To test the hypothesis that pulsing of intracranial pressure has an association with cognition, we measured cognitive score and pulsing of the tympanic membrane in 290 healthy subjects. This hypothesis was formed on the assumptions that large intracranial pressure pulses impair cognitive performance and tympanic membrane pulses reflect intracranial pressure pulses.290 healthy subjects, aged 20–80 years, completed the Montreal Cognitive Assessment Test. Spontaneous tympanic membrane displacement during a heart cycle was measured from both ears in the sitting and supine position. We applied multiple linear regression, correcting for age, heart rate, and height, to test for an association between cognitive score and spontaneous tympanic membrane displacement. Significance was set at P < 0.0125 (Bonferroni correction.)

A significant association was seen in the left supine position (p = 0.0076.) The association was not significant in the right ear supine (p = 0.28) or in either ear while sitting. Sub-domains of the cognitive assessment revealed that executive function, language and memory have been primarily responsible for this association.

In conclusion, we have found that spontaneous pulses of the tympanic membrane are associated with cognitive performance and believe this reflects an association between cognitive performance and intracranial pressure pulses.

BackgroundDementia diagnosis is challenging and often delayed. Brain imaging techniques such as single-photon emission computed tomography (SPECT) imaging can help identify subtle changes in brain perfusion. Artificial intelligence methods may support results interpretation for early diagnosis.ObjectiveTo develop and validate multivariate models for the early diagnosis of Alzheimer's disease (AD), using brain perfusion SPECT imaging and interpretable artificial intelligence methods in a real-world clinical setting.MethodsTwo logistic regression models were developed using a training dataset of 420 SPECT scans and tested on an independent clinical dataset of 443 scans. Model 1 was designed to identify abnormal perfusion patterns, while Model 2 identified perfusion changes associated with AD. Input features were extracted from anatomical volumes of interest, with feature selection performed using the Minimum Redundancy Maximum Relevance (MRMR) algorithm.ResultsThe models demonstrated good classification performance using real-world clinical data. Model 1 achieved an area under receiver operator characteristic (AUROC) Curve of 0.89 (Sensitivity 76%, Specificity 87%) in identifying abnormal brain perfusion. Model 2 achieved an AUROC of 0.86 (Sensitivity 87%, Specificity 72%) in identifying AD.ConclusionsMultivariate logistic regression models trained on real-world clinical data show promise as clinical decision support tools for the diagnosis of AD from brain perfusion SPECT imaging. The models use features from clinically relevant brain regions, which enhances interpretability. Future research should focus on expanding model applicability to other dementia types and on prospective evaluation of their utility in improving diagnostic accuracy, consistency, and care pathways in diverse clinical environments.

BackgroundPeriodontitis is a chronic bacterial infection that elicits systemic inflammation. While retrospective studies have linked periodontal pathogens with Alzheimer's disease (AD) and dementia, few have combined cognitive assessments, pathogen exposure, and inflammatory markers.ObjectiveTo investigate the longitudinal risk between periodontitis, cognitive impairment and dementia.MethodsWe examined the relationship between periodontitis and onset of mild cognitive impairment (MCI) and dementia over 15.6 years (SD 1.6) in older men from Northern Ireland enrolled in the PRIME-COG cohort, using logistic regression. We also assessed associations between exposure to periodontal pathogens and blood inflammatory markers.ResultsAmong 642 men, baseline periodontitis was not significantly associated with later onset of dementia and/or MCI (severe versus mild/none, OR 0.83, 95% CI 0.45-1.50, p = 0.923). However, having more teeth predicted lower risk (OR 0.95, 95% CI 0.91-0.99, p = 0.023). Dementia and/or MCI was associated with higher serum IL-6, IL-8, and IFN-γ at baseline, and IL-8 and TGF-β at follow-up. IgG levels to periodontal pathogens remained stable in men who developed dementia and/or MCI but declined in cognitively normal men. A positive correlation between IgG to periodontal pathogens and proinflammatory cytokines was observed in men who developed dementia and/or MCI.ConclusionsClinical periodontitis was not associated with dementia or MCI onset, but tooth retention was protective. Elevated inflammatory markers in affected men suggest systemic inflammation may contribute to cognitive decline. Larger, more diverse cohort studies are needed to clarify the role of periodontal disease in dementia and AD risk.

There is growing evidence that inflammation impairs erythrocyte structure and function. We assessed the impact of mild systemic inflammation on erythrocyte fragility in three different settings. In order to investigate causation, erythrocyte osmotic fragility was measured in mice challenged with a live attenuated bacterial strain to induce low-grade systemic inflammation; a significant increase in erythrocyte osmotic fragility was observed. To gather evidence that systemic inflammation is associated with erythrocyte fragility in humans, two observational studies were conducted. First, using a retrospective study design, the relationship between reticulocyte-based surrogate markers of haemolysis and high-sensitivity C-reactive protein was investigated in 9292 healthy participants of the UK Biobank project. Secondly, we prospectively assessed the relationship between systemic inflammation (measured by the urinary neopterin/creatinine ratio) and erythrocyte osmotic fragility in a mixed population (n = 54) of healthy volunteers and individuals with long-term medical conditions. Both human studies were in keeping with a relationship between inflammation and erythrocyte fragility. Taken together, we conclude that mild systemic inflammation increases erythrocyte fragility and may contribute to haemolysis. Further research is needed to assess the molecular underpinnings of this pathway and the clinical implications in inflammatory conditions.

Introduction: The relationship between cognitive impairment and a phenotype comprising low muscle strength coupled with excess adiposity, representative of sarcopenic obesity, is not well defined. The present study aimed to elucidate the relationship between low hand grip strength (HGS), representative of "probable sarcopenia," coupled with obesity, thus representing "probable sarcopenic obesity" and cognitive impairment.

•AI-driven tools and multimodal biomarkers emerged as key for early VCID detection.•Novel neuroimaging, fluid, and retinal markers show promise for precision diagnostics.•BBB leakage and inflammation could early drive small vessel disease and VCID.•Clinical trials explore drug repurposing and hybrid lifestyle-pharmacological interventions.•Genetic insights into CADASIL reveal shared pathways with sporadic SVD.