Search Results (92)

Background: People living with dementia (PLWD) are at increased risk for medical complications, including urinary tract infections (UTIs), which are often presented atypically with delirium or behavioral changes. These atypical presentations frequently prompt psychiatric consultation and complicated medical management. As the aging population grows, understanding how dementia influences UTI-related outcomes is critical for C-L psychiatrists working at the interface of medicine and psychiatry. Methods: This retrospective cohort study used the 2021 National Inpatient Sample (NIS) to identify adult inpatients with a principal diagnosis of UTI. Patients were stratified by the presence of a comorbid dementia diagnosis. Multivariate logistic and linear regression models adjusted for demographic, clinical, and hospital-level covariates were used to examine associations between dementia and outcomes: in-hospital mortality (primary), length of stay (LOS), hospital charges, and discharge disposition (secondary). Adjusted models included available demographic, socioeconomic, comorbidity, and hospital-level covariates, including age, sex, race/ethnicity, median household income quartile by patient ZIP code, insurance type, Charlson Comorbidity Index, hospital region, urban hospital location, and hospital teaching status. Results: Among 295,494 hospitalizations for UTI, 78,990 (26.7%) involved patients with dementia. Compared to those without dementia, PLWD were significantly older (mean age 82.5 vs. 69.5 years), more likely to be female, and had greater comorbidity burden. Adjusted analyses revealed that dementia was linked to higher odds of in-hospital mortality (aOR: 1.28, 95% CI: 1.03–1.58), longer LOS (+0.93 days, p < 0.01), and increased hospital charges (+$3243.50, p < 0.01). Additionally, PLWD had lower odds of discharge to home (aOR: 0.53) and higher odds of discharge to skilled nursing facilities (aOR: 1.94). Conclusions: Among patients hospitalized with a principal diagnosis of UTI, comorbid dementia was linked with higher in-hospital mortality, longer length of stay, higher hospital charges, and lower likelihood of discharge home. These findings should be interpreted in the context of important limitations of administrative data, including residual confounding and inability to distinguish symptomatic UTI from asymptomatic bacteriuria. Full article

Background/Objectives: Current trends show a significant increase in Alzheimer’s disease and related dementias (ADRD) rates, reflecting a growing need for interventions. Recently, non-pharmacological interventions have received increased recognition as a viable option for ADRD prevention and disease modification. The current study focuses on a music-based community engagement program, titled B Sharp, to investigate the effects of music experiences on domain- and subtest-specific cognitive processing in ADRD. Methods: Participants were provided season tickets (six performances over ten months) to a local MasterWorks Symphony. Across the program’s three seasons (18 individual musical performances), a total of 55 individuals with ADRD participated. Subtest- and domain-specific changes in cognition were assessed before and after each individual symphony performance of 1.5–3 h duration. Variables of interest include auditory-verbal (N = 67) and visuospatial (N = 49) cognitive subtests. Results: In a comparison of pre- and post-symphony performance scores, results indicate statistically significant improvements on a visuospatial working memory task (Coding) (p = 0.021) and statistically significant decline on verbal working memory/immediate memory (List Learning/Story Memory) (p = 0.045). Significant differences were not observed on the remaining subtests. Discussion: Results suggest that even brief exposure to music results in cognitive benefits on visuospatial working memory and contribute to a body of findings which suggest that non-pharmacological arts-based programs may be beneficial for adults with ADRD for specific types of cognition, even for single or sporadic attendance. As research in arts programming increases, it is hoped that findings will guide how to apply various types of programs for specific cognitive deficits accompanying ADRD. Full article

Background: Alzheimer’s disease (AD) and dementia are growing global health challenges, yet public understanding of these conditions remains poorly characterized. Methods: This study analyzed 17,578 English-language tweets from Twitter/X collected throughout 2024 to characterize public discourse using dual sentiment analysis and topic modeling. Sentiment was assessed using two lexicon-based tools, VADER (Valence Aware Dictionary and sEntiment Reasoner) and TextBlob, with inter-method agreement evaluated via Cohen’s Kappa and confusion matrix analysis. Latent Dirichlet Allocation (LDA) with coherence-based model selection (c_v) identified latent discussion topics. Results: All reported sentiment proportions are tool-specific estimates rather than absolute characterisations of public discourse and should be interpreted in light of the fair inter-method agreement observed between VADER and TextBlob. VADER classified 43.3% of tweets as positive, 32.2% as negative, and 24.5% as neutral (mean compound score = 0.065, SD = 0.499; 95% CI: 0.058 to 0.073; note that the large SD relative to the mean reflects the broad, near-zero-centred distribution of compound scores). TextBlob produced a partially divergent distribution (45.9% positive, 36.2% neutral, 17.8% negative) with fair inter-method agreement (κ = 0.297), indicating that exact sentiment proportions depend meaningfully on the choice of classifier. Approximately 14% of tweets contained political content related to the U.S. presidential election cycle, which may represent an important source of noise in health discourse. LDA identified six optimal topics (c_v = 0.407): research studies, blood-based diagnostics, comorbidities and personal loss, research advocacy, clinical developments, and risk factors and treatment. Sentiment differed significantly across topics (Kruskal–Wallis H = 235.92, p < 0.001), with research and advocacy topics showing the most positive VADER-classified sentiment (50.0%) and comorbidity discussions showing the highest negative proportion (41.4%). Positive tweets received significantly higher engagement than negative tweets (Mann–Whitney p < 0.001), though follower count was the strongest predictor of engagement (β = 0.198). Conclusions: These findings, interpreted as tool-conditional estimates, have implications for health communication strategies, public education campaigns, stigma reduction, and the responsible design of social media-based health surveillance systems. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder traditionally characterized by the extracellular accumulation of amyloid-beta (Abeta) plaques and the formation of intracellular neurofibrillary tau tangles; however, the prevailing scientific paradigm has shifted toward an integrative model of pathogenesis that recognizes neuroinflammation as a critical, self-perpetuating driver of cognitive attrition. This multifaceted interplay is mediated by the brain–body axis, wherein chronic systemic inflammation—stemming from metabolic dysfunction, cardiovascular disease, or environmental stressors such as fine particulate matter PM_2.5—compromises the structural integrity of the blood–brain barrier. Such environmental insults serve as priming agents for the innate immune system, shifting peripheral immune populations toward a pro-inflammatory phenotype that is further exacerbated by the stabilization of hypoxia-inducible factors (HIFs) through oxidative stress-induced pseudohypoxia, even under normoxic conditions. The subsequent activation of microglia and astrocytes transitions the cerebral microenvironment from a homeostatic, neurosupportive state into a neurotoxic milieu that actively promotes synaptic loss and neuronal death. Consequently, contemporary research has pivoted from broad-spectrum anti-inflammatory interventions toward targeted immune modulation, emphasizing that a comprehensive understanding of how systemic dysfunction perpetuates neuroinflammatory cascades is essential for developing efficacious therapies capable of attenuating AD progression and mitigating its global health burden. Full article

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by memory loss and cognitive decline, reflecting widespread brain dysfunction across multiple neural systems. Early detection of pathological changes is critical for enabling timely intervention, improved management, and better therapeutic outcomes. Methods: Using non-transgenic AD rats (Samaritan) and sham rats (Long–Evans), we explored structural and functional differences with multimodal MRI and multi-unit activity (MUA). Results: Diffusion tensor imaging (DTI) revealed no significant changes in mean diffusivity of water, but AD-related microstructural alterations of fractional anisotropy were confined to subcortical regions with cortical areas and white matter tracts remaining intact. We used functional MRI (fMRI) with blood oxygenation level-dependent (BOLD) contrast in rest-state (R-fMRI) and task-based (T-fMRI) paradigms. R-fMRI revealed much stronger functional connectivity in subcortical vs. cortical areas in AD rats, implicating AD-related functional changes in subcortical areas in agreement with DTI data. T-fMRI with sensory stimulation revealed reproducible fMRI responses in both groups; however, AD rats exhibited reduced BOLD response amplitude and spatial activation extent, which was accompanied by attenuated stimulus-evoked MUA responses. These suggest that attenuated evoked BOLD response reflects diminished neuronal activity in AD, rather than impaired neurovascular and/or neurometabolic coupling. Conclusions: Together these findings suggest that AD-induced anatomical and functional changes in subcortical areas are related to altered cortical responses, highlighting multimodal MRI as a sensitive tool for early AD-related brain changes. Full article

Background/Objectives: Persons living with dementia (PLwD) receive informal care services from loved ones, commonly referred to as care partners (CPs). While the symptoms (e.g., depressive affect, cognitive impairment) experienced by PLwD are recognized to influence CP wellbeing, longitudinal investigations into the association of CP QoL and PLwD symptoms have yet to be fully explored. The present study sought to address this gap and highlight how CP QoL and PLwD symptoms systematically covary over time. Methods: Participants were composed of 33 dyads (PLwD and their CP) who partook in the Voices in Motion project, a social-cognitive intervention for dementia. CP QoL (WHOQOL-BREF), PLwD depressive symptomology (Patient Health Questionnaire-9) and PLwD global cognitive functioning (Mini-Mental State Examination) were assessed every three to four weeks in an intensive repeated-measures design. Time-varying covariation models using multilevel modeling examined systematic covariation between CP QoL and PLwD symptoms between and within dyads. Results: Increased CP psychological and social QoL were both associated with increased PLwD global cognitive functioning between dyads and vice versa (p < 0.05). Within dyads, increased CP social QoL was associated with improved PLwD depressive symptoms (p < 0.05), while increased CP environmental QoL was associated with increased depressive symptoms (p < 0.05). Conclusions: Significant coupling associations were observed both between and within dyads. Such results highlight the association between CP QoL and the symptoms experienced by their care recipient and provide important, novel longitudinal contributions to the literature. Full article

Background/Objectives: Alzheimer’s disease (AD) disproportionately affects women, who account for nearly two-thirds of affected individuals worldwide. This sex imbalance cannot be explained by longevity alone and likely reflects complex interactions among biological sex, endocrine aging, genetic susceptibility, and brain-specific mechanisms of vulnerability. Neuroimaging has played a pivotal role in characterizing these sex-related differences in vivo, enabling the assessment of amyloid-β deposition, tau propagation, neurodegeneration, cerebral glucose metabolism, and network reorganization. This invited review examines AD through a rigorously sex-specific neuroimaging perspective, with particular emphasis on implications for women’s brain health. Methods: We integrated evidence from structural MRI, FDG-PET, amyloid-PET, tau-PET, estrogen receptor PET, diffusion MRI, and fluid biomarkers, together with epidemiological, molecular, genetic, and endocrine studies. The review focuses on female-specific trajectories of AD initiation and progression, highlighting the contribution of neuroendocrine aging, menopause, metabolic dysfunction, and sex-modulated genetic risk factors. Results: Available evidence indicates that women exhibit distinct biological and neuroimaging signatures across the AD continuum. Menopause emerges as a critical neuroendocrine transition associated with metabolic decline, altered brain connectivity, increased amyloid and tau vulnerability, and progressive neurodegeneration. Female-specific patterns of tau propagation and sex-dependent interactions with genetic risk factors further contribute to differential disease trajectories. Advanced multimodal neuroimaging approaches have substantially improved the characterization of these mechanisms and their relationship with cognitive decline and clinical progression. Conclusions: A sex-specific neuroimaging framework is essential to improve understanding of AD pathophysiology and to advance precision medicine approaches tailored to women’s brain health. Recognition of endocrine aging and female-specific biological vulnerability may inform earlier identification of at-risk individuals and the development of targeted prevention and treatment strategies. Future research should prioritize sex-aware longitudinal studies and multimodal biomarker integration to optimize personalized interventions in AD. Full article

Dementia affects approximately 55 million people worldwide, yet the psychological experience of diagnosis and the determinants of post-diagnostic well-being remain underexplored relative to biomedical research priorities. The existing literature has been predominantly deficit-oriented, focusing on cognitive decline, neuropsychiatric symptoms, and carer burden, with limited attention to preserved psychological capacities and what supports flourishing following diagnosis. This narrative review applies a positive psychology framework to synthesise evidence on meaning, purpose, hope, and post-diagnostic adjustment in early-stage dementia. A central empirical observation motivating the review: the well-being paradox—subjective well-being in early-to-moderate dementia is frequently higher than carers and clinicians predict. It is also more strongly associated with psychosocial variables than with objective cognitive status. Evidence from the IDEAL (Improving the experience of Dementia and Enhancing Active Life) cohort and related longitudinal research demonstrates that emotional responsiveness, need satisfaction, and capacity for meaning-making are preserved in early-stage dementia and constitute clinically relevant assets. Four positive psychology constructs are identified as evidence-based targets for intervention: hope, self-compassion, social identity, and meaningful engagement. Clinical implications include integrating strengths-based assessment, meaning-centred group interventions, structured peer support, and validated positive outcome measures into post-diagnostic care pathways. Health equity considerations and research priorities are addressed, including the underrepresentation of minority ethnic communities and people with young-onset dementia in existing research. The review argues that meaningful progress requires deliberate reorientation of clinical, commissioning, and research priorities toward a positive psychology framework for dementia care. Full article

Background: Dementia and Type 2 diabetes (T2D) represent two of the most pressing global public health challenges of our time, both exacerbated by physical inactivity. These conditions disproportionately affect Global Majority populations, who experience earlier onset, higher prevalence, and poorer access to culturally appropriate preventive care. However, conventional research and interventions often overlook the sociocultural and structural factors that underpin this disparity. This study synthesises current evidence to understand how these three conditions intersect and to identify equitable pathways for prevention and support. Methods: A meta-narrative review approach was employed to integrate evidence from diverse biomedical, public health, sociocultural and intervention science traditions. Searches were undertaken across MEDLINE/PubMed-adapted searches, CINAHL, PsycINFO, Web of Science Core Collection, AMED and ASSIA, supplemented by grey literature searching and citation chasing. Five meta-narratives were identified: biomedical and epidemiological, public health, health disparities, sociocultural and behavioural, and intervention science. Cross-narrative synthesis produced a conceptual framework linking upstream determinants, lifestyle factors, and disease outcomes. Results: The review revealed that structural inequities such as deprivation, environmental barriers and sociocultural factors including stigma, gendered norms, limited access to culturally appropriate facilities that restrict physical activity (PA) opportunities within Global Majority communities. These constraints elevate T2D and dementia risk through biological pathways involving insulin resistance, vascular injury, and neuroinflammation. Community-based participatory research (CBPR) interventions particularly those delivered in trusted cultural or faith settings emerged as effective strategies to improve PA, glycaemic control, and cognitive well-being. Conclusions: This synthesis reframes dementia and diabetes as interlinked within a wider syndemic driven by structural and sociocultural inequities. The proposed framework underscores the importance of culturally grounded, community-led approaches to promote brain health, reduce risk, and achieve equitable healthy ageing among Global Majority populations. Full article

Dietary polyphenols such as quercetin, resveratrol, and (−)-epigallocatechin-3-gallate (EGCG) have shown neuroprotective effects in epidemiologic and experimental studies of Alzheimer’s disease (AD), although clinical evidence remains limited. This review highlights the importance of investigating glucuronide and sulfate conjugates of these polyphenols, as well as their intestinal microbial metabolites, at bioavailable low nanomolar concentrations, particularly those capable of reaching the brain. Although many in vitro studies use micromolar concentrations of aglycones, the relevance of such concentrations to neuroprotection remains uncertain. While polyphenols are redox-sensitive, their direct antioxidant or prooxidant effects may be limited at nanomolar concentrations. Instead, their neuroprotective actions appear to be mediated through high-affinity interactions with molecular targets such as the 67-kDa laminin receptor (67LR). This receptor binds both aglycones and conjugates at low nanomolar concentrations through a peptide G region containing glycosaminoglycan- and palindromic sequence-related motifs. The same region also binds the prion–amyloid-β complex, suggesting that polyphenols may antagonize amyloid-β binding and thereby prevent its neurotoxicity. The peptide G region may also function as a redox sensor. Binding of polyphenols to 67LR activates cAMP signaling and downstream neuroprotective pathways involving CREB, SIRT1, and protein phosphatase 2A. In addition, nanomolar concentrations of resveratrol and quercetin inhibit quinone reductase 2, an enzyme associated with cognitive decline and reported to be elevated in AD. Given their low bioavailability in the brain and their distinct molecular targets, combining multiple polyphenols at low doses may produce additive or synergistic effects, enhance efficacy, and minimize potential toxicity in the prevention of AD. Full article

Background/Objectives: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder for which MRI-based AI systems are increasingly used for diagnosis and prognosis. However, many published approaches remain misaligned with the requirements of trustworthy clinical use. Predicted risks are often poorly calibrated, explanations are frequently limited or non-actionable, guideline-aligned reporting is uncommon, and longitudinal prediction is inconsistently evaluated. In this paper, we conduct a PRISMA-guided structured review with scoping-style breadth of MRI-centric AI methods for AD diagnosis. This design supports a theme-based synthesis across heterogeneous study designs and is intended to summarize the current evidence base and derive practical design requirements for next-generation, clinically oriented pipelines that integrate calibrated staging, explainable outputs, and longitudinal risk modeling. Methods: Searches were conducted across Scopus, PubMed/PMC, and arXiv/bioRxiv (2014–2026; English; human AD/MCI imaging) and were supplemented by backward and forward snowballing. These searches yielded 2460 records. After deduplication, screening, and full-text eligibility assessment, 90 papers were included in the final synthesis. The included literature was organized into thematic streams spanning counterfactual reasoning and explainable AI (XAI), vision–language approaches for report and caption generation, longitudinal and survival-style modeling, and multimodal fusion and transformer-based methods combining MRI with clinical variables and other biomarkers. Vision–language methods were considered together with retrieval-augmented paradigms. Results: Key findings are that the field has shifted toward transformer architectures and multimodal fusion and shows increased interest in richer explanation mechanisms. Nevertheless, calibration metrics and robustness checks are inconsistently reported, external site-held-out validation and subgroup analyses remain relatively uncommon, and guideline-aligned structured reporting with explicit numeric provenance is rare. Vision–language and retrieval-augmented reporting methods are far more mature in general radiology than in AD MRI, highlighting a translational opportunity. Conclusions: Based on these findings, we recommend standardized reporting of classification calibration and longitudinal risk calibration, stronger site-held-out validation with subgroup robustness evaluation, clinically meaningful counterfactuals, and guideline-aligned reporting with reproducible numeric provenance embedded within reproducible pipelines. Full article

Background: The Testamentary Capacity Assessment Tool (ΤCAT) is a brief instrument with good psychometric properties, specifically designed for the assessment of testamentary capacity (TC) in individuals with dementia. It assesses memory, perception of financial matters, and judgment, as well as cognitive functions, such as theory of mind, not measured by other traditional tools. Additionally, it does not require collateral sources of financial information. The aim of the present study was to provide an updated report on the use of the TCAT in research and systematic review studies. Methods: This narrative review includes studies that have used the TCAT for clinical use, validation in different cultures, and comparison with the two other specialized TC assessment tools. The PubMed database was searched using the keyword “Testamentary Capacity Assessment Tool”. Results: The TCAT has been validated in a healthy Italian population and was found to be a useful adjunct instrument for TC assessments in older adults. Another study demonstrated its clinical utility in patients with acute ischemic stroke. A systematic review compared the TCAT to the other two existing specialized TC assessment tools, namely the Testamentary Capacity Instrument (TCI) and the Testamentary Definition Scale (TDS), highlighting the superiority of the TCAT in clinical practice. Conclusions: The TCAT is a useful, specialized screening tool that is easily applicable in clinical practice by both experts and non-experts. Further studies are recommended across different cultures, in both healthy and cognitively impaired adults, to support its standardized use in forensic and clinical settings. Full article

Introduction: Delirium in older adults is strongly associated with and can predate dementia. While GLP-1 receptor agonists (GLP-1 RAs) may provide neuroprotective benefits, their role in reducing dementia risk among older patients with type 2 diabetes mellitus (T2DM) and prior delirium is unclear. This study compares the effectiveness of GLP-1 RAs and metformin in preventing dementia among patients with a history of delirium using an extensive healthcare database. Methods: A retrospective cohort study was conducted from 2005 to 2025 using data from the TriNetX Global Federated Research Network. We identified adults aged 65 and older with T2DM and delirium, who received either GLP-1 RAs (exposure) or metformin (control). Propensity score matching (PSM) was performed. We determined dementia outcomes and all-cause mortality using Kaplan–Meier survival curves, Cox proportional hazards models, and estimated odds ratio (OR). Subgroup analyses were conducted by age, sex, race, body mass index (BMI), and dementia types. Results: In a study involving 23,980 patients treated with GLP-1RAs and 23,980 matched patients treated with metformin, the mean age was 74 years, with 53% being female. The use of GLP-1RAs therapy was associated with a significantly lower risk of dementia compared to metformin among adults aged 65 years and older with T2DM with delirium with the adjusted hazard ratio (AHR) for dementia was 0.778 [95% confidence interval (CI): 0.736–0.822 p < 0.0001], and OR was 0.617 (95% CI: 0.582–0.655 p < 0.0001). The reduction in dementia risk varied by age, race, BMI, and dementia type. We observed a time-dependent decrease in mortality risk with GLP-1 RA users. Conclusions: In older adults with T2DM and delirium, GLP-1 RA therapy was associated with a reduced risk of dementia compared with metformin. Variations in subgroups suggest individualized treatment. Prospective randomized controlled trials are needed to confirm these findings and clarify differential effects across various subgroups. Full article

Background: Sleep disturbance is highly prevalent in dementia syndromes and increasingly viewed as a correlate of disease expression, not just ageing. This study investigated associations between subjective sleep quality, cognitive performance, and structural MRI markers in a dementia syndromes sample, comparing Alzheimer’s disease (AD) and non-AD groups, with exploratory inclusion of objective sleep and nocturnal blood pressure in a sub-sample. Methods: Observational cross-sectional design with 128 memory clinic patients (41 AD, 87 non-AD). Subjective sleep quality assessed via Pittsburgh Sleep Quality Index (PSQI). Cognitive measures: Mini-Mental State Examination (MMSE) for global cognition, Symbol Digit Modalities Test (SDMT) for processing speed, Trail Making Tests (TMT-A/B), and CLOX-1/2 for executive function. MRI markers: Scheltens scale (medial temporal atrophy), Fazekas scale (white matter hyperintensities). An exploratory sub-sample (N = 24) included additional nocturnal and daytime blood pressure monitoring; these data were analyzed descriptively and are reported as hypothesis-generating only. Analyses: group comparisons, Spearman correlations, hierarchical and logistic regression models in the full sample, and descriptive analyses with Spearman correlations in the exploratory sub-sample. Results: The AD group reported poorer sleep quality (higher PSQI) and worse cognitive performance across domains compared with the non-AD group (p < 0.001). Higher PSQI scores were associated with poorer cognitive outcomes, particularly executive function and processing speed, after adjustment for demographics and structural MRI markers (e.g., β = −0.181 to −0.425 for MMSE/SDMT). In the exploratory sub-sample (N = 24), PSQI was correlated with SDMT (ρ = −0.653) and TMT-A (ρ = 0.788). Conclusions: Subjective sleep quality was associated with cognitive performance in individuals with dementia syndromes after accounting for structural MRI markers. These findings suggest that subjective sleep disturbance may represent a complementary clinical dimension warranting further longitudinal research, including evaluation of whether sleep-focused interventions may offer clinical benefits. Full article

Background/Objectives: Amyloid-PET is accurate but costly and capacity-limited. Blood-based biomarkers (BBMs), particularly plasma p-tau217, offer a scalable alternative for triaging patients. Objective of this study is to evaluate the diagnostic accuracy and clinical utility of plasma p-tau217 as a pre-screening tool for amyloid-PET positivity, identifying operating thresholds for rule-out and rule-in strategies. Methods: We analyzed 1681 participants from the ADNI cohort with concurrent plasma biomarkers (Fujirebio Lumipulse assays) and ¹⁸F-florbetapir PET. The primary outcome was discrimination of amyloid-PET positivity (Centiloid > 20). We compared p-tau217 alone against multivariable models (including Aβ42/40, GFAP, NfL, APOE) using Area Under the Curve (AUC) and Decision Curve Analysis (DCA). Two clinical thresholds were defined: a high-sensitivity “rule-out” cut-off (≥95% sensitivity) and a Youden-optimal “balanced” cut-off. These were validated using stratified bootstrap resampling. Results: Of 1681 participants, 679 (40.4%) were amyloid-positive. In the full sample, plasma p-tau217 alone achieved an AUC of 0.902 (95% CI 0.885–0.918). Operating thresholds were derived on a development split and applied to an independent validation split (N = 505). In the validation cohort, the high-sensitivity threshold (0.106 pg/mL) yielded 94.6% sensitivity and 93.7% NPV, effectively ruling out amyloid pathology. The Youden threshold (0.177 pg/mL) offered 78.9% sensitivity and 86.0% specificity. DCA demonstrated net benefit for p-tau217 screening over “PET all” strategies across clinically relevant probability ranges. Conclusions: Plasma p-tau217 provides high discrimination and clinically interpretable operating points for prioritizing confirmatory PET. Implementing a p-tau217-first strategy could significantly reduce unnecessary imaging without compromising diagnostic safety. Full article