Preservation Of Cognitive Function Research Articles

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 < 0.07) and categories also showed a tendency towards significance between groups in the first session (p < 0.06) (Figs. 3, 4 & 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 < 0.0001); one subgroup lacked flexibility and remained the same (CTRL group: 30%; MCI group: 66.66%; chi2 = 13; df = 1, p < 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.

TREM2 as an evolving therapeutic target in Alzheimer's disease.

TREM2 as an evolving therapeutic target in Alzheimer's disease.

Cognitive reserve and dementia risk management in people with an intellectual disability.

This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Cognition in People Aged 80 Years and Older: Determinants and Predictors of Change from a Population-Based Representative Study in Germany

BackgroundThe number of people aged 80 years and older (80+) will increase drastically in the upcoming decades. The preservation of cognitive functions will contribute to their quality of life and independence.ObjectivesTo identify determinants of cognition and predictors of change in cognitive performance in the population 80+.DesignCross-sectional and longitudinal population-based on the representative NRW80+ survey.SettingRandomly drawn cases of people aged 80+ from the municipal registration offices, including people living in private homes and institutional settings.ParticipantsThe participants in the cross-sectional sample (N=1503, 65.5%female) were 84.7 years old (95%CI[84.5,85.0]) and had 12.3 years of education (95%CI[12.1,12.4]). The participants in the longitudinal sample (N=840, 62.5%female) were 84.9 years old (95%CI[84.6,85.2]) and had 12.3 years of education (95%CI[12.0,12.5]).MeasurementsThe cognitive screening DemTect, age, sex, education, and social, physical, and cognitive lifestyle activities, as well as subjective general health status and depressive symptoms, were assessed at baseline and 24-month follow-up.ResultsYounger age, more years of education, and more cognitive lifestyle activities were identified as the most consistent determinants of both better cognitive performance and preservation of cognitive performance for both global cognition as well as the DemTect subtests on memory and executive functions.ConclusionsOur findings reveal that commonly investigated determinants of, and change in, cognitive performance are valid for the people 80+ and highlight the importance of cognitive lifestyle activities for cognitive health. The maintenance of cognitive functions is a key aspect of healthy aging in terms of preserving independence in people 80+.

Analysis of sociodemographic, clinical, and lifestyle factors associated with cognitive aging

IntroductionCognitive aging is defined as the cognitive decline during the aging process. Most cognitive skills deteriorate in old age; however, there are individual differences in the speed of the decline and severity of neuropsychological deficits.ObjectivesThe aim of the study was to delineate the associations of sociodemographic, clinical, and lifestyle factors with cognitive aging.Methods302 participants aged 60 years and above (mean age 69,6±7,2; range 60-92 years) were included in the study. Women were 69.9% of the group (N = 211). Subjects completed the questionnaire (sociodemographic and anthropometric data, chronic diseases), and depression intensity was assessed by Beck Depression Inventory (BDI). Cognitive functions were evaluated using MiniMental State Examination, Trail Making Test, Stroop test, and selected tests from CANTAB battery (Pattern Recognition Memory, Spatial Recognition Memory, Spatial Span, Spatial Working Memory).ResultsAge influenced most of the studied cognitive functions. Higher education level and more frequent cognitive activities (e.g. reading and crosswords) had a protective effect on the performance of tests assessing working memory and executive functions. Working memory and attention assessed in the Stroop test in part B were most sensitive to the negative impact of age, lower education level, and lower frequency of cognitive activity. Higher body mass index (BMI≥28) and diabetes were associated with worse spatial working memory.ConclusionsThe results suggesting the association between lifestyle factors – cognitive activity and cognitive functions can contribute to the development of interventions aimed at the preservation of cognitive functions in older age.Disclosure of InterestNone Declared

Negative symptoms and associated factors in older people with schizophrenia

IntroductionThe evolution of schizophrenia with age remains poorly studied. The prevalence of negative symptoms in elderly people with schizophrenia is even less described in the literature.Objectivesto evaluate the prevalence of remission of negative symptoms in the elderly and to study the sociodemographic and clinical variables associated with this remission.MethodsThe sample consisted of 83 subjects aged 55 years and over, followed at the psychiatry department "G" of the Razi hospital in Tunis and suffering from schizophrenia according to the DSM5 criteria. Global remission was defined as a score below 4 on the seven negative symptom items of the PANSS. A questionnaire was administered to each patient to collect epidemiological and anamnestic data.Results59% of the sample showed remission of global negative symptoms. 84% and 60% were in remission on the emotional and cognitive subscales, respectively. The existence of remission was correlated with lower PANSS global score, more preserved cognitive functioning, later age of onset, more family and social support, and the absence of a concomitant somatic illness.ConclusionsThis study showed that measures to optimize treatment of positive symptoms and cognitive functioning may have an impact on negative symptoms. Similarly, quality of social network in later life impacts the level of negative symptoms.Disclosure of InterestNone Declared

Neurocognitive criteria for predicting recovery in a primary psychotic episode

Were examined 160 patients with primary psychotic episode (49 patients diagnosed with schizophrenia (F20), 59 with a diagnosis of acute polymorphic psychotic disorder (F23) and 52 with a diagnosis of schizoaffective disorder (F25)), who were under observation for 1 year. Were analyzed and described neurocognitive features of patients, which cause complete and incomplete exit from psychosis. It has been found that complete recovery in primary psychotic episode causes the preservation of cognitive functioning, in particular memory and verbal speed, as well as greater variability in methods of cognitive regulation of emotions and the presence of an outfit with mal- adaptive methods of adaptive regulation options, in particular positive focusing and acceptance

PS-BPP04-3: ASSOCIATION BETWEEN URINARY NA/K RATIO AND CHANGES IN COGNITIVE FUNCTION AND ALBUMINURIA OVER 10 YEARS IN A GENERAL POPULATION

Objective: Preservation of cognitive function is an important issue in extending healthy life expectancy in an aging society. To elucidate factors associated with changes in cognitive function over a 10-year period in a general population. Design and method: A total of 984 subjects (381 males, 603 females, mean age 62.4 years) underwent a physical examination, blood test, urinalysis and the mini-mental state examination as an evaluation of cognitive function in 2009 and 2018. After excluding subjects with diabetes at baseline, the remaining subjects were followed-up 10 years later. Complete data sets were available from 890 subjects (330 males, 560 females, mean age 62.4 years) for prospective analysis. Logistic regression was performed to determine factors associated with changes in cognitive function and albuminuria after 10 years. Results: The logistic regression analysis revealed that the age (OR 1.11; 95%C.I: 1.08–1.14, p &lt; 0.0001), sex (male, OR 0.59; 95%C.I: 0.38–0.91,P &lt; 0.05), HbA1c (OR 2.18; 95%C.I: 1.13–4.23, P &lt; 0.05), hs-CRP (OR 1.22; 95%C.I: 1.03–1.46, P &lt; 0.05), and albuminuria(OR 1.48; 95%C.I: 1.19–1.83, p &lt; 0.001) were associated with cognitive decline over 10 years. The age (OR 1.11; 95% C.I: 1.08–1.14, p &lt; 0.0001) and albuminuria (OR 1.26; 95%C.I: 1.01–1.59, p &lt; 0.05) were independently correlated to cognitive decline in stepwise logistic regression analysis. Furthermore, the age (OR 1.01; 95%C.I: 1.05–1.12, p &lt; 0.0001), uric acid (OR 1.36; 95%C.I: 1.15–1.62, p &lt; 0.001), insulin (OR 1.48; 95%C.I: 1.01–2.04, p &lt; 0.05) and urinary Na/K ratio (OR 1.14; 95%C.I: 1.05–1.25, p &lt; 0.01) were independently related to the progression of albuminuria over 10 years in stepwise logistic regression analysis. Conclusions: Urinary albuminuria and age were independently associated with 10-year cognitive decline, and urinary Na/K ratio was independently associated with progression of urinary albuminuria. The urinary Na/K ratio may have important significance in cognitive decline.

Changes in clinical and neuropsychological parameters in children with chiasmal-sellar tumors operated on via endoscopic transsphenoidal and transcranial approaches

The aim of the research was to study changes in clinical and neuropsychological deficits in children with neoplasms of the chiasmal-sellar region (CSR) operated on via transcranial and endoscopic transsphenoidal approaches. The analysis of clinical and neuropsychological examination and surgical treatment of 24 children with CSR tumors was carried out. Two leading neuropsychological symptom complexes in children with CSR neoplasms were identified. Changes in neuropsychological parameters in children with CSR neoplasms during the studied observation period do not directly depend on the volume of the tumor. In the early postoperative period, timely correction of the identified fluid and electrolyte disorders is necessary for better recovery of the patient’s neuropsychological deficit. The preservation of cognitive functions in children after the removal of a CSR neoplasm is influenced not so much by the volume of the tumor or surgical access, as by the gentle technique of the operation.

Electroencephalography signals and neurodevelopment after Kawasaki disease: A pilot study.

Acute Kawasaki disease (KD) induces central nervous system inflammation and excessive irritability. Long-term impacts on children's neurodevelopment have only been studied marginally. This pilot study aimed to describe the neuropsychological profile of primary school-aged children with a history of KD and to explore the impacts of KD on electroencephalography (EEG) markers associated with attention and brain maturation. Fifteen children (8.8 ± 2.5 years) were recruited 4.9 ± 2.7 years after KD onset. Intellectual abilities, long-term memory, and auditory sustained attention were evaluated. Parents completed standardized questionnaires assessing (1) executive functioning; (2) internalizing and externalizing difficulties; (3) attention deficit hyperactivity disorder symptoms; and (4) autism spectrum disorder symptoms. Theta/beta ratio (TBR) and alpha peak (AP) were extracted from resting-state EEG and compared with 32 controls (8.9 ± 2.1 years). The alpha band was analyzed using a feature reduction algorithm to detect potential groupings. Performances showed preserved intellectual abilities and memory. Sustained attention performance was within the lower range for 4/14 participants (29%), with considerable parental reports of inattention (43%), working memory difficulties (50%), and hyperactivity-impulsivity (36%). No alterations in the TBR were found but the KD group presented a significantly lower AP amplitude ratio. A clear separation of KD cohort into two clusters showed that acute irritability is associated with a weaker AP. Despite overall preserved cognitive functions, there is a possible association between KD and attention deficit concerns. This first EEG-based study indicates alpha peak abnormality after KD, predominantly in children with acute irritability. Longitudinal studies are warranted to better characterize patients' neurodevelopmental trajectory.

INPP5D deficiency attenuates amyloid pathology in a mouse model of Alzheimer's disease.

Inositol polyphosphate-5-phosphatase (INPP5D) is a microglia-enriched lipid phosphatase in the central nervous system. A non-coding variant (rs35349669) in INPP5D increases the risk for Alzheimer's disease (AD), and elevated INPP5D expression is associated with increased plaque deposition. INPP5D negatively regulates signaling via several microglial cell surface receptors, including triggering receptor expressed on myeloid cells 2 (TREM2); however, the impact of INPP5D inhibition on AD pathology remains unclear. We used the 5xFAD mouse model of amyloidosis to assess how Inpp5d haplodeficiency regulates amyloid pathogenesis. Inpp5d haplodeficiency perturbs the microglial intracellular signaling pathways regulating the immune response, including phagocytosis and clearing of amyloid beta (Aβ). It is important to note that Inpp5d haploinsufficiency leads to the preservation of cognitive function. Spatial transcriptomic analysis revealed that pathways altered by Inpp5d haploinsufficiency are related to synaptic regulation and immune cell activation. These data demonstrate that Inpp5d haplodeficiency enhances microglial functions by increasing plaque clearance and preserves cognitive abilities in 5xFAD mice. Inhibition of INPP5D is a potential therapeutic strategy for AD.