Cognitive Brain Research Articles

Short Sleep Duration and Hypertension: A Double Hit for the Brain.

Short sleep duration has been associated with an increased risk of cognitive impairment and dementia. Short sleep is associated with elevated blood pressure, yet the combined insult of short sleep and hypertension on brain health remains unclear. We assessed whether the association of sleep duration with cognition and vascular brain injury was moderated by hypertensive status. A total of 682 dementia-free participants (mean age, 62±9 years; 53% women) from the Framingham Heart Study completed assessments of cognition, office blood pressure, and self-reported habitual and polysomnography-derived sleep duration; 637 underwent brain magnetic resonance imaging. Linear regressions were performed to assess effect modification by hypertensive status on total sleep time (coded in hours) and cognitive and magnetic resonance imaging outcomes. There was a significant interaction between sleep duration and hypertensive status when predicting executive function/processing speed (Trail Making B-A) and white matter hyperintensities. When results were stratified by hypertensive status, longer sleep duration was associated with better executive functioning/processing speed scores in the hypertensive group (meaning that shorter sleep duration was associated with poorer executive function/processing speed scores) (self-report sleep: β=0.041 [95% CI, 0.012-0.069], P=0.005; polysomnography sleep: β=0.045 [95% CI, 0.002-0.087], P=0.038), but no association was observed for the normotensive group. Similarly, shorter subjective sleep duration was associated with higher white matter hyperintensity burden in the hypertensive group (β=-0.115 [95% CI, -0.227 to -0.004], P=0.042), but not in the normotensive group. In individuals with hypertension, shorter sleep duration was associated with worse cognitive performance and greater brain injury.

Prenatal alcohol exposure and associations with physical size, dysmorphology and neurodevelopment: a systematic review and meta-analysis

BackgroundFetal alcohol spectrum disorder (FASD) is a significant public health concern, yet there is no internationally agreed set of diagnostic criteria or summary of underlying evidence to inform diagnostic decision-making. This systematic review assesses associations of prenatal alcohol exposure (PAE) and outcomes of diagnostic assessments, providing an evidence base for the improvement of FASD diagnostic criteria.MethodsSix databases were searched (inception–February 2023). Case-controls or cohort studies examining associations between participants with/without PAE or a FASD diagnosis and the domains of physical size, dysmorphology, functional neurodevelopment and/or brain structure/neurology were included. Excluded studies were non-empirical, sample size < 10, PAE determined via biological markers only, or no suitable comparison group. Summary data were extracted and associations between outcomes and standardised levels of PAE or FASD diagnosis determined using random-effects meta-analyses. Certainty of the evidence was assessed using GRADE.ResultsOf the 306 included studies, 106 reported physical size, 43 dysmorphology, 195 functional neurodevelopment and 110 structural/neurological outcomes, with 292 different outcomes examined. There was a dose–response relationship between PAE and head circumference, as well as measures of physical size, particularly at birth. There was also an association between higher PAE levels and characteristic sentinel facial dysmorphology, as well as many of the current functional neurodevelopmental outcomes considered during diagnosis. However, data were often lacking across the full range of exposures. There was a lack of evidence from studies examining PAE to support inclusion of non-sentinel dysmorphic features, social cognition, speech-sound impairments, neurological conditions, seizures, sensory processing or structural brain abnormalities (via clinical MRI) in diagnostic criteria. GRADE ratings ranged from very low to moderate certainty of evidence.ConclusionsThis comprehensive review provides guidance on which components are most useful to consider in the diagnostic criteria for FASD. It also highlights numerous gaps in the available evidence. Future well-designed pregnancy cohort studies should specifically focus on dose–response relationships between PAE and dysmorphology, neurodevelopment and brain structure/neurological outcomes.Systematic review registrationPROSPERO: CRD42021230522.

Preserved working memory performance along with subcortical modulation during peri-ictal phases in spontaneous migraine attacks.

To analyze cognitive performance and brain activation during a working memory task in patients with migraine during various phases of the migraine cycle and compare to healthy participants. Cognitive difficulties reported during migraine attacks remain poorly understood, despite evidence that the lateral frontoparietal network undergoes reversible disturbances and decreased activation during attacks. Recent findings in resting state functional magnetic resonance imaging suggest that brain areas involved in this network interact with subcortical regions during spontaneous migraine attacks. In this prospective, within-subject study, 10 patients with diagnosed menstrual-related episodic migraine without aura underwent 3T functional magnetic resonance imaging assessments while performing a working memory task across four phases of the natural migraine cycle: peri-ictal (preictal, ictal, postictal) phases and interictally (between attacks). Migraine prophylaxis was an exclusion criterion. Fourteen healthy controls were assessed during the corresponding phases of their menstrual cycles. The protocol was completed by 24 female participants aged 21 to 47 years: 10 with migraine (four sessions each) and 14 healthy controls (two sessions each) yielding a total of 68 analyzed datasets. Patients and controls showed similar performance on the working memory task and displayed increased brain activity in regions linked to this function, namely the middle frontal gyrus, inferior parietal lobe, and anterior cingulate cortex, during all phases of the migraine/menstrual cycle. Patients with migraine (N = 10) exhibited a significant decrease in hypothalamic activity (p = 0.007) as measured by the percent signal change (PSC) during the postictal phase compared to perimenstrual controls (N = 14), with -2 (16) and 31 (35) PSC, respectively. Comparing across the migraine cycle, the change in hypothalamic activity relative to controls in the postictal phase -0.33 (0.2) ΔPSC was significantly different from the ones in the interictal (0.006 [0.5] ΔPSC; p = 0.002) and preictal (-0.08 [0.4] ΔPSC; p = 0.034) phases. During a working memory task, cognition-related brain activation was present across all phases of the migraine cycle similarly to healthy control participants. Patients with migraine, however, displayed lower neural activity at the subcortical level in the postictal phase. Nonetheless, the sample size is a limitation for the generalization of our results. More research is needed to fully understand how the brain copes with cognitive demands during spontaneous migraine attacks.

Association of omega-3 polyunsaturated fatty acids intake and cognitive function in middle-aged and older adults

ABSTRACT Objective Omega-3 polyunsaturated fatty acids (PUFAs) play a crucial role in maintaining and improving cognitive function and brain health. The aim of this study was to assess the association between omega-3 PUFA intake and cognitive function in middle-aged and older adults in Saudi Arabia. Methods Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). The frequency and quantity of omega-3 PUFA intake were assessed using an omega-3 food frequency questionnaire. Results A total of 175 participants were recruited for this study. Participants in the lowest omega-3 PUFA tertile group scored significantly lower in the visuospatial/executive and attention cognitive domains (p < 0.05). After adjusting for confounders, the higher intake of alpha-linolenic acid (ALA) was significantly associated with higher scores in the visuospatial/executive domain (p = 0.02) and the higher intake of docosahexaenoic acid (DHA) was significantly associated with higher scores in the attention domain (p = 0.04). The participants who did not consume walnuts showed a significant lower MoCA score than those who did (p = 0.005). No significant differences were found with other omega-3 PUFA sources. Conclusion Higher intake of omega-3 PUFAs was positively associated with visuospatial/executive and attention cognitive functions in middle-aged and older adults.

Cortical surface area profile mediates effects of childhood disadvantage on later-life general cognitive ability.

Childhood disadvantage is associated with lower general cognitive ability (GCA) and brain structural differences in midlife and older adulthood. However, the neuroanatomical mechanisms underlying childhood disadvantage effects on later-life GCA remain poorly understood. Although total surface area (SA) has been linked to lifespan GCA differences, total SA does not capture the non-uniform nature of childhood disadvantage effects on neuroanatomy, which varies across unimodal and transmodal cortices. Here, we examined whether cortical SA profile-the extent to which the spatial patterning of SA deviates from the normative unimodal-transmodal cortical organization-is a mediator of childhood disadvantage effects on later-life GCA. In 477 community-dwelling men aged 56-72 years old, childhood disadvantage index (CDI) was derived from four indicators of disadvantages and GCA was assessed using a standardized test. Cortical SA was obtained from structural magnetic resonance imaging. For cortical SA profile, we calculated the spatial similarity between maps of individual cortical SA and MRI-derived principal gradient (i.e., unimodal-transmodal organization). Mediation analyses were conducted to examine the indirect effects of CDI through cortical SA profile on GCA. Around 1.31% of CDI effects on later-life GCA were mediated by cortical SA profile, whereas total SA did not. Higher CDI was associated with more deviation of the cortical SA spatial patterning from the principal gradient, which in turn related to lower later-life GCA. Childhood disadvantage may contribute to later-life GCA differences partly by influencing the spatial patterning of cortical SA in a way that deviates from the normative cortical organizational principle.

Diagnosis of Alzheimer's Disease in Clinical Practice: Time to Incorporate Biomarkers?

Hippocampal dysfunction is associated with early clinical signs of Alzheimer's disease (AD). Due to the limited availability or invasiveness of current biomarkers, the AD diagnosis is usually based on cognitive assessment and structural brain imaging. The recent study by Lalive and colleagues examined the specificity of brain morphometry for the AD diagnosis in a memory clinic cohort with hippocampal-type amnestic syndrome. The results indicate that memory deficits and hippocampal atrophy are similar in AD and non-AD patients, highlighting their low diagnostic specificity. These findings challenge the traditional AD diagnosis and underscore the need for biomarkers to differentiate specific neuropathological entities.

Effects of Combined Visual-Motor Response Training on Cognitive Function and Brain Plasticity Mechanisms in Various Populations: Protocol for a Single-Center, Open-Label, Controlled Clinical Trial.

Cognitive impairment is one of the major diseases facing the aging population. The progressive decline of cognitive function can lead to declining health or even the loss of life, work, and social ability. Exercise and behavioral stimulation can increase neurotransmitters in the brain and improve overall health and cognitive function. Reactivity training can mobilize neuromuscular function and induce changes in brain plasticity, which may effectively improve cognitive dysfunction and delay the occurrence and development of Alzheimer disease; however, the evidence supporting its effectiveness is still limited. This study aims to explore the effectiveness and reliability of visual-motor reaction training in improving cognitive function, thereby promoting the application of novel nonpharmacological therapies. This study is a single-center, open-label, controlled clinical trial. A total of 78 participants will be recruited for the study, including an equal number of athletes, ordinary healthy college students, and ordinary older adults in the community. Participants will receive 2 weeks of visual-motor response training. The primary outcome of this study is to assess differences in functional magnetic resonance imaging (fMRI) at 2 weeks. The secondary outcomes were the following: acousto-optic response time, Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Mini Mental State Examination (MMSE), Activity of Daily Living (ADL) Scale, Subjective Cognitive Decline Questionnaire-9 (SCD-Q9), a 10-word memory test, and safety. The study was approved by the Shanghai Clinical Research Ethics Committee on January 2, 2024 (SECCR/2023-162-01). As of September 11, 2024, we have completed the recruitment of all 3 groups of volunteers. We expect to complete data collection and analysis by February 2025. The purpose of this study is to compare improvements in brain perceptual motor functions and cognitive levels across different populations through response ability training and to explore the efficacy and safety of exercise-based nonpharmacological therapies in improving cognitive function. Other potential benefits include understanding the functional differences and perceptual characteristics of the brain's perceptual-motor system between athletes and the general population and exploring the adaptability of the brain in acquiring skills during competitive sports training. This could provide an evidence base for early sports talent development and broader youth development. Chinese Clinical Trial Registry ChiCTR2400079602; https://tinyurl.com/23fbbndw. DERR1-10.2196/56424.

6953 Bridging the Gender Gap: Sexually Dimorphic Brain Responses in Distressing Low Sexual Desire

Abstract Disclosure: J. Tsoutsouki: None. N. Ertl: None. E.G. Mills: None. M.B. Wall: None. L. Thurston: None. L. Yang: None. S. Suladze: None. T. Hunjan: None. M. Phylactou: None. B. Patel: None. J. Howard: None. A. Abbara: None. D. Golmeier: None. A.N. Comninos: None. W.S. Dhillo: None. Background: Distressing low sexual desire, termed Hypoactive Sexual Desire Disorder (HSDD), affects 10% of women and 8% of men. The established ‘top-down’ neurofunctional model of HSDD in women suggests that in response to erotic cues, excessive activation of higher-level cognitive brain regions (involved in introspection/self-monitoring) suppresses lower-level sexual brain centres, thereby impeding normal sexual function. By contrast, the neurodysfunction in men with HSDD remains to be fully characterised and crucially unlike in women, there are currently no licensed therapies. Herein, we report the first direct comparison of the neural bases of HSDD in women and men. Methods: 32 premenopausal women with HSDD [mean age±SD (y) 29.2±6.7] and 32 men with HSDD [age 37.9±8.6] underwent a task-based functional MRI (fMRI) measuring sexual brain activity during erotic versus control (exercise) videos. Participants completed psychometric questionnaires before and after the fMRI scan, providing functional relevance for the brain activity changes. Results: Women displayed significantly greater activation in higher-level cortical regions (e.g. inferior frontal gyrus, superior frontal gyrus) and lower-level limbic brain regions (e.g. amygdala, striatum, thalamus) in response to erotic videos, compared to the men. Lower activation in lower-limbic sexual regions in women correlated with more severe HSDD, which along with a hyperactivation in the inferior-frontal gyrus relative to the men, supports the ‘top-down’ mechanism underlying HSDD in women. By contrast, men exhibited lower activation in both higher-cortical and lower-limbic regions, but greater activation than the women in the visual cortex in response to erotic videos. Hence, a heightened sensitivity to visual erotic cues in men might not be effectively relayed to the limbic system. In women only, hypothalamic hyperactivation in response to erotic videos correlated with ‘increased heartbeat’ (r=0.5, P=0.001), and ‘tingling all over’ (r=0.6, P&amp;lt;0.001), while higher striatal activation correlated with feeling more ‘stimulated’ (r=0.4, P=0.001) and ‘genital tingling’ (r=0.6, P&amp;lt;0.001) on the psychometric questionnaires. Crucially, these findings were specific to erotic stimuli as no differences were identified in the control comparison (exercise&amp;gt;baseline contrast). Discussion: This is the first study to directly compare the neural bases of distressing low sexual desire in women and men. While supporting the ‘top-down’ mechanism of HSDD in women, it suggests a different neurodysfunctional process in men with HSDD, highlighting a potential functional disconnection between sensory/attention and sexual centres. Our findings have key clinical implications as they identify a sexual dimorphism in the neural bases of low sexual desire relevant to the escalating development of therapeutics for patients with HSDD. Presentation: 6/3/2024

Cognitive function and brain structure in COVID-19 survivors: The role of persistent symptoms

Persistent COVID-19 symptoms post-acute state have been shown to have a significant negative impact on brain structure and function. In this study, we conducted magnetic resonance imaging (MRI) of the whole brain in 43 working-age adults (mean age: 44.79±10.80; range: 24–65 years) with a history of COVID-19 (731.17±312.41 days post-diagnosis), and also assessed their cognitive function (processing speed, attention, working memory, executive function, and recognition memory), mental health, and sleep quality. MRI data were processed using FSL to derive regional volumes for bilateral nucleus accumbens, caudate, pallidum, putamen, thalamus, amygdala, and hippocampus, and total grey matter, white matter, and cerebral spinal fluid volume, and analysed in relation to persistent COVID-19 symptom load, mental health, and sleep quality. Higher persistent COVID-19 symptom load was significantly associated with smaller putamen volume, lower response accuracy on working memory, executive function, and recognition memory tasks, as well as a longer time to complete the executive function task, and poorer mental health and sleep quality. Smaller putamen fully mediated the relationship between persistent COVID-19 symptom load and lower executive function. Further research is required to confirm whether reduced putamen volume and its association with poor executive function persists in COVID-19 survivors in the long term.

Investigating the relationship between cognitive impairment and brain white matter tracts using diffusion tensor imaging in patients with prolactinoma.

Cognitive impairment is known to occur in patients with prolactinoma, but the underlying mechanism is unclear. To evaluate cognitive function in patients with prolactinoma and to investigate the basis of possible cognitive impairment in brain white matter changes using diffusion tensor imaging (DTI). 37 consecutive patients with prolactinoma and 37 healthy controls of similar age, sex, and education were enrolled in the study. Hormone levels were determined in all participants, comprehensive neuropsychological testing was performed, and DTI was used to reconstruct and evaluate white matter tracts. In patients with prolactinoma, short- and long-term visual and verbal memory, attention, concentration, and executive and language functions were impaired compared to the healthy group. When comparing the DTI results, lower fractional anisotropy (FA) values were found in the patients' right uncinate fasciculus (R-UF), indicating neuronal damage. After applying the Bonferroni correction, the two groups had no significant difference in 42 tracts (p > 0.0012 for all). A positive correlation was found between poor FA scores on the R-UF and low scores on long-term memory, category and letter fluency tests. In addition, patients with hypoprolactinemia had the worst short-term memory scores, while normoprolactinemia had the best scores. Also, the poorer R-UF FA values were found in the patients with hypoprolactinemia and the highest in those with normoprolactinemia. This study is the first to investigate reasons for cognitive dysfunction in patients with prolactinoma by DTI. No significant structural changes were found in brain tracts of patients with prolactinoma. Still, there may be a link between potential damage in the R-UF and cognitive dysfunction, and further research is needed. In addition, the results showed that the development of hypoprolactinemia is associated with cognitive dysfunction and emphasized that overtreatment should be avoided.

COVID-19 related cognitive, structural and functional brain changes among Italian adolescents and young adults: a multimodal longitudinal case-control study

Coronavirus disease 2019 (COVID-19) has been associated with brain functional, structural, and cognitive changes that persist months after infection. Most studies of the neurologic outcomes related to COVID-19 focus on severe infection and aging populations. Here, we investigated the neural activities underlying COVID-19 related outcomes in a case-control study of mildly infected youth enrolled in a longitudinal study in Lombardy, Italy, a global hotspot of COVID-19. All participants (13 cases, 27 controls, mean age 24 years) completed resting-state functional (fMRI), structural MRI, cognitive assessments (CANTAB spatial working memory) at baseline (pre-COVID) and follow-up (post-COVID). Using graph theory eigenvector centrality (EC) and data-driven statistical methods, we examined differences in ECdelta (i.e., the difference in EC values pre- and post-COVID-19) and Volumetricdelta (i.e., the difference in cortical volume of cortical and subcortical areas pre- and post-COVID) between COVID-19 cases and controls. We found that ECdelta significantly between COVID-19 and healthy participants in five brain regions; right intracalcarine cortex, right lingual gyrus, left hippocampus, left amygdala, left frontal orbital cortex. The left hippocampus showed a significant decrease in Volumetricdelta between groups (p = 0.041). The reduced ECdelta in the left amygdala associated with COVID-19 status mediated the association between COVID-19 and disrupted spatial working memory. Our results show persistent structural, functional and cognitive brain changes in key brain areas associated with olfaction and cognition. These results may guide treatment efforts to assess the longevity, reversibility and impact of the observed brain and cognitive changes following COVID-19.

Cholinesterase inhibitor use in amyloid PET-negative mild cognitive impairment and cognitive changes

BackgroundCholinesterase inhibitors (ChEIs) are prescribed for Alzheimer’s disease (AD) and sometimes for mild cognitive impairment (MCI) without knowing underlying pathologies and its effect on cognition. We investigated the frequency of ChEI prescriptions in amyloid-negative MCI and their association with cognitive changes in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort.MethodsWe included participants with amyloid positron emission tomography (PET)-negative MCI from the ADNI. We analyzed the associations of ChEI use with cognitive changes, brain volume, and cerebrospinal fluid (CSF) total tau (t-tau), hyperphosphorylated tau181 (p-tau181), and p-tau181/t-tau ratio.ResultsChEIs were prescribed in 27.4% of amyloid PET-negative MCI and were associated with faster cognitive decline, reduced baseline hippocampal volume and entorhinal cortical thickness, and a longitudinal decrease in the frontal lobe cortical thickness.ConclusionsThe association between ChEI use and accelerated cognitive decline may stem from underlying pathologies involving reduced hippocampal volume, entorhinal cortical thickness and faster frontal lobe atrophy. We suggest that ChEI use in amyloid PET-negative MCI patients might need further consideration, and studies investigating the causality between ChEI use and cognitive decline are warranted in the future.

Depressive symptoms are linked to age-specific neuroanatomical and cognitive variations

Depression is a heterogeneous disorder, both in terms of patient symptomatology and in patient sociodemographic factors. Here, we examine the contribution of age to this heterogeneity, by characterizing the associations of depressive symptoms with cognitive performance and brain structure across the lifespan. We analyzed data from the Cambridge Centre for Aging Neuroscience (Cam-CAN) cohort (N = 2591, age 18–99). A subset of this cohort (N = 647) underwent structural MRI. Depressive symptoms were measured using the Hospital Anxiety and Depression Scale. Cognitive assessments were performed using The Addenbrooke's Cognitive Examination Revised. Generalized linear models were employed to examine the relationship between depressive symptoms and cognitive performance. Statistical parametric mapping explored age-dependent associations between depressive symptoms and grey matter volume. Cognitive performance was associated with a significant age by depression by cognitive domain interaction, indicating that older individuals with more depressive symptoms had a lower cognitive performance, particularly in the fluency domain. Structural MRI revealed preferential depression-related reduction in grey matter volume in the left and right hippocampi in older adults. By contrast, in younger adults, depressive symptoms were more strongly associated with grey matter volume reduction in the left superior frontal gyrus and left middle frontal gyrus. Collectively, these findings indicate that the associations of depression with cognitive performance and brain structure are age-dependent, suggesting that the pathophysiological mechanisms underlying depression may differ between young and older adults. Recognizing these differences will support the development of better diagnostic tools and therapeutic interventions for depression across the lifespan.

Blood-derived microRNAs are related to cognitive domains in the general population.

Blood-derived microRNAs (miRNAs) are potential candidates for detecting and preventing subclinical cognitive dysfunction. However, replication of previous findings and identification of novel miRNAs associated with cognitive domains, including their relation to brain structure and the pathways they regulate, are still lacking. We examined blood-derived miRNAs and miRNA co-expression clusters in relation to cognitive domains, structural magnetic resonance imaging measures, target gene expression, and genetic variants in 2869 participants of a population-based cohort. Five previously identified and 14 novel miRNAs were associated with cognitive domains. Eleven of these were also associated with cortical thickness and two with hippocampal volume. Multi-omics analysis showed that certain identified miRNAs were genetically influenced and regulated genes in pathways like neurogenesis and synapse assembly. We identified miRNAs associated with cognitive domains, brain regions, and neuronal processes affected by aging and neurodegeneration, making them promising candidate blood-based biomarkers or therapeutic targets of subclinical cognitive dysfunction. We investigated the association of blood-derived microRNAs with cognitive domains. Five previously identified and 14 novel microRNAs were associated with cognition. Eleven cognition-related microRNAs were also associated with cortical thickness. Identified microRNAs were linked to genes associated with neuronal functions. Results provide putative biomarkers or therapeutic targets of cognitive aging.

Continuous theta burst stimulation ameliorates cognitive deficits in microinfarcts mice via inhibiting glial activation and promoting paravascular CSF-ISF exchange

Microinfarcts are widespread in the elderly, accompanied by varying degrees of cognitive decline. Continuous theta burst stimulation (cTBS) has been demonstrated to be neuroprotective on cognitive dysfunction, but the underlying cellular mechanism has been still not clear. In the present study, we evaluated the effects of cTBS on cognitive function and brain pathological changes in mice model of microinfarcts. The spatial learning and memory was assessed by Morris water maze (MWM), Glymphatic clearance efficiency was evaluated using in vivo two-photon imaging. The loss of neurons, activation of astrocytes and microglia, the expression and polarity distribution of the astrocytic aquaporin-4 (AQP4) were assessed by immunofluorescence staining. Our results showed that cTBS treatment significantly improved the spatial learning and memory, accelerated the efficiency of glymphatic clearance, up-regulated the AQP4 expression and improved the polarity distribution of AQP4 in microinfarcts mice. Besides, cTBS treatment increased the number of surviving neurons, whereas decreased the activated astrocytes and microglia. Our study suggested that cTBS accelerated glymphatic clearance and inhibited the excessive gliogenesis, which ultimately exerted neuroprotective effects on microinfarcts mice.

Lead Acetate Exposure and Cerebral Amyloid Accumulation: Mechanistic Evaluations in APP/PS1 Mice.

The role of environmental factors in Alzheimer's disease (AD) pathogenesis remains elusive. Mounting evidence suggests that acute and past exposure to the environmental toxicant lead (Pb) is associated with longitudinal decline in cognitive function, brain atrophy, and greater brain -amyloid () deposition. However, the nature of Pb-induced amyloid deposition and how it contributes to AD development remain unclear. This study investigates the role of Pb in the pathogenesis of cerebral amyloid angiopathy (CAA) and whether plasminogen activator inhibitor-1 (PAI-1) contributes to this process in the APP/PS1 mouse model. Female APP/PS1 mice at 8 wk of age were administered either Pb-acetate (PbAc) (i.e., ) or an equivalent molar concentration of sodium acetate (NaAc) via oral gavage once daily for 8 wk. Amyloid deposition and vascular amyloid were determined by immunostaining. In addition, perivascular drainage, vascular binding assay, and microglial endocytosis were examined to determine underlying mechanisms. Furthermore, magnetic resonance imaging demyelination imaging was performed invivo measure the level of demyelination. Finally, Y-maze and Morris water maze tests were assessed to evaluate the cognitive function of mice. APP/PS1 mice (an AD mice model) exposed to PbAc demonstrated more vascular amyloid deposition less neocortical myelination, and lower cognitive function, as well as greater vascular binding to , higher ratios, strikingly lower levels in the perivascular drainage, and microglial endocytosis. Importantly, exposure to a specific PAI-1 inhibitor, tiplaxtinin, which previously was reported to lower CAA pathology in mice, resulted in less CAA-related outcomes following PbAc exposure. Our findings suggest that PbAc induced CAA/AD pathogenesis via the PAI-1 signaling in the APP/PS1 mouse model, and the inhibition of PAI-1 could be a potential therapeutic target for PbAc-mediated CAA/AD disorders. https://doi.org/10.1289/EHP14384.

Effect of autaptic synapse on signal transmission performance of dressed Hodgkin–Huxley neuron

Astrocytes, which have complex relationships with neurons, are the most important biological arguments that support neurons in the performance of cognitive functions. Another important biological argument in nervous systems is autapse, a special type of synapse through which the neuron provides feedback to itself. It is well known that both astrocyte and autapse modulate neuron dynamics and they affect memory functions. Considering the idea that some cognitive brain functions occur through chaotic firings, more complex models in which structures such as astrocytes and autaptic synapses are included in the system are needed to better understand the neural system. In this study, the signal detection abilities of astrocyte-dressed Hodgkin–Huxley neurons which have electrical, excitatory, and inhibitory chemical autaptic synapses are examined separately under chaotic environmental conditions. The results show that astrocyte-supported neurons, especially those with electrical and excitatory-chemical autapse, exhibit a strong chaotic resonance for appropriate parameters. After the autaptic synapse, the astrocyte is a second modulator of the neuron’s signal detection success. Additionally, it is observed that autaptic time delay is more effective than autaptic conductance in modulating the signal transmission success of the neuron. For all autapse types, the parameter values at which the supportive effect of the astrocyte in the model is obtained are presented. Furthermore, multiple chaotic resonance is detected in neurons with electrical and excitatory chemical autapse when the autaptic delay is equal to integer multiples of the weak signal period. This is observed for neurons with inhibitory chemical autapse when half of the weak signal period is added to whole multiples of the weak signal period. We hope that our findings will shed light on the chaotic environment behavior of complex nervous systems interacting with astrocytes and autapse.

Structural and functional brain markers of cognitive impairment in healthcare workers following mild SARS-CoV-2 infection during the original stream.

Severe acute respiratory syndrome coronavirus 2 infection often involves the nervous system, leading to cognitive dysfunctions, fatigue and many other neurological signs that are becoming increasingly recognized. Despite mild forms of the disease accounting for most cases worldwide, research on the pathophysiology driving mild coronavirus disease 2019 (COVID-19) has received little attention. In this respect, recent evidence has pointed out that around 30-40% of non-critical, mild-to-moderate severity COVID-19 survivors may display cognitive disturbances several months post-illness. Hence, the impact of COVID-19 on the brain structure and function, through potential neuropathological mechanisms underpinning cognitive alterations in post-mild COVID-19 infections, remains largely unexplored. This retrospective multicentre observational cohort study, entirely based on a healthcare worker sample (n = 65; 55% females, aged 21-61), investigated the cognitive status and the structural and functional brain integrity among non-hospitalized individuals who developed mild COVID-19 symptoms during the occurrence of severe acute respiratory syndrome coronavirus 2 variants Alpha to Delta, compared with healthy controls tested before the pandemic onset. All evaluations were performed at an average of 9-month follow-up post-infection period. Participants completed a comprehensive neuropsychological assessment and structural and functional MRI exams. Radiological inspection sought to detect the presence of white matter hyperintensities on axial fluid-attenuated inversion recovery images. Global and regional grey matter integrity assessment, analysing changes in grey matter volumes and cortical thinning, and functional connectivity alterations of resting-state brain networks were also conducted. Regression analyses tested the relationships between the presence of specific cognitive impairments and potential structural and functional brain findings. Our results revealed that clinical, cognitive screening and neuropsychological examinations were average between both groups, except for specific impairments related to executive functions in the mild COVID-19. Compared to healthy controls, mild COVID-19 subjects exhibited increased juxtacortical white matter hyperintensities, thalamic and occipital volume loss and diminished resting-state functional connectivity involving the left precuneus and cuneus in default-mode network and affecting the right angular gyrus and left precuneus in the dorsal attentional network. Reduced thalamic volume was the only variable selected in the final model explaining the observed executive function impairment in mild COVID-19. The presence of cognitive, structural and functional brain abnormalities over time suggests that the action of widespread neurovascular and inflammatory phenomena on the nervous system might also occur in mild forms following COVID-19 infection rather than permanent brain damage linked to the direct or indirect action of the virus. Our findings emphasize the need to pay attention to the long-term brain-related consequences of mild COVID-19 infections during the original stream.

Approved and Late Clinical Trial Monoclonal Antibodies for the Treatment of Alzheimer’s Disease

Alzheimer’s disease is a major type of dementia characterized by progressive neurodegeneration that leads to cognitive decline and brain atrophy. The progression of the disease is marked by the accumulation of amyloid β plaques and tau tangles that are proposed to be the driver of subsequent neural death and atrophy. Targeting these hallmarks with monoclonal antibodies has become a promising approach to treating Alzheimer’s disease. As of 2021, the FDA approved the amyloid β targeting monoclonal antibody aducanumab as the first approved treatment for Alzheimer’s disease. Since this landmark, significant work has been done to develop monoclonal antibodies to treat Alzheimer’s disease. In this review, we discuss the development of FDA-approved monoclonal antibodies aducanumab, lecanemab, and donanemab, as well as the monoclonal antibodies remternetug and E2814 that are currently in late-phase clinical trials.

Don't Forget About Your Memory...Exploring Need And Impact Of A Cognitive Strategies Group On Older Adults Following Comprehensive Geriatric Assessment

Abstract Background The increasing prevalence of mild cognitive impairment (MCI) and dementia in older adults in Ireland, with projections of up to 20% of over 80-year-olds affected, is widely documented (TILDA 2023). Due attention is required in service planning to provide tailored non-pharmacological and lifestyle interventions to this growing cohort. This review aims to analyse the need for and impact of a cognitive strategies and brain health intervention group on older adults attending the Integrated Day Hospital (IDH) as part of an ICPOP service. Methods Retrospective analysis of the health care record was complete on older adults over 70 years with recent deterioration in cognitive or functional status. Cognitive screening scores and diagnoses received at the IDH were gathered to inform presence of MCI or dementia. Permission was sought from the authors of a cognitive strategies and brain health intervention group which was delivered to a sample of older adults and evaluated as part of the Jog Your Memory Program (HSE 2020). Results Preliminary results indicate a cohort of 355 older adults. Analysis of cognitive screening scores reflect prevalence of MCI at 15% and dementia at 35%. The Jog Your Memory program is implemented over 4 sessions. 2 programs were complete in October 2023 and April 2024 with 16 participants. Evaluation was complete with 100% of participants reporting benefits including acquisition of memory strategies, improved confidence and increased knowledge of MCI. Implementing this program optimises therapist time indicating cost saving. Final findings will be available for the purpose of this poster presentation. Conclusion The prevalence of cognitive impairment is broadly in keeping with previous audit (2023). The intervention group implementation and evaluation are ongoing. Participant feedback suggests the intervention is meeting the needs of this cohort. Future work will focus on scaling up the intervention group and integrating with other local services.