Alterations In Cognitive Function Research Articles

Do pregnancy and motherhood have an impact on cognitive functions in women

ABSTRACT Pregnancy and motherhood are some of the most physically and mentally challenging periods in a woman’s life. The aim of current study was to examine aspects of cognitive functions in pregnancy and motherhood that are controversial in the literature. The study included 30 healthy pregnant women aged between 18–40 years in their second and third trimesters, 30 healthy controls (nulliparous and non-pregnant women) and 30 healthy mothers matched with the pregnant women for age, handedness and education level. Edinburgh Postpartum Depression Scale, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Trail Making, Stroop, Digit Span, Verbal Fluency and Rey Auditory and Verbal Learning Tests (RAVLT) were applied to all participants. The pregnant group showed significantly lower performance in trail making, digit span, verbal fluency as well as RAVLT compared to other two groups suggesting deficiencies in cognitive areas such as attention, set-shifting, planning, learning, language functions, semantic memory, working memory, encoding memory and retrieval. A trend toward increased function in response inhibition was observed in the mothers. Regression analyses revealed that pregnancy significantly decreased performance in verbal fluency, trail making, and RAVLT. Our findings from rigorously selected participants may help comprehend alterations in cognitive functioning during pregnancy and motherhood, as well as shed light on the contradictory literature.

Association between subclinical thyroid dysfunction and cognitive decline: findings from the ELSA-Brasil study.

Thyroid dysfunction has been associated with cognitive decline and dementia. However, the role of subtle thyroid hormone alterations in cognitive function is still debatable. Participants without overt thyroid dysfunction aged 35-74 years at baseline were evaluated in three study waves (2008-10, 2012-14, and 2017-19). We assessed baseline thyroid stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). Cognitive performance was evaluated every four years in each wave using 10-word immediate and late recall, word recognition, semantic (animals category) and phonemic (letter f) verbal fluency, and the trail-making B-version tests. A global composite z-score was derived from these tests. The associations of TSH, FT4, and FT3 levels with cognitive decline over time were evaluated using linear mixed-effect models adjusted for sociodemographic, clinical, and lifestyle variables. In 9,524 participants (mean age 51.2±8.9 years old, 51% women, 52% White), there was no association between baseline TSH, FT4, and FT3 levels and cognitive decline during the follow-up. However, increase in FT4 levels over time was associated with faster memory (β=-0.004, 95%CI=-0.007; -0.001, p=0.014), verbal fluency (β=-0.003, 95%CI=-0.007; -0.0005, p=0.021), executive function (β=-0.004, 95%CI=-0.011; -0.003, p<0.001), and global cognition decline (β=-0.003, 95%CI=-0.006; -0.001, p=0.001). Decrease in FT4 levels over time was associated with faster verbal fluency (β=-0.003, 95%CI=-0.007; -0.0004, p=0.025) and executive function (β=-0.004, 95%CI=-0.007; -0.0003, p=0.031) decline. An increase or decrease in FT4 levels over time was associated with faster cognitive decline in middle-aged and older adults without overt thyroid dysfunction during 8 years of follow-up.

Exploring the challenges of avoiding collisions with virtual pedestrians using a dual-task paradigm in individuals with chronic moderate to severe traumatic brain injury.

Individuals with a moderate-to-severe traumatic brain injury (m/sTBI), despite experiencing good locomotor recovery six months post-injury, face challenges in adapting their locomotion to the environment. They also present with altered cognitive functions, which may impact dual-task walking abilities. Whether they present collision avoidance strategies with moving pedestrians that are altered under dual-task conditions, however, remains unclear. This study aimed to compare between individuals with m/sTBI and age-matched control individuals: (1), the locomotor and cognitive costs associated with the concurrent performance of circumventing approaching virtual pedestrians (VRPs) while attending to an auditory-based cognitive task and; (2) gaze behaviour associated with the VRP circumvention task in single and dual-task conditions. Twelve individuals with m/sTBI (age = 43.3 ± 9.5 yrs; >6 mo. post injury) and 12 healthy controls (CTLs) (age = 41.8 ± 8.3 yrs) were assessed while walking in a virtual subway station viewed in a head-mounted display. They performed a collision avoidance task with VRPs, as well as auditory-based cognitive tasks (pitch discrimination and auditory Stroop), both under single and dual-task conditions. Dual-task cost (DTC) for onset distance of trajectory deviation, minimum distance from the VRP, maximum lateral deviation, walking speed, gaze fixations and cognitive task accuracy were contrasted between groups using generalized estimating equations. In contrast to CTLs who showed locomotor DTCs only, individuals with m/sTBI displayed both locomotor and cognitive DTCs. While both groups walked slower under dual-task conditions, only individuals with m/sTBI failed to modify their onset distance of trajectory deviation and maintained smaller minimum distances and smaller maximum lateral deviation compared to single-task walking. Both groups showed shorter gaze fixations on the approaching VRP under dual-task conditions, but this reduction was less pronounced in the individuals with m/sTBI. A reduction in cognitive task accuracy under dual-task conditions was found in the m/sTBI group only. Individuals with m/sTBI present altered locomotor and gaze behaviours, as well as altered cognitive performances, when executing a collision avoidance task involving moving pedestrians in dual-task conditions. Potential mechanisms explaining those alterations are discussed. Present findings highlight the compromised complex walking abilities in individuals with m/sTBI who otherwise present a good locomotor recovery.

Hyponatremia as a predictor of cognitive deterioration in hospitalized post-stroke patients

PurposeEvidence is scarce regarding the association between hyponatremia and alterations in cognitive function among hospitalized older patients. We aimed to investigate the associations between hyponatremia and the baseline cognitive status, as well as the improvement in cognitive function, in hospitalized post-stroke patients. MethodsThis retrospective cohort study included consecutive hospitalized post-stroke patients. Serum sodium concentrations were extracted from medical records based on blood tests performed within 24 h of admission, with hyponatremia defined as a serum sodium concentration < 135 mEq/L. The main outcomes included admission and discharge scores for cognitive levels, assessed through the cognitive domain of the Functional Independence Measure (FIM-cognition), as well as the score changes observed during the hospitalization period. Multivariate linear regression analyses were used to determine the association between hyponatremia and outcomes of interest, adjusted for potential confounders. ResultsData from 955 patients (mean age 73.2 years; 53.6 % men) were included in the analysis. The median baseline blood sodium level was 139 [137, 141], and 84 patients (8.8 %) exhibited hyponatremia. After full adjustment for confounders, the baseline hyponatremia was significantly and negatively associated with FIM-cognition values at admission (β = -0.009, p = 0.016), discharge (β = -0.038, p = 0.043), and the gain during hospital stay (β = -0.040, p = 0.011). ConclusionBaseline hyponatremia has demonstrated a correlation with decline in cognitive level over the course of rehabilitation in individuals after stroke. Assessing hyponatremia at the outset proves to be a pivotal prognostic indicator.

Altered patterns of dynamic functional connectivity of brain networks in deficit and non-deficit schizophrenia.

This study aims to investigate the altered patterns of dynamic functional network connectivity (dFNC) between deficit schizophrenia (DS) and non-deficit schizophrenia (NDS), and further explore the associations with cognitive impairments. 70 DS, 91 NDS, and 120 matched healthy controls (HCs) were enrolled. The independent component analysis was used to segment the whole brain. The fMRI brain atlas was used to identify functional networks, and the dynamic functional connectivity (FC) of each network was detected. Correlation analysis was used to explore the associations between altered dFNC and cognitive functions. Four dynamic states were identified. Compared to NDS, DS showed increased FC between sensorimotor network and default mode network in state 1 and decreased FC within auditory network in state 4. Additionally, DS had a longer mean dwell time of state 2 and a shorter one in state 3 compared to NDS. Correlation analysis showed that fraction time and mean dwell time of states were correlated with cognitive impairments in DS. This study demonstrates the distinctive altered patterns of dFNC between DS and NDS patients. The associations with impaired cognition provide specific neuroimaging evidence for the pathogenesis of DS.

Bisphenol-F and Bisphenol-S (BPF and BPS) Impair the Stemness of Neural Stem Cells and Neuronal Fate Decision in the Hippocampus Leading to Cognitive Dysfunctions.

Neurogenesis occurs throughout life in the hippocampus of the brain, and many environmental toxicants inhibit neural stem cell (NSC) function and neuronal generation. Bisphenol-A (BPA), an endocrine disrupter used for surface coating of plastic products causes injury in the developing and adult brain; thus, many countries have banned its usage in plastic consumer products. BPA analogs/alternatives such as bisphenol-F (BPF) and bisphenol-S (BPS) may also cause neurotoxicity; however, their effects on neurogenesis are still not known. We studied the effects of BPF and BPS exposure from gestational day 6 to postnatal day 21 on neurogenesis. We found that exposure to non-cytotoxic concentrations of BPF and BPS significantly decreased the number/size of neurospheres, BrdU+ (proliferating NSC marker)and MAP-2+ (neuronal marker) cells and GFAP+ astrocytes in the hippocampus NSC culture, suggesting reduced NSC stemness and self-renewal and neuronal differentiation and increased gliogenesis. These analogs also reduced the number of BrdU/Sox-2+, BrdU/Dcx+, and BrdU/NeuN+ co-labeled cells in the hippocampus of the rat brain, suggesting decreased NSC proliferation and impaired maturation of newborn neurons. BPF and BPS treatment increases BrdU/cleaved caspase-3+ cells and Bax-2 and cleaved caspase protein levels, leading to increased apoptosis in hippocampal NSCs. Transmission electron microscopy studies suggest that BPF and BPS also caused degeneration of neuronal myelin sheath, altered mitochondrial morphology, and reduced number of synapses in the hippocampus leading to altered cognitive functions. These results suggest that BPF and BPS exposure decreased the NSC pool, inhibited neurogenesis, induced apoptosis of NSCs, caused myelin degeneration/synapse degeneration, and impaired learning and memory in rats.

Functional brain network controllability dysfunction in Alzheimer’s disease and its relationship with cognition and gene expression profiling

Objective. In recent studies, network control theory has been applied to clarify transitions between brain states, emphasizing the significance of assessing the controllability of brain networks in facilitating transitions from one state to another. Despite these advancements, the potential alterations in functional network controllability associated with Alzheimer’s disease (AD), along with the underlying genetic mechanisms responsible for these alterations, remain unclear. Approach. We conducted a comparative analysis of functional network controllability measures between patients with AD (n = 64) and matched normal controls (NCs, n = 64). We investigated the association between altered controllability measures and cognitive function in AD. Additionally, we conducted correlation analyses in conjunction with the Allen Human Brain Atlas to identify genes whose expression was correlated with changes in functional network controllability in AD, followed by a set of analyses on the functional features of the identified genes. Main results. In comparison to NCs, patients with AD exhibited a reduction in average controllability, predominantly within the default mode network (DMN) (63% of parcellations), and an increase in average controllability within the limbic (LIM) network (33% of parcellations). Conversely, AD patients displayed a decrease in modal controllability within the LIM network (27% of parcellations) and an increase in modal controllability within the DMN (80% of parcellations). In AD patients, a significant positive correlation was found between the average controllability of the salience network and the mini-mental state examination scores. The changes in controllability measures exhibited spatial correlation with transcriptome profiles. The significant genes identified exhibited enrichment in neurobiologically relevant pathways and demonstrated preferential expression in various tissues, cell types, and developmental periods. Significance. Our findings have the potential to offer new insights into the genetic mechanisms underlying alterations in the controllability of functional networks in AD. Additionally, these results offered perspectives for a deeper understanding of the pathogenesis and the development of therapeutic strategies for AD.

Examining the relationships between cognition and auditory hallucinations: A systematic review.

Auditory hallucinations (hearing voices) have been associated with a range of altered cognitive functions, pertaining to signal detection, source-monitoring, memory, inhibition and language processes. Yet, empirical results are inconsistent. Despite this, several theoretical models of auditory hallucinations persist, alongside increasing emphasis on the utility of a multidimensional framework. Thus, clarification of current evidence across the broad scope of proposed mechanisms is warranted. A systematic search of the Web of Science, PubMed and Scopus databases was conducted. Records were screened to confirm the use of an objective behavioural cognitive task, and valid measurement of hallucinations specific to the auditory modality. Auditory hallucinations were primarily associated with difficulties in perceptual decision-making (i.e. reduced sensitivity/accuracy for signal-noise discrimination; liberal responding to ambiguity), source-monitoring (i.e. self-other and temporal context confusion), working memory and language function (i.e. reduced verbal fluency). Mixed or limited support was observed for perceptual feature discrimination, imagery vividness/illusion susceptibility, source-monitoring for stimulus form and spatial context, recognition and recall memory, executive functions (e.g. attention, inhibition), emotion processing and language comprehension/hemispheric organisation. Findings were considered within predictive coding and self-monitoring frameworks. Of concern was the portion of studies which - despite offering auditory-hallucination-specific aims and inferences - employed modality-general measures, and/or diagnostic-based contrasts with psychologically healthy individuals. This review highlights disparities within the literature between theoretical conceptualisations of auditory hallucinations and the body of rigorous empirical evidence supporting such inferences. Future cognitive investigations, beyond the schizophrenia-spectrum, which explicitly define and measure the timeframe and sensory modality of hallucinations, are recommended.

Neurometabolic and Brain Functional Alterations Associated with Cognitive Impairment in Patients with Myasthenia Gravis: A Combined 1H-MRS and fMRI Study

Whether patients with myasthenia gravis (MG) exhibit cognitive impairment is controversial. Also the underlying mechanisms are unknown. We aimed to investigate alterations in cognitive function, neurometabolite levels, and brain function in patients with MG and to explore the associations between abnormal regional brain functional activity, neurometabolite concentrations in the MPFC and left thalamus, and cognitive activity in patients with MG. Neuropsychological tests, proton magnetic resonance spectroscopy, and resting-state functional magnetic resonance imaging were performed on 41 patients with MG and 45 race-, sex-, age-, and education-matched healthy controls (HCs). The results suggest that MG is accompanied by cognitive decline, as indicated by global cognitive function, visual-spatial function, language, memory, abnormalities in regional brain functional activity, and neurometabolite alterations (including GABA, NAA, and Cho) in the medial prefrontal cortex (MPFC) and left thalamus. Cognitive impairment in patients with MG may be related to abnormal regional brain functional activity and changes in neurometabolites, and regional brain functional activity may be modulated by specific neurometabolites.

Association of Rare NOTCH3 Variants With Prevalent and Incident Stroke and Dementia in the General Population.

It is uncertain whether rare NOTCH3 variants are associated with stroke and dementia in the general population and whether they lead to alterations in cognitive function. This study aims to determine the associations of rare NOTCH3 variants with prevalent and incident stroke and dementia, as well as cognitive function changes. In the prospective community-based Shunyi Study, a total of 1007 participants were included in the baseline analysis. For the follow-up analysis, 1007 participants were included in the stroke analysis, and 870 participants in the dementia analysis. All participants underwent baseline brain magnetic resonance imaging, carotid ultrasound, and whole exome sequencing. Rare NOTCH3 variants were defined as variants with minor allele frequency <1%. A total of 137 rare NOTCH3 carriers were enrolled in the baseline study. At baseline, rare NOTCH3 variant carriers had higher rates of stroke (8.8% versus 5.6%) and dementia (2.9% versus 0.8%) compared with noncarriers. After adjustment for associated risk factors, the epidermal growth factor-like repeats (EGFr)-involving rare NOTCH3 variants were associated with a higher risk of prevalent stroke (odds ratio [OR], 2.697 [95% CI, 1.266-5.745]; P=0.040) and dementia (OR, 8.498 [95% CI, 1.727-41.812]; P=0.032). After 5 years of follow-up, we did not find that the rare NOTCH3 variants increased the risk of incident stroke and dementia. There was no statistical difference in the change in longitudinal cognitive scale scores. Rare NOTCH3 EGFr-involving variants are genetic risk factors for stroke and dementia in the general Chinese population.

Pycnogenol® improves cognitive function in post-stroke patients: a 6 month-study.

This pilot study in post-stroke patients evaluated the effects of supplementation with Pycnogenol® on alterations in cognitive functions (COFU) over a period of 6 months, starting 4 weeks after the stroke. The effects of supplementation - possibly acting on residual brain edema, on global cognitive function, attention and on mental performance - were studied. A control group used standard management (SM) and the other group added Pycnogenol®, 150 mg daily to SM. 38 post-stroke patients completed the 6-month-study, 20 in the Pycnogenol® group and 18 in the control group. No side effects were observed with the supplement. The tolerability was very good. The patients included into the two groups were comparable for age, sex and clinical distribution. There were 2 dropouts in the control group, due to non-medical problems. Main COFU parameters (assessed by a cognitive questionnaire) were significantly improved (all single items) with the supplement compared to controls (P<0.05). Additional observations indicate that Pycnogenol® patients experienced significantly less mini-accidents (including falls) than controls (P<0.05). The incidences of (minor) psychotic episodes or conflicts and distress and other problems including rare occurrence of minor hallucinations, were lower with the supplementation than in controls (P<0.05). Single observations concerning daily tasks indicated a better effect of Pycnogenol® compared to controls (P<0.05). Plasma free radicals also decreased significantly with the supplement in comparison to controls (P<0.05). Globally, supplemented subjects had a better recovery than controls. In post-stroke subjects, Pycnogenol® supplementation resulted in better recovery outcome and faster COFU 'normalization' after the stroke in comparison with SM; it can be considered a safe, manageable post-stroke, adjuvant management possibly reducing local brain edema. Nevertheless, more patients and a longer period of evaluation are needed to confirm these results.

Alterations in cognitive function and blood biomarkers following transcranial direct current stimulation in patients with amyloid positron emission tomography-positive Alzheimer's disease: a preliminary study.

Alzheimer's disease (AD), the most common form of dementia, is characterized by progressive cognitive decline. To address this, we conducted a randomized, double-blinded, sham-controlled study to investigate the therapeutic potential of transcranial direct current stimulation (tDCS) on patients with amyloid positron emission tomography (PET)- positive AD. Participants already undergoing pharmacological treatment and testing positive for amyloid PET were divided into Active-tDCS (n = 8) and Sham-tDCS (n = 8) groups. For 12 weeks, participants or their caregivers administered daily bi-frontal tDCS (YMS-201B+, Ybrain Inc., Seongnam, Korea) at home (2 mA, 30 min). Pre- and post-intervention assessments included neuropsychological tests and blood sample measurements for oligomerized beta-amyloid. The Active-tDCS group demonstrated significant improvements in cognitive domains such as language abilities, verbal memory, and attention span and in frontal lobe functions compared to the Sham-tDCS group. Furthermore, the Active-tDCS group showed a marked reduction in post-intervention plasma Aβ oligomerization tendency level, suggesting changes in pivotal AD-associated biomarkers. Our results emphasize the potential therapeutic benefits of tDCS for mild AD patients with amyloid PET positivity and stress the urgency for broader research, considering the global challenges of dementia and the need to pursue innovative therapeutic strategies.

Arctigenin attenuated spatial memory impairment in pR5 mice by regulating mitochondrial energy metabolism.

Arctigenin (ATG) is a natural product with a variety of biological activity, which can improve the pathological changes of Alzheimer's disease (AD) model mice through multiple mechanisms. This study aims to further elucidate the potential mechanism by which ATG improves memory impairment in AD mice. Here, we used pR5 mice as an experimental model, and ATG was administered continuously for 90 days. Novel object recognition, Y-maze, and Morris water maze were used to evaluate the therapeutic effect of ATG on memory impairment in AD mice. Immunohistochemical and immunofluorescence analyses were used to evaluate the effects of ATG on tau hyperphosphorylation and neuroinflammation, respectively. Finally, proteomics techniques were used to explore the possible mechanism of ATG. ATG significantly improved memory impairment in pR5 mice and inhibited tau phosphorylation in the hippocampus and neuroinflammation in the cortex. According to the proteomic analysis, the altered cognitive function of ATG was associated with the proteins of the tricarboxylic acid cycle and the electron transport chain. These results suggest that ATG is a potential therapeutic agent for diseases related to aberrant energy metabolism that can treat AD by improving mitochondrial function.

Alteration of cognitive function and locomotor coordination by top-of-the-foot applied perturbations

Footwear is essential for human locomotion and can influence various aspects of human behaviour. While the impact of most footwear features on locomotion and human behaviours has been studied extensively during the last 50 years, the footwear upper is very little studied. In particular, the impact of the footwear upper on cognition, movement coordination, and task performance is virtually unknown. In this study, vibrations of different intensities applied to the foot upper during the execution of basic locomotory tasks were used to determine the impact of the footwear upper on cognition and movement coordination. Sixteen participants were recruited for this study and asked to perform several locomotory tasks while undergoing an auditory Stroop test. Vibrations of various intensities were applied to the footwear upper using a set of five vibrators placed on high-sensitivity areas of the foot. The effects of vibrations on comfort level using a Visual Analog Scale (VAS), and cognition, postural balance, and sway were quantified using an auditory Stroop test, and inertial sensors derived movement coordination. The findings revealed a clear linear relationship between the intensity of vibrations and the perceived level of comfort. However, during walking, no linear correlation was observed between the vibration intensity and reaction time. On the other hand, during standing, a significant correlation between the vibration intensity and reaction time was observed. Moreover, the results demonstrated that as the vibration intensity increased during the standing condition, the magnitude of body sway also increased non-linearly. Finally, the results suggest that attaining an optimal level of comfort can improve attention and cognitive processes. This study highlights the importance of footwear uppers on cognitive and biomechanical performance. Vibration intensity affects comfort and reaction time differently for standing and walking. Some of these findings could have implications for footwear design both from a comfort and performance perspective.

Baseline thyroid hormone levels are not associated with cognitive decline: the ELSA‐Brasil study

AbstractBackgroundThyroid dysfunction has been associated with cognitive decline and dementia. However, the role of subtle thyroid hormone alterations in cognitive function is still debatable. Additionally, most studies have been conducted in high‐income countries. The aim of this study was to investigate the longitudinal association between baseline thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels with cognitive decline in the Brazilian Longitudinal Study of Adult Health (ELSA‐Brasil) during 8 years of follow‐up.MethodParticipants were evaluated every four years in three study waves (2008‐10, 2012‐14, and 2017‐19). Baseline TSH, FT4, and FT3 were collected after overnight fast and analyzed using immunoenzymatic assay. Cognitive performance was evaluated using the immediate and late recall, semantic and phonemic verbal fluency, and the trail‐making tests. A global composite z‐score was derived from these tests. Association of TSH, FT4 and FT3 levels with cognitive decline over time was evaluated using linear mixed‐effects models, adjusted for sociodemographic, lifestyle, and clinical variables.ResultIn 9,524 participants (mean age 51.2±8.9 y, 51% women, 52% White), the mean baseline TSH level was 2.3 ± 1.3 mIU/L, the mean baseline FT4 level was 1.2 ± 0.1 ng/dL, and the mean FT3 level was 0.2 ± 0.04 pg/mL (Table 1). There was no association between circulating TSH, FT4, and FT3 levels and cognitive decline during the follow‐up (Table 2 and Figure 1).ConclusionThyroid hormone levels were not associated with cognitive decline in middle‐aged and older adults without overt thyroid dysfunction during 8 years of follow‐up.

Role of primary cerebrovascular cilia in the pathogenesis of blood pressure and Alzheimer’s disease manifestations

AbstractBackgroundPrimary cilia are solitary membrane‐bound organelles emanating from the apical surface of most mammalian cells. They serve as sensory organelles sampling the extracellular environment and reprogramming the transcriptional machinery in response to changes in fluid flow. Ciliopathies, a group of genetic disorders characterized by disrupted cilia structure and/or function, share common phenotypes such as vascular dysfunction and cognitive impairment. Ciliopathies present with a broad range of clinical symptoms, including hypertension (HTN), developmental delays and cognitive and memory deficits, symptoms also observed in Alzheimer’s Disease (AD). This suggests that cilia may house signaling cascades critical for vascular integrity and learning and memory and may also be important contributors to AD and HTN. Therefore, investigation of cilia function in the vascular system may reveal cilia‐modulating mechanisms in neurodevelopmental processes. We propose a bold idea to look at the pathophysiological roles of cerebrovascular ciliary receptors in BP and AD.MethodImmunofluorescence of human brain endothelial cells (HBECs) were employed to study AChM3R localization and its downstream effectors. Cilia length and function (eNOS activation) studies were carried out to examine if mAChRs activation would enhance cilia structure and function. siRNA‐mediated knockdown of Tulp‐3 was performed to block AChM3R trafficking to primary cilia and study its activity. HBECs were exposed to synthetic Aβ to study their effect on cilia structure and ciliogenesis. Vascular‐specific cilia and AChM3R knockout mice were generated to study blood pressure and AD manifestations.ResultWe discovered that AChM3R, PIP2, and eNOS localize to primary cilia. mAChR‐specific activation increases cilia length in HBECs and cilia formation in cilialess Tg737 cells and was also associated with an increase in eNOS activity. Exposure to 2.5 μM human Aβ42 resulted in significant reduction in primary cilia length and ciliation percentage. RNAi‐mediated knockdown of Tulp3 caused a significant decrease in AChM3R trafficking to the cilia, associated with altered activity, suggesting that ciliary AChM3R localization is important for its activity. Vascular‐specific AChM3R and Tg737 KO mice developed high BP. Preliminary studies to examine cognitive function indicate altered cognitive function associated cerebrovascular cilia dysfunction.ConclusionPrimary cilia play an important sensory role for the regulation of blood pressure and cognitive function.

The level of serum retinol-binding protein is associated with diabetic mild cognitive impairment

BackgroundSeveral studies have shown that retinol-binding protein (RBP) is linked to diabetes and neurodegenerative diseases. However, no studies have elucidated the relationship between RBP and diabetic cognitive disorders. ObjectiveTo determine whether the change characteristics of serum RBP are associated with alterations in cognitive functioning in type 2 diabetes mellitus (T2DM). MethodsIn this study, 252 patients with T2DM and 34 people as healthy controls were included. According to the Montreal Cognitive Assessment (MoCA), the diabetic subjects were divided into the mild cognitive impairment (MCI) group and the Non-MCI group. Demographic characteristics and clinical indicators as well as serum RBP levels were analyzed. ResultsThe serum RBP levels in the MCI group were lower compared with the Non-MCI group (P = 0.02). The level of RBP was higher in the diabetes without MCI group than in the healthy control (P < 0.001). Serum RBP levels were positively correlated with MoCA scores (r = 0.178, P = 0.003). Binary Logistic regression model analysis showed that low RBP [odds ratio (OR) = 0.936], old age (OR = 1.074), high fasting blood glucose (OR = 1.164), and low fasting C-peptide (OR = 0.722) may be independent risk factors for diabetic MCI. The ROC curve of serum RBP for predicting diabetic MCI showed that the area under the curve was 0.630. ConclusionsOur study revealed an association between serum RBP and diabetic MCI. Serum RBP levels in diabetic MCI are lower and correlated with cognitive function.

Analysis of Genetic and MRI Changes, Blood Markers, and Risk Factors in a Twin Pair Discordant of Progressive Supranuclear Palsy.

Background and Objectives: Progressive supranuclear palsy (PSP) is a neurodegenerative disease, a tauopathy, which results in a wide clinical spectrum of neurological symptoms. The diagnosis is mostly based on clinical signs and neuroimaging; however, possible biomarkers for screening have been under investigation, and the role of the gut microbiome is unknown. The aim of our study was to identify potential blood biomarkers and observe variations in the gut microbiome within a PSP discordant monozygotic twin pair. Materials and Methods: Anthropometric measurements, neuropsychological tests, and the neurological state were evaluated. Blood was collected for metabolic profiling and for the detection of neurodegenerative and vascular biomarkers. Both the gut microbiome and brain MRI results were thoroughly examined. Results: We found a relevant difference between alpha-synuclein levels and moderate difference in the levels of MMP-2, MB, Apo-A1, Apo-CIII, and Apo-H. With respect to the ratios, a small difference was observed for ApoA1/SAA and ApoB/ApoA1. Using a microbiome analysis, we also discovered a relative dysbiosis, and the MRI results revealed midbrain and frontoparietal cortical atrophy along with a reduction in overall brain volumes and an increase in white matter lesions in the affected twin. Conclusions: We observed significant differences between the unaffected and affected twins in some risk factors and blood biomarkers, along with disparities in the gut microbiome. Additionally, we detected abnormalities in brain MRI results and alterations in cognitive functions.

Biobased nanoemulsions for targeted drug delivery to treat dementia and aging

Early changes in cerebrovascular hemodynamics and endothelial function can contribute to altered cognitive function and systemic vascular stiffness later in life. Accordingly, vascular pathology accompanies the mechanisms underlying aging. The development of chronic cerebral hypoperfusion, which leads to a lack of blood flow to the brain, is a common trait despite the various and complex pathogenic mechanisms causing these vascular alterations. Drugs or other bioactive compounds can be incorporated into a "high density lipoprotein-like" ("HDL-like") lipid nanocarrier to create a multifunctional "combination therapeutic" that can target cell-surface scavenger receptors, primarily class B type I (i.e., SR-BI). The enhanced endocytosis of the nanocarrier's drug contents into various target cells, made possible by this proposed (biomimetic-nanocarrier) therapeutic vehicle, increases the likelihood that this multitasking "combination therapeutic" will be more effective at various stages of dementia.

Alteration of Cognitive Function in Aging and Alzheimer's Disease Mice Is Related to Dysfunction of the Neuroimmune System.

Both Alzheimer's disease (AD) and aging have aging-related cognitive dysfunction with a high incidence. These neurological diseases cause serious cognitive problems in patients' daily life. But the cognitive dysfunction mechanism in-depth of aging is far less known than that of AD. To reveal the different mechanisms of AD and aging-related cognitive dysfunction, we compared the mechanisms of aging and AD through analysis of differentially expressed genes. Mice were divided into four groups (3-month C57BL, 16-month C57BL, 3-month 3xTg AD mice, and 16-month 3xTg AD mice) according to genotype and age. The Morris water maze was employed to investigate the spatial cognition of mice. Differential expressions of genes of AD and aging were analyzed through RNA sequencing and GO, KEGG, Reactome analysis, and the dynamic change trend analysis. Microglia was stained with immunofluorescence and its numbers were counted for analysis. The cognitive function of elderly mice were worse through testing with the Morris water maze. The cognitive function of 16-month 3xTg AD mice were worse than 16-month C57BL mice. The alteration tendencies of DE genes were uncovered, and microglia numbers increased during aging and AD progression through immunofluorescence. These results suggest that immune-related pathways might play a critical role in aging and AD-related cognitive dysfunction. Our research will help to provide some new potential targets for treating cognitive dysfunction in aging and AD.