Secondhand Smoke Exposure and Risk of Dementia in Nonsmokers: A Population-Based Cohort Study.

BACKGROUND: Large population-based prospective studies are necessary to provide clarification on the associations of panoramic secondhand smoking burden, including prenatal and postnatal secondhand smoke (SHS) exposure, with the risk of developing dementia. METHODS: Our study comprised a sample of 353,756 dementia-free individuals from the UK Biobank who were nonsmokers had data on the exposure of maternal smoking as well as SHS exposure in daily life, which was quantified in terms of hours per week (h/week) and whether they lived with household smokers. Multivariable Cox regression models were utilized to analyze the independent and joint associations of maternal smoking and daily life SHS exposure with dementia risk. RESULTS: During a median follow-up of 11.8 years, 4,113 participants developed dementia. Compared with those who lived in the environment without smokers, multivariable-adjusted hazard ratios (HRs) (95% CIs) were 1.11 (1.02, 1.20) and 1.31 (1.13, 1.52) for those who exposed to SHS for >0 but ≤4 h/week and >4 h/week, respectively, and was 1.25 (1.13, 1.39) for those who lived with smokers in the household. A positive history of maternal smoking was associated with a modestly higher risk of dementia (HR = 1.07; 95% CI: 1.01, 1.15). Furthermore, compared with participants with neither history of maternal smoking nor exposure to SHS, a particularly higher risk of dementia was observed among those with both exposures (HR = 1.48; 95% CI: 1.18, 1.86). Additionally, the HR (95% CI) was 1.32 (1.10, 1.59) when comparing participants with a history of maternal smoking who lived with smokers in their households with those who had neither exposures. CONCLUSIONS: Having a history of maternal smoking, longer exposure to SHS, and living with smokers in the household were each associated with an increased risk of developing dementia. Individuals who were simultaneously exposed to maternal smoking and SHS or lived with household smokers had a particularly higher dementia risk.

Sexual dimorphism in the social behaviour of Cntnap2-null mice correlates with disrupted synaptic connectivity and increased microglial activity in the anterior cingulate cortex.

A biological understanding of the apparent sex bias in autism is lacking. Here we have identified Cntnap2 KO mice as a model system to help better understand this dimorphism. Using this model, we observed social deficits in juvenile male KO mice only. These male-specific social deficits correlated with reduced spine densities of Layer 2/3 and Layer 5 pyramidal neurons in the Anterior Cingulate Cortex, a forebrain region prominently associated with the control of social behaviour. Furthermore, in male KO mice, microglia showed an increased activated morphology and phagocytosis of synaptic structures compared to WT mice, whereas no differences were seen in female KO and WT mice. Our data suggest that sexually dimorphic microglial activity may be involved in the aetiology of ASD, disrupting the development of neural circuits that control social behaviour by overpruning synapses at a developmentally critical period.