Neurocognitive outcomes: too much data, not enough clarity

The umbrella review by D'Amico et al. attempts an ambitious synthesis of 114 meta-analyses evaluating interventions to prevent postoperative neurocognitive complications [1]. The attempt to consolidate such an expansive evidence base is commendable; however, several methodological considerations require clarification to ensure accurate clinical interpretation. A central concern relates to the intrinsic limitations of umbrella reviews [2]. The included meta-analyses span markedly heterogeneous surgical populations, including cardiac, non-cardiac and orthopaedic cohorts, and use inconsistent definitions and diagnostic criteria for postoperative delirium and cognitive dysfunction. Assessment timings, outcome definitions and screening tools varied widely across the primary trials. Collapsing these disparate data sources into a single pooled estimate (OR 0.57, I2 = 94%) amplifies heterogeneity and risks obscuring clinically meaningful subgroup differences. When inconsistency reaches such extremes, any overarching summary effect becomes difficult to interpret and may not reflect real-world practice. Umbrella reviews can be powerful tools when they synthesise high-quality and methodologically robust meta-analyses. However, when the included meta-analyses exhibit substantial risk of bias, heterogeneity and non-standardised outcome definitions, the certainty of any umbrella-level conclusion becomes limited. A more focused, outcome-oriented methodology, preferentially targeting high-quality meta-analyses or those aligning with standardised definitions of postoperative neurocognitive complications, may have yielded clearer and more clinically meaningful insights. The reported protective association must also be understood in the context of the underlying certainty of evidence. Although the umbrella review reports an overall benefit, the majority of included meta-analyses were rated as low or very low certainty using AMSTAR-2, Ioannidis classification and GRADE. Many of the primary trials were small, underpowered and characterised by methodological concerns such as unclear randomisation; variable blinding; inconsistent intervention protocols; and selective reporting. Under these circumstances, statistically significant pooled estimates may provide an inflated sense of confidence. Dexmedetomidine and depth of anaesthesia monitoring, often highlighted as promising interventions, derive much of their apparent benefit from trials with considerable heterogeneity in blinding; dosing strategies; monitoring algorithms; peri-operative interventions; and publication bias. The aggregation of conceptually distinct interventions into broad categories such as ‘sleep interventions’, ‘multicomponent protocols’ or ‘non-pharmacological approaches’ may further limit interpretability. These strategies differ fundamentally in mechanism and implementation fidelity, resource requirement and peri-operative context. Without distinguishing between targeted pharmacological interventions, environmental modifications and comprehensive delirium prevention bundles, readers may incorrectly infer equivalence across modalities that have no comparative evidence base. Delirium prevention is inherently multifactorial [3] and intervention-specific conclusions require intervention-specific evidence rather than umbrella-level aggregation. In addition, the absence of stratification by surgical speciality and anaesthetic technique limits clinical applicability. Neurocognitive outcomes differ substantially between cardiac and non-cardiac populations, between patients exposed to deep vs. light anaesthesia and between those receiving regional vs. general anaesthesia [4]. Factors such as depth of anaesthesia; intra-operative hypotension; opioid exposure; benzodiazepine use; postoperative sleep disruption; and complications are known modifiers of delirium risk but remain poorly addressed when analyses aggregate heterogeneous trials. Without surgery-specific and technique-specific synthesis, clinicians may struggle to translate umbrella-level findings into actionable peri-operative pathways. The evolving definitions of peri-operative neurocognitive disorders merit explicit consideration. The Nomenclature Consensus Working Group distinguishes clearly between postoperative delirium, delayed neurocognitive recovery and postoperative neurocognitive disorder [5]. Many included meta-analyses were conducted before adoption of these harmonised definitions, complicating comparisons and potentially contributing to inconsistent effect estimates. Future evidence syntheses should align with contemporary diagnostic frameworks to enable more reliable interpretation.