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.]

Age-related macular degeneration (AMD) is associated with mitochondrial dysfunction and oxidative stress, yet the relationship between mitochondrial remodeling, redox homeostasis, and disease progression remains poorly understood. Nonhuman primates (NHPs) develop spontaneous AMD-related phenotypes, including punctate deposits and soft drusen, providing a unique animal model to investigate mitochondrial pathology in the aging retinal pigment epithelium (RPE). We integrated quantitative mitochondrial ultrastructural profiling with flavoprotein fluorescence imaging, plasma metabolomics, and whole-exome sequencing to characterize mitochondrial and redox alterations in aged rhesus macaques with AMD-related lesions. Flavoprotein fluorescence imaging demonstrated increased metabolic heterogeneity in eyes with soft drusen, consistent with altered mitochondrial redox states and oxidative stress. Morphometric analysis identified distinct mitochondrial remodeling patterns across phenotypes. Normal aging was characterized by concentric cristae and type I paracrystalline inclusions. Eyes with punctate deposits exhibited increased mitochondrial fusion-associated morphology, hyperbranching, and type I paracrystalline inclusions, consistent with a stress-responsive mitochondrial remodeling pattern. In contrast, eyes with soft drusen exhibited reduced fusion-associated morphology, reduced structural complexity, and ultrastructural features consistent with mitochondrial deterioration. These ultrastructural patterns were accompanied by distinct plasma metabolomic signatures. Punctate deposits were associated with altered glycolytic, tricarboxylic acid cycle, and redox-buffering metabolites, consistent with differences in stress-responsive metabolism, whereas soft drusen exhibited metabolomic signatures consistent with altered redox homeostasis. Whole-exome sequencing identified a mitochondrial DNA variant, MT:9582G > A, in cytochrome c oxidase subunit III (COX3) associated with the drusen phenotype. Collectively, these findings identify distinct mitochondrial remodeling patterns associated with AMD-related phenotypes in aged rhesus macaques. The convergence of ultrastructural, imaging, metabolomic, and genetic analyses suggests that punctate deposits and soft drusen are associated with different mitochondrial and redox-related responses to chronic retinal stress. These findings provide a framework for future studies investigating mitochondrial biology and redox-driven mechanisms in AMD.

Objective: People with epilepsy of childbearing potential in low-resource settings face unique challenges related to anti-seizure medication (ASM) selection and access. These challenges may be particularly pronounced in regions where neurocysticercosis (NCC), a leading cause of acquired epilepsy worldwide, contributes substantially to the burden of disease. We characterized ASM prescribing patterns and factors associated with the use of higher-risk medications among people with epilepsy of childbearing potential in northern Peru. Methods: We analyzed data from females aged 15-49 years who were enrolled in a prospective, population-based epilepsy cohort in Tumbes, Peru, from 2006 to 2020. ASMs were categorized according to pregnancy-associated safety profiles as Lower-risk (lamotrigine, levetiracetam, oxcarbazepine, clonazepam, diazepam), Intermediate-High risk (carbamazepine, phenytoin, phenobarbital, topiramate), and Highest-risk (valproic acid). We evaluated ASM utilization, polytherapy, and factors associated with valproate use, the highest-risk medication. Results: Among 1,975 individuals with epilepsy, 685 were of childbearing potential. Approximately one-third met criteria for probable or definite NCC (34.9%). Nearly all participants (98.6%) were prescribed carbamazepine, phenytoin, phenobarbital, or valproic acid, while use of newer-generation agents was rare. Most prescriptions (86.3%) were classified as Intermediate-High-risk, and 12.8% as Highest-risk. In multivariable analyses, prior ASM use and polytherapy were independently associated with receipt of valproate. Discussion: In this population-based epilepsy cohort from northern Peru, ASM treatment among people of childbearing potential was overwhelmingly limited to older medications with an elevated risk of teratogenicity. These prescribing patterns likely reflect medication availability rather than clinical preference and highlight the challenges of implementing guideline-recommended epilepsy care in resource-constrained settings. Given the substantial burden of NCC-related epilepsy in this population, improving access to safer and more diverse ASM options may represent an important strategy for reducing treatment inequities among people with epilepsy of childbearing potential.

The increasing prevalence of cannabis use, including among pregnant women, highlights the critical need for a deeper understanding of prenatal cannabis exposure. This study aimed to develop a standardized cross-species inhalation exposure protocol to administer the principal psychoactive component of cannabis, Δ9-tetrahydrocannabinol (THC), to prairie voles (Microtus ochrogaster) and laboratory rats (Rattus norvegicus), and to investigate the distribution of THC in maternal and fetal tissues following prenatal exposure. Using an established e-cigarette system for delivering vaporized THC, we administered THC to pregnant prairie voles and rats. THC concentrations were measured in maternal plasma and fetal brain tissue using LC-MS/MS (liquid chromatography coupled with tandem mass spectrometry). We found that THC readily crossed the placental barrier in both species, resulting in significantly higher concentrations of THC in the fetal brain within the THC-exposed groups compared to the vehicle controls. Interspecies comparison revealed higher THC concentrations in rat fetal brain tissue compared to prairie voles. No significant effects of fetal position on THC levels were found for either species. The findings confirm placental transfer of THC and reveal species-specific patterns of THC distribution. Additional studies were then carried out in voles to compare plasma and brain THC levels in maternal and virgin adult prairie voles. Maternal brain THC concentrations were significantly higher than fetal brain concentrations in prairie voles. This study establishes a translational model for investigating prenatal cannabis exposure using an aerosolized administration method in voles compared to established methods in rats. The standardized protocol and results provide a foundation for future research into the developmental consequences of prenatal cannabis exposure and offer crucial insights for informing public health policies and clinical practices in response to the global increase in cannabis use.

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.