Association between postoperative delirium and adverse outcomes in older surgical patients: A systematic review and meta-analysis.

STUDY OBJECTIVE: To assess the incidence of postoperative delirium and its outcomes in older non-cardiac surgical patients. DESIGN: A systematic review and meta-analysis with multiple databases searched from inception to February 22, 2022. SETTING: Postoperative assessments. PATIENTS: Non-cardiac and non-neurological surgical patients aged ≥60 years with and without postoperative delirium. Included studies must report ≥1 postoperative outcome. Studies with a small sample size (N < 100 subjects) were excluded. MEASUREMENTS: Outcomes comprised the pooled incidence of postoperative delirium and its postoperative outcomes, including mortality, complications, unplanned intensive care unit admissions, length of stay, and non-home discharge. For dichotomous and continuous outcomes, OR and difference in means were computed, respectively, with a 95% CI. MAIN RESULTS: Fifty-four studies (20,988 patients, 31 elective studies, 23 emergency studies) were included. The pooled incidence of postoperative delirium was 19% (95% CI: 16%, 23%) after elective surgery and 32% (95% CI: 25%, 39%) after emergency surgery. In elective surgery, postoperative delirium was associated with increased mortality at 1-month (OR: 6.60; 95% CI: 1.58, 27.66), 6-month (OR: 5.69; 95% CI: 2.33, 13.88), and 1-year (OR: 2.87; 95% CI: 1.63, 5.06). The odds of postoperative complications, unplanned intensive care unit admissions, prolonged length of hospital stay, and non-home discharge were also higher in delirium cases. In emergency surgery, patients with postoperative delirium had greater odds of mortality at 1-month (OR: 3.56; 95% CI: 1.77, 7.15), 6-month (OR: 2.60; 95% CI: 1.88, 3.61), and 1-year (OR: 2.30; 95% CI: 1.77, 3.00). CONCLUSIONS: Postoperative delirium was associated with higher odds of mortality, postoperative complications, unplanned intensive care unit admissions, length of hospital stay, and non-home discharge. Prevention and perioperative management of delirium may optimize surgical outcomes.

Plasma inflammation for predicting phenotypic conversion and clinical progression of autosomal dominant frontotemporal lobar degeneration.

BACKGROUND: Measuring systemic inflammatory markers may improve clinical prognosis and help identify targetable pathways for treatment in patients with autosomal dominant forms of frontotemporal lobar degeneration (FTLD). METHODS: We measured plasma concentrations of IL-6, TNFα and YKL-40 in pathogenic variant carriers (MAPT, C9orf72, GRN) and non-carrier family members enrolled in the ARTFL-LEFFTDS Longitudinal Frontotemporal Lobar Degeneration consortium. We evaluated associations between baseline plasma inflammation and rate of clinical and neuroimaging changes (linear mixed effects models with standardised (z) outcomes). We compared inflammation between asymptomatic carriers who remained clinically normal ('asymptomatic non-converters') and those who became symptomatic ('asymptomatic converters') using area under the curve analyses. Discrimination accuracy was compared with that of plasma neurofilament light chain (NfL). RESULTS: We studied 394 participants (non-carriers=143, C9orf72=117, GRN=62, MAPT=72). In MAPT, higher TNFα was associated with faster functional decline (B=0.12 (0.02, 0.22), p=0.02) and temporal lobe atrophy. In C9orf72, higher TNFα was associated with faster functional decline (B=0.09 (0.03, 0.16), p=0.006) and cognitive decline (B=-0.16 (-0.22, -0.10), p<0.001), while higher IL-6 was associated with faster functional decline (B=0.12 (0.03, 0.21), p=0.01). TNFα was higher in asymptomatic converters than non-converters (ß=0.29 (0.09, 0.48), p=0.004) and improved discriminability compared with plasma NfL alone (ΔR2=0.16, p=0.007; NfL: OR=1.4 (1.03, 1.9), p=0.03; TNFα: OR=7.7 (1.7, 31.7), p=0.007). CONCLUSIONS: Systemic proinflammatory protein measurement, particularly TNFα, may improve clinical prognosis in autosomal dominant FTLD pathogenic variant carriers who are not yet exhibiting severe impairment. Integrating TNFα with markers of neuronal dysfunction like NfL could optimise detection of impending symptom conversion in asymptomatic pathogenic variant carriers and may help personalise therapeutic approaches.

Serum S100A8/A9 and MMP-9 levels are elevated in systemic lupus erythematosus patients with cognitive impairment.

Objective: Cognitive impairment (CI) is one of the most common manifestations of Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). Despite its frequency, we have a limited understanding of the underlying immune mechanisms, resulting in a lack of pathways to target. This study aims to bridge this gap by investigating differences in serum analyte levels in SLE patients based on their cognitive performance, independently from the attribution to SLE, and exploring the potential for various serum analytes to differentiate between SLE patients with and without CI. Methods: Two hundred ninety individuals aged 18-65 years who met the 2019-EULAR/ACR classification criteria for SLE were included. Cognitive function was measured utilizing the adapted ACR-Neuropsychological Battery (ACR-NB). CI was defined as a z-score of ≤-1.5 in two or more domains. The serum levels of nine analytes were measured using ELISA. The data were randomly partitioned into a training (70%) and a test (30%) sets. Differences in the analyte levels between patients with and without CI were determined; and their ability to discriminate CI from non-CI was evaluated. Results: Of 290 patients, 40% (n=116) had CI. Serum levels of S100A8/A9 and MMP-9, were significantly higher in patients with CI (p=0.006 and p=0.036, respectively). For most domains of the ACR-NB, patients with CI had higher S100A8/A9 serum levels than those without. Similarly, S100A8/A9 had a negative relationship with multiple CI tests and the highest AUC (0.74, 95%CI: 0.66-0.88) to differentiate between patients with and without CI. Conclusion: In this large cohort of well-characterized SLE patients, serum S100A8/A9 and MMP-9 were elevated in patients with CI. S100A8/A9 had the greatest discriminatory ability in differentiating between patients with and without CI.

Alpha-Synuclein RT-QuIC in Idiopathic Normal Pressure Hydrocephalus.

This study quantified the occurrence of an underlying synucleinopathy in 50 patients with idiopathic normal pressure hydrocephalus by means of real-time quaking-induced conversion, a highly sensitive and specific technique capable of detecting and amplifying misfolded aggregated forms of α-synuclein in the cerebrospinal fluid. Seven patients were positive and they did not differ from negative cases, except for a more frequent L-dopa responsiveness and gait characterized by a wider base. The two groups did not differ in terms of response rate to tap test or shunt surgery, although step length and gait velocity improved by a lesser extent in positive cases. ANN NEUROL 2022;92:985-991.

Physical activity perceptions, experiences, and beliefs of older adults with mild cognitive impairment or Alzheimer's disease and their care partners.

Physical activity (PA) participation provides functional and social benefits for persons with mild cognitive impairment (MCI) and Alzheimer's disease (AD), but PA participation in these populations is low. To support health promotion initiatives for cognitively impaired older adults, this study explored the perceptions, experiences, and beliefs of older adults with cognitive impairment and their caregivers concerning PA. Ten care dyads (community-dwelling adult aged ≥65 years diagnosed with MCI or mild-to-moderate AD and their care partner) participated in semi-structured interviews informed by the Theoretical Domains Framework about their PA perceptions, experiences, and beliefs. Interpretive phenomenological analysis of interview transcripts yielded 4 emergent themes: (1) PA as a meaningful activity, (2) experience versus evidence as motivating, (3) participation is possible despite dementia, and (4) care partners as enablers. Findings from this study address a research gap concerning the PA perceptions, experiences, and beliefs of cognitively impaired older adults and their care partners. Novelty Older adults with MCI/AD want to and are capable of engaging in PA. Care partners are critical supporters of PA participation in MCI/AD. Adapted health promotion strategies could enhance PA in MCI/AD.

Clinical Report: Cognitive decline in a patient with Cardiofaciocutaneous syndrome.

Cardiofaciocutaneous Syndrome (CFCS) is a rare genetic syndrome caused by mutations in one of four genes: BRAF, MAP2K1, MAP2K2, and KRAS. There is tremendous phenotypic heterogeneity in patients with CFCS and so confirmation of diagnosis requires genetic testing. Neurologic and/or cognitive symptoms are present in almost all CFCS individuals. Little is known about cognitive function in older patients with CFCS. In this report, we present the cognitive, neuropsychiatric, and imaging findings of a patient diagnosed with CFCS who after having remained stable developed progressive cognitive/behavioral and motor decline.

Assessing behavioral syndromes in patients with brain tumors using the frontal systems behavior scale (FrSBe).

BACKGROUND: Personality changes following brain tumors may be due to disruption of frontal-subcortical networks. The relation between personality changes and tumor parameters such as volumes of the surgical cavity, residual tumor, or nonspecific white matter abnormalities is unknown. In this study we examined the relation between these tumor parameters and abnormal behaviors typically associated with frontal lobe dysfunction. METHODS: Thirty-one patients with intracranial tumors who completed the Frontal Systems Behavior Scale (FrSBe) during clinical neuropsychological assessment and had a solitary, well-delimited brain lesion on MRI within 3 months of that assessment were included. Tumor parameters were manually segmented using OsiriX. Nonparametric statistics were used to determine the relationship between tumor parameters and frontal behavioral dysfunction as measured by FrSBe scores. RESULTS: Patients reported significantly more behavior problems after tumor diagnosis. Tumor cavity volume was correlated with self-reported Executive Dysfunction (rho = 0.450, P = .047), and there was a trend in the relationship with self-reported Apathy (rho = 0.438, P = .053). Nonspecific white matter abnormality volume was also correlated with self-reported Apathy (rho = 0.810, P = .01). There were no correlations between FrSBe scores and residual tumor volume or summed volumes of tumor-related parameters. CONCLUSION: Our results suggest that tumor parameters have differential effects on behaviors associated with frontal-subcortical networks and corroborate the high frequency of behavioral dysfunction in brain tumor patients. Examination of these relationships in a prospective trial is warranted to establish incidence, prevalence, risk factors, and consequences of behavioral disturbances in brain tumor patients.

Frontotemporal lobar degeneration: new understanding brings new approaches.

Frontotemporal dementia (FTD) describes a group of clinical syndromes united by underlying frontotemporal lobar degeneration (FTLD) pathology. The clinical syndromes associated with FTLD are heterogeneous and are based on whether the patients present with behavioral, language, or motor impairments. FTLD is at the center of a paradigm shift in neurodegenerative diseases, with thought being given at diagnosis of underlying disease. There is pathologic heterogeneity of certain clinical syndromes such as behavioral variant FTD. Differentiation between the proteinopathies will become imperative as protein-specific treatments become available. This review provides an overview of FTLD, with an update of recent discoveries.