimal, with the groups characterized as severe decline trajectory (SDT) (15% of the cohort), slight decline (59%), or stable (26%). Of pre-surgical factors, age (relative risk [RR]: 1.06, 95% confidence interval [CI] 1.03-1.10 per 1 year increase) and 3MS (Modified-Mini-Mental) score (RR 0.95, 95% CI 0.92-0.99 per one point increase) were significantly associated with SDT. Participants who developed delirium had over two-fold higher risk of SDT compared to those who did not (RR: 2.15, 95% CI: 1.35-3.42). CONCLUSIONS:Among older adults undergoing major surgery, 15% experienced severe cognitive decline over the ensuing 6 years, 59% experienced slight decline, and 26% remained stable. Older age, baseline cognitive impairment, and delirium were associated with severe decline, with delirium having the strongest association. Our findings provide valuable information for older patients considering major surgery and may help clinicians target interventions.

Background: Preoperative blood Tau phosphorylated at threonine 217 (Tau-PT217), a newly identified blood biomarker of Alzheimer’s disease, is associated with postoperative delirium in patients. Anesthesia/surgery is also associated with postoperative increased blood Tau-PT217 amounts in patients. Moreover, in female aged mice, anesthesia/surgery increases Tau-PT217 in lungs, blood and brain tissues, leading to behavioral changes. However, whether these effects are sex-dependent remain largely undetermined. Methods: Eighteen-month-old female and male mice (C57BL/6J) underwent abdominal surgery under general anesthesia (1.4% isoflurane and 40% oxygen). Levels of Tau-PT217, inflammatory markers, and GSK3β activity were measured in lungs, blood, and brain tissues of aged mice using nanoneedle technology, Western blot, immunohistochemistry, RT-PCR and others. Postoperative delirium-like behavior was assessed using a battery of behavioral tests (buried food, open filed and Y maze). To explore causality, we performed orchiectomy and administered androgen receptor antagonist enzalutamide in aged male mice. Finally, testosterone was delivered via inhalation to aged female mice. Results: Anesthesia/surgery increased the amounts of Tau-PT217 in lungs (2.29±0.16 fold versus 1.15±0.71 fold, P<0.01), blood, and brain tissues of aged female, but not male, mice compared to control condition, leading to postoperative delirium-like behavior, as evidenced by increases in the composite Z score (3.74±1.46 versus 0.60±1.17, P<0.01), in the aged female, but not male, mice. Anesthesia/surgery elevated inflammatory markers and GSK3β activity in aged female mice, which exhibited lower baseline testosterone levels and androgen receptor expression in lungs compared to males. Both orchiectomy and enzalutamide treatment in male mice reduced testosterone levels and androgen receptor expression, leading to elevation of Tau-PT217 amounts and behavior changes following anesthesia/surgery. Conversely, testosterone inhalation in aged female mice mitigated the anesthesia/surgery-induced elevation of Tau-PT217 amounts and behavior changes. Conclusions: Testosterone and androgen receptor signaling may contribute to the sex-dependent differences in Tau phosphorylation and postoperative behavior changes in aged mice.

Objective:Studies and settings designed to identify incident cases of dementia can take advantage of imaging, biomarkers, and specialist clinicians to aid in diagnosis. This is not always feasible for large cohort studies. Design Setting and Participants:The Successful AGing after Elective Surgery (SAGES) study is a long-term, observational study of 560 community-dwelling adults aged ≥70, with serial neuropsychological assessments completed up to 72 months postsurgery. Measurement:Mild cognitive impairment (MCI) and dementia diagnoses were determined retrospectively using a rigorous multimodal approach with nested subsamples. This included 1) an expert panel consensus based on serial neuropsychological testing in all participants; 2) diagnosis based on chart review in a subsample of participants; and 3) an in-person neurologist examination in a subsample. An expert adjudication panel then used a Delphi approach to assign research diagnoses incorporating information from all available modalities. Results:During 72 months of follow-up, 63 incident cases of MCI (11.3%) and four cases of dementia (0.7%) were identified. The most frequent multimodal approach involved combined expert panel consensus and chart review in 41% of MCI (n = 26) diagnoses. Twelve MCI (19%) and three dementia (75%) diagnoses used all three modalities. Eight cases (12%) were diagnosed by a single modality. Diagnostic confidence considered both number and type of information sources used, for example, if agreement by more than one source, or diagnosis only by an in-person exam with a neurologist. Of the 63 MCI and four dementia diagnoses, the expert panel rated their confidence as moderate in four cases (all were MCI) and high in the remaining 63 cases (4 dementia and 59 MCI). Conclusions:A novel approach that integrates multiple sources of information and a robust adjudication process to determine incident MCI and dementia in a long-term cohort study may be useful for research applications. Such an approach may be useful when access to expert specialists, biomarkers, advanced neuroimaging and other diagnostic tests may be limited.

Importance:Postoperative delirium is associated with long-term cognitive decline in older adults. This might be caused by the delirium itself or because delirium is more common in persons who are ill and frail, and these conditions are also associated with cognitive decline. Objective:To determine whether cognitive decline associated with postoperative delirium is mediated by illness and frailty, as measured by recurrent hospitalizations. Design, Setting, and Participants:This prospective cohort study included community-dwelling older adults (age ≥70 years), enrolled from June 2010 to August 2013 with 5 years of follow-up data in the ongoing Successful Aging after Elective Surgery longitudinal study. Data were analyzed from November 2022 to May 2026. Exposures:Incident delirium following major elective surgery, with and without rehospitalizations, combined and by type (rehospitalization alone, rehospitalization with intensive care unit stay, rehospitalization with postacute care stay). Main Outcomes and Measures:The main outcome was long-term cognitive decline, measured as change in General Cognitive Performance (GCP) score, a composite measure of 11 neuropsychological tests, between preoperative baseline and 10 repeated assessments over 5 years. Results:In the cohort of 560 older adults (mean [SD] age, 76.7 [5.2] years; 326 female [58%]), the mean (SD) GCP score at baseline was 57.6 (7.3). Each rehospitalization was associated with a decline of -0.19 (95% CI, -0.31 to -0.09) GCP units per year. Delirium was associated with more marked cognitive decline of -0.33 (95% CI, -0.67 to -0.06) GCP units per year. Rehospitalizations were more common among patients who developed delirium (adjusted incidence rate ratio, 1.42 [95% CI, 1.17 to 1.72]). However, adjustment for combined rehospitalizations and for each type of rehospitalization resulted in only a minimal percentage change that was not statistically significant (-6% to -9%) in the association of delirium with cognitive decline. Conclusions and Relevance:In this cohort study, contrary to expectations, rehospitalization did not mediate the association between delirium and long-term cognitive decline. Future work will be needed to elucidate the pathways by which delirium is associated with long-term cognitive decline.

BACKGROUND:Nearly half of hospitalized adults with dementia develop delirium superimposed on dementia (DSD), which is associated with adverse outcomes. Family caregivers play an essential role in preventing, identifying, and responding to DSD, yet relatively little is known about how caregivers experience and respond to acute cognitive changes during illness and their preferences for involvement in DSD care. METHODS:We performed a qualitative study of caregivers (N = 22) for patients with dementia admitted to two hospitals within a single health system. Because caregivers may be engaged in DSD prevention prior to an episode of DSD, we included caregivers to patients with a history of delirium (N = 19) and without (N = 3). We conducted semi-structured interviews during hospitalization or within 1 week of discharge focused on caregiver experiences with acute cognitive changes during illness and preferences for involvement in DSD care. Interviews were analyzed using thematic analysis. RESULTS:Caregivers readily described experiences identifying acute cognitive changes during illness, but few were familiar with the term "delirium." Caregivers described navigating acute cognitive changes via common phases of (1) recognizing acute cognitive changes, (2) interpreting their meaning, and (3) deciding how to act. Some recognized and interpreted changes as normative in the context of dementia, while others expressed concern about the potential impact and seriousness of symptoms. Caregivers described several factors-perceived caregiving role and context, care priorities, delirium knowledge, and distress from delirium-that affected how they navigated symptoms as well as their preferences and motivations for involvement in DSD care. Participants reported substantial variation in factors that influenced their involvement in DSD care. CONCLUSIONS:Caregivers navigate and engage with acute cognitive changes during illness in heterogeneous ways, shaped by their preferences for involvement in care. Findings support flexible, caregiver-centered intervention strategies for DSD that recognize variability in caregiver roles, needs, and readiness for engagement.

Background: Amyloid positron emission tomography (PET) is gaining popularity for clinical and research purposes, particularly since the US Food and Drug Administration approval of anti-amyloid therapies. While the benefits of PET imaging in clinical care outweigh the risks associated with radiation exposure, the risks from elective radiation exposure in research should be carefully considered. Currently, no published or widely used guidelines consider prior radiation exposure as part of the eligibility determination for prospective participants in a clinical trial that includes ionizing radiation exposure. Methods: We reviewed the medical literature and current studies listed on ClinicalTrials.gov for radiation safety criteria and study protocols that include amyloid PET scans. We then developed a safety screening procedure to systematically estimate prior radiation exposure to determine eligibility for participation in an amyloid PET substudy and implemented this procedure in the Successful AGing after Elective Surgery (SAGES) study. Results: Of the studies including amyloid PET that were listed on ClinicalTrials.gov (n=92), prespecified exclusion criteria with specific amounts of radiation exposure were provided in only 1% of studies; 37% of studies did not report any screening for prior radiation exposure. Using the screening protocol we developed for the SAGES study, 17% of 101 participants were deemed ineligible for the amyloid PET procedure because of prior exposure. Conclusion: A systematic, standardized screening protocol to determine the prior radiation exposure of potential participants should be used as a tool in clinical studies involving elective radiologic procedures to minimize risk to participants.

This Editorial discusses the health challenges immigrants without legal status face and what individual clinicians can do.

Importance The 2014 Improving Medicare Post-Acute Care Transformation (IMPACT) Act aimed to improve postacute care quality and outcomes. This study examines changes in delirium, a key quality indicator, over 5 years following its implementation. Objective To compare the persistence and resolution of delirium within skilled nursing facilities (SNFs) between 2014 and 2019. Design, Setting, and Participants This cross-sectional study included SNF admissions from a 5% Medicare random sample, with delirium assessments conducted between January 1 and December 31 in 2014 and 2019. The analysis of persistent delirium consisted of patients with delirium at SNF admission and a subsequent delirium assessment during their SNF stay. Analyses were conducted from December 2023 to October 2024. Exposures Year 2019 compared with year 2014. Main Outcomes and Measures Delirium was measured using the Minimum Data Set (MDS) Confusion Assessment Method at SNF admission and at a subsequent assessment within 30 days of admission. Multinomial logistic regression was used to compare the rates of resolved delirium, persistent delirium, and death between 2014 and 2019 after adjusting for patient characteristics and SNF care factors. Results The sample included a total of 432 037 SNF admissions before exclusions and 306 998 after exclusions. For SNF admissions in 2014, 6933 of 162 161 patients (4.3%) had delirium at admission, compared with 3595 of 144 837 patients (2.5%) in 2019. In 2014, there were 6096 patients (mean [SD] age, 80.6 [11.0] years; 3565 women [58.5%]), and in 2019, there were 2778 patients (mean [SD] age, 80.2 [10.7] years; 1546 women [55.7%]) with delirium and follow-up assessments. The adjusted prevalence of persistent delirium decreased from 3347 of 6096 patients (62.3%; 95% CI, 60.2%-64.4%) in 2014 to 1316 of 2778 patients (54.7%; 95% CI, 52.0%-57.4%) in 2019, whereas delirium resolution increased from 1734 of 6096 patients (29.1%; 95% CI, 27.1%-31.1%) in 2014 to 1010 of 2778 patients (37.4%; 95% CI, 34.7%-40.0%) in 2019. Conclusions and Relevance This cross-sectional study found a reduction in the prevalence of delirium at SNF admission and an improvement in delirium resolution during the stay in the 5 years following the IMPACT Act. However, the high prevalence of persistent delirium warrants further efforts to improve delirium management in SNF.

Delirium is a common complication of hospitalization among older adults, and is associated with cognitive decline, but the underlying mechanisms are poorly understood. Delirium and dementia are closely interrelated; therefore, blood biomarkers for Alzheimer’s disease (AD) and neural injury may yield insight to potential mechanisms in delirium. Data were obtained from the Successful Aging after Elective Surgery (SAGES) study (n = 530). Glial fibrillary acidic protein (GFAP), a marker of reactive astrocytosis elevated in neurodegeneration and neural injury, and tau phosphorylated at residue 217 (p-Tau217), a marker of AD pathology, were measured from plasma collected prior to surgery. Post-operative delirium incidence and severity were assessed using the Confusion Assessment Method (CAM) and CAM-S (0-19, 19 worst), respectively. Higher GFAP (4th vs. 1st quartile) was associated with delirium incidence (relative risk (RR) 1.7, 95% confidence interval (CI): 1.1-2.8) and greater CAM-S severity (adjusted mean difference=0.5, 95% CI: 0.1-1.0). p-Tau217 did not significantly predict delirium incidence, though higher levels were associated with greater severity (adjusted mean CAM-S difference 1st to 4th quartile=0.6, 95% CI: 0.1-1.0). High pre-operative plasma GFAP was associated with higher delirium incidence and severity, whereas high p-Tau217 was associated only with higher severity. Overall, GFAP appears to be a stronger risk marker than p-Tau217 for delirium. Further work is needed to establish whether astrocytosis contributes to delirium pathophysiology.

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Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast JAMA+ AI Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2025 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal

Delirium and its severity (i.e., the intensity or degree of delirium symptoms) can be difficult to measure in people with dementia due to substantial overlap in symptoms and clinical features, complicating both diagnosis and research. In this descriptive study, we used data from the Better Assessment of Illness II (BASIL II) study of adults aged ≥70 years recruited from medical inpatient (Site 1), inpatient elective surgery (Site 2), or skilled nursing facility (Site 3) settings, to characterize delirium and its severity in settings with varying dementia prevalence. Trained staff conducted patient and proxy interviews, chart review, and delirium assessments at baseline and 1-2 days after acute illness or surgery using the Confusion Assessment Method (CAM; delirium present/absent) and CAM-Severity (CAM-S; scored 0-19, 19 = worst). Among 488 participants (mean [SD] age 79 [6] years; 58% female; 75% white), dementia prevalence was 23% (Site 1), 11% (Site 2), and 83% (Site 3). Following acute illness or surgery, the proportion meeting criteria for delirium and median (IQR) CAM-S scores among those with delirium were: Site 1, 50%, score 6 (4-6); Site 2, 1%, score 3 (3-3); Site 3, 24%, score 8 (6-10). Delirium rates and severity showed different patterns of variation across settings. Dementia prevalence may be associated with greater delirium severity; however, it is possible that chronic cognitive symptoms may also elevate delirium severity scores. These findings underscore the pressing need for studies validating measures of delirium severity in populations with dementia to advance research and patient care.