Adverse childhood experiences (ACEs), or childhood adversities, refer to a wide range of potentially stressful experiences that occur in childhood. The most widely used ACE scales, ie, the conventional ACEs, include 10 items covering abuse, neglect, and household challenges from the Centers for Disease Control and Prevention (CDC)–Kaiser Permanente ACE Study.^1,2 However, it is generally accepted that conventional ACEs may not adequately reflect perceived childhood adversity in populations that are different from those in the CDC–Kaiser Permanente ACE Study.³ An additional set of expanded ACEs have been included to measure community-level stressors such as neighborhood or school bullying and unsafe communities.⁴ In addition, several new ACE indicators (eg, somatic illness or death of family members) have also been reported to be prevalent and should be considered in ACE-related studies.^5,6

Importance: Studies investigating the association of threat-related and deprivation-related adverse childhood experiences (ACEs) with later-life cognitive decline are lacking.Objectives: To evaluate the independent association of threat-related and deprivation-related ACEs with cognitive decline over time among middle-aged and older Chinese adults and to examine the modifying role of social isolation in such associations.Design, Setting, and Participants: This prospective cohort study used cognitive data from the China Health and Retirement Longitudinal Study (CHARLS) baseline survey that was administered between June 1, 2011, and March 31, 2012, and the CHARLS follow-up survey administered between July 1 and September 30, 2015. The life history survey with information of ACEs was additionally administered between June 1 and December 31, 2014. Statistical analysis was performed from March 1 to July 31, 2022. The study population consisted of middle-aged and older adults (age range, 45-97 years) with complete data on ACEs and 2 cognitive assessments and without cognitive impairment at baseline.Exposures: Five threat-related ACEs (ie, physical abuse, household substance abuse, domestic violence, unsafe neighborhood, and bullying) and 5 deprivation-related ACEs (ie, emotional neglect, household mental illness, incarcerated household member, parental separation or divorce, and parental death) before 17 years of age were queried by questionnaires. The cumulative scores of the 2 ACE dimensions were calculated and grouped into 3 categories as 0, 1, and 2 or more in main analyses.Main Outcomes and Measures: Cognitive function was measured by episodic memory and executive function. Global cognition was further calculated as the total score of these 2 dimensions. The raw scores of each cognitive test were standardized to z scores using baseline means and SDs. Linear mixed-effects models were constructed to examine the association between 2 dimensions of ACEs and the rate of annual cognitive decline. The modifying role of baseline social isolation in such associations was assessed with 3-way interaction tests.Results: Of the 6466 participants included in main analyses, 3301 (51.1%) were men and the mean (SD) age was 57.2 (8.3) years. Compared with no exposures, experience of 1 deprivation-related ACE was associated with faster cognitive decline in global cognition (β = −0.012 [95% CI, −0.022 to −0.002] SD/y) and executive function (β = −0.010 [95% CI, −0.020 to −0.00002] SD/y), whereas individuals with at least 2 childhood deprivations had faster cognitive declines in all cognitive tests (β = −0.035 [95% CI, −0.050 to −0.019] SD/y for global cognition; β = −0.047 [95% CI, −0.068 to −0.025] SD/y for episodic memory; β = −0.019 [95% CI, −0.034 to −0.004] SD/y for executive function). However, such an association was not observed for threat-related ACEs. In addition, baseline social isolation was a significant modifier in the associations between deprivation-related ACEs and cognitive declines in global cognition (β = −0.033 [95% CI, −0.061 to −0.005] SD/y; P = .02 for 3-way interaction) and executive function (β = −0.032 [95% CI, −0.059 to −0.005] SD/y; P = .02 for 3-way interaction).Conclusions and Relevance: Deprivation-related ACEs, but not threat-related ACEs, were associated with faster decline in later-life cognitive function, whereas social isolation could modify such detrimental impact. These findings highlight the potential benefits of promoting social integration in maintaining later-life cognitive function among individuals who have experienced childhood deprivation.

Beta-amyloid (Aβ ) neurotoxicity is important in Alzheimer’s disease (AD) pathogenesis. Aβ neurotoxicity causes oxidative stress, inflammation and mitochondrial damage resulting in neuronal degeneration and death. Oxidative stress, inflammation and mitochondrial failure are also pathophysiological mechanisms of type 2 diabetes (T₂DM) which is characterized by insulin resistance. Interestingly, T₂DM increases risk to develop AD which is associated with reduced neuronal insulin sensitivity (central insulin resistance). We studied the potential protective effect of adiponectin (an adipokine with insulin-sensitizing, anti-inflammatory and anti-oxidant properties) against Aβ neurotoxicity in human neuroblastoma cells (SH-SY5Y) transfected with the Swedish amyloid precursor protein (Sw-APP) mutant, which overproduced Aβ with abnormal intracellular Aβ accumulation. Cytotoxicity was measured by assay for lactate dehydrogenase (LDH) released upon cell death and lysis. Our results revealed that Sw-APP transfected SH-SY5Y cells expressed both adiponectin receptor 1 and 2, and had increased AMP-activated protein kinase (AMPK) activation and enhanced nuclear factor-kappa B (NF-κB) activation compared to control empty-vector transfected SH-SY5Y cells. Importantly, adiponectin at physiological concentration of 10 µg/ml protected Sw-APP transfected SH-SY5Y cells against cytotoxicity under oxidative stress induced by hydrogen peroxide. This neuroprotective action of adiponectin against Aβ neurotoxicity-induced cytotoxicity under oxidative stress involved 1) AMPK activation mediated via the endosomal adaptor protein APPL1 (adaptor protein with phosphotyrosine binding, pleckstrin homology domains and leucine zipper motif) and possibly 2) suppression of NF-κB activation. This raises the possibility of novel therapies for AD such as adiponectin receptor agonists.

Background: Both excessive screen time and early screen exposure have been linked to children’s health outcomes, but few studies considered these two exposures simultaneously. The aim of this study was to explore the independent and interactive associations of excessive screen time and early screen exposure with health-related quality of life (HRQOL) and behavioral problems among Chinese children attending preschools. Methods: A cross-sectional study of 4985 children aged between 3 and 6 years was conducted in Chengdu, China. Each parent has finished an online questionnaire regarding their children’s screen use, HRQOL, and behavioral problems. Children with screen time over 1 h/day were considered as having excessive screen time. Early screen exposure was defined if the children had started using screen-based media before the age of 2 years. HRQOL was assessed by the Pediatric Quality of Life Inventory version 4.0 (PedsQL 4.0), while behavioral problems were confirmed with the 48-item Conners’ Parent Rating Scale (CPRS-48). Results: Of the 4985 children (2593 boys and 2392 girls) included, the mean age was 4.6 (SD: 1.0) years. After adjustment for confounders and early screen exposure, excessive screen time was significantly associated with worse HRQOL scores in all dimensions and summary scales, as well as each type of behavioral problems (all p values < 0.05). We also found that compared to children with later initiation of screen exposure, those with screen use before the age of 2 years had significantly lower emotional functioning score (β: − 2.13, 95%CI: − 3.17, − 1.09) and psychosocial health summary score (β: − 0.82, 95%CI: − 1.54, − 0.10) of HRQOL, as well as higher risks of conduct problems, learning problems, psychosomatic problems, impulsive-hyperactive, and hyperactivity index, which were independent of excessive screen use. Furthermore, there were significant interactive effects of excessive screen time and early screen exposure on emotional functioning domain of HRQOL scores and conduct problems. Conclusion: Excessive screen time and early screen exposure are two independent and interactive factors to children’s HRQOL and behavioral problems. Our findings support current guidelines to limit screen exposure in children. Appropriate screen use may represent an important intervention target to improve children’s HRQOL and reduce their behavioral problems.