Primary familial brain calcification is a monogenic disease characterized by bilateral calcifications in the basal ganglia and other brain regions, and commonly presents motor, psychiatric, and cognitive symptoms. Currently, four autosomal dominant (SLC20A2, PDGFRB, PDGFB, XPR1) and one autosomal recessive (MYORG) causative genes have been identified. Compared with patients with autosomal dominant primary familial brain calcification, patients with the recessive form of the disease present with more severe clinical and imaging phenotypes, and deserve more clinical and research attention. Biallelic mutations in MYORG cannot explain all autosomal recessive primary familial brain calcification cases, indicating the existence of novel autosomal recessive genes. Using homozygosity mapping and whole genome sequencing, we detected a homozygous frameshift mutation (c.140delT, p.L48*) in the JAM2 gene in a consanguineous family with two affected siblings diagnosed with primary familial brain calcification. Further genetic screening in a cohort of 398 probands detected a homozygous start codon mutation (c.1A>G, p.M1?) and compound heterozygous mutations [c.504G>C, p.W168C and c.(67+1_68-1)_(394+1_395-1), p.Y23_V131delinsL], respectively, in two unrelated families. The clinical phenotypes of the four patients included parkinsonism (3/4), dysarthria (3/4), seizures (1/4), and probable asymptomatic (1/4), with diverse onset ages. All patients presented with severe calcifications in the cortex in addition to extensive calcifications in multiple brain areas (lenticular nuclei, caudate nuclei, thalamus, cerebellar hemispheres, ± brainstem; total calcification scores: 43–77). JAM2 encodes junctional adhesion molecule 2, which is highly expressed in neurovascular unit-related cell types (endothelial cells and astrocytes) and is predominantly localized on the plasma membrane. It may be important in cell-cell adhesion and maintaining homeostasis in the CNS. In Chinese hamster ovary cells, truncated His-tagged JAM2 proteins were detected by western blot following transfection of p.Y23_V131delinsL mutant plasmid, while no protein was detected following transfection of p.L48* or p.1M? mutant plasmids. In immunofluorescence experiments, the p.W168C mutant JAM2 protein failed to translocate to the plasma membrane. We speculated that mutant JAM2 protein resulted in impaired cell-cell adhesion functions and reduced integrity of the neurovascular unit. This is similar to the mechanisms of other causative genes for primary familial brain calcification or brain calcification syndromes (e.g. PDGFRB, PDGFB, MYORG, JAM3, and OCLN), all of which are highly expressed and functionally important in the neurovascular unit. Our study identifies a novel causative gene for primary familial brain calcification, whose vital function and high expression in the neurovascular unit further supports impairment of the neurovascular unit as the root of primary familial brain calcification pathogenesis.

No abstract

BackgroundConstipation and dementia have similar epidemiological characteristics. Changes in intestinal flora and characteristics of the brain-gut axis play roles in the pathogeneses of the two diseases, suggesting that there may be a close connection between the two. Most of the studies on constipation in dementia patients have focused on the population with α-synucleinopathies [Parkinson’s disease dementia (PDD), dementia with Lewy bodies (DLB)]. Few studies have reported the prevalence of constipation in all-cause dementia and mild cognitive impairment (MCI) populations.ObjectiveTo assess the prevalence of constipation in patients with all-cause dementia and MCI subtypes and to explore the association between constipation with dementia and MCI subtypes.MethodsFrom May 2019 to December 2019, we conducted a population-based cross-sectional survey. A total of 11,743 participants aged 65 or older from nine cities in China were surveyed. Participants underwent a series of clinical examinations and neuropsychological measurements. Constipation, dementia, MCI and MCI subtype were diagnosed according to established criteria through standard diagnostic procedures.ResultsThe overall age- and sex-adjusted prevalence of constipation in individuals aged 65 years and older was 14.8% (95% CI, 14.6–15.0). The prevalence rates of constipation were19.2% (95% CI, 17.3–21.0), 19.1% (95% CI, 16.8–21.5), 14.4% (95% CI, 12.8–15.9), and 13.8% (95% CI, 13.0–14.6) in the dementia, non-amnestic (na)-MCI, amnestic (a)-MCI and normal cognition populations, respectively. Multivariate logistic regression analysis showed that higher prevalence of constipation was associated with dementia (p = 0.0.032, OR = 1.18, 95% CI: 1.02–1.38) and na-MCI (p = 0.003, OR = 1.30, 95% CI: 1.09–1.54).ConclusionThe present study found a high prevalence of constipation in elderly individuals in China, and higher in patients with dementia and na-MCI.

Given the current environmental situation and social change in China, we explored the relationships between the Dark Triad traits (Machiavellianism, narcissism and psychopathy) and environmental attitudes (beliefs regarding environmentally related issues), and the mediating roles of future orientation (the tendency to plan for meeting long-term objectives) and place attachment (the emotional connection with the place of residence) in these relationships. Using a national sample from all 31 provinces of mainland China (N = 998), we found that the psychometric structure of the Dark Triad was well confirmed under Chinese culture. The Dark Triad as a whole was negatively related to environmental attitudes, but narcissism was not significantly associated with environmental attitudes when the three Dark Triad traits were considered as the predictors simultaneously. Future orientation and place attachment mediated the association between the Dark Triad and environmental attitudes. These findings enrich our understanding of the relevant variables of environmental attitudes and provide references for China's government and other developing countries to improve environmental issues. The uniqueness of narcissism could expand the understanding of the commonality and diversity among the Dark Triad traits, and an efficient tool of the Dark Triad was provided under Chinese culture.

Background: Marital status may have an impact on the elderly population's health, but few studies in China discussed about the association between marital status and cognitive impairment.Objective: To investigate the relationship between marital status and cognitive impairment. To compare the influences of marital status on dementia between men and women.Methods: This study was based on a representative national cross-sectional epidemiological survey in China. We randomly selected 13 provinces and municipalities and included 19,276 participants aged 65 years or older in our study. Data was collected by interviewing the participants about their sociodemographic characteristics, and neuropsychological testing was administered to the participants by neurologists. To analyze the association between marital status and cognitive impairment, multiple logistic regression was based on a series of models.

Implicit theories drastically affect an individual’s processing of social information, decision making, and action. The present research focuses on whether individuals who hold the implicit belief that people’s moral character is fixed (entity theorists) and individuals who hold the implicit belief that people’s moral character is malleable (incremental theorists) make different choices when facing a moral decision. Incremental theorists are less likely to make the fundamental attribution error (FAE), rarely make moral judgment based on traits and show more tolerance to immorality, relative to entity theorists, which might decrease the possibility of undermining the self-image when they engage in immoral behaviors, and thus we posit that incremental beliefs facilitate immorality. Four studies were conducted to explore the effect of these two types of implicit theories on immoral intention or practice. The association between implicit theories and immoral behavior was preliminarily examined from the observer perspective in Study 1, and the results showed that people tended to associate immoral behaviors (including everyday immoral intention and environmental destruction) with an incremental theorist rather than an entity theorist. Then, the relationship was further replicated from the actor perspective in Studies 2–4. In Study 2, implicit theories, which were measured, positively predicted the degree of discrimination against carriers of the hepatitis B virus. In Study 3, implicit theories were primed through reading articles, and the participants in the incremental condition showed more cheating than those in the entity condition. In Study 4, implicit theories were primed through a new manipulation, and the participants in the unstable condition (primed incremental theory) showed more discrimination than those in the other three conditions. Taken together, the results of our four studies were consistent with our hypotheses.

BackgroundPost-stroke dementia (PSD) has adverse effects on the quality of work and life in elderly stroke survivors. There are inconsistent results on the impacts of blood pressure control on the risk of PSD in people aged 65 years and above.ObjectiveThis study was performed to explore whether poorly-controlled blood pressure was associated with an increasing risk of PSD.MethodsThe study population was enrolled from cross-sectional research conducted in 106 communities of rural northern China. In Phase I, a total of 7,448 people aged ≥65 years, including 830 with stroke history, completed a questionnaire, a physical examination, and a cognitive assessment. Phase II further confirmed the diagnosis of PSD. Well-controlled blood pressure was defined as an average systolic blood pressure of <140 mmHg and average diastolic blood pressure of <90 mmHg over two readings in person. Failure to meet these criteria was considered as poorly-controlled blood pressure.ResultsThe crude prevalence rate of PSD among stroke survivors aged 65 years and over was 17.8% [95% confidence interval (CI) 15.2–20.4%]. Among the 830 stroke survivors, the proportions of PSD gradually increased with age and the crude prevalence rates for PSD were 10.2% (95% CI 5.6–14.9%), 14.8% (95% CI 10.1–19.5%), 18.8% (95% CI 14.1–23.5%), and 27.4% (95% CI 20.8–34.1%) in subjects aged 65–69, 70–74, 75–79 and ≥80 years, respectively. Participants in the poorly-controlled blood pressure group were more likely to suffer from PSD (28.4 vs.15.3%, P < 0.001), be older (75.81 ± 4.97 vs. 74.74 ± 5.83, P < 0.05), and have a worse cognitive level (22.26 ± 7.05 vs. 24.10 ± 6.02, P < 0.05). Compared with well-controlled blood pressure patients, poorly-controlled blood pressure in stroke survivors significantly increased risk of PSD (odds ratio = 2.20, 95% CI 1.45–3.32) after adjusting for age, gender, and education.ConclusionsThe crude prevalence of PSD among stroke survivors aged ≥65 years was 17.8% at community level. In addition to lower education level and older age, poorly-controlled blood pressure was also an independent risk factor for PSD among the elderly, which is amenable to intervention. Therefore, it is essential to control blood pressure to reduce PSD incidence.

In the era of technology, smartphone use occupies an important position in our lives. The present research focused on the psychological consequence of frequent smartphone use and possible way to remedy it. We proposed that frequent smartphone use could damage people’s sense of control and in turn trigger nostalgia. Moreover, nostalgia could directly compensate for the low sense of control induced by frequent smartphone use. Five studies ( N = 918) were conducted. Study 1 found through a field study that frequent smartphone use increases nostalgia. Studies 2 and 3 found through 14-day tracking and a laboratory experiment that frequent smartphone use decreased people’s sense of control and then triggered nostalgia. Furthermore, nostalgia could enhance the low sense of control, and it worked by increasing self-esteem (Studies 4 and 5). The findings show the negative impact of frequent smartphone use, and nostalgia is an effective way to remedy it without preventing people from using smartphones.