Namhee Kim

Background: Benzodiazepines (BZDs) are commonly prescribed for anxiety, insomnia, and muscle relaxation, but concerns remain regarding their potential long-term cognitive effects. Prior reviews have reported inconsistent associations between BZD use and cognitive risk, often limited by methodological heterogeneity and unresolved biases. Objective: This systematic review critically evaluates the evidence on BZD exposure and cognitive outcomes, with a specific focus on study design, potential biases, and other factors of methodological heterogeneity. Methods: Following PRISMA 2020 guidelines, we searched PubMed and Google Scholar for studies published between 2010 and 2025. The final search was conducted on 1 July 2025. Eligible studies assessed cognitive performance or incident dementia in community-dwelling adults with regard to BZD use. One reviewer independently screened titles, abstracts, and full texts to determine the eligibility of each study. The other two reviewers participated in the inclusion and exclusion decisions. Any disagreements were resolved by consensus among all three reviewers to minimize bias. No statistical data handling, data conversions, or missing imputation was conducted, as this review did not include quantitative synthesis or meta-analysis. Results: Of 79 references screened by titles, abstracts, and full texts, seventeen articles met the inclusion criteria for this review. Participants in the cohort studies were mostly older adults and cognitively healthy at baseline, while those from case–control studies were dementia patients and their matched controls. Overall, findings remain inconsistent, with five studies reporting an association between BZD use and cognition in the entire cohort, six reporting effects only in specific contexts or subgroups, and six finding no evidence at all. Potential contributing factors to this variability include protopathic bias, operational definitions of BZD exposure, and whether analyses were stratified by factors such as sex, drug half-life, or dose. Conclusions: Due to inconsistencies among findings and limitations in study design rigor, the current review cannot determine whether BZDs independently raise cognitive risk. Future research should adopt more rigorous study designs, with particular attention to addressing protopathic bias, and clarify limitations related to the operational definition of BZD. In addition, our findings support the need for further investigation of BZD association with vulnerable populations, including those with sex-specific susceptibility, low socioeconomic status, and exposure to high-risk prescribing practices.

Background: Canine leishmaniasis is notoriously difficult to manage by chemotherapy alone, necessitating the consideration of supplemental or alternative treatment. Evidence is presented to support the feasibility of immunotherapy of diseased dogs through vaccination. Methods: The vaccine format used consisted of cultured promastigotes of Leishmania infantum, which were rapidly and completely killed by intracellularly generated singlet oxygen. A total of 33 owned dogs of different breeds and ages diagnosed positive for leishmaniasis were enrolled and divided into three groups for treatments as follows: (1) immunotherapy alone (9 dogs); (2) immunotherapy after chemotherapy (14 dogs); and (3) chemotherapy alone (10 dogs). All dogs in Groups 1 and 2 received intradermally three identical dosages of the vaccine format mentioned at the same schedules. The outcomes were assessed for one year at a post-treatment interval of 2–4 months by determining lymph node parasite loads and clinical scores based on established methodologies. Results: Spaghetti plots of the values for parasite loads obtained revealed that they scattered widely over time with a significant decline by 8–12 months post-treatment in all three groups. Sankey plots of clinical scores in stacked bars also showed that they followed erratic patterns of flow over time, albeit toward lower levels in all cases. Ordinal logistic regression analysis of clinical scores indicated that, while the odds for the emergence of severe clinical symptoms declined in all three groups, the lowest risk was associated with Group 2 dogs treated with immunotherapy after chemotherapy. The evidence presented thus suggests that immunotherapy of the diseased dogs with the vaccine format diminished their parasite loads and improved their clinical scores, especially when applied after chemotherapy. Dogs in Groups 1 and 2 that received immunotherapy, on average, lived twice as long as those in Group 3 that received chemotherapy alone. The risk of death estimated by analysis of the clinical scores using the Cox proportional hazard model was also found to be lower for Groups 1–2 dogs receiving immunotherapy than those in Group 3 receiving chemotherapy alone. Conclusions: Post-therapeutic survival time thus may be an additional parameter suitable to assess treatment efficacy by vaccination. In vitro approaches to mitigate some limitations of this study were proposed for future investigation.

The Mini-Mental State Examination (MMSE) is a widely employed screening tool for the severity of cognitive impairment. Among the MMSE items, the pentagon copying test (PCT) requires participants to accurately replicate a sample of two interlocking pentagons. While the PCT is traditionally scored on a binary scale, there have been limited developments of granular scoring scale to assess task performance. In this paper, we present a novel three-stage algorithm, called Quantification of Interlocking Pentagons (QIP) which quantifies PCT performance by computing the areas of individual pentagons and their intersection areas, and a balance ratio between the areas of the two individual pentagons. The three stages of the QIP algorithm include: (1) detection of line segments, (2) unraveling of the interlocking pentagons, and (3) quantification of areas. A set of 497 PCTs from 84 participants including their baseline and follow-up PCTs from the Rush Memory and Aging Project was selected blinded about their cognitive and clinical status. Analysis of the quantified data revealed a significant inverse relationship between age and balance ratio (beta = − 0.49, p = 0.0033), indicating that older age was associated with a smaller balance ratio. In addition, balance ratio was associated with perceptual speed (r = 0.71, p = 0.0135), vascular risk factors (beta = − 3.96, p = 0.0269), and medical conditions (beta = − 2.78, p = 0.0389). The QIP algorithm can serve as a useful tool for enhancing the scoring of performance in the PCT.

Backgrounds Linear association has widely been assumed for prediction of aging-related fractional anisotropy (FA) decline in white matter of the brain. While useful for testing significance of the aging effect, it fails to identify a threshold age before and after which the age-FA association changes. Identification of such a threshold is often of clinical interest for timely intervention. Methods We employed a sigmoidal growth function to test a threshold effect in age triggering onset of cerebral decline in 21 white matter tracts, and compared its fitting performance to those of linear, and power regression. The study sample was a normal healthy cohort of 106 participants with ages in mid-life ranging from 18 to 60 years. Results Of the 21 white matter tracts analyzed, the posterior thalamic radiation showed better fit with sigmoidal curve model, compared to a linear or power regression. The estimated threshold age in years (95% confidence interval) were 47.2 (44.1-48.4). Conclusion While available evidence regarding the presence of a specific age threshold for cerebral decline in mid-life based on FA was limited, the posterior thalamic radiation exhibited a threshold age of 47.2. Beyond this age point, we observed a significant change in the FA risk pattern.

The Mini-Mental State Examination (MMSE) is a widely employed assessment tool for measuring the severity of cognitive impairment. Among the MMSE items, the pentagon copying test (PCT) requires participants to accurately replicate a sample of two interlocking pentagons. While the PCT are traditionally scored on a binary scale, there has been limited developments of granular scoring scale to assess task performance. In this paper, we present a novel three-stage algorithm, called Quantification of Interlocking Pentagons (QIP), which quantifies PCT performance by computing the areas of individual pentagons and their intersection areas, and a balance ratio between the areas of the two individual pentagons. The three stages of the QIP algorithm include: (1) detection of line segments, (2) unraveling of the interlocking pentagons, and (3) quantification of areas. The QIP algorithm was applied to 497 cases from 84 participants. Analysis of the quantified data revealed a significant inverse relationship between age and balance ratio between two pentagon areas (beta = -0.49, p = 0.0033), indicating that older age was associated with a smaller balance ratio. The QIP algorithm enhanced the scoring of performance in the PCT. It can serve as a useful tool for granular level scoring of PCT.

Background: The role of cervical muscle (neck) strength in traumatic brain and spine injury and chronic neck pain disorders is an area of active research. Characterization of the normal ranges of neck strength in healthy young adults is essential to designing future investigations of how strength may act as a modifier for risk and progression in head and neck disorders.Objective: To develop a normative reference database of neck strength in a healthy young adult population, and to evaluate the relationship of neck strength to anthropometric measurements.Design: Cross‐sectional.Setting: An academic medical center research institution.Participants: A total of 157 healthy young adults (18‐35 years of age) had their neck strength measured with fixed frame dynamometry (FFD) during 1 visit to establish a normative neck strength database.Interventions: Not applicable.Main Outcome Measurements: Peak and average strength of the neck muscles were measured in extension, forward flexion, and right and left lateral flexion using FFD. The ranges of peak and average neck strength were characterized and correlated with anthropometric characteristics.Results: In all, 157 subjects (84 male, 73 female; average age 27 years) were included in the normative sample. Neck strength ranged from 38 to 383 Newtons in men and from 15 to 223 Newtons in women. Normative data are provided for each gender in all 4 directions. Weight, body mass index, neck circumference, and estimated neck muscle volume were modestly correlated with neck strength in multiple directions (correlation coefficients < .4). In a multivariate regression model, weight in women and neck volume in men were significant predictors of neck strength.Conclusions: Neck strength in healthy young adults exhibits a broad range, is significantly different in men from that in women, and correlates only modestly with anthropometric characteristics.Level of Evidence: Not applicable.