Characterising activity and diet compositions for dementia prevention: protocol for the ACTIVate prospective longitudinal cohort study

Introduction Approximately 40% of late-life dementia may be prevented by addressing modifiable risk factors, including physical activity and diet. Yet, it is currently unknown how multiple lifestyle factors interact to influence cognition. The ACTIVate Study aims to (1) explore associations between 24-hour time-use and diet compositions with changes in cognition and brain function; and (2) identify duration of time-use behaviours and the dietary compositions to optimise cognition and brain function.Methods and analysis This 3-year prospective longitudinal cohort study will recruit 448 adults aged 60-70 years across Adelaide and Newcastle, Australia. Time-use data will be collected through wrist-worn activity monitors and the Multimedia Activity Recall for Children and Adults. Dietary intake will be assessed using the Australian Eating Survey food frequency questionnaire. The primary outcome will be cognitive function, assessed using the Addenbrooke's Cognitive Examination-III. Secondary outcomes include structural and functional brain measures using MRI, cerebral arterial pulse measured with diffuse optical tomography, neuroplasticity using simultaneous transcranial magnetic stimulation and electroencephalography, and electrophysiological markers of cognitive control using event-related potential and time frequency analyses. Compositional data analysis, testing for interactions between time point and compositions, will assess longitudinal associations between dependent (cognition, brain function) and independent (time-use and diet compositions) variables. Conclusions The ACTIVate Study will be the first to examine associations between time-use and diet compositions, cognition and brain function. Our findings will inform new avenues for multidomain interventions that may more effectively account for the co-dependence between activity and diet behaviours for dementia prevention. Ethics and dissemination Ethics approval has been obtained from the University of South Australia's Human Research Ethics committee (202639). Findings will be disseminated through peer-reviewed manuscripts, conference presentations, targeted media releases and community engagement events. Trial registration number >Australia New Zealand Clinical Trials Registry (ACTRN12619001659190).Ashleigh E Smith, Alexandra T Wade, Timothy Olds, Dorothea Dumuid, Michael J Breakspear, Kate Laver ... et al

A Study on Residential Houses Using Shape Grammar (Case Study: Houses of Pahlavi Era in Tehran Province)

This article aims to explain a new model and achieve a basic pattern for the shape of houses using shape grammar. This study is a qualitative research based on description, explanation and interpretation. Phenomenological research is one of the most widely used traditions of qualitative research. The phenomenological method of this study is based on van Manen's methodology. The data analysis is conducted using shape grammar. In shape grammar process, the data are the houses selected by the researcher (five houses of Pahlavi era in Tehran). Finally, the main themes of research, e.g. connection to environment, calm, happiness and separation from everyday life, are extracted from spaces such as the Iwan (porch), basement, Howzkhaneh (spring house), green space, Hashti (vestibule) and Shahneshin (alcove room). Eventually, new patterns are created using shape grammar process in the decision tree. After understanding the concept, the basic shape pattern is created using shape grammar. Thus, the role of user in architectural quality of space and its types and evaluation of language pattern are identified by gathering the literature and researches, deepening the views of experts and architects and classifying them as introversion, privacy and types and typology

Clopidogrel Administration Impairs Post-Stroke Learning and Memory Recovery in Mice

Clopidogrel, which is one of the most prescribed antiplatelet medications in the world, is given to stroke survivors for the prevention of secondary cardiovascular events. Clopidogrel exerts its antiplatelet activity via antagonism of the P2Y12 receptor (P2RY12). Although not widely known or considered during the initial clinical trials for clopidogrel, P2RY12 is also expressed on microglia, which are the brain’s immune cells, where the receptor facilitates chemotactic migration toward sites of cellular damage. If microglial P2RY12 is blocked, microglia lose the ability to migrate to damaged sites and carry out essential repair processes. We aimed to investigate whether administering clopidogrel to mice post-stroke was associated with (i) impaired motor skills and cognitive recovery; (ii) physiological changes, such as survival rate and body weight; (iii) changes in the neurovascular unit, including blood vessels, microglia, and neurons; and (iv) changes in immune cells. Photothrombotic stroke (or sham surgery) was induced in adult male mice. From 24 h post-stroke, mice were treated daily for 14 days with either clopidogrel or a control. Cognitive performance (memory and learning) was assessed using a mouse touchscreen platform (paired associated learning task), while motor impairment was assessed using the cylinder task for paw asymmetry. On day 15, the mice were euthanized and their brains were collected for immunohistochemistry analysis. Clopidogrel administration significantly impaired learning and memory recovery, reduced mouse survival rates, and reduced body weight post-stroke. Furthermore, clopidogrel significantly increased vascular leakage, significantly increased the number and appearance of microglia, and significantly reduced the number of T cells within the peri-infarct region post-stroke. These data suggest that clopidogrel hampers cognitive performance post-stroke. This effect is potentially mediated by an increase in vascular permeability post-stroke, providing a pathway for clopidogrel to access the central nervous system, and thus, interfere in repair and recovery processes.Marina Paul, Jonathan W. Paul, Madeleine Hinwood, Rebecca J. Hood, Kristy Martin, Mahmoud Abdolhoseini, Sarah J. Johnson, Michael Pollack, Michael Nilsson, and Frederick R. Walke