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Several (inter)national longitudinal dementia observational datasets encompassing demographic information, neuroimaging, biomarkers, neuropsychological evaluations, and muti-omics data, have ushered in a new era of potential for integrating machine learning (ML) into dementia research and clinical practice. ML, with its proficiency in handling multi-modal and high-dimensional data, has emerged as an innovative technique to facilitate early diagnosis, differential diagnosis, and to predict onset and progression of mild cognitive impairment and dementia. In this review, we evaluate current and potential applications of ML, including its history in dementia research, how it compares to traditional statistics, the types of datasets it uses and the general workflow. Moreover, we identify the technical barriers and challenges of ML implementations in clinical practice. Overall, this review provides a comprehensive understanding of ML with non-technical explanations for broader accessibility to biomedical scientists and clinicians. [ABSTRACT FROM AUTHOR]

CD8+ T cells are critical to the adaptive immune response against viral pathogens. However, overwhelming antigen exposure can result in their exhaustion, characterised by reduced effector function, failure to clear virus, and the upregulation of inhibitory receptors, including programmed cell death 1 (PD-1). However, exhausted T cell responses can be "re-invigorated" by inhibiting PD-1 or the primary ligand of PD-1: PD-L1. Further, the absence of the type I interferon receptor IFNAR1 also results in T cell exhaustion and virus persistence in lymphocytic choriomeningitis virus Armstrong (LCMV-Arm)-infected mice. In this study, utilizing single- and double-knockout mice, we aimed to determine whether ablation of PD-1 could restore T cell functionality in the absence of IFNAR1 signalling in LCMV-Arm-infected mice. Surprisingly, this did not re-invigorate the T cell response and instead, it converted chronic LCMV-Arm infection into a lethal disease characterized by severe lung inflammation with an infiltration of neutrophils and T cells. Depletion of CD8+ T cells, but not neutrophils, rescued mice from lethal disease, demonstrating that IFNAR1 is required to prevent T cell exhaustion and virus persistence in LCMV-Arm infection, and in the absence of IFNAR1, PD-L1 is required for survival. This reveals an important interplay between IFNAR1 and PD-L1 with implications for therapeutics targeting these pathways. [ABSTRACT FROM AUTHOR]