In this issue, we will share the latest articles from Professor Shu-Min Duan, Professor Kwok-Fai So, Professor Kristine Yaffe from the AND Editorial Board.
Title: Sleep Timing and Risk of Dementia Among the Chinese Elderly in an Urban Community: The Shanghai Aging Study
Authors: Xiantao Li, Ding Ding, Qianhua Zhao, Wanqing Wu, Zhenxu Xiao, Jianfeng Luo, Kristine Yaffe, Yue Leng
Type: Research Articles from Frontiers in Neurology
Growing evidence has suggested a link between poor sleep quality and increased risk of dementia. However, little is known about the association between sleep timing, an important behavior marker of circadian rhythms, and dementia risk in older adults, and whether this is independent of sleep duration or quality.
We included data from 1,051 community-dwelling older men and women (aged ≥ 60y) without dementia from the Shanghai Aging Study. At baseline, participants reported sleep timing, duration, and quality using the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI). Dementia diagnosis over the following 7.3 years was determined by neurologists using DSM-IV criteria. We used Cox proportional hazards models to examine the association between bedtime (before 9 p.m., after 11 p.m. vs. 9–11 p.m.), rise time (before 6 a.m., after 8 a.m. vs. 6–8 a.m.), and risk of dementia.
A total of 238 (22.8%), 675 (64.5%), and 133 (12.7%) participants reported going to bed before 9 p.m., between 9 and 11 p.m., and after 11 p.m., respectively, while 272 (26%), 626 (59.9%), and 148 (14.2%) reported getting up before 6 a.m., between 6 and 8 a.m., and after 8 a.m., respectively. Participants who reported going to bed earlier had a lower education level, were less likely to be smokers, more likely to have hypertension or diabetes, and had longer sleep duration but poorer sleep quality compared to those who reported a later bedtime. We found 47 incidents of dementia among 584 participants followed up over an average of 7.3 years. After adjustment for demographics, education, income, body mass index, depressive symptoms, smoking, alcohol use, physical activity, comorbidities, APOE4 genotype, and baseline MMSE, those with a bedtime of before 9 p.m. were two times more likely to develop dementia [hazard ratio (HR)=2.16 (95%CI: 1.06–4.40)], compared to those going to bed between 9 and 11 p.m. Later bedtime (i.e., after 11 p.m.) showed the opposite but had a non-significant association with dementia risk (HR=0.15, 95%CI: 0.02–1.29). We did not find an association for rise time and risk of dementia.
Earlier sleep timing in older adults without dementia was associated with an increased risk of dementia. Future studies should examine the underlying mechanisms of this association and explore the usefulness of sleep timing as a preclinical marker for dementia.
Access this article: https://doi.org/10.3389/fneur.2021.629507
Title: Computer Vision for Brain Disorders Based Primarily on Ocular Responses
Authors: Xiaotao Li, Fangfang Fan, Xuejing Chen, Juan Li, Li Ning, Kangguang Lin, Zan Chen, Zhenyun Qin, Albert S. Yeung, Xiaojian Li, Liping Wang, Kwok-Fai So
Type: Perspective Article from Frontiers in Neurology
Real-time ocular responses are tightly associated with emotional and cognitive processing within the central nervous system. Patterns seen in saccades, pupillary responses, and spontaneous blinking, as well as retinal microvasculature and morphology visualized via office-based ophthalmic imaging, are potential biomarkers for the screening and evaluation of cognitive and psychiatric disorders. In this review, we outline multiple techniques in which ocular assessments may serve as a non-invasive approach for the early detections of various brain disorders, such as autism spectrum disorder (ASD), Alzheimer's disease (AD), schizophrenia (SZ), and major depressive disorder (MDD). In addition, rapid advances in artificial intelligence (AI) present a growing opportunity to use machine learning-based AI, especially computer vision (CV) with deep-learning neural networks, to shed new light on the field of cognitive neuroscience, which is most likely to lead to novel evaluations and interventions for brain disorders. Hence, we highlight the potential of using AI to evaluate brain disorders based primarily on ocular features.
Access this article: https://doi.org/10.3389/fneur.2021.584270
Title: Changes in electroencephalography and sleep architecture as potential electrical biomarkers for Alzheimer's disease
Authors: Hang Yu, Man-Li Wang, Xiao-Lan Xu, Rong Zhang, Wei-Dong Le
Type: Perspective from Chinese Medical Journal (English)
Access this article: https://doi.org/10.1097/CM9.0000000000001394
Title: Research advances in neuroimaging and genetic characteristics of the non-fluent/agrammatic variant of primary progressive aphasia
Authors: Yi-Jing Bai, Xiao-Wei Liu, Wei-Dong Le
Type: Perspective from Chinese Medical Journal (English)
Access this article: https://doi.org/10.1097/CM9.0000000000001424
Title: Sex Differences in Cognitive Decline Among US Adults
Authors: Deborah A. Levine, Alden L. Gross, Emily M. Briceño, Nicholas Tilton, Bruno J. Giordani, Jeremy B. Sussman, Rodney A. Hayward, James F. Burke, Stephanie Hingtgen, Mitchell S. V. Elkind, Jennifer J. Manly, Rebecca F. Gottesman, Darrell J. Gaskin, Stephen Sidney, Ralph L. Sacco, Sarah E. Tom, Clinton B. Wright, Kristine Yaffe, Andrzej T. Galecki
Type: Original Investigation from JAMA Netw Open
Question: Does the risk of cognitive decline among US adults vary by sex?
Findings: In this cohort study using pooled data from 26 088 participants, women, compared with men, had higher baseline performance in global cognition, executive function, and memory. Women, compared with men, had significantly faster declines in global cognition and executive function, but not memory.
Meaning: These findings suggest that women may have greater cognitive reserve but faster cognitive decline than men.
Importance: Sex differences in dementia risk are unclear, but some studies have found greater risk for women.
Objective: To determine associations between sex and cognitive decline in order to better understand sex differences in dementia risk.
Design, Setting, and Participants: This cohort study used pooled analysis of individual participant data from 5 cohort studies for years 1971 to 2017: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, and Northern Manhattan Study. Linear mixed-effects models were used to estimate changes in each continuous cognitive outcome over time by sex. Data analysis was completed from March 2019 to October 2020.
Main Outcomes and Measures: The primary outcome was change in global cognition. Secondary outcomes were change in memory and executive function. Outcomes were standardized as t scores (mean [SD], 50 ); a 1-point difference represents a 0.1-SD difference in cognition.
Results: Among 34 349 participants, 26 088 who self-reported Black or White race, were free of stroke and dementia, and had covariate data at or before the first cognitive assessment were included for analysis. Median (interquartile range) follow-up was 7.9 (5.3-20.5) years. There were 11 775 (44.7%) men (median [interquartile range] age, 58 [51-66] years at first cognitive assessment; 2229 [18.9%] Black) and 14 313 women (median [interquartile range] age, 58 [51-67] years at first cognitive assessment; 3636 [25.4%] Black). Women had significantly higher baseline performance than men in global cognition (2.20 points higher; 95% CI, 2.04 to 2.35 points; P < .001), executive function (2.13 points higher; 95% CI, 1.98 to 2.29 points; P < .001), and memory (1.89 points higher; 95% CI, 1.72 to 2.06 points; P < .001). Compared with men, women had significantly faster declines in global cognition (−0.07 points/y faster; 95% CI, −0.08 to −0.05 points/y; P < .001) and executive function (−0.06 points/y faster; 95% CI, −0.07 to −0.05 points/y; P < .001). Men and women had similar declines in memory (−0.004 points/y faster; 95% CI, −0.023 to 0.014; P = .61).
Conclusions and Relevance: The results of this cohort study suggest that women may have greater cognitive reserve but faster cognitive decline than men, which could contribute to sex differences in late-life dementia.
Access this article: https://doi.org/10.1001/jamanetworkopen.2021.0169
Title: AdipoRon Treatment Induces a Dose-Dependent Response in Adult Hippocampal Neurogenesis
Authors: Thomas H. Lee, Brian R. Christie, Henriette van Praag, Kangguang Lin, Parco Ming-Fai Siu, Aimin Xu, Kwok-Fai So, Suk-yu Yau
Type: Article from International Journal of Molecular Sciences
AdipoRon, an adiponectin receptor agonist, elicits similar antidiabetic, anti-atherogenic, and anti-inflammatory effects on mouse models as adiponectin does. Since AdipoRon can cross the blood-brain barrier, its chronic effects on regulating hippocampal function are yet to be examined. This study investigated whether AdipoRon treatment promotes hippocampal neurogenesis and spatial recognition memory in a dose-dependent manner. Adolescent male C57BL/6J mice received continuous treatment of either 20 mg/kg (low dose) or 50 mg/kg (high dose) AdipoRon or vehicle intraperitoneally for 14 days, followed by the open field test to examine anxiety and locomotor activity, and the Y maze test to examine hippocampal-dependent spatial recognition memory. Immunopositive cell markers of neural progenitor cells, immature neurons, and newborn cells in the hippocampal dentate gyrus were quantified. Immunosorbent assays were used to measure the serum levels of factors that can regulate hippocampal neurogenesis, including adiponectin, brain-derived neurotrophic factor (BDNF), and corticosterone. Our results showed that 20 mg/kg AdipoRon treatment significantly promoted hippocampal cell proliferation and increased serum levels of adiponectin and BDNF, though there were no effects on spatial recognition memory and locomotor activity. On the contrary, 50 mg/kg AdipoRon treatment impaired spatial recognition memory, suppressed cell proliferation, neuronal differentiation, and cell survival associated with reduced serum levels of BDNF and adiponectin. The results suggest that a low-dose AdipoRon treatment promotes hippocampal cell proliferation, while a high-dose AdipoRon treatment is detrimental to the hippocampus function.
Access this article: https://doi.org/10.3390/ijms22042068
Title: Electroacupuncture activates inhibitory neural circuits in the somatosensory cortex to relieve neuropathic pain
Authors: Ji-an Wei, Xuefei Hu, Borui Zhang, Linglin Liu, Kai Chen, Kwok-Fai So, Man Li, Li Zhang
Type: Article from iScience
Electroacupuncture (EA) has been accepted to effectively relieve neuropathic pain. Current knowledge of its neural modulation mainly covers the spinal cord and subcortical nuclei, with little evidence from the cortical regions. Using in vivo two-photon imaging in mice with chronic constriction injury, we found that EA treatment systemically modulated the Ca2+ activity of neural circuits in the primary somatosensory cortex, including the suppression of excitatory pyramidal neurons, potentiation of GABAergic somatostatin-positive interneurons, and suppression of vasoactive intestinal peptide-positive interneurons. Furthermore, EA-mediated alleviation of pain hypersensitivity and cortical modulation were dependent on the activation of endocannabinoid receptor 1. These findings collectively reveal a cortical circuit involved in relieving mechanical or thermal hypersensitivity under neuropathic pain and identify one molecular pathway directing analgesic effects of EA.
Access this article: https://doi.org/10.1016/j.isci.2021.102066
Title: Integrity of the uncinate fasciculus is associated with the onset of bipolar disorder: a 6-year followed-up study
Authors: Xiaoyue Li, Weicong Lu, Ruoxi Zhang, Wenjin Zou, Yanling Gao, Kun Chen, Suk-Yu Yau, Robin Shao, Roger S. McIntyre, Guiyun Xu, Kwok-Fai So, Kangguang Lin
Type: Article from Translational Psychiatry
Patients with Bipolar Disorder (BD) are associated with aberrant uncinate fasciculus (UF) that connects amygdala-ventral prefrontal cortex (vPFC) system, but the casual relationship is still uncertain. The research aimed to investigate the integrity of UF among offspring of patients with BD and investigate its potential causal association with subsequent declaration of BD. The fractional anisotropy (FA) and mean diffusivity (MD) of UF were compared in asymptomatic offspring (AO, n = 46) and symptomatic offspring (SO, n = 45) with a parent with BD, and age-matched healthy controls (HCs, n = 35). Logistic regressions were performed to assess the predictive effect of UF integrity on the onset of BD. The three groups did not differ at baseline in terms of FA and MD of the UF. Nine out of 45 SO developed BD over a follow-up period of 6 years, and the right UF FA predicted the onset of BD (p = 0.038, OR = 0.212, 95% CI = 0.049–0.917). The ROC curve revealed that the right UF FA predicted BD onset (area-under-curve = 0.859) with sensitivity of 88.9% and specificity of 77.3%. The complementary whole-brain tract-based spatial statistics (TBSS) showed that widespread increases of FA were found in the SO group compared with HCs, but were not associated with the onset of BD. Our data provide evidence supporting the causal relationship between the white matter structural integrity of the amygdala-vPFC system and the onset of BD in genetically at-risk offspring of BD patients.
Access this article: https://doi.org/10.1038/s41398-021-01222-z
Title: Tactile modulation of memory and anxiety requires dentate granule cells along the dorsoventral axis
Authors: Chi Wang, Hui Liu, Kun Li, Zhen-Zhen Wu, Chen Wu, Jing-Ying Yu, Qian Gong, Ping Fang, Xing-Xing Wang, Shu-Min Duan, Hao Wang, Yan Gu, Ji Hu, Bing-Xing Pan, Mathias V. Schmidt, Yi-Jun Liu, Xiao-Dong Wang
Type: Article from Nature Communications
Touch can positively influence cognition and emotion, but the underlying mechanisms remain unclear. Here, we report that tactile experience enrichment improves memory and alleviates anxiety by remodeling neurons along the dorsoventral axis of the dentate gyrus (DG) in adult mice. Tactile enrichment induces differential activation and structural modification of neurons in the dorsal and ventral DG, and increases the presynaptic input from the lateral entorhinal cortex (LEC), which is reciprocally connected with the primary somatosensory cortex (S1), to tactile experience-activated DG neurons. Chemogenetic activation of tactile experience-tagged dorsal and ventral DG neurons enhances memory and reduces anxiety respectively, whereas inactivation of these neurons or S1-innervated LEC neurons abolishes the beneficial effects of tactile enrichment. Moreover, adulthood tactile enrichment attenuates early-life stress-induced memory deficits and anxiety-related behavior. Our findings demonstrate that enriched tactile experience retunes the pathway from S1 to DG and enhances DG neuronal plasticity to modulate cognition and emotion.
Access this article: https://doi.org/10.1038/s41467-020-19874-8