Applying Deep Learning to Predicting Dementia and Mild Cognitive Impairment

Dementia has a large negative impact on the global healthcare and society. Diagnosis is rather challenging as there is no standardised test. The purpose of this paper is to conduct an analysis on ADNI data and determine its effectiveness for building classification models to differentiate the categories Cognitively Normal (CN), Mild Cognitive Impairment (MCI), and Dementia (DEM), based on tuning three Deep Learning models: two Multi-Layer Perceptron (MLP1 and MLP2) models and a Convolutional Bidirectional Long Short-Term Memory (ConvBLSTM) model. The results show that the MLP1 and MLP2 models accurately distinguish the DEM, MCI and CN classes, with accuracies as high as 0.86 (SD 0.01). The ConvBLSTM model was slightly less accurate but was explored in view of comparisons with the MLP models, and for future extensions of this work that will take advantage of time-related information. Although the performance of ConvBLSTM model was negatively impacted by a lack of visit code data, opportunities were identified for improvement, particularly in terms of pre-processing

Dopamine Receptor Activation Increases HIV Entry into Primary Human Macrophages

Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers