The Latest Articles on Cognitive Impairment

Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.

This week, we would like to share several latest articles on Cognitive Impairment.

Title: Teleneuropsychology for Vascular Cognitive Impairment: which tools do we have?
Authors: Emilia Salvadori, Leonardo Pantoni, Società Italiana di NeuroGeriatria (SINEG)
Type: Review
Abstract:

The halt of clinical activities imposed during the COVID-19 pandemic forced clinicians to find alternative strategies to provide continuity of care and services, and led to a renewed interest in use of teleneuropsychology (TNP) to remotely assess patients. Recent TNP guidelines recommend maximizing the reproduction of standard in-person assessment, particularly through videoconferences. However, consistency of the adaptations of usual cognitive tests to videoconference needs further elucidation.

This review aims at critical reviewing which cognitive tests could be recommended for a remote evaluation of patients with vascular cognitive impairment (VCI) among those widely recognized as reference standards.

Current evidence supports the use of global cognitive efficiency (MMSE and MoCA), verbal memory (Revised Hopkins Verbal Learning Test), and language tests (phonemic and semantic verbal fluencies, Boston Naming Test), while there is a lack of strong validity support for measures of visuospatial functions (Rey-Osterreith Complex Figure), and executive functioning and processing speed (Trail making Test, and Digit symbol or Symbol digit tests). This represents a major limitation in the evaluation of VCI because its cognitive profile in often characterized by attention and executive deficits.

At present, a videoconference TNP visit appears useful for a brief evaluation of global cognitive efficiency, and to ‘triage’ patients towards a second level in person evaluation. In future, hybrid models of TNP based on data collected across multiple modalities, incorporating both adaptation of usual cognitive tools and new computerized tools in the supervised videoconference setting, are likely to become the best option for a comprehensive remote cognitive assessment.

Access this article: https://doi.org/10.1016/j.cccb.2023.100173

Title: Inability to suppress head rotation during the saccade test as a clinical biomarker for cognitive dysfunction in Parkinson’s disease
Authors: Jung Hwan Shin, Dong Ah Shin, Chan Young Lee, Hee Jin Chang, Kyung Ah Woo, Han-Joon Kim, Jung Chan Lee, Beomseok Jeon
Type: Research Article
Abstract:

Background:
There is a need for development of reliable and accessible clinical biomarker for detecting cognitive dysfunction in PD. This study aimed to investigate whether involuntary head rotation during the saccade test could serve as a potential biomarker for screening cognitive dysfunction in PD.

Methods:
A total of 27 PD patients and nine age- and sex-matched healthy controls were prospectively enrolled in this study. A custom-designed gyroscope was attached to the forehead of each participant, and a saccade test consisting of 20 trials was conducted. The entire test was recorded on video, and two movement disorder experts independently rated the degree of head rotation, blinded to the patients' clinical information. The peak angular velocity of head rotation was derived from the gyroscope data. Participants underwent Montreal Cognitive Assessment (MoCA) as the cognitive evaluation. Correlation analysis was performed to assess the relationship between head rotation and MoCA scores.

Results:
The mean peak angular velocity of head rotation significantly correlated with the MoCA scores (R = -0.52, p = 0.0023) including age, sex, disease duration, and education duration as cofactors. The optimal peak angular velocity thresholds for head rotation, which aligned with the manual ratings, were determined to be 5°/s and 10°/s for raters 1 and 2, respectively. The MoCA scores exhibited significant correlations with the number of head rotations, using both the 5°/s (R = -0.36, p = 0.042) and 10°/s (R = -0.49, p = 0.0048) thresholds. Furthermore, the mean angular velocity of the head demonstrated a 100% positive predictive value and specificity for the detection of cognitive impairment (MoCA < 26), based on the cut-offs of 5°/s and 10°/s.

Conclusion:
Inability to suppress head rotation during saccades may serve as a potential clinical biomarker for screening cognitive dysfunction in PD.

Access this article: https://doi.org/10.1016/j.neulet.2023.137356

Title: Astrocytic AT1R deficiency ameliorates Aβ-induced cognitive deficits and synaptotoxicity through β-arrestin2 signaling
Authors: Xinyue Chen, Ruiqi Gao, Yizhi Song, Tao Xu, Liangyun Jin, Wanning Zhang, Ziyan Chen, Hongqi Wang, Wenxing Wu, Suli Zhang, Guitao Zhang, Ning Zhang, Lirong Chang, Huirong Liu, Hui Li, Yan Wu
Type: Research Article
Abstract:
Alzheimer's disease (AD) seriously influences human health, and there is no effective treatment to prevent or cure AD. Recent studies have shown that angiotensin II type 1 receptor (AT1R) blockers significantly reduce the prevalence of AD, while the precise role and mechanism of AT1R in AD remain obscure. In this study, for the first time, we identified that astrocytic but not neuronal AT1R levels were significantly increased in AD model rats and found that astrocyte-specific knockout of AT1R significantly ameliorated amyloid β (Aβ)-induced cognitive deficits and synaptotoxicity. Pretreating astrocytes with an AT1R blocker also alleviated Aβ-induced synaptotoxicity in the coculture system of hippocampal neurons and astrocytes. Moreover, AT1R could directly bind to Aβ1-42 and biasedly activate the astrocytic β-arrestin2 pathway, and biased inhibition of the astrocytic AT1R/β-arrestin2 pathway relieved Aβ-induced neurotoxicity. Furthermore, we demonstrated that astrocytic AT1R/β-arrestin2 pathway-mediated synaptotoxicity was associated with the aggregation of autophagosomes, which triggered the disordered degradation of Aβ. Our findings reveal a novel molecular mechanism of astrocytic AT1R in Aβ-induced neurodegeneration and might contribute to establishing new targets for AD prevention and therapy.
Access this article: https://doi.org/10.1016/j.pneurobio.2023.102489

Title: Complement C1q drives microglia-dependent synaptic loss and cognitive impairments in a mouse model of lipopolysaccharide-induced neuroinflammation
Authors: Xinmiao Wu, Yuzhu Gao, Cuina Shi, Jianhua Tong, Daqing Ma, Jinchun Shen, Jianjun Yang, Muhuo Ji
Type: Research Article
Abstract:
Activated microglia and subsequent release of pro-inflammatory cytokines result in neuroinflammatory status which further damage neurological function including cognitive impairments in various neurological conditions. However, the underlying molecular mechanisms during these pathological processing remain unknown. In the current study, mice received intraperitoneal administrations of LPS (0.5 mg/kg, daily, Escherichia coli O55:B5) for seven consecutive days and their different cohorts were used for behavioral assessment with open field, Y maze, and novel object recognition test or for electrophysiology recordings of mEPSC, LFP or LTP in in vivo or ex vivo preparation. The hippocampus from some cohorts were harvested for immunostaining or Western blotting of c1q, Iba-1, CD68, PSD95 and dendritic spine density or for transcriptome and proteomics analysis. Repeated LPS injections induced an up-regulation of complement system protein c1q and distinct microglial phenotype with an enrichment of the complement–phagosome pathway. Microglial synaptic engulfment and profound synaptic loss were found. These pathological changes were accompanied with the significantly decreased excitatory synaptic transmission, disturbed theta oscillations, impaired hippocampal long-term potentiation, and cognitive impairments. Notably, neutralization of c1q signaling robustly prevented these changes. Collectively, our data provide evidence that activated microglia and complement cascade c1q signaling in the hippocampus may account for synaptic loss and cognitive impairments in a mouse model of neuroinflammation induced by repeated LPS injections. Our work implicates that complement system may be a therapeutic target for developing therapies to prevent or treat cognitive disorders related to neuroinflammation or other disease conditions including neurodegenerative disease per se.
Access this article: https://doi.org/10.1016/j.neuropharm.2023.109646

Title: Dysfunctional synaptic pruning by microglia correlates with cognitive impairment in sleep-deprived mice: Involvement of CX3CR1 signaling
Authors: Lu Wang, Hanyi Ling, Hui He, Nan Hu, Lin Xiao, Yue Zhang, Lei Xie, Zili You
Type: Research Article
Abstract:
Microglia are involved in sleep/wake cycles and the response to sleep loss. Synaptic pruning by microglia is necessary for central nervous system circuit refinement and contributes to cognitive function. Here, we investigated whether and how microglia-mediated synaptic pruning may be involved in cognitive deficits induced by sleep deprivation in mice. Mice were deprived of sleep by leaving them in a spontaneously rotating rod for 72 h, after which their cognitive function was assessed using an object location test, Y maze, and novel object recognition test. Sleep deprivation lowered the discrimination index for familiar locations in the object location test and Y maze. Microglial morphology was assessed using immunostaining Iba1, while microglia-mediated synaptic pruning was examined based on immunostaining PSD95, CD68, and Iba1. Sleep deprivation also activated microglial cells in the hippocampus, as reflected in bigger soma as well as fewer and shorter branches than normal sleep. Sleep deprivation downregulated phagocytic markers and internalization of postsynaptic protein 95 (PSD95), suggesting impaired synaptic pruning. CX3C motif chemokine receptor 1 (CX3CR1) signaling was detected in in vitro experiments. Sleep deprivation also downregulated CX3CR1. Activation of CX3CR1 signaling increased phagocytosis activity of BV2 microglia in vitro. Sleep deprivation dysregulates microglial CX3CR1 signaling and inhibits synaptic pruning, contributing to associated cognitive deficits. These findings identify CX3CR1-dependent synaptic pruning as a potential therapeutic target in which sleep deprivation causes recognition impairments.
Access this article: https://doi.org/10.1016/j.ynstr.2023.100553