Preservation Of Cognitive Function Research Articles

SuperAgers and centenarians, dynamics of healthy ageing with cognitive resilience

Graceful healthy ageing and extended longevity is the most desired goal for human race. The process of ageing is inevitable and has a profound impact on the gradual deterioration of our physiology and health since it triggers the onset of many chronic conditions like dementia, osteoporosis, diabetes, arthritis, cancer, and cardiovascular disease. However, some people who lived/live more than 100 years called ‘Centenarians” and how do they achieve their extended lifespans are not completely understood. Studying these unknown factors of longevity is important not only to establish a longer human lifespan but also to manage and treat people with shortened lifespans suffering from age-related morbidities. Furthermore, older adults who maintain strong cognitive function are referred to as "SuperAgers" and may be resistant to risk factors linked to cognitive decline. Investigating the mechanisms underlying their cognitive resilience may contribute to the development of therapeutic strategies that support the preservation of cognitive function as people age. The key to a long, physically, and cognitively healthy life has been a mystery to scientists for ages. Developments in the medical sciences helps us to a better understanding of human physiological function and greater access to medical care has led us to an increase in life expectancy. Moreover, inheriting favorable genetic traits and adopting a healthy lifestyle play pivotal roles in promoting longer and healthier lives. Engaging in regular physical activity, maintaining a balanced diet, and avoiding harmful habits such as smoking contribute to overall well-being. The synergy between positive lifestyle choices, access to education, socio-economic factors, environmental determinants and genetic supremacy enhances the potential for a longer and healthier life. Our article aims to examine the factors associated with healthy ageing, particularly focusing on cognitive health in centenarians. We will also be discussing different aspects of ageing including genomic instability, metabolic burden, oxidative stress and inflammation, mitochondrial dysfunction, cellular senescence, immunosenescence, and sarcopenia.

Cognitive reserve in ALS: the role of occupational skills and requirements

Objective Amyotrophic Lateral Sclerosis (ALS) is a heterogeneous neurodegenerative condition featuring variable degrees of motor and cognitive impairment. We assessed the impact of specific, empirically derived occupational skills and requirements on cognitive and motor functioning in ALS. Methods Individuals with ALS (n = 150) were recruited from the University of Pennsylvania’s Comprehensive ALS Clinic. The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) measured cognition, and the Penn Upper Motor Neuron (PUMNS) and ALS Functional Rating Scales (ALSFRS-R) measured motor symptoms. We derived 17 factors representing distinct occupational skills and requirements from the Occupational Information Network (O*NET), which were related to cognitive and motor scores using multiple linear regression. Results Occupational roles involving greater reasoning ability (β = 2.12, p < .05), social ability (β = 1.73, p < .05), analytic skills, (β = 3.12, p < .01) and humanities knowledge (β = 1.83, p<.01) were associated with better performance on the ECAS, while jobs involving more exposure to environmental hazards (β=−2.57, p < .01) and technical skills (β=−2.16, p<.01) were associated with lower ECAS scores. Jobs requiring more precision skills (β = 1.91, p < .05) were associated with greater motor dysfunction on the PUMNS. Conclusions Occupational histories involving more cognitively complex skills and activities were related to preserved cognitive functioning in ALS consistent with the cognitive reserve hypothesis, while jobs with greater exposure to environmental hazards and technical demands were linked to poorer cognitive functioning. Jobs involving more repetitive movements were associated with worse motor functioning, possibly due to overuse. Occupational history provides insight into protective and risk factors for variable degrees of cognitive and motor dysfunction in ALS.

Digital interventions for healthy ageing and cognitive health in older adults: a systematic review of mixed method studies and meta-analysis

BackgroundCurrently, there is no systematic review to investigate the effectiveness of digital interventions for healthy ageing and cognitive health of older adults. This study aimed to conduct a systematic review to evaluate the effectiveness of digital intervention studies for facilitating healthy ageing and cognitive health and further identify the considerations of its application to older adults.MethodsA systematic review and meta-analysis of literature were conducted across CINAHL, Medline, ProQuest, Cochrane, Scopus, and PubMed databases following the PRISMA guideline. All included studies were appraised using the Mixed Methods Appraisal Tool Checklist by independent reviewers. Meta-analyses were performed using JBI SUMARI software to compare quantitative studies. Thematic analyses were used for qualitative studies and synthesised into the emerging themes.ResultsThirteen studies were included. Quantitative results showed no statistically significant pooled effect between health knowledge and healthy behaviour (I2 =76, p=0.436, 95% CI [-0.32,0.74]), and between cardiovascular-related health risks and care dependency I2=0, p=0.426, 95% CI [0.90,1.29]). However, a statistically significant cognitive function preservation was found in older adults who had long-term use of laptop/cellphone devices and had engaged in the computer-based physical activity program (I2=0, p<0.001, 95% CI [0.01, 0.21]). Qualitative themes for the considerations of digital application to older adults were digital engagement, communication, independence, human connection, privacy, and cost.ConclusionsDigital interventions used in older adults to facilitate healthy ageing were not always effective. Health knowledge improvement does not necessarily result in health risk reduction in that knowledge translation is key. Factors influencing knowledge translation (i.e., digital engagement, human coaching etc) were identified to determine the intervention effects. However, using digital devices appeared beneficial to maintain older adults’ cognitive functions in the longer term. Therefore, the review findings suggest that the expanded meaning of a person-centred concept (i.e., from social, environmental, and healthcare system aspects) should be pursued in future practice. Privacy and cost concerns of technologies need ongoing scrutiny from policy bodies. Future research looking into the respective health benefits can provide more understanding of the current digital intervention applied to older adults.Study registrationPROSPERO record ID: CRD42023400707 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=400707.

Cognitive Impairment and Brain Atrophy in Patients with Chronic Kidney Disease.

In Japan, the aging of the population is rapidly accelerating, with an increase in patients with chronic kidney disease (CKD) and those undergoing dialysis. As a result, the number of individuals with cognitive impairment (CI) is rising, and addressing this issue has become an urgent problem. A notable feature of dementia in CKD patients is the high frequency of vascular dementia, making its prevention through the management of classical risk factors such as hypertension, diabetes mellitus, dyslipidemia, smoking, etc., associated with atherosclerosis and arteriosclerosis. Other effective measures, including the use of renin-angiotensin system inhibitors, addressing anemia, exercise therapy, and lifestyle improvements, have been reported. The incidence and progression of CI may also be influenced by the type of kidney replacement therapy, with reports suggesting that long-duration dialysis, low-temperature hemodialysis, peritoneal dialysis, and kidney transplantation can have a preferable effect on the preservation of cognitive function. In conclusion, patients with CKD are at a higher risk of developing CI, with brain atrophy being a contributing factor. Despite the identification of various preventive measures, the evidence substantiating their efficacy remains limited across all studies. Future expectations lie in large-scale randomized controlled trials.

Linking structural and functional changes during aging using multilayer brain network analysis

Brain structure and function are intimately linked, however this association remains poorly understood and the complexity of this relationship has remained understudied. Healthy aging is characterised by heterogenous levels of structural integrity changes that influence functional network dynamics. Here, we use the multilayer brain network analysis on structural (diffusion weighted imaging) and functional (magnetoencephalography) data from the Cam-CAN database. We found that the level of similarity of connectivity patterns between brain structure and function in the parietal and temporal regions (alpha frequency band) is associated with cognitive performance in healthy older individuals. These results highlight the impact of structural connectivity changes on the reorganisation of functional connectivity associated with the preservation of cognitive function, and provide a mechanistic understanding of the concepts of brain maintenance and compensation with aging. Investigation of the link between structure and function could thus represent a new marker of individual variability, and of pathological changes.

Is catheter ablation associated with preservation of cognitive function? An analysis from the SAGE-AF observational cohort study.

To examine the associations between catheter ablation treatment (CA) vs. medical management and cognitive impairment among older adults with atrial fibrillation (AF). Ambulatory patients who had AF, were ≥65-years-old, and were eligible to receive oral anticoagulation could be enrolled into the SAGE (Systematic Assessment of Geriatric Elements)-AF study from internal medicine and cardiology clinics in Massachusetts and Georgia between 2016 and 2018. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) tool at baseline, 1-, and 2 years. Cognitive impairment was defined as a MoCA score ≤ 23. Multivariate-adjusted logistic regression of longitudinal repeated measures was used to examine associations between treatment with CA vs. medical management and cognitive impairment. 887 participants were included in this analysis. On average, participants were 75.2 ± 6.7 years old, 48.6% women, and 87.4% white non-Hispanic. 193 (21.8%) participants received a CA before enrollment. Participants who had previously undergone CA were significantly less likely to be cognitively impaired during the 2-year study period (aOR 0.70, 95% CI 0.50-0.97) than those medically managed (i.e., rate and/or rhythm control), even after adjusting with propensity score for CA. At the 2-year follow-up a significantly greater number of individuals in the non-CA group were cognitively impaired (MoCA ≤ 23) compared to the CA-group (311 [44.8%] vs. 58 [30.1%], p = 0.0002). In this 2-year longitudinal prospective cohort study participants who underwent CA for AF before enrollment were less likely to have cognitive impairment than those who had not undergone CA.

Resective Epilepsy Surgery after Corpus Callosotomy in Children with Lennox-Gastaut Syndrome

Purpose: This study examined the characteristics and outcomes of resective epilepsy surgery following corpus callosotomy (CC) in children with Lennox-Gastaut syndrome (LGS).Methods: We retrospectively analyzed 17 children with LGS who underwent resective surgery (RS) after CC over a span of 10 years, with a minimum of 2 years of follow-up, at a single tertiary epilepsy center in Korea.Results: Of the 17 patients, 13 (73.5%) demonstrated favorable surgical outcomes (Engel class I or II) at 1 year after RS, and eight (47.1%) were ultimately free of seizures 2 years after surgery. A significantly larger decrease in the number of anti-seizure medications taken from before to 2 years after the final surgical procedure was observed in the group that became seizure-free than in the group with persistent seizures (&lt;i&gt;P&lt;/i&gt;=0.062). Furthermore, a significantly greater decline in daily adaptive function was found in the persistent seizure group (&lt;i&gt;P&lt;/i&gt;=0.059). The baseline characteristics, results of presurgical evaluation, and treatment-related factors assessed prior to surgery showed no significant differences between the seizure-free group and the group with persistent seizures.Conclusion: In conclusion, RS may be a viable option for patients with LGS who exhibit lateralization and/or localization on presurgical evaluation after CC, as the procedure may reveal a concealed primary focus. The proactive implementation of two-stage epilepsy surgery could provide significant seizure reduction and preservation of cognitive function in carefully selected patients with LGS.

INPP5D inhibition attenuates amyloid pathology through the regulation of microglial functions

AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by accumulated beta‐amyloid (Aβ) deposits and robust microgliosis. Recent genome‐wide association studies have identified genetic risk factors in late‐onset AD (LOAD) which are largely microglia. Among the risk factors, Inositol polyphosphate‐5‐phosphatase D (INPP5D) confers an increased risk of developing AD and is associated with increased plaque deposition. As a microglia‐specific lipid phosphatase, INPP5D negatively regulates signaling via several microglial cell surface receptors, including TREM2; however, the impact of INPP5D inhibition on AD pathology remains unclear.MethodsTo determine the impact of Inpp5d on disease pathogenesis and microglial phenotypes, we utilized the 5xFAD model expressing Inpp5d haplodeficiency.ResultsInpp5d deficiency perturbs microglial intracellular signaling pathways that regulate the immune response, including phagocytosis, microglia‐plaque engagement, and Aβ clearance. Importantly, Inpp5d haploinsufficiency leads to the preservation of cognitive function in 5xFAD mice. Furthermore, a novel spatial transcriptomic analysis revealed genetic profiles altered by Inpp5d haploinsufficiency are related to microglial functions, synaptic regulation, and immune cell activation.ConclusionThese data demonstrate that Inpp5d deficiency enhances microglial functions by increasing plaque clearance and preserves cognitive abilities in 5xFAD mice. Inhibition of INPP5D may serve as a potential therapeutic strategy targeting microglia for AD.

Comparison of Hippocampal Volume Change after Whole-Brain Radiotherapy with and without Hippocampal Avoidance: A Post-Hoc Analysis of a Phase II Randomized Trial

Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) preserves verbal memory compared to conformal WBRT in the previously reported randomized phase II clinical trial. In the present study, we analyzed the changes in hippocampus volume between groups at longitudinal follow-up time points. We hypothesize better preservation of hippocampus volumes with time in the HA-WBRT group. In this post-hoc analysis of a single institution, single-blind, randomized phase II trial, patients with brain metastases were randomized to receive either HA-WBRT or conformal WBRT with 30 Gy in 10 fractions. Patients received gadolinium contrast-enhanced MRI every three months or when clinically indicated after WBRT until progression. Only patients with at least one follow-up MRI were included. The MRI was used to assess baseline intracranial volume, hippocampal volume, the ratio of the total hippocampus to total intracranial volume (HT%), and the ratio of the left (HL%) or right (HR%) hippocampus to total intracranial volume. The volumes were automatically calculated by volBrain, an online MRI brain volumetry system. We used linear mixed models with fixed and random effects to compare the changes of repeated measures of the hippocampus volumes over time between the two groups. Among 70 randomized patients, 51 (25 in the HA-WBRT group and 26 in the WBRT group) were included in the present analysis. There were no significant differences between the two groups in the baseline demographics, HT%, HR%, and HL%. The median follow-up time was 13.9 months (range 2.1-31.8 months), and more than 60% of patients had at least one year of follow-up. Linear mixed model analyses showed a more significant decrease of HT% over time in the WBRT arm (regression coefficient β = -0.002, p = 0.001) compared to the HA-WBRT arm (regression coefficient, β = -0.001, p = 0.254), with a significant group by time interaction (F-value = 4.27, p = 0.050). The HL% was stable over time in the HA-WBRT arm (β = 0.0001, p = 0.769) while it decreased in the WBRT arm (β = -0.001, p = 0.003), with a significant group by time interaction (F-value = 6.51, p = 0.015). In contrast, the HR% decreased over time in both groups (HA-WBRT: regression coefficient β = -0.001, p = 0.006; WBRT: regression coefficient β = -0.001, p < 0.001) without significant group by time interaction (F-value = 0.20, p = 0.662). HA-WBRT better preserves total hippocampus volume with time compared to WBRT, with the main effect contributed by preserving the left hippocampus volume. Further research is warranted to establish the relationship between hippocampus volume perpetuation and cognitive function preservation. The future goal is to investigate whether left-side unilateral HA-WBRT provides similar neurocognitive function preservation compared to standard bilateral HA-WBRT.

Pharmacological inhibition of plasminogen activator inhibitor-1 prevents memory deficits and reduces neuropathology in APP/PS1 mice.

Extracellular proteolytic activity plays an important role in memory formation and the preservation of cognitive function. Previous studies have shown increased levels of plasminogen activator inhibitor-1 (PAI-1) in the brain of mouse models of Alzheimer's disease (AD) and plasma of AD patients, associated with memory and cognitive decline; however, the exact function of PAI-1 in AD onset and progression is largely unclear. In this study, we evaluated a novel PAI-1 inhibitor, TM5A15, on its ability to prevent or reverse memory deficits and decrease Aβ levels and plaque deposition in APP/PS1 mice. We administered TM5A15 mixed in a chow diet to 3-month and 9-month-old APP/PS1 mice before and after neuropathological changes were distinguishable. We then evaluated the effects of TM5A15 on memory function and neuropathology at 9 months and 18 months of age. In the younger mice, 6 months of TM5A15 treatment protected against recognition and short-term working memory impairment. TM5A15 also decreased oligomer levels and amyloid plaques, and increased mBDNF expression in APP/PS1 mice at 9 months of age. In aged mice, 9 months of TM5A15 treatment did not significantly improve memory function nor decrease amyloid plaques. However, TM5A15 treatment showed a trend in decreasing oligomer levels in APP/PS1 mice at 18 months of age. Our results suggest that PAI-1 inhibition could improve memory function and reduce the accumulation of amyloid levels in APP/PS1 mice. Such effects are more prominent when TM5A15 is administered before advanced AD pathology and memory deficits occur.

A neural mechanism of cognitive reserve: The case of bilingualism

Cognitive Reserve (CR) refers to the preservation of cognitive function in the face of age- or disease-related neuroanatomical decline. While bilingualism has been shown to contribute to CR, the extent to which, and what particular aspect of, second language experience contributes to CR are debated, and the underlying neural mechanism(s) unknown. Intrinsic functional connectivity reflects experience-dependent neuroplasticity that occurs across timescales ranging from minutes to decades, and may be a neural mechanism underlying CR. To test this hypothesis, we used voxel-based morphometry and resting-state functional connectivity analyses of MRI data to compare structural and functional brain integrity between monolingual and bilingual older adults, matched on cognitive performance, and across levels of second language proficiency measured as a continuous variable. Bilingualism, and degree of second language proficiency specifically, were associated with lower gray matter integrity in a hub of the default mode network – a region that is particularly vulnerable to decline in aging and dementia – but preserved intrinsic functional network organization. Bilingualism moderated the association between neuroanatomical differences and cognitive decline, such that lower gray matter integrity was associated with lower executive function in monolinguals, but not bilinguals. Intrinsic functional network integrity predicted executive function when controlling for group differences in gray matter integrity and language status. Our findings confirm that lifelong bilingualism is a CR factor, as bilingual older adults performed just as well as their monolingual peers on tasks of executive function, despite showing signs of more advanced neuroanatomical aging, and that this is a consequence of preserved intrinsic functional network organization.

Subacute Partially Reversible Leukoencephalopathy Expands the Aicardi-Goutières Syndrome Phenotype.

To report a series of atypical presentations of Aicardi-Goutières syndrome. Clinical, neuroimaging, and genetic data. We report a series of six unrelated patients (five males) with a subacute loss of developmental milestones, pyramidal signs, and regression of communication abilities, with onset at ages ranging from 7 to 20 months, reaching a nadir after 4 to 24 weeks. A remarkable improvement of lost abilities occurred in the follow-up, and they remained with residual spasticity and dysarthria but preserved cognitive function. Immunization or febrile illness occurred before disease onset in all patients. CSF was normal in two patients, and in four, borderline or mild lymphocytosis was present. A brain CT scan disclosed a subtle basal ganglia calcification in one of six patients. Brain MRI showed asymmetric signal abnormalities of white matter with centrum semi-ovale involvement in five patients and a diffuse white matter abnormality with contrast enhancement in one. Four patients were diagnosed and treated for acute demyelinating encephalomyelitis (ADEM). Brain imaging was markedly improved with one year or more of follow-up (average of 7 years), but patients remained with residual spasticity and dysarthria without cognitive impairment. Demyelination relapse occurred in a single patient four years after the first event. Whole-exome sequencing (WES) was performed in all patients: four of them disclosed biallelic pathogenic variants in RNASEH2B (three homozygous p.Ala177Thr and one compound heterozygous p.Ala177Thr/p.Gln58*) and in two of them the same homozygous deleterious variants in RNASEH2A (p.Ala249Val). This report expands the phenotype of AGS to include subacute developmental regression with partial clinical and neuroimaging improvement. Those clinical features might be misdiagnosed as ADEM.

Whole brain atlas-based diffusion kurtosis imaging parameters for the evaluation of multiple cognitive-related brain microstructure injuries after radiotherapy in lung cancer patients with brain metastasis.

Whole brain radiation therapy (WBRT) can cause cognitive dysfunctions in lung cancer patients with brain metastasis (BM). Diffusion kurtosis imaging (DKI) can detect brain microstructural alterations sensitivly. We aimed to identify the potential of DKI parameters for early radiation-induced brain injury and investigate the association between microstructure changes and neurocognitive function (NCF) decline. Lung cancer patients with BM (n=35) who underwent WBRT in a single center in Zhejiang, China, were consecutively and prospectively enrolled between June 24th, 2020 and December 22nd, 2021, and the median follow-up time was 6.0 months (3.6-6.6 months). DKI and T1-weighted (T1W) MRI scans were acquired prior to and following WBRT. Diffusivity-based (mean diffusivity, MD; fractional anisotropy, FA) and kurtosis-based (mean kurtosis, MK; axial kurtosis, AK) parameters were calculated within the automated anatomical labeling (AAL) atlas-based regions. Reliable change indices practice effects (RCI-PE) scores of the Mini-Mental State Examination (MMSE) were calculated to determine significant neurocognitive decline by a one-sample t-test from baseline to 2-6 months post-WBRT. To assess the subacute induced effects within the whole brain, percentage changes of DKI parameters were evaluated at 170 atlas-based regions by a one-sample t-test. Linear regression analyses were used to evaluate the association between DKI parameter changes and RCI-PE scores. Finally, the study included 19 patients in the longitudinal follow-up. RCI-PE scores declined at 2-6 months post-WBRT (mean RCI-PE =-0.842, 95% CI, -0.376 to -1.310; P=0.002). With the atlas-based analysis of subacute effects after post-WBRT, a total of 28 regions changed in at least one diffusion parameter, revealing region-wise microstructural alterations in the brain. Significant correlations of at least one diffusion parameters with RCI-PEs were observed in 9 regions, such as the right orbital part of the inferior frontal gyrus [right IFGorb, r(AK) =0.47, P=0.03] and left middle temporal gyrus [left MTG, r(MK) =-0.49, P=0.03]. DKI parameters can be used to detect early microstructure changes and represent important imaging predictors for cognitive decline. The reported 9 regions are more particularly vulnerable to neurocognitive radiation-induced impairment for lung cancer patients with BM, representing potential dose-avoidance targets for cognitive function preservation.

Evidence accumulation rate moderates the relationship between enriched environment exposure and age-related response speed declines.

Older adults exposed to enriched environments (EE) maintain relatively higher levels of cognitive function, even in the face of compromised markers of brain health. Response speed (RS) is often used as a simple proxy to measure the preservation of global cognitive function in older adults. However, it is unknown which specific selection, decision, and/or motor processes provide the most specific indices of neurocognitive health. Here, using a simple decision task with electroencephalography (EEG), we found that the efficiency with which an individual accumulates sensory evidence was a critical determinant of the extent to which RS was preserved in older adults (63% female, 37% male). Moreover, the mitigating influence of EE on age-related RS declines was most pronounced when evidence accumulation rates were shallowest. These results suggest that the phenomenon of cognitive reserve, whereby high EE individuals can better tolerate suboptimal brain health to facilitate the preservation of cognitive function, is not just applicable to neuroanatomical indicators of brain ageing, but can be observed in markers of neurophysiology. Our results suggest that EEG metrics of evidence accumulation may index neurocognitive vulnerability of the ageing brain.SIGNIFICANCE STATEMENT:Response speed in older adults is closely linked with trajectories of cognitive ageing. Here, by recording brain activity while individuals perform a simple computer task, we identify a neural metric which is a critical determinant of response speed. Older adults exposed to greater cognitive and social stimulation throughout a lifetime could maintain faster responding, even when this neural metric was impaired. This work suggests EEG is a useful technique for interrogating how a lifetime of stimulation benefits brain health in ageing.

Computerized test‐retest of the Wisconsin Card Sorting Test in day‐to‐day consecutive performances in Mild Cognitive Impairment

AbstractBackgroundWe examined executive functions by testing cognitive flexibility, problem solving and response maintenance by means of the Wisconsin Card Sorting Test (WCST) on two consecutive days. This could render the performance gains obtained in the second assessment in Mild Cognitive Impaired (MCI) subjects, in contrast to a preserved cognitive function group (Control, CTRL group).Method17 older adults were evaluated with several tests (Fig. 1) and with the Neuropsi battery to classify them in two groups: those with three standard deviations below the mean in at least one of the cognitive functions (MCI group, n = 7) and those without this characteristic (n = 10) (Fig. 2). The WCST was delivered twice in a day‐to‐day assessment (1 subject did not repeat his session). A computerized version of the WCST was programmed using e‐prime software, v. 1, at the same time of day. The first three categories were randomly selected, and the categories were then repeated. A special keypad was designed, which included four keys for each card option. Written feedback on the screen was provided immediately.ResultANOVAs results did not show significant differences; nevertheless, the % of correct responses was almost significant within sessions in both groups (p &lt; 0.07) and categories also showed a tendency towards significance between groups in the first session (p &lt; 0.06) (Figs. 3, 4 &amp; 5). Different subgroups emerged: from the first to the second session, one subgroup increased their frequency of categories (CTRL group: 50%; MCI group: 16.66%; chi2 = 16.6; df = 1, p &lt; 0.0001); one subgroup lacked flexibility and remained the same (CTRL group: 30%; MCI group: 66.66%; chi2 = 13; df = 1, p &lt; 0.0001), and one subgroup decreased the number of categories (CTRL group: 20%; MCI group: 16.66%; chi2 = 0.30; df = 1, p = 0.581).ConclusionIn this study, the percentage of correct responses, and the number of categories achieved may provide a more flexible profile of the execution abilities in older adults, which could be more informative for the detection of groups and so, of transitional stages from normality to cognitive impairment.

The Impact of Bilingualism on Cognitive Reserve as a Protectant Against Cognitive Decline

Cognitive decline exists on a spectrum, ranging from mild cognitive impairment to dementia. These two diagnoses encompass a group of symptoms rooted in the progressive decline of cognitive function, impairing aspects like memory, decision-making, language use, and locomotion. This review centers upon the premise of cognitive reserve, an intangible measure of the brain’s resilience and capacity to compensate for damage, and its relationship with the preservation of cognitive function later in life. Bilingualism constitutes one of many contributing factors to a higher cognitive reserve; however, this term fails to reflect the unique linguistic profile intrinsic to every individual—including whether a second language was acquired during childhood or later in life. Therefore, a distinction between “acquired” and “lifelong” bilingualism is made. Through the analysis of task-based and neuroimaging data, this review article elucidates the impact both forms of bilingualism have on cognitive reserve as a protectant against cognitive decline, revealing that resultant neuroprotective advantage is most salient when both languages are used regularly, in diverse environments, and in an active manner. These practices are observed in both acquired and lifelong bilinguals to varying degrees, which are contextualized and explored in detail within the review.

Sustained Preservation of Cognition and Prevention of Patient-Reported Symptoms With Hippocampal Avoidance During Whole-Brain Radiation Therapy for Brain Metastases: Final Results of NRG Oncology CC001

Initial report of NRG Oncology CC001, a phase 3 trial of whole-brain radiation therapy plus memantine (WBRT+memantine) with or without hippocampal avoidance (HA), demonstrated neuroprotective effects of HA with a median follow-up of fewer than 8 months. Herein, we report the final results with complete cognition, patient-reported outcomes, and longer-term follow-up exceeding 1 year. Adult patients with brain metastases were randomized to HA-WBRT+memantine or WBRT+memantine. The primary endpoint was time to cognitive function failure, defined as decline using the reliable change index on the Hopkins Verbal Learning Test-Revised (HVLT-R), Controlled Oral Word Association, or the Trail Making Tests (TMT) A and B. Patient-reported symptom burden was assessed using the MD Anderson Symptom Inventory with Brain Tumor Module and EQ-5D-5L. Between July 2015 and March 2018, 518 patients were randomized. The median follow-up for living patients was 12.1 months. The addition of HA to WBRT+memantine prevented cognitive failure (adjusted hazard ratio, 0.74, P=.016) and was associated with less deterioration in TMT-B at 4 months (P=.012) and HVLT-R recognition at 4 (P=.055) and 6 months (P=.011). Longitudinal modeling of imputed data showed better preservation of all HVLT-R domains (P < .005). Patients who received HA-WBRT+Memantine reported less symptom burden at 6 (P < .001 using imputed data) and 12 months (P=.026 using complete-case data; P < .001 using imputed data), less symptom interference at 6 (P=.003 using complete-case data; P=.0016 using imputed data) and 12 months (P=.0027 using complete-case data; P=.0014 using imputed data), and fewer cognitive symptoms over time (P=.043 using imputed data). Treatment arms did not differ significantly in overall survival, intracranial progression-free survival, or toxicity. With median follow-up exceeding 1 year, HA during WBRT+memantine for brain metastases leads to sustained preservation of cognitive function and continued prevention of patient-reported neurologic symptoms, symptom interference, and cognitive symptoms with no difference in survival or toxicity.

NREM sleep as a novel protective cognitive reserve factor in the face of Alzheimer's disease pathology

BackgroundAlzheimer’s disease (AD) pathology impairs cognitive function. Yet some individuals with high amounts of AD pathology suffer marked memory impairment, while others with the same degree of pathology burden show little impairment. Why is this? One proposed explanation is cognitive reserve i.e., factors that confer resilience against, or compensation for the effects of AD pathology. Deep NREM slow wave sleep (SWS) is recognized to enhance functions of learning and memory in healthy older adults. However, that the quality of NREM SWS (NREM slow wave activity, SWA) represents a novel cognitive reserve factor in older adults with AD pathology, thereby providing compensation against memory dysfunction otherwise caused by high AD pathology burden, remains unknown.MethodsHere, we tested this hypothesis in cognitively normal older adults (N = 62) by combining 11C-PiB (Pittsburgh compound B) positron emission tomography (PET) scanning for the quantification of β-amyloid (Aβ) with sleep electroencephalography (EEG) recordings to quantify NREM SWA and a hippocampal-dependent face-name learning task.ResultsWe demonstrated that NREM SWA significantly moderates the effect of Aβ status on memory function. Specifically, NREM SWA selectively supported superior memory function in individuals suffering high Aβ burden, i.e., those most in need of cognitive reserve (B = 2.694, p = 0.019). In contrast, those without significant Aβ pathological burden, and thus without the same need for cognitive reserve, did not similarly benefit from the presence of NREM SWA (B = -0.115, p = 0.876). This interaction between NREM SWA and Aβ status predicting memory function was significant after correcting for age, sex, Body Mass Index, gray matter atrophy, and previously identified cognitive reserve factors, such as education and physical activity (p = 0.042).ConclusionsThese findings indicate that NREM SWA is a novel cognitive reserve factor providing resilience against the memory impairment otherwise caused by high AD pathology burden. Furthermore, this cognitive reserve function of NREM SWA remained significant when accounting both for covariates, and factors previously linked to resilience, suggesting that sleep might be an independent cognitive reserve resource. Beyond such mechanistic insights are potential therapeutic implications. Unlike many other cognitive reserve factors (e.g., years of education, prior job complexity), sleep is a modifiable factor. As such, it represents an intervention possibility that may aid the preservation of cognitive function in the face of AD pathology, both present moment and longitudinally.

Longitudinal Cognitive Screening Findings in Pediatric MS vs. Pediatric Controls and Adult MS in a Multi-center Cohort (S31.008)

Longitudinal Cognitive Screening Findings in Pediatric MS vs. Pediatric Controls and Adult MS in a Multi-center Cohort (S31.008)

Determination of the effective dose of dexmedetomidine to achieve loss of consciousness during anesthesia induction.

Dexmedetomidine (DEX) is a sedative with greater preservation of cognitive function, reduced respiratory depression, and improved patient arousability. This study was designed to investigate the performance of DEX during anesthesia induction and to establish an effective DEX induction strategy, which could be valuable for multiple clinical conditions. Patients undergoing abdominal surgery were involved in this dose-finding trial. Dixon's up-and-down sequential method was employed to determine the effective dose of DEX to achieve the state of "loss of consciousness", and an effective induction strategy was established with continuous infusion of DEX and remifentanil. The effects of DEX on hemodynamics, respiratory state, EEG, and anesthetic depth were monitored and analyzed. Through the strategy mentioned, the depth of surgical anesthesia was successfully achieved by DEX-led anesthesia induction. The ED50 and ED95 of the initial infusion rate of DEX were 0.115 and 0.200 μg/kg/min, respectively, and the mean induction time was 18.3 min. The ED50 and ED95 of DEX to achieve the state of "loss of consciousness" were 2.899 (95% CI: 2.703-3.115) and 5.001 (95% CI: 4.544-5.700) μg/kg, respectively. The mean PSI on the loss of consciousness was 42.8 among the patients. During anesthesia induction, the hemodynamics including BP and HR were stable, and the EEG monitor showed decreased α and β powers and increased θ and δ in the frontal and pre-frontal cortices of the brain. This study indicated that continuous infusion of combined DEX and remifentanil could be an effective strategy for anesthesia induction. The EEG during the induction was similar to the physiological sleep process.