Association of Herpes Simplex Virus Type-1 With Dementia Outcomes: Longitudinal Retrospective Cohort Study Using Real-World Electronic Health Record Data
Background: Global dementia cases, currently exceeding 55 million, are projected to triple by 2050. In the absence of disease-modifying therapies, identifying modifiable risk factors is critical. Preclinical studies show that herpes simplex virus type-1 (HSV-1) is neurotropic and can drive amyloid-beta accumulation and tau hyperphosphorylation. Epidemiologic findings remain inconsistent, partly because many studies lack standardized designs for real-world data. Objective: To quantify the association between clinically coded HSV-1 diagnosis and incident cognitive impairment or dementia among patients receiving care in a health-system electronic health record (EHR) network. Methods: We assembled a retrospective cohort within an Observational Medical Outcomes Partnership (OMOP)–mapped EHR data lake (2010‐2024), comparing patients with a first HSV-1 diagnosis (n=6274) to those without HSV-1 codes but with parallel baseline criteria (n=379,975). Eligibility required at least 365 days of prior observation and absence of baseline cognitive, HIV, selected neurotropic viral, or recent transplant codes. The outcome combined mild cognitive impairment and Alzheimer disease and related dementias (ADRD). A high-dimensional propensity score (PS) incorporating approximately 17,000 baseline covariates was estimated with regularized logistic regression; 4 strata weights were applied in a Cox model. Sensitivity analyses examined equipoise trimming, doubly adjusted models, fixed 1-, 5-, and 10-year censoring horizons, and a dementia-only outcome subset. Negative-control outcomes (n=271) were prespecified to assess empirical calibration. Results: The HSV-1 cohort contributed 23,186 person-years (PY) and 469 events; the non-HSV-1 cohort contributed 1,519,827 PY and 24,764 events. Crude incidence was 20.23 (95% CI 18.44‐22.14) per 1000 PY in the HSV-1 cohort and 16.29 (95% CI 16.09‐16.50) in the non-HSV-1 cohort, an absolute difference of 3.94 events per 1000 PY. PS-stratified analysis yielded a hazard ratio (HR) of 1.14 (95% CI 1.03‐1.25; =.007). Estimates were comparable after equipoise trimming (HR 1.12, 95% CI 1.01‐1.25, =.04), doubly adjusted modeling (HR 1.13, 95% CI 1.02‐1.24, =.01), and fixed 5-year (=.008) and 10-year follow-up (=.004) (both HR 1.15). The 1-year censored model showed HR 1.00 (95% CI 0.84‐1.20; =.96). The dementia-only endpoint mirrored the primary analysis (HR 1.14, 95% CI 1.03‐1.25; =.008). No postindex events occurred for any negative-control outcome, so empirical calibration could not be performed and all estimates are uncalibrated. Conclusions: Within an OMOP-standardized EHR cohort, an HSV-1 diagnosis was associated with a small elevation in the hazard of subsequent cognitive impairment or dementia compared with individuals with no recorded HSV-1 diagnosis. Given the ubiquity of HSV-1, even a modest elevation in individual hazard could translate to a meaningful population-level increment if the association is causal. Confirmation in external data sets with laboratory viral typing, antiviral treatment records, and mortality linkage is warranted.
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Emerging Adults’ Experiences of Digital Measurement-Based Care in Routine Mental Health Care: Qualitative Study and Conceptual Synthesis
Background: Emerging adults (aged 18‐29 years) experience a high burden of mental health (MH) concerns during a developmental period marked by increasing autonomy and vulnerability to symptom onset. Many emerging adults face challenges in accessing and sustaining engagement with developmentally appropriate care. Digital measurement-based care (dMBC), which involves the routine use of patient-reported outcome measures (PROMs), has been introduced as an approach to support emerging adult engagement and improve responsiveness of care through ongoing monitoring and informed clinical decision-making. However, its integration into routine care remains variable, and there is limited understanding of how emerging adults experience and engage with dMBC in practice. Objective: This study aimed to examine how emerging adults experience dMBC within routine MH care and identify factors relevant to its use and integration in clinical practice. Methods: Using a descriptive qualitative design, semistructured interviews were conducted with 23 purposively sampled emerging adults who were either actively receiving care or had recently been discharged from 1 of 2 outpatient MH clinics in southern Alberta, Canada. dMBC was delivered through a web-based platform that enabled emerging adults to complete PROMs and view their results, which were also available to clinicians to inform care. All participants completed PROMs at baseline, with subsequent completion varying across participants and over the course of care. Interview data were analyzed using thematic analysis. Results: Four interconnected themes were identified and synthesized into a higher-level conceptual representation of emerging adults’ experiences with dMBC: technology, tracking, translation, and therapeutic guidance. Technology captured participants’ varied experiences with accessing and using the digital platform, including its usability and accessibility. Tracking reflected how monitoring PROM results over time supported reflection on changes in MH. Translation described how PROM data were interpreted and incorporated into therapeutic discussions, while therapeutic guidance reflected the role of clinician involvement in supporting the use of dMBC in care. Across the themes, participants described variation in the relevance and burden of measurement and in how consistently dMBC was integrated into clinical care. Conclusions: Emerging adults’ experiences of dMBC were shaped by both their interactions with digital measurement and the integration of PROMs into routine MH care. The findings highlight the importance of considering dMBC within the broader therapeutic context in which measurement occurs, rather than as a stand-alone digital activity. The conceptual synthesis provides a way of organizing these experiences and can inform future research and implementation efforts focused on the use of dMBC in emerging adult MH services.
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A Mobile App for Student Veterans With Co-Occurring Academic and Psychiatric Concerns: Pilot Usability and Feasibility Study
Therapist Skepticism and Adaptation to Teletherapy Under Enforced Uptake, With Theoretical Considerations for AI-Mediated Care: Qualitative Study
Comparative efficacy of neuromodulation techniques for Alzheimer’s disease: a systematic review and network meta-analysis of randomized controlled trials
Large language models for late-life depression: a blinded benchmark of clinical safety, geriatric appropriateness, and triage
Recovery-phase symptoms after COVID-19 infection and anxiety levels among college students
An Evidence-Based AI Virtual Assistant for Young People With Attention Deficit Hyperactivity Disorder: Co-Design and Prototype Development
Tool or Companion? Reframing Conversational AI to Prevent Psychological Harm
People increasingly turn to conversational AI for companionship, emotional support, and well-being, using both purpose-built companion apps, such as Replika and Character.AI, and general-purpose assistants, such as ChatGPT and Claude. While some evidence suggests potential benefits, including short-term reductions in loneliness and mood improvement, several adverse outcomes have been reported in both clinical and nonclinical populations, including emotional dependence, exacerbation of symptoms, and self-harm. The fluent and apparently empathic responses from these models lead users to engage with them not only as tools but also as if they were social entities. This framing is conceptually misleading and may pose risks across different user profiles, particularly for vulnerable individuals. Drawing on research in AI, psychiatry, psychology, and network science, we highlight mechanisms through which emotional reliance develops and the boundary between tool and companion erodes. Design choices that evoke personality and warmth encourage users to anthropomorphize these systems. Simulated empathy, generated through probabilistic language patterns rather than genuine emotional experience, creates a structurally asymmetric interaction, in which the user discloses and the system responds, but without reciprocity, vulnerability, or accountability. Overvalidation and sycophancy can reinforce maladaptive cognitions, delusional ideation, and distorted perceptions of reality, as they tend to reinforce people’s beliefs, even at the expense of the accuracy of models’ responses. These mechanisms are not incidental: they emerge from alignment procedures that reward responses perceived as warm and empathic. The result is a self-reinforcing feedback loop between the model and the user that may amplify maladaptive beliefs, delusional ideation, and emotional distress, even in those who engage for largely functional purposes. Understanding these dynamics requires an examination of both what these agents can do—considering their technical limitations and implementations—and what humans believe they can do, including social and psychological impacts. We argue that conversational AI should be treated primarily as a tool supporting human systems rather than as a substitute for human relationships. Perhaps more importantly, reviewing the current hype surrounding AI interactions can help reformulate a paradigm that contributes to human well-being and societal value, while minimizing misconceptions, maladaptive interactions, or social disintegration.
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