This week, we've collected the latest articles in the field of cognitive dysfunction. Welcome your all to read and share articles, and follow AND journals.
Title: White matter damage as a consequence of vascular dysfunction in a spontaneous mouse model of chronic mild chronic hypoperfusion with eNOS deficiency
Authors: Xingyong Chen, Ling Chen, Geng Lin, Zhengjun Wang, Mahesh C Kodali, Mingqi Li, Huimin Chen, Sarah G Lebovitz, Tyler C Ortyl, Lexiao Li, Saifudeen Ismael, Purnima Singh, Kafait U Malik, Tauheed Ishrat, Fu-Ming Zhou, Wei Zheng, Francesca-Fang Liao
Vascular cognitive impairment and dementia (VCID) is the second most common form of dementia after Alzheimer's disease (AD). Currently, the mechanistic insights into the evolution and progression of VCID remain elusive. White matter change represents an invariant feature. Compelling clinical neuroimaging and pathological evidence suggest a link between white matter changes and neurodegeneration. Our prior study detected hypoperfused lesions in mice with partial deficiency of endothelial nitric oxide (eNOS) at very young age, precisely matching to those hypoperfused areas identified in preclinical AD patients. White matter tracts are particularly susceptible to the vascular damage induced by chronic hypoperfusion. Using immunohistochemistry, we detected severe demyelination in the middle-aged eNOS-deficient mice. The demyelinated areas were confined to cortical and subcortical areas including the corpus callosum and hippocampus. The intensity of demyelination correlated with behavioral deficits of gait and associative recognition memory performances. By Evans blue angiography, we detected blood-brain barrier (BBB) leakage as another early pathological change affecting frontal and parietal cortex in eNOS-deficient mice. Sodium nitrate fortified drinking water provided to young and middle-aged eNOS-deficient mice completely prevented non-perfusion, BBB leakage, and white matter pathology, indicating that impaired endothelium-derived NO signaling may have caused these pathological events. Furthermore, genome-wide transcriptomic analysis revealed altered gene clusters most related to mitochondrial respiratory pathways selectively in the white matter of young eNOS-deficient mice. Using eNOS-deficient mice, we identified BBB breakdown and hypoperfusion as the two earliest pathological events, resulting from insufficient vascular NO signaling. We speculate that the compromised BBB and mild chronic hypoperfusion trigger vascular damage, along with oxidative stress and astrogliosis, accounting for the white matter pathological changes in the eNOS-deficient mouse model. We conclude that eNOS-deficient mice represent an ideal spontaneous evolving model for studying the earliest events leading to white matter changes, which will be instrumental to future therapeutic testing of drug candidates and for targeting novel/specific vascular mechanisms contributing to VCID and AD.
Access this article: https://doi.org/10.1038/s41380-022-01701-9
Title: Sex differences in brain functional connectivity of hippocampus in mild cognitive impairment
Authors: Jordan Williamson, Andriy Yabluchanskiy, Peter Mukli, Dee H. Wu, William Sonntag, Carrie Ciro, Yuan Yang
Type: ORIGINAL RESEARCH article
Mild cognitive impairment (MCI) is the prodromal stage of Alzheimer’s Disease (AD). Prior research shows that females are more impacted by MCI than males. On average females have a greater incidence rate of any dementia and current evidence suggests that they suffer greater cognitive deterioration than males in the same disease stage. Recent research has linked these sex differences to neuroimaging markers of brain pathology, such as hippocampal volumes. Specifically, the rate of hippocampal atrophy affects the progression of AD in females more than males. This study was designed to extend our understanding of the sex-related differences in the brain of participants with MCI. Specifically, we investigated the difference in the hippocampal connectivity to different areas of the brain. The Resting State fMRI and T2 MRI of cognitively normal individuals (n = 40, female = 20) and individuals with MCI (n = 40, female = 20) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were analyzed using the Functional Connectivity Toolbox (CONN). Our results demonstrate that connectivity of hippocampus to the precuneus cortex and brain stem was significantly stronger in males than in females. These results improve our current understanding of the role of hippocampus-precuneus cortex and hippocampus-brainstem connectivity in sex differences in MCI. Understanding the contribution of impaired functional connectivity sex differences may aid in the development of sex specific precision medicine to manipulate hippocampal-precuneus cortex and hippocampal-brainstem connectivity to decrease the progression of MCI to AD.
Access this article: https://doi.org/10.3389/fnagi.2022.959394
Title: Effects of comorbid posttraumatic stress disorder on cognitive dysfunction in Chinese male methamphetamine patients
Authors: Wei Jiang, Yang Tian, Fusheng Fan, Fabing Fu, Dejun Wei, Shanshan Tang, Jiajing Chen, Yuqing Li, Rongrong Zhu, Li Wang, Zhanbiao Shi, Dongmei Wang, Xiang-Yang Zhang
Type: Research article
Cognitive dysfunction and posttraumatic stress disorder (PTSD) are common in methamphetamine patients. However, few studies have investigated the cognitive performance of methamphetamine patients with PTSD. The purpose of this study was to investigate the impact of comorbid PTSD on cognitive function in Chinese male methamphetamine patients.
We analyzed 464 methamphetamine patients and 156 healthy volunteers. The PTSD Screening Scale (PCL-5) was used to assess PTSD and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to assess cognitive function.
Compared with healthy controls, methamphetamine patients had more cognitive dysfunction in immediate memory, visuospatial/constructional, language, attention and delayed memory. Moreover, methamphetamine patients with PTSD had less cognitive dysfunction in immediate memory, attention, and delayed memory than methamphetamine patients without PTSD. Further stepwise regression analysis showed that PTSD alterations in arousal and reactivity cluster were risk predictors for language, and PTSD negative alteration in cognition and mood cluster were risk predictors for delayed memory.
Our results indicate that methamphetamine patients without PTSD have poorer cognitive dysfunction than those with PTSD. Some demographic and PTSD symptom clusters are protective or risk factors for cognitive dysfunction in methamphetamine patients.
Access this article: https://doi.org/10.1016/j.pnpbp.2022.110611
Title: Closing the mechanistic gap: the value of microarchitecture in understanding cognitive networks
Authors: Casey Paquola, Katrin Amunts, Alan Evans, Jonathan Smallwood, Boris Bernhardt
Cognitive neuroscience aims to provide biologically relevant accounts of cognition. Contemporary research linking spatial patterns of neural activity to psychological constructs describes 'where' hypothesised functions occur, but not 'how' these regions contribute to cognition. Technological, empirical, and conceptual advances allow this mechanistic gap to be closed by embedding patterns of functional activity in macro- and microscale descriptions of brain organisation. Recent work on the default mode network (DMN) and the multiple demand network (MDN), for example, highlights a microarchitectural landscape that may explain how activity in these networks integrates varied information, thus providing an anatomical foundation that will help to explain how these networks contribute to many different cognitive states. This perspective highlights emerging insights into how microarchitecture can constrain network accounts of human cognition.
Access this article: https://doi.org/10.1016/j.tics.2022.07.001
Title: Odor Enrichment Attenuates the Anesthesia/Surgery-induced Cognitive Impairment
Authors: Ce Zhang, Yuan Han, Xiaojun Liu, Hong Tan, Yuanlin Dong, Yiying Zhang, Feng Liang, Hui Zheng, Gregory Crosby, Deborah J Culley, Edward R Marcantonio, Yuan Shen, Jun-Li Cao, Zhongcong Xie
Type: Original Study
Determine the association between olfactory function and cognition in patients and rodents.
Summary Background Data:
Perioperative neurocognitive disorders include delayed neurocognitive recovery (dNCR). The contribution of olfactory function to dNCR remains undetermined. It is unknown whether odor enrichment could mitigate dNCR.
We performed a prospective observational cohort study to determine potential association between olfactory impairment and dNCR in patients. We assessed the effects of anesthesia/surgery on olfactory and cognitive function in mice using the block test and Barnes maze. We measured interleukin-6, olfactory mature protein, GAP43, mature and premature olfactory neurons, PSD-95, and synaptophysin in blood, nasal epithelium, and hippocampus of mice. Odor enrichment, interleukin-6 antibody, and knockout of interleukin-6 were used in the interaction experiments.
Patients with dNCR had worse odor identification than the patients without dNCR [preoperative: 7 (1.25, 9) versus 10 (8, 11), median (interquartile range), P<0.001; postoperative: 8 (2.25, 10) versus 10 (8, 11), P<0.001]. Olfactory impairment associated with dNCR in patients before and after adjusting age, sex, education, preoperative mini-mental state examination score, and days of the neuropsychological tests. Anesthesia/surgery induced olfactory and cognitive impairment, increased levels of interleukin-6 in blood and nasal epithelium, decreased amounts of olfactory receptor neurons and their markers in the nasal epithelium, and reduced amounts of synapse markers in the hippocampus of mice. These changes were attenuated by odor enrichment and interleukin-6 antibody.
The anesthesia/surgery-induced olfactory impairment may contribute to dNCR in patients and postoperative cognitive impairment in mice. Odor enrichment could be a potential intervention.
Access this article: https://doi.org/10.1097/SLA.0000000000005599