Department of Neurology, UC Davis School of Medicine

Introduction: The objective of this study was to compare long-term neurological outcomes in low-risk patients with traumatic intracranial hemorrhage (tICH) admitted to the ICU (intensive care unit) versus patients admitted to the floor.

Methods: This retrospective study was conducted at a Level 1 trauma center from October 1, 2008, to February 1, 2013. We defined low-risk patients as age less than 65 years, isolated head injury, normal admission mental status, and no shift or swelling on initial head CT (computed tomography). Clinical data were abstracted from a trauma registry and linked to a brain injury database. We compared the Extended Glasgow Outcome Scale (GOS-E) score at six months between patients admitted to the ICU and patients admitted to the floor. We did a risk-adjusted analysis of the influence of floor admission on a normal GOS-E.

Results: We identified 151 patients; 45 (30%) were admitted to the floor and 106 (70%) to the ICU. Twenty-three (51%; 95% CI [36-66%]) patients admitted to the floor and 55 (52%; 95% CI [42-62%]) patients admitted to the ICU had a normal GOS-E. On adjusted analysis; the odds ratio for floor admission was 0.77 (95% CI [0.36-1.64]) for a normal GOS-E at six months.

Conclusion: Long-term neurological outcomes in low-risk patients with tICH were not markedly different between patients admitted to the ICU and those admitted to the floor. However, we were unable to demonstrate non-inferiority on adjusted analysis. Future work aimed at a larger, prospective cohort may better evaluate the relative impacts of admission type on outcomes. [West J Emerg Med. 2015;16(2):284–290.]

Stroke is a multifaceted disease with genetic and environmental components like diet and lifestyle. The central nervous and immune systems display complex interactions, with the peripheral immune response participating in brain injury and repair mechanisms following stroke. The bidirectional communication between the injured brain and peripheral blood presents an opportunity to investigate the molecular changes in the latter. There is substantial heterogeneity in stroke pathogenesis, pathophysiology, comorbidities, and response to treatment and outcome. This is captured and underscored by heterogeneity in the peripheral blood transcriptome. The current review highlights the role of the human peripheral blood transcriptome architecture for molecular phenotyping of different stroke etiologies and comorbidities, and for identifying underlying molecular correlates with clinically important variables and outcomes. Specific transcriptome features can potentially provide targets for clinical translation and for prioritizing genes and pathways for evaluation in experimental models. We also propose an approach to study the patient-specific transcriptional architecture and uncover the combinatorial heterogeneity in altered pathways in stroke patients that can also guide the search for treatment and prevention targets. Deciphering the molecular heterogeneity of stroke in a tissue that can be easily accessed and monitored, such as peripheral blood, may improve clinical trial success.

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Machine learning enables scalable quantification of neuropathology, offering deeper phenotyping of Alzheimer's disease (AD). In this validation study, we quantified amyloid-beta (Aβ) deposits, evaluating multiple brain regions across institutions, and evaluated associations with clinical, demographic, and genetic factors in persons pathologically diagnosed with AD. All linear models were adjusted for sex, age of death, ethnicity, and center. We analyzed densities (#/mm2) of cored plaques, diffuse plaques, and cerebral amyloid angiopathy (CAA) in 273 individuals from 3 Alzheimer's Disease Research Centers. Formalin-fixed paraffin-embedded sections of frontal, temporal, and parietal cortices were immunostained and digitized, generating 799 whole-slide images (WSIs). Following log transformation, mixed-effects modeling revealed the parietal cortex had the highest cored plaque densities (P < .001); the temporal cortex had the highest diffuse plaque (P < .001); CAA showed no regional differences. Wilcoxon rank-sum test, and covariates adjusted linear models showed ApoE ε4- status was associated with higher cored plaque densities in the temporal lobe (P = .04). ApoE ε4+ status was associated with diffuse plaques in the temporal lobe (P = .001), and CAA in the frontal lobe (P = .004). These findings provide further validation and provide exploratory associations advancing deeper phenotyping of AD.

INTRODUCTION: To examine the generalizability of Alzheimer's disease (AD) biomarker models in real-world older adults, we examined AD biomarker relationships with cognition in two multicenter cohorts that differ with respect to recruitment approach and health risk factors but were matched on a variety of characteristics. METHODS: We compared harmonized health and demographic data, AD and cerebrovascular biomarkers, and cognitive performance in the community-recruited U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) Imaging substudy and a matched sample from the Alzheimer's Disease Neuroimaging Initiative (ADNI) which recruited primarily from academic specialty clinics. RESULTS: Elevated β-amyloid (Aβ) and tau were associated with cognitive performance in ADNI but not U.S. POINTER. Findings were consistent across different cohort matching schemes, and were not explained by discrepancies in vascular risk. DISCUSSION: The role of Aβ and tau in cognitive performance may be reduced in real world samples compared to academic specialty clinics.

Millions of people live with cognitive impairment from Alzheimer’s disease and related dementias (ADRD). Voice-enabled smart home systems offer promise for supporting daily living but rely on automatic speech recognition (ASR) to transcribe their speech to text. Prior work has shown reduced ASR performance for adults with cognitive impairment; however, the acoustic factors underlying these disparities remain poorly understood. This paper evaluates ASR performance for 83 older adults across cognitive groups (cognitively normal, mild cognitive impairment, dementia) reading commands to a voice assistant (Amazon Alexa). Results show that ASR errors are significantly higher for individuals with dementia, revealing a critical usability gap. To better understand these disparities, we conducted an acoustic analysis of speech features and found that a speaker’s intensity, voice quality, and pause ratio predicted ASR accuracy. Based on these findings, we outline HCI design implications for AgeTech and voice interfaces, including speaker-personalized ASR, human-in-the-loop correction of ASR transcripts, and interaction-level personalization to support ability-based adaptation.

INTRODUCTION: Monoclonal antibodies (mAbs) for Alzheimer's disease (AD) represent major therapeutic advances, but their economic value is uncertain. This review narratively examines cost-effectiveness analyses (CEAs) of aducanumab, lecanemab, and donanemab for early-onset AD. METHODS: We searched Medline (via PubMed) and EMBASE in April 2026 and incremental cost-effectiveness ratio (ICER) reports for CEAs of these mAbs. Inclusion required sufficient data to calculate ICERs. Two reviewers independently screened studies, and risk of bias was assessed using Risk of Bias in Systematic Reviews. Data were synthesized narratively due to methodological heterogeneity. RESULTS: Of 755 records screened, 16 CEAs met inclusion criteria (six aducanumab, eight lecanemab, one aducanumab/donanemab, one lecanemab/donanemab). Almost all aducanumab studies reported ICERs that exceeded commonly cited US willingness‑to‑pay thresholds (e.g., $100,000-$150,000 per quality-adjusted life year [QALY]), with ratios ranging from $127,461 to $1,581,276/QALY (2026 USD). Lecanemab results were mixed, with manufacturer‑funded models reporting ICERs below commonly cited thresholds, while other models generally exceeded them. The single donanemab analysis versus standard of care reported an ICER of $214,760/QALY (2026 USD), above commonly cited thresholds, and a Brazilian analysis comparing donanemab with lecanemab reported an ICER of $1,477,604/QALY (2026 USD). No independent study found any mAb cost savings. DISCUSSION: ICER variability across studies, despite reliance on the same clinical trials, reflects sensitivity to assumptions and potential sponsorship bias. Evidence is limited by small numbers of CEAs, reliance on modeled rather than real-world data, and absence of formal risk-of-bias scoring for individual CEAs. The cost-effectiveness of AD mAbs in the US context remains uncertain.

Cognitive and psychiatric comorbidities are among the most persistent and disabling challenges experienced by children and adults with epilepsy, with serious implications for daily functioning, health-care utilization, long-term social outcomes and quality of life. Traditionally, research has focused on epilepsy-specific biological risk factors, such as seizure frequency or epilepsy syndrome, but growing evidence indicates that non-medical factors also shape neurodevelopmental, cognitive and neurobehavioural trajectories. This Review explores how individual-level and neighbourhood-level social factors, including income, education, health-care access and neighbourhood deprivation, contribute to disparities in cognitive and neurobehavioural outcomes across the lifespan in people with epilepsy. We propose the SocioBioCognitive Epilepsy framework, which integrates biological and social factors to better explain the heterogeneity of these outcomes, emphasizing critical developmental windows. We also recommend strategies to address social contributors to epilepsy, including self-management programmes, integration of community health workers into care teams and policy initiatives to address social needs in clinical settings. We highlight the need for a paradigm shift in epilepsy care from a seizure-centric model to a strategy that embraces holistic approaches across medical, educational and community domains. Future research should investigate the reversibility of social factors, explore biological mechanisms that link social adversity to brain outcomes and evaluate the real-world impact of integrated interventions.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease. However, APOE-ε4 is not deterministic, highlighting the need to identify additional genetic and environmental factors. APOE-ε4 has been linked to accelerated cognitive decline, so we sought to investigate genetic factors that modify APOE-ε4–associated cognitive decline. We conduct cross-ancestry APOE-ε4-stratified and interaction GWAS using harmonized cognitive data from 32,778 participants, including 29,354 non-Hispanic White and 3,424 non-Hispanic Black individuals. Our primary outcome is late-life cognition, measured using harmonized composite scores for memory, executive function, and language, modeled as continuous traits reflecting both normative cognitive aging and disease-related decline. We identify two genome-wide significant loci in APOE-ε4 carriers, reaching genome-wide significance for executive function. These loci also demonstrate nominal associations across the other domains, suggesting broad effects on cognition. In non-carriers, we identify a genome-wide significant association at ITGB8 restricted to executive function, and another locus associated with language. We further link these loci to SEMA6D, GRIN3A, and ITGB8 through expression and methylation databases. Post-GWAS analyses implicate additional genes including SLCO1A2, and DNAH11. Genetic correlation analyses reveal differences by APOE-ε4 status for immune-related traits, suggesting immune-related predispositions may exacerbate cognitive risk in APOE-ε4 carriers.

INTRODUCTION: We standardized positron emission tomography (PET) data across multiple cohorts and tracers to characterize the frequency of amyloid and tau PET severity along the clinical continuum. METHODS: Clinical stage was defined using cohort-specific criteria and included cognitively unimpaired (CU), mild cognitive impairment (MCI), and dementia. Amyloid severity was staged using Centiloids (CL). Tau severity was staged using a hierarchical Braak-based schema. The cumulative probabilities of PET-based stages were estimated using ordinal logistic regressions. RESULTS: Among 10,396 individuals (mean [standard deviation] age: 71.9 [7.1] years), amyloid levels ≥ 25 CL increased with age among CU and MCI, while amyloid levels ≥ 100 CL were most common in dementia. In 3295 with tau PET, tau severity increased with amyloid and clinical stage and showed complex associations with age. Within each clinical stage, the full spectrum of amyloid and tau PET severity was observed. DISCUSSION: PET-based staging revealed heterogeneous amyloid and tau burden along the clinical continuum. HIGHLIGHTS: PET-based staging is feasible across multiple cohorts and PET tracers. There is heterogeneity in amyloid and tau severity across the clinical spectrum. The frequency of amyloid and tau PET severity increased with clinical severity. The likelihood of tau PET severity differed by age, amyloid, and clinical severity.