Search Results (310)

Background: Depression and delirium are common neuropsychiatric disorders in older adults. Although studies suggest an association between the two conditions, evidence regarding the long-term risk of delirium in older patients with depression in outpatient primary care remains limited. Objective: This study examined the relationship between depression and delirium in individuals aged ≥65 years. Methods: This retrospective cohort study used data from the German IQVIA Disease Analyzer database. It included individuals aged ≥65 years who received their first diagnosis of depression between 2005 and 2023. Using propensity score matching, patients with depression were matched 1:1 with individuals without depression. The primary outcome was incident delirium (ICD-10: F05). Time-dependent Cox regression models were applied for up to ten years of follow-up. Results: After matching, the study population consisted of 203,888 individuals (mean age: 75.8 years; 66% female). The incidence of delirium was higher in patients with depression than in controls (2.0% vs. 1.3%). Depression was associated with an elevated risk of delirium within the first two years after diagnosis (HR 1.42; 95% CI 1.14–1.75) and between six and ten years (HR 1.48; 95% CI 1.05–2.11). No statistically significant association was observed between years 3 and 5. Incident dementia was also associated with delirium (HR 1.52; 95% CI 1.14–2.02). Conclusions: Among older adults receiving outpatient care, depression was associated with a higher rate of subsequently documented delirium. These results complement existing evidence from inpatient settings. Due to the observational nature of the study, causal inferences cannot be made. In a sensitivity analysis excluding individuals with dementia at baseline, the association remained statistically significant across all intervals (HR 1.74, 1.53, and 1.82 for 0–2, 3–5, and 6–10 years, respectively). Full article

Background: Adolescent and adult citrin deficiency (AACD), formerly known as adult-onset citrullinemia type II, is a rare autosomal recessive disorder caused by biallelic pathogenic variants in SLC25A13. It is an underrecognized cause of recurrent hyperammonemic encephalopathy, particularly when hepatic function is relatively preserved. Methods: We report two unrelated Vietnamese young men, aged 21 and 18 years, who presented with recurrent neuropsychiatric episodes. Clinical, biochemical, imaging, electrophysiological, and genetic findings were evaluated; whole-exome sequencing findings were confirmed by Sanger sequencing. Results: Both patients had long-standing preferences for protein- and fat-rich foods and avoidance of carbohydrate-rich foods, together with episodic hyperammonemia (345.21 and 103.07 µmol/L during symptomatic episodes). The first patient had a history of neonatal jaundice, mild cirrhosis, and severe behavioral disturbances, whereas the second was markedly lean and had no structural liver disease. Acquired causes of hyperammonemia and portosystemic shunting were excluded. Both patients harbored the homozygous pathogenic SLC25A13 variant NM_014251.3.852_855del (p.Met285ProfsTer2). Ammonia-lowering therapy and a low-carbohydrate, protein- and fat-enriched diet supplemented with medium-chain triglycerides resulted in clinical improvement, with no recurrent encephalopathic episodes during 6 months of follow-up in either patient. Conclusions: AACD should be considered in adolescents and adults with otherwise unexplained recurrent hyperammonemic encephalopathy, especially when ammonia elevation is disproportionate to liver disease. Characteristic dietary preferences provide an important diagnostic clue, and molecular testing enables definitive diagnosis and timely management. Full article

Background/Objectives: Dementia with Lewy bodies (DLB) is a clinically heterogeneous neurodegenerative disorder characterized by cognitive, neuropsychiatric, motor, and autonomic manifestations. Reduced striatal dopamine transporter availability on ¹²³I-ioflupane single-photon emission computed tomography (SPECT) is an established indicative biomarker of DLB. However, the associations among expert visual interpretation, regional semiquantitative dopamine transporter measurements, autonomic manifestations, and dementia severity remain incompletely characterized. This study aimed to evaluate the relationship between visual ¹²³I-ioflupane SPECT classification and regional DaTQUANT z-scores in patients with clinically probable DLB and to explore their associations with autonomic manifestations and dementia severity. Methods: This retrospective, cross-sectional study included 30 patients who received a clinical diagnosis of probable DLB according to the 2017 DLB Consortium criteria before the ¹²³I-ioflupane SPECT results became available. SPECT images were assessed visually by experienced nuclear medicine physicians and semiquantitatively using DaTQUANT software. Bilateral striatal, putaminal, caudate, and putamen-to-caudate ratio z-scores were analyzed in relation to visual scan classification, Clinical Dementia Rating (CDR) scores, and retrospectively ascertained autonomic manifestations, including orthostatic hypotension, delayed orthostatic hypotension, supine hypertension, postprandial hypotension, constipation, and urinary incontinence. Results: Scans were visually classified as supportive of nigrostriatal dopaminergic degeneration in 23 of 30 patients (76.7%) and as non-supportive in seven (23.3%). Bilateral striatal, putaminal, and caudate z-scores were significantly lower in visually supportive scans than in non-supportive scans (all p < 0.001), whereas putamen-to-caudate ratio z-scores did not differ significantly between the groups. None of the evaluated autonomic manifestations was significantly associated with either visual scan classification or regional DaTQUANT measurements. No regional DaTQUANT measurement was significantly associated with dementia severity. A modest positive correlation was observed between the left putamen-to-caudate ratio z-score and CDR (Spearman’s ρ = 0.373, nominal p = 0.050); however, given the small sample size and multiple regional comparisons, this borderline finding was considered exploratory. Conclusions: Regional DaTQUANT measurements were consistent with expert visual interpretation of ¹²³I-ioflupane SPECT in patients with clinically probable DLB. Associations of dopaminergic imaging measurements with autonomic manifestations and dementia severity were limited. Semiquantitative analysis may complement visual interpretation, but its findings should be interpreted within the broader clinical and biomarker context. Larger prospective studies incorporating standardized autonomic testing, appropriate control groups, longitudinal follow-up, and complementary biomarkers are warranted. Full article

Background: Acute confusional state, or delirium, is a common neuropsychiatric disorder in older adults, particularly in emergency departments. It is associated with high morbidity and mortality, as well as difficult detection. Its early identification is crucial to prevent complications and improve prognosis. This study aims to identify and analyze available strategies for the early diagnosis of delirium in geriatric patients in emergency departments. Methods: A literature review and meta-analysis were conducted between 2020 and 2026 using the PubMed, Scopus, Web of Science, CINAHL, and Cochrane databases (PRISMA 2020). To estimate the prevalence of patients with delirium in emergency departments, a meta-analysis was performed using Stats Direct statistical software (Version 4). Methodological quality was evaluated according to the Oxford Centre for Evidence-Based Medicine levels of evidence. Results: Eleven studies were included, demonstrating that delirium in emergency departments is highly prevalent among older adults, particularly those with dementia, polypharmacy, or functional impairment. The 4AT scale was the most frequently used screening tool, notable for its strong sensitivity. Hypoactive delirium emerged as the most common subtype and carried the poorest prognosis. Furthermore, its presence was associated with longer hospital stays, increased complications, and higher mortality rates, while a lack of training among healthcare staff continues to limit early detection. The meta-analysis detected no publication bias and revealed a 20.6% prevalence of delirium among patients in emergency departments. Conclusions: One in five patients attending the emergency department presents with delirium. Delirium in geriatric emergency care demands a structured clinical response grounded in prevention, early detection, and professional training. Integrating validated diagnostic tools and reinforcing the role of nursing professionals are key to improving patient outcomes and safety. Full article

Insulin resistance (IR) represents one of the most pressing problems in contemporary public health. Its estimated global prevalence ranges from approximately 15.5% to over 61%, depending on the population studied, the diagnostic criteria applied, and the method used for its assessment. Despite the scale of the problem, IR remains underrecognized and lacks formal definition as a distinct disease entity, even as a growing number of clinicians and researchers worldwide describe it as such. Its asymptomatic or mildly symptomatic course allows it to remain undetected for years, during which it makes a significant contribution to the development of type 2 diabetes, cardiovascular disease (CVD) and metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD), and has been increasingly linked to cellular senescence, certain cancers, neuropsychiatric disorders, and other metabolic conditions. The aim of this review was to summarize current knowledge on the pathophysiology, diagnosis, and clinical implications of insulin resistance, to discuss current challenges in its diagnosis, and to evaluate whether available scientific evidence supports its recognition as a distinct disease entity. This narrative review is based on clinical, epidemiological, and mechanistic data retrieved from PubMed and Google Scholar. Meta-analyses, systematic reviews, clinical and observational studies, clinical guidelines, and expert position statements were analyzed. Animal studies were excluded to maintain a focus on human public health implications. The diagnostic gold standard—the hyperinsulinemic-euglycemic clamp—was discussed, along with surrogate methods used in clinical practice (HOMA-IR, OGTT with insulin measurements, the TyG index, and the TG/HDL-C ratio). Factors potentially contributing to the pathogenesis of IR were examined, including hyperinsulinemia (HI), high-carbohydrate diets, inflammation, stress, and sleep disturbances, as well as conditions in which IR occurs physiologically. The findings indicate that current evidence supports the need for a clearer clinical and diagnostic framework for insulin resistance and suggest that its recognition as a distinct disease entity could facilitate earlier diagnosis, improve the standardization of clinical management, and enable earlier metabolic intervention. Given the steadily rising prevalence of metabolic disease, systemic efforts directed at the early identification and treatment of IR may be a key component of strategies aimed at reducing the population-level burden of metabolic disease and its negative consequences. Full article

Background and Objectives: Postoperative delirium (POD) is a frequent neuropsychiatric complication following hip fracture surgery in older adults and is associated with prolonged hospitalization, functional decline, and increased mortality. Systemic inflammation is thought to play a central role in its pathogenesis, and the C-reactive protein CRP-to-albumin ratio (CAR) has emerged as a promising inflammatory biomarker. This study aimed to investigate the association between the preoperative CAR and POD and to identify clinical and perioperative factors independently associated with POD. Materials and Methods: This retrospective cohort study included 962 consecutive patients who underwent surgery for hip fractures between January 2022 and December 2025. Patients with femoral neck fractures underwent hemiarthroplasty, whereas those with intertrochanteric fractures were treated with proximal femoral nailing. Cases of postoperative delirium were evaluated following psychiatric consultation requested based on clinical suspicion by the orthopedic team, nursing staff or the patient’s caregiver; the definitive diagnosis was made by consultant psychiatrists according to the DSM-5 diagnostic criteria. Demographic characteristics, perioperative variables, and preoperative laboratory parameters were analyzed. Univariable and prespecified multivariable logistic regression analyses were performed to identify factors independently associated with POD. Model discrimination and calibration were assessed using receiver operating characteristic analysis, bootstrap internal validation, and the Hosmer–Lemeshow goodness-of-fit test. Results: Postoperative delirium developed in 112 of 962 patients (11.6%). Patients who developed POD had significantly higher preoperative CAR values than those without POD (0.76 vs. 0.33, p < 0.001). In the multivariable analysis, male sex (OR 1.567, 95% CI 1.007–2.438; p = 0.046), hemiarthroplasty (OR 1.931, 95% CI 1.213–3.075; p = 0.006), perioperative blood transfusion (OR 1.870, 95% CI 1.178–2.971; p = 0.008), general anesthesia (OR 1.829, 95% CI 1.093–3.061; p = 0.021), higher ASA physical status classification (OR 2.154, 95% CI 1.346–3.446; p = 0.001), longer time from hospital admission to surgery (OR 1.250 per 24 h increase, 95% CI 1.103–1.417; p < 0.001), and a higher log₂-transformed CAR (OR 1.184 per doubling, 95% CI 1.037–1.352; p = 0.013) were independently associated with POD. The final model demonstrated acceptable discrimination (AUC 0.764; optimism-corrected AUC 0.744) and satisfactory calibration (Hosmer–Lemeshow p = 0.242). Conclusions: A higher preoperative C-reactive protein-to-albumin ratio was independently associated with postoperative delirium after hip fracture surgery, even after adjustment for established demographic and perioperative risk factors. Male sex, hemiarthroplasty, general anesthesia, higher ASA physical status classification, perioperative blood transfusion, and delayed surgery were also independently associated with POD. These findings suggest that CAR may be a low-cost and readily available inflammatory biomarker that could be used to develop a preoperative risk classification system for the development of postoperative delirium. However, since routine standardized delirium screening was not performed during the study, cases of hypoactive delirium in particular may not have been adequately identified. For this reason, the findings should be interpreted with caution. Prospective, multicenter studies incorporating standardized delirium screening methods are needed to validate these results and determine the additional predictive value of CAR beyond established clinical risk factors. Full article

Background: Psychiatric inpatients may be vulnerable to head trauma; however, associations among psychiatric diagnosis, trauma mechanisms, and acute trauma-related neuroimaging findings among patients requiring neurosurgical consultation remain unclear. Methods: This retrospective observational study included psychiatric inpatients referred for neurosurgical consultation after head trauma at a tertiary neuropsychiatric specialty hospital between July 2022 and December 2025. Psychiatric diagnoses were grouped into psychotic, mood, substance use, organic/symptomatic, and other disorders. Trauma mechanisms were classified as falls, self-harm, assault/fight-related injuries, and other trauma types. Radiological findings were classified as trauma-related abnormalities or secondary incidental findings, including age-related changes. Associations were evaluated using chi-square tests, with false discovery rate correction applied to global and binary comparisons. Exploratory multivariable regression models were used as sensitivity analyses. Results: The cohort comprised 461 psychiatric inpatients who sustained head trauma, underwent radiological imaging, and were referred for neurosurgical consultation. Trauma mechanisms differed significantly across psychiatric diagnostic groups (χ² = 30.89, p = 0.002). Falls were the most common mechanism (189/461, 41.0%). Assault/fight-related trauma showed the clearest diagnosis-associated pattern (χ² = 19.72, p < 0.001, Cramér’s V = 0.207) and remained the only significant binary outcome after false discovery rate correction. Acute trauma-related imaging findings were observed in 35 patients (7.6%) and were not associated with psychiatric diagnosis (χ² = 6.16, p = 0.187). Calcifications were the most frequent imaging finding (191/461, 41.4%). Conclusions: In psychiatric inpatients, while head trauma patterns and neuroimaging findings have the potential to be explained by psychiatric diagnoses, they may also reflect unmeasured behavioral and clinical factors. Full article

Background: The COVID-19 pandemic and related containment measures profoundly affected child and adolescent mental health, with increasing evidence of a rise in psychiatric symptomatology and healthcare burden. This study aimed to evaluate temporal changes in neuropsychiatric presentations before, during, and after the COVID-19 pandemic in a pediatric clinical population. Methods: In this retrospective single-center study, 505 children and adolescents referred to a pediatric neuropsychiatry service were included and stratified into three periods: pre-pandemic (n = 112), pandemic (n = 231), and post-pandemic (n = 162). Clinical and healthcare-related variables were retrospectively collected, including reasons for referral, psychiatric diagnoses, premorbid conditions, and pharmacological treatments. Comparative analyses were performed to identify temporal variations in psychopathological profiles and clinical management. Results: A significant increase in psychiatric symptomatology emerged in the post-pandemic period compared with the pre-pandemic period. In particular, eating disorders, mood disturbances, self-harm, and somatic symptom presentations showed a marked increase over time, presenting as recurrent and associated phenotypes that peaked or consolidated after the acute emergency. The pandemic period was primarily characterized by a greater need for psychopharmacological intervention, specifically driven by the clinical need to manage acute behavioral crises. Overall, findings indicated a persistent increase in the complexity and severity of neuropsychiatric presentations beyond the acute phase of the pandemic. Conclusions: The COVID-19 pandemic was associated with substantial changes in pediatric neuropsychiatric presentations and treatment needs. The persistence of the increased psychopathological burden in the post-pandemic period highlights long-term mental health trajectories associated with the pandemic era. These emerging patterns of phenotypic complexity demonstrate that child and adolescent psychiatric services must transition from single-diagnosis models toward integrated care networks. Practically, strengthening community-based early intervention and creating rapid-access crisis support are essential to manage severe emotional dysregulation in the community and reduce acute psychiatric hospitalizations. Full article

Background: Glycemic control influences a wide range of psychiatric and physiological symptoms. Many psychiatric conditions are linked to poor glucose regulation. Anti-nuclear antibodies (ANAs), widely used to screen for autoimmune disease, may sometimes reflect transient metabolic immune activation rather than chronic pathology. Evidence suggests that glucose dysregulation, including glycemic variability, reactive hypoglycemia, and postprandial spikes, can trigger systemic inflammation, neuropsychiatric symptoms, and temporary autoantibody production. This review explores how these metabolic phenomena complicate diagnosis and may contribute to misclassification or overtreatment. Methods: We conducted a narrative literature review prioritizing studies on immune activation, psychiatric outcomes, metabolic measures (including continuous glucose monitoring), and therapeutic interventions. Articles from the last ten years were emphasized, with older foundational studies included when relevant. Results: Metabolic instability drives immune dysregulation through macrophage polarization, mitochondrial dysfunction, oxidative stress, and impaired clearance of apoptotic debris. Glycemic variability correlates with increased inflammatory cytokines, autonomic dysfunction, and psychiatric symptoms such as anxiety, depression, and cognitive impairment. Emerging evidence from small studies suggests that correcting glucose abnormalities may reduce metabolic dysfunction and improve neuropsychiatric symptoms. Conclusions: Recognizing glucose dysregulation as a contributor to autoimmune-like and psychiatric symptoms may refine diagnostic and therapeutic approaches. Incorporating a dynamic holistic approach, which in practice includes metabolic assessments, dietary interventions, use of continuous glucose monitoring, and history of blood sugar instability, into rheumatologic and psychiatric evaluations could improve diagnostic precision, reduce unnecessary immunosuppression, and enhance patient outcomes. Full article

Background/Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) describes the rapid onset of obsessive–compulsive symptoms or severe food restriction, accompanied by neuropsychiatric or somatic features that are not better explained by another disorder. PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections) is a related, more narrowly defined construct in which symptoms are temporally associated with group A Streptococcus infection. This review examines clinical symptoms, infectious associations, proposed immune mechanisms, biomarker limitations, and treatment strategies for infection-associated PANS/PANDAS. Methods: A structured narrative search of PubMed/MEDLINE, Embase, the Cochrane Library, Google Scholar/publisher-indexed literature, ClinicalTrials.gov, and reference lists was performed up to 16 June 2026. Original cohorts, case series, systematic reviews, narrative reviews, consensus guidance, mechanistic studies, and registered prospective studies were prioritized. The review was not designed as a PRISMA-ScR scoping review; however, the methods were expanded to improve transparency and align with SANRA principles. Results: Group A Streptococcus remains the best characterized infectious association, although prospective studies have not uniformly demonstrated a consistent temporal relationship between streptococcal infection and neuropsychiatric exacerbations. Parent-reported surveys and case-based literature also describe temporal associations with Mycoplasma pneumoniae, influenza-like illnesses, upper respiratory infections, Borrelia burgdorferi, Epstein–Barr virus, and SARS-CoV-2. Proposed mechanisms include molecular mimicry, anti-D1R and anti-D2R antibodies, other antineuronal antibodies, calcium/calmodulin-dependent protein kinase II signaling, blood–brain barrier vulnerability, cytokine and Th17 effects, neuroinflammatory amplification, basal ganglia/CSTC circuit dysfunction, and gut–oral–brain immune interactions. None currently provides a definitive diagnostic biomarker. Conclusions: Infection-associated PANS is best approached as a clinically defined, heterogeneous neuroimmune presentation that requires rigorous differential diagnosis, multidisciplinary care, cautious treatment escalation, prospective biomarker validation, and large, multicenter treatment trials. Full article

Background/Objectives: Catatonia is a severe transdiagnostic neuropsychiatric syndrome for which accessible biological correlates remain insufficiently characterized. This study explored whether complete blood count (CBC)-derived inflammatory indices differ between psychiatric inpatients with catatonia and matched psychiatric controls without catatonia. Methods: This retrospective matched case–control study included 46 patients with catatonia and 46 psychiatric controls selected from the same clinical setting and study period. Controls were frequency-matched by sex, age distribution, and broad psychiatric diagnosis. CBC parameters obtained within the first 24 h of admission were used to calculate the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune–inflammation index (SII), and systemic inflammation response index (SIRI). Group comparisons, adjusted log–linear regression models, Spearman correlations with documented catatonic signs, and exploratory receiver operating characteristic analyses were performed. Results: SII was higher in patients with catatonia than in controls and remained significant after Bonferroni correction (median 584 [IQR 468–823] vs. 476 [IQR 339–619], Bonferroni-adjusted p = 0.032). In secondary adjusted models, catatonia was associated with higher SII and SIRI after adjustment for body mass index, smoking, antipsychotic exposure, diabetes mellitus, and arterial hypertension. No inflammatory index correlated significantly with the number of documented catatonic signs after correction. Exploratory discrimination was poor to fair, with SII showing the highest AUC (0.665, 95% CI 0.550–0.773). Conclusions: CBC-derived indices, particularly SII, may reflect systemic inflammatory or physiological stress burden in catatonia, but they should be interpreted as exploratory markers rather than diagnostic biomarkers. Full article

The main purpose of this work is to critically review the literature on neurocognitive disorders (ND) diagnosis. A critical review was conducted in PubMed, Scopus, and EBSCO. Systematic reviews and meta-analyses focusing on ND diagnosis were included. The selected studies were critically analyzed and conceptually integrated to identify relevant dimensions for the diagnosis of ND. The review included 88 studies. Most studies focused on Alzheimer’s disease and mild cognitive impairment. The literature remained predominantly centred on isolated diagnostic domains, and important limitations were consistently identified, including methodological heterogeneity, lack of standardized thresholds, and reduced clinical applicability. Based on the identified conceptual and methodological limitations, a Multidimensional Model of Neurocognitive Disorders (MOND model) for ND diagnosis was proposed. The MOND model was developed as a multidimensional, multilevel, transdiagnostic model integrating biological, neurocognitive, neuropsychiatric, motor, functional, frailty, reserve-related, and socio-environmental dimensions. The model may contribute to research, symptom classification, severity characterization, prognosis, and personalized intervention planning across different ND trajectories. Future studies using the MOND model should focus on refining algorithms to estimate the risk of ND. Full article

Pernicious anemia (PA) represents a significant diagnostic challenge in neuropsychiatric patients due to its subtle and variable presentation. While PA is traditionally associated with clinical and biochemical manifestations of anemia, many patients, particularly those with neuropsychiatric symptoms, may have normal hematologic parameters, delaying recognition and appropriate treatment. Neurological and psychiatric symptoms, ranging from cognitive impairment and mood disorders to subacute combined degeneration (SCD) of the spinal cord, can precede hematologic abnormalities, leading to misdiagnosis or inappropriate management. The lack of a definitive gold standard test for cobalamin deficiency (CD) further complicates identification. Commonly used biomarkers, such as serum cobalamin, methylmalonic acid (MMA), homocysteine (Hcy), intrinsic factor antibodies (IFAs), and parietal cell antibodies (PCAs), each have limitations in diagnosing PA, especially in the absence of overt anemia. The variability in diagnostic criteria and cutoff values across studies adds to the challenge of achieving early and accurate diagnosis. This article reviews the complexities of diagnosing PA in neuropsychiatric patients, evaluates the limitations of current diagnostic methods, and emphasizes the need for a more comprehensive, standardized approach to early detection and treatment. Combining clinical awareness with improved biomarker interpretation is essential for preventing irreversible neurological damage and improving patient outcomes. Improved diagnostic protocols and further research are essential to optimize detection and minimize the risk of long-term neurological damage. Full article

Background/Objectives: Assessment of cognitive function in patients with dementia is often hindered by functional and environmental barriers. Although caregiver reports are an alternative source, their clinical utility for estimating patients’ cognitive function remains uncertain. This study aimed to estimate cognitive function using caregiver-reported data combined with patient demographics and to evaluate its clinical utility. Methods: This retrospective cross-sectional study enrolled participants who visited a memory clinic and completed the Montreal Cognitive Assessment (MoCA) for cognitive assessment, together with caregiver-reported questionnaires for activities of daily living (ADL) and neuropsychiatric symptoms (NPS). Multivariable linear regression models were constructed to predict the MoCA score, with Model 1 including demographics, ADL, and NPS as covariates and Model 2 further incorporating clinical diagnosis. The intraclass correlation coefficient, Bland–Altman analysis, and regression error characteristic curves were assessed. Results: Among 2650 participants (56.5% women; mean age, 70.4 years), the NPS variable was excluded from both models. Model 1, which included demographics and ADL, explained 65.4% of the variance, whereas Model 2, which incorporated clinical diagnosis, explained 75.9%. Model 2 yielded an intraclass correlation coefficient of 0.853, compared to 0.778 for Model 1. At a 4-point error tolerance, Model 2 yielded an accuracy of 75.5%. Bland–Altman biases were near zero, with 95% limits of agreement of approximately ±7 points for Model 2. Conclusions: MoCA scores can be estimated using caregiver-reported ADL scores, demographics, and clinical diagnosis. NPS scores provided no additional predictive value when these factors were included. These models provide valid quantitative tools for indirect cognitive assessment when in-person testing is impossible. Full article

Delirium is a transient neuropsychiatric condition that is a severe and prevalent condition affecting 2.6 million older adults each year. Alzheimer’s disease (AD) and anticholinergic medication use are risk factors for delirium. This study evaluated the association between cumulative anticholinergic burden (CAB) and risk of delirium among older adults with AD initiating cholinesterase inhibitors (ChEIs). This retrospective cohort study used 2013–2017 Medicare claims data, and included adults 65 years and older with AD who initiated any of the ChEIs (donepezil, rivastigmine, and galantamine) after a 12-month washout period. CAB, as the primary exposure, was measured on the index date and calculated as the monthly total standardized daily dose of anticholinergic medications. A multivariable Cox proportional hazards regression model with inverse probability of treatment weighting (IPTW) generated using generalized boosted models was used to evaluate the risk of delirium associated with the CAB. This study identified 143,320 older adults with AD who initiated ChEIs. Most patients were in the low/no burden (62.73%) group, followed by high burden (21.12%) and moderate burden (16.14%). Overall, delirium diagnosis was observed in 19.11% of the cohort. The Cox regression model with IPTW found that moderate (aHR, 1.56; 95% CI, 1.52–1.61; p < 0.0001) and high CAB (aHR, 1.45; 95% CI, 1.42–1.49; p < 0.0001) were associated with an increased risk of delirium compared to low/no burden. Among older adults with AD initiating ChEIs, moderate and high CAB were associated with an increased risk of delirium compared with low/no CAB. These findings highlight the need to carefully reduce the CAB, especially dose and duration, along with utilizing anticholinergic alternatives in older adults with AD. Full article