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Emergency department visits (EDV) are common among older adults with and without dementia. The risk factors and demands of EDVs for people with dementia have been well studied; however, the association between EDVs and conversion to dementia among people with predementia has not been thoroughly explored. To study the predictive value of EDVs in predementia’s progression to dementia. The baseline predementia cohort registered from September 2015 to August 2017, with longitudinal follow-up in the History-based Artificial Intelligent Clinical Dementia Diagnostic System database, was retrospectively analyzed. The rates of conversion among the different EDVs were compared. Multivariate logistic regression and Cox proportional hazards analyses were applied to study the influence of EDVs on progression. Age, education, sex, neuropsychological tests, activities of daily living, neuropsychiatric symptoms, parkinsonism, and multiple vascular risk factors were adjusted for. A total of 512 participants were analyzed, including 339 (66.2%) non-converters and 173 (33.8%) converters with a mean follow-up of 3.3 (range 0.4–6.1) and 2.8 (range 0.5–5.9) years, respectively. Compared to people without EDV (EDV 0), the hazard ratios for conversion to dementia were 3.6, 5.9, and 6.9 in those with EDV once (EDV 1), twice (EDV 2), and more than twice (EDV >2), respectively. In addition, older age, lower education, poorer cognition, poorer ADL performance, and longer follow-up periods also increased the conversion rates. EDVs in the predementia stages highly predict progression to dementia. Therefore, a sound public health as well as primary healthcare system that provide strategies for better management of mental and physical condition might help prevention of EDVs among older people in the predementia stages.

Genomic imprinting is a phenomenon that some genes are expressed differentially according to the parent of origin. Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are neurobehavioral disorders caused by deficiency of imprinted gene expression from paternal and maternal chromosome 15q11-q13, respectively. Imprinted genes at the PWS/AS domain are regulated through a bipartite imprinting center, the PWS-IC and AS-IC. The PWS-IC activates paternal-specific gene expression and is responsible for the paternal imprint, whereas the AS-IC functions in the maternal imprint by allele-specific repression of the PWS-IC to prevent the paternal imprinting program. Although mouse chromosome 7C has a conserved PWS/AS imprinted domain, the mouse equivalent of the human AS-IC element has not yet been identified. Here, we suggest another dimension that the PWS-IC also functions in maternal imprinting by negatively regulating the paternally expressed imprinted genes in mice, in contrast to its known function as a positive regulator for paternal-specific gene expression. Using a mouse model carrying a 4.8-kb deletion at the PWS-IC, we demonstrated that maternal transmission of the PWS-IC deletion resulted in a maternal imprinting defect with activation of the paternally expressed imprinted genes and decreased expression of the maternally expressed imprinted gene on the maternal chromosome, accompanied by alteration of the maternal epigenotype toward a paternal state spread over the PWS/AS domain. The functional significance of this acquired paternal pattern of gene expression was demonstrated by the ability to complement PWS phenotypes by maternal inheritance of the PWS-IC deletion, which is in stark contrast to paternal inheritance of the PWS-IC deletion that resulted in the PWS phenotypes. Importantly, low levels of expression of the paternally expressed imprinted genes are sufficient to rescue postnatal lethality and growth retardation in two PWS mouse models. These findings open the opportunity for a novel approach to the treatment of PWS.

Autism, a pervasive neurodevelopmental disorder manifested by deficits in social behavior and interpersonal communication, and by stereotyped, repetitive behaviors, is inexplicably biased towards males by a ratio of ∼4∶1, with no clear understanding of whether or how the sex hormones may play a role in autism susceptibility. Here, we show that male and female hormones differentially regulate the expression of a novel autism candidate gene, retinoic acid-related orphan receptor-alpha (RORA) in a neuronal cell line, SH-SY5Y. In addition, we demonstrate that RORA transcriptionally regulates aromatase, an enzyme that converts testosterone to estrogen. We further show that aromatase protein is significantly reduced in the frontal cortex of autistic subjects relative to sex- and age-matched controls, and is strongly correlated with RORA protein levels in the brain. These results indicate that RORA has the potential to be under both negative and positive feedback regulation by male and female hormones, respectively, through one of its transcriptional targets, aromatase, and further suggest a mechanism for introducing sex bias in autism.