Early Behavioral Changes Research Articles

Identifying and Addressing Functional Communication Challenges in Patients With Behavioral Variant Frontotemporal Dementia.

We describe the communication challenges of four patients with a neurodegenerative disorder consistent with behavioral variant frontotemporal dementia (bvFTD), characterized by early behavioral and personality changes. By describing their clinical profiles, we identify common barriers to functional communication in this population and provide recommendations for how speech-language pathologists (SLPs) might contribute to minimizing them. Four patients with bvFTD were selected from a cohort of patients with progressive communication impairments. Three of them returned for at least one follow-up visit. Case histories are presented along with the results of comprehensive speech and language, neuropsychological, and neurological testing. At the time of initial evaluation, patients were between the ages of 54 and 66 years and had been experiencing symptoms for 1.5-6 years. Consistent with their bvFTD diagnoses, all patients had prominent behavioral and personality changes that impacted communication. Patients 1 and 2 also had mild aphasia at enrollment, primarily characterized by anomia and loss of word meaning. Patients 3 and 4 both had apraxia of speech and moderate-to-severe aphasia at enrollment with prominent anomia and agrammatism. All four patients had impaired executive functioning and relative sparing of visuospatial skills; episodic memory was also impaired for Patients 2 and 4. Even though functional communication was progressively limited for all patients, none of them received regular support from an SLP. This case series adds to a scant, but growing, literature demonstrating that patients with bvFTD have communication impairments. SLPs are uniquely positioned to identify barriers to functional communication and to provide tailored strategy training to the patients and their care partners over the course of their disease. Systematic evaluation of the efficacy of treatment in this population would be valuable. https://doi.org/10.23641/asha.25933762.

Causal relationship between neuroticism and frailty: A bidirectional Mendelian randomization study

BackgroundObservational studies have shown that neuroticism is associated with frailty, but the causal relationship between them remains unclear. MethodsA two-sample Mendelian randomization (MR) study was conducted to explore the bidirectional causal relationship between neuroticism (n = 380,506 for the primary analysis, n = 79,004 for the validation) and frailty (n = 175,226) using publicly available genome-wide association study data. The inverse variance weighted (IVW), weighted median, and MR-Egger were used to obtain the causal estimates. Findings were verified through extensive sensitivity analyses and validated using another dataset. Multivariable MR (MVMR) analysis was performed to estimate the direct causal effects with adjustment of potential confounders. Two-step MR technique was then conducted to explore the mediators in the causal effects of neuroticism on frailty. ResultsGenetically-predicted higher neuroticism score was significantly correlated with higher frailty index (IVW beta: 0.53, 95%CI: 0.48 to 0.59, P = 9.3E-83), and genetically-determined higher frailty index was significantly associated with higher neuroticism score (IVW beta: 0.28, 95%CI: 0.21 to 0.35, P = 1.3E-16). These results remained robust across sensitivity analyses and were reproducible using another dataset. The MVMR analysis indicated that the causal relationships remained significant after adjusting for the potential confounding factors. Mediation analysis revealed that depression, years of schooling, and smoking were significantly mediated the causal effects of neuroticism on frailty. ConclusionsA bidirectional causal relationship existed between neuroticism and frailty. Our findings suggested that early intervention and behavioral changes might be helpful to reduce the neuroticism levels and prevent the development of frailty.

Insights into early pathogenesis of sporadic Alzheimer's disease: role of oxidative stress and loss of synaptic proteins.

Oxidative stress, induced by impaired insulin signaling in the brain contributes to cognitive loss in sporadic Alzheimer's disease (sAD). This study evaluated early hippocampal oxidative stress, pre- and post-synaptic proteins in intraperitoneal (IP) and intracerebroventricular (ICV) streptozotocin (STZ) models of impaired insulin signaling. Adult male Wistar rats were injected with STZ, IP, or ICV, and sacrificed 1-, 3-, or 6-weeks post injection. Rat's cognitive behavior was assessed using Morris water maze (MWM) tests at weeks 3 and 6. Hippocampal synaptosomal fractions were examined for oxidative stress markers and presynaptic [synapsin I, synaptophysin, growth-associated protein-43 (GAP-43), synaptosomal-associated protein-25 (SNAP-25)] and postsynaptic [drebrin, synapse-associated protein-97 (SAP-97), postsynaptic density protein-95 (PSD-95)] proteins. IP-STZ and ICV-STZ treatment impaired rat's cognition, decreased the levels of reduced glutathione (GSH) and increased the levels of thiobarbituric acid reactive species (TBARS) in a time dependent manner. In addition, it reduced the expression of pre- and post-synaptic proteins in the hippocampus. The decline in cognition is significantly correlated with the reduction in synaptic proteins in the hippocampus. In conclusion, impaired insulin signaling in the brain is deleterious in causing early synaptosomal oxidative damage and synaptic loss that exacerbates with time and correlates with cognitive impairments. Our data implicates oxidative stress and synaptic protein loss as an early feature of sAD and provides insights into early biochemical and behavioral changes during disease progression.

Depressive symptoms and hippocampal volume in autosomal dominant Alzheimer's disease.

Depressive symptoms are among early behavioral changes in Alzheimer's disease (AD); however, the relationship between neurodegeneration and depressive symptoms remains inconclusive. To better understand this relationship in preclinical AD, we examined hippocampal volume and depressive symptoms in cognitively unimpaired carriers of the presenilin-1 (PSEN1) E280A mutation for autosomal dominant AD. A total of 27 PSEN1 mutation carriers and 26 non-carrier family members were included. Linear regression was used to test the relationship between hippocampal volume and 15-item Geriatric Depression Scale. Carriers and non-carriers did not differ in depressive symptoms or hippocampal volume. Within carriers, lower hippocampal volume was associated with greater depressive symptoms, which remained significant after adjusting for age and cognition. This relationship was not significant in non-carriers. Hippocampal neurodegeneration may underlie depressive symptoms in preclinical autosomal dominant AD. These findings provide support for the utility of targeting depressive symptoms in AD prevention. We compared unimpaired autosomal dominant Alzheimer's disease (AD) mutation carriers and non-carriers. Carriers and non-carriers did not differ in severity of depressive symptoms. In carriers, hippocampal volume was inversely associated with depressive symptoms. Depressive symptoms may be a useful target in AD prevention.

The Topics and Publication Trends in Emergence Deliri-Um: A Bibliometric Analysis from 2002 to 2022.

Emergence delirium is an early postoperative behavior change in pediatric patients, posing risks to patient safety and leading to prolonged hospital stays and increased medical costs. As a result, the research on emergence delirium has grown substantially. This study aims to identify the most influential literature, trends, and topics in emergence delirium research, as well as to quantify the fundamental data of academic publications on this topic. We searched for articles on emergence delirium in the Science Citation Index Expanded databases, covering the period from 2002 to 2022. Bibliographic information, including countries, institutions, journals, authorships, references, and keywords, was collected for further analysis. A total of 739 articles on emergence delirium published between 2002 and 2022 were collected. China emerged as the most prolific publisher in this field, accounting for over 30% of all articles (226 publications), followed by the United States (n = 143) and South Korea (n = 92). The top three productive journals were Pediatric anesthesia (n=78, IF=2.129), Anesthesia and Analgesia (n=28, IF=6.627), and BMC Anesthesiology (n=28, IF=2.583). Yonsei University was the most active institution, with 22 publications related to emergence delirium. Among authors, Kin, Hee-Soo (n = 9) published the most articles in this field, followed by Yao, Yusheng (n = 7), Lee, Ji-Hyun (n = 7). The prominent topics in emergence delirium research during the past two decades were "children", "emergence delirium" and "propofol". Through bibliometric analysis, this study provides a comprehensive overview of the trends and developments in the field of emergence delirium over the past two decades. The results demonstrate a significant growth in emergence delirium research worldwide, with China leading in the number of publications. Despite the wealth of literature on strategies for preventing and managing emergence delirium in clinical settings, further basic research is needed to elucidate the underlying mechanisms of emergence delirium.

2'-Fucosyllactose Alleviates Early Weaning-Induced Anxiety-Like Behavior, Amygdala Hyperactivity, and Gut Microbiota Changes.

Early life stress has a significant impact on development of the central nervous system (CNS), with lasting rather than transient consequences; therefore, it is important to alleviate these effects. In recent years, functional communication between the CNS and gut microbiota through the so-called brain-gut-microbiota axis has been examined, and it is likely that prebiotics contribute to development of the CNS through the gut microbiota. In this study, we performed behavioral, neurohistological, and fecal microbiota analyses in early-weaned mice to examine the effects of 2'-fucosyllactose (2'-FL), a human milk oligosaccharide, on anxiety induced by early life stress. Mice weaned at 17 d old (17-d mice) showed anxiety-like behaviors, such as decreased time in the open arms in the elevated plus maze test, compared to mice weaned at 24 d old (24-d mice). The number of cells that were positive for the neuronal activity marker c-Fos in the amygdala was also higher in 17-d mice. The behavioral and neural abnormalities caused by early weaning were alleviated by post-weaning ingestion of 2'-FL. The composition of the fecal microbiota differed among control diet-fed 24-d and 17-d mice, and 2'-FL diet-fed 17-d mice. These findings indicate that human milk oligosaccharides 2'-FL alleviate early stress-induced anxiety, amygdala hyperactivity, and gut microbiota changes.

Frontotemporal dementia presentation in patients with heterozygous p.H157Y variant of TREM2

BackgroundThe triggering receptor expressed on myeloid cell 2 (TREM2) is a major regulator of neuroinflammatory processes in neurodegeneration. To date, the p.H157Y variant of TREM2 has been reported only in...

Are We #Stayinghome to Flatten the Curve?

The recent spread of COVID-19 across the U.S. led to concerted efforts by states to ``flatten the curve through the adoption of stay-at-home mandates that encourage individuals to reduce travel and maintain social distance. Combining data on changes in travel activity with COVID-19 health outcomes and state policy adoption timing, we characterize nationwide changes in mobility patterns and isolate the portion attributable to statewide mandates. We find evidence of dramatic nationwide declines in mobility prior to adoption of any statewide mandates. Once states adopt a mandate, we estimate further mandate-induced declines between 2.1 and 7.0 percentage points across methods that account for states' differences in travel behavior prior to policy adoption. In addition, we investigate the effects of stay-at-home mandates on changes in COVID-19 health outcomes while controlling for pre-trends and observed pre-treatment mobility patterns. We estimate mandate-induced declines between 0.13 and 0.17 in deaths (5.6 to 6.0 in hospitalizations) per 100 thousand across methods. Across 43 adopting states, this represents 23,366-30,144 fewer deaths (and roughly one million averted hospitalizations) for the months of March and April - which indicates that death rates could have been 42-54% higher had states not adopted statewide policies. We further find evidence that changes in mobility patterns prior to adoption of statewide policies also played a role in reducing COVID-19 mortality and morbidity. Adding in averted deaths due to pre-mandate social distancing behavior, we estimate a total of 48-71,000 averted deaths from COVID-19 for the two-month period. Given that the actual COVID-19 death toll for March and April was 55,922, our estimates suggest that deaths would have been 1.86-2.27 times what they were absent any stay-at-home mandates during this period. These estimates represent a lower bound on the health impacts of stay-at-home policies, as they do not account for spillovers or undercounting of COVID-19 mortality. Our findings indicate that early behavior changes and later statewide policies reduced death rates and helped attenuate the negative consequences of COVID-19. Further, our findings of substantial reductions in mobility prior to state-level policies convey important policy implications for re-opening. Take Away Link https://are.berkeley.edu/sites/are.berkeley.edu/files/PolicyTakeAway_Web.pdf

Striatal Activity to Reward Anticipation as a Moderator of the Association Between Early Behavioral Inhibition and Changes in Anxiety and Depressive Symptoms From Adolescence to Adulthood

The early childhood temperament of behavioral inhibition (BI), characterized by inhibited and fearful behaviors, has been associated with heightened risk for anxiety and depression across the lifespan. Although several neurocognitive correlates underlying vulnerability to the development of anxiety among inhibited children have been identified, little is known about the neurocognitive correlates underlying vulnerability to the development of depression. To examine whether blunted striatal activation to reward anticipation, a well-documented neurocognitive vulnerability marker of depression, moderates the association between early BI and the developmental changes in depression and anxiety from adolescence to adulthood. Participants in this prospective longitudinal study were recruited at age 4 months between 1989 and 1993 in the US. Follow-up assessments extended into 2018 (age 26 years). Data were analyzed between September 2021 to March 2022. BI was measured through an observation paradigm in infancy (ages 14 and 24 months). Neural activity to anticipated rewards during a monetary incentive delay task was measured using functional magnetic resonance imaging in adolescence (between ages 15-18 years; 83 individuals had usable data). Anxiety and depressive symptoms were self-reported across adolescence to young adulthood (ages 15 and 26 years; n = 108). A latent change score model, accounting for the interdependence between anxiety and depression, tested the moderating role of striatal activity to reward anticipation in the association between early BI and changes in anxiety and depressive symptoms. A region of interest approach limited statistical tests to regions within the striatum (ie, nucleus accumbens, caudate head, caudate body, putamen). Of 165 participants, 84 (50.1%) were female and 162 (98%) were White. Preliminary analyses revealed significant increases in anxiety and depressive symptoms across ages 15 to 26 years, as well as individual variation in the magnitude of changes. Main analyses showed that reduced activity in the nucleus accumbens to reward anticipation moderated the association between early BI and increases in depressive (β = -0.32; b = -4.23; 95% CI, -7.70 to -0.76; P = .02), and more depressive symptoms at age 26 years (β = -0.47; b = -5.09; 95% CI, -7.74 to -2.43; P < .001). However, there were no significant interactions associated with latent changes in anxiety across age nor anxiety at age 26 years. Activity in the caudate and putamen did not moderate these associations. Blunted reward sensitivity in the ventral striatum may be a developmental risk factor connecting an inhibited childhood temperament and depression over the transition to adulthood. Future studies should examine the efficacy of prevention programs, which target maladaptive reward processing and motivational deficits among anxious youths, in reducing risks for later depression.

Social cognition deficits and biometric signatures in the behavioural variant of Alzheimer's disease.

The behavioural variant of Alzheimer's disease (bvAD) is characterized by early predominant behavioural changes, mimicking the behavioural variant of frontotemporal dementia (bvFTD), which is characterized by social cognition deficits and altered biometric responses to socioemotional cues. These functions remain understudied in bvAD. We investigated multiple social cognition components (i.e. emotion recognition, empathy, social norms and moral reasoning), using the Ekman 60 faces test, Interpersonal Reactivity Index, empathy eliciting videos, Social Norms Questionnaire and moral dilemmas, while measuring eye movements and galvanic skin response. We compared 12 patients with bvAD with patients with bvFTD (n = 14), typical Alzheimer's disease (tAD, n = 13) and individuals with subjective cognitive decline (SCD, n = 13), using ANCOVAs and age- and sex-adjusted post hoc testing. Patients with bvAD (40.1 ± 8.6) showed lower scores on the Ekman 60 faces test compared to individuals with SCD (49.7 ± 5.0, P < 0.001), and patients with tAD (46.2 ± 5.3, P = 0.05) and higher scores compared to patients with bvFTD (32.4 ± 7.3, P = 0.002). Eye-tracking during the Ekman 60 faces test revealed no differences in dwell time on the eyes (all P > 0.05), but patients with bvAD (18.7 ± 9.5%) and bvFTD (19.4 ± 14.3%) spent significantly less dwell time on the mouth than individuals with SCD (30.7 ± 11.6%, P < 0.01) and patients with tAD (32.7 ± 12.1%, P < 0.01). Patients with bvAD (11.3 ± 4.6) exhibited lower scores on the Interpersonal Reactivity Index compared with individuals with SCD (15.6 ± 3.1, P = 0.05) and similar scores to patients with bvFTD (8.7 ± 5.6, P = 0.19) and tAD (13.0 ± 3.2, P = 0.43). The galvanic skin response to empathy eliciting videos did not differ between groups (all P > 0.05). Patients with bvAD (16.0 ± 1.6) and bvFTD (15.2 ± 2.2) showed lower scores on the Social Norms Questionnaire than patients with tAD (17.8 ± 2.1, P < 0.05) and individuals with SCD (18.3 ± 1.4, P < 0.05). No group differences were observed in scores on moral dilemmas (all P > 0.05), while only patients with bvFTD (0.9 ± 1.1) showed a lower galvanic skin response during personal dilemmas compared with SCD (3.4 ± 3.3 peaks per min, P = 0.01). Concluding, patients with bvAD showed a similar although milder social cognition profile and a similar eye-tracking signature to patients with bvFTD and greater social cognition impairments and divergent eye movement patterns compared with patients with tAD. Our results suggest reduced attention to salient facial features in these phenotypes, potentially contributing to their emotion recognition deficits.

Early Identification of Different Behavioral Phenotypes in the Behavioral Variant of Frontotemporal Dementia with the Aid of the Mini-Frontal Behavioral Inventory (mini-FBI).

The Frontal Behavioral Inventory (FBI) is a questionnaire designed to quantify behavioral changes in frontotemporal dementia (FTD). Literature showed heterogeneous FBI profiles in FTD versus Alzheimer's disease (AD) with variable occurrence of positive and negative symptoms. In this study, we constructed a short FBI version (i.e., mini-FBI) with the aim to provide clinicians with a brief tool for the identification of early behavioral changes in behavioral variant of FTD (bvFTD), also facilitating the differential diagnosis with AD. 40 bvFTD and 33 AD patients were enrolled. FBI items were selected based on internal consistency and exploratory factor analysis. Convergent validity of mini-FBI was also assessed. A behavioral index (i.e., B-index) representing the balance between positive and negative mini-FBI symptoms was computed in order to analyze its distribution in bvFTD through a cluster analysis and to compare performance among patient groups. The final version of the mini-FBI included 12 items, showing a significant convergent validity with the Neuropsychiatric Inventory scores (rp = 0.61, p &lt; 0.001). Cluster analysis split patients in four clusters. bvFTD were included in three different clusters characterized by prevalent positive symptoms, both positive and negative symptoms, or prevalent negative behavioral alterations, similar to a subset of AD patients. A fourth cluster included only AD patients showing no positive symptoms. The mini-FBI is a valuable easily administrable questionnaire able to early identify symptoms effectively contributing to the bvFTD behavioral syndrome, aiding clinician in diagnosis and management.

Children’s social and emotional behavior: Role of maternal emotion regulation, psychopathological symptomatology, and family functioning

Research has demonstrated that maternal emotion regulation strategies (self-criticism and self-compassion), mental health, and family functioning impacts child functioning. Due to the paucity of studies, we aimed to analyze: (1) the associations between maternal emotion regulation strategies, psychopathological symptomatology, family functioning, and mother’s perceived child social and emotional behavior (SEB); (2) the differences in mother’s perceived child SEB, according to maternal, child and family characteristics; (3) the predictive role of maternal emotion regulation in mother’s perceived child SEB. A sample of 431 mothers (25-59 years), with children aged 4-17 years (55.5% male), answered the Strengths and Difficulties Questionnaire, the Systemic Clinical Outcome and Routine Evaluation, the Brief Symptom Inventory, the Forms of Self-Criticizing/Attacking and Self-Reassuring Scale, and the Self-Compassion Scale. The results showed positive associations between self-criticism, maternal psychopathological symptomatology, worse family functioning and child social and emotional problems, as well between maternal self-compassion and child prosocial behaviors. Mothers who reported low income, elementary school education, a history of psychiatric illness and whose children had early behavior changes perceived more social and emotional difficulties in their children. Maternal self-criticism was the main predictor of child social and emotional difficulties. In conclusion, maternal emotion regulation strategies and psychopathological symptomatology are associated with family functioning and child SEB.

Sensitivity of the Social Behavior Observer Checklist to Early Symptoms of Patients With Frontotemporal Dementia.

Changes in social behavior are common symptoms of frontotemporal lobar degeneration (FTLD) and Alzheimer disease syndromes. For early identification of individual patients and differential diagnosis, sensitive clinical measures are required that are able to assess patterns of behaviors and detect syndromic differences in both asymptomatic and symptomatic stages. We investigated whether the examiner-based Social Behavior Observer Checklist (SBOCL) is sensitive to early behavior changes and reflects disease severity within and between neurodegenerative syndromes. Asymptomatic individuals and patients with neurodegenerative disease were selected from the multisite ALLFTD cohort study. In a sample of participants with at least 1 time point of SBOCL data, we investigated whether the Disorganized, Reactive, and Insensitive subscales of the SBOCL change as a function of disease stage within and between these syndromes. In a longitudinal subsample with both SBOCL and neuroimaging data, we examined whether change over time on each subscale corresponds to progressive gray matter atrophy. A total of 1,082 FTLD pathogenic variant carriers and noncarriers were enrolled (282 asymptomatic, 341 behavioral variant frontotemporal dementia, 114 semantic and 95 nonfluent variant primary progressive aphasia, 137 progressive supranuclear palsy, and 113 Alzheimer disease syndrome). The Disorganized score increased between asymptomatic to very mild (p = 0.016, estimate = -1.10, 95% CI = -1.99 to -0.22), very mild to mild (p = 0.013, estimate = -1.17, 95% CI = -2.08 to -0.26), and mild to moderate/severe (p < 0.001, estimate = -2.00, 95% CI = -2.55 to -1.45) disease stages in behavioral variant frontotemporal dementia regardless of pathogenic variant status. Asymptomatic GRN pathogenic gene variant carriers showed more reactive behaviors (preoccupation with time: p = 0.001, estimate = 1.11, 95% CI = 1.06 to 1.16; self-consciousness: p = 0.003, estimate = 1.77, 95% CI = 1.52 to 2.01) than asymptomatic noncarriers (estimate = 1.01, 95% CI = 0.98 to 1.03; estimate = 1.31, 95% CI = 1.20 to 1.41). The Insensitive score increased to a clinically abnormal level in advanced stages of behavioral variant frontotemporal dementia (p = 0.003, estimate = -0.73, 95% CI = -1.18 to -0.29). Higher scores on each subscale corresponded with higher caregiver burden (p < 0.001). Greater change over time corresponded to greater fronto-subcortical atrophy in the semantic-appraisal and fronto-parietal intrinsically connected networks. The SBOCL is sensitive to early symptoms and reflects disease severity, with some evidence for progression across asymptomatic and symptomatic stages of FTLD syndromes; thus, it may hold promise for early measurement and monitoring of behavioral symptoms in clinical practice and treatment trials. This study provides Class II evidence that the SBOCL is sensitive to early behavioral changes in FTLD pathogenic variants and early symptomatic individuals in a highly educated patient cohort.

How to differentiate behavioral variant frontotemporal dementia from primary psychiatric disorders: practical aspects for the clinician.

Due to the early and prominent behavioral changes which characterize behavioral variant frontotemporal dementia (bvFTD), patients are more likely to seek psychiatric help and are often initially diagnosed with a primary psychiatric disorder (PPD). Differentiating these conditions is critical because of the dramatically different outcomes, differences in patient management, family counseling and caregiver education. To propose a practical guide to distinguish between bvFTD and PDD. We conducted a non-systematic review of the published manuscripts in the field, including some previous investigations from our own group and work on which we have collaborated, and summarized the main findings and proposals that may be useful for neurological practice. The reviewed literature suggests that a comprehensive clinical history, brief cognitive and neuropsychological evaluations, detailed neurological examination with special attention to motor alterations related to bvFTD, structural and functional neuroimaging evaluation, genetic investigation in selected cases, and assistance from a multidisciplinary team, including a neurologist and a psychiatrist with expertise in bvFTD, are very helpful in differentiating these conditions. Although the clinician may commonly face great difficulty in differentiating between bvFTD and PPD, the use of appropriate tools in a systematic way and the availability of a well-trained multidisciplinary group can significantly increase diagnostic accuracy.

Critical Role of Maternal Selenium Nutrition in Neurodevelopment: Effects on Offspring Behavior and Neuroinflammatory Profile

Research in both animals and humans shows that some nutrients are important in pregnancy and during the first years of life to support brain and cognitive development. Our aim was to evaluate the role of selenium (Se) in supporting brain and behavioral plasticity and maturation. Pregnant and lactating female rats and their offspring up to postnatal day 40 were fed isocaloric diets differing in Se content—i.e., optimal, sub-optimal, and deficient—and neurodevelopmental, neuroinflammatory, and anti-oxidant markers were analyzed. We observed early adverse behavioral changes in juvenile rats only in sub-optimal offspring. In addition, sub-optimal, more than deficient supply, reduced basal glial reactivity in sex dimorphic and brain-area specific fashion. In female offspring, deficient and sub-optimal diets reduced the antioxidant Glutathione peroxidase (GPx) activity in the cortex and in the liver, the latter being the key organ regulating Se metabolism and homeostasis. The finding that the Se sub-optimal was more detrimental than Se deficient diet may suggest that maternal Se deficient diet, leading to a lower Se supply at earlier stages of fetal development, stimulated homeostatic mechanisms in the offspring that were not initiated by sub-optimal Se. Our observations demonstrate that even moderate Se deficiency during early life negatively may affect, in a sex-specific manner, optimal brain development.

Early Cellular, Molecular, Morphological and Behavioral Changes in the Humanized Amyloid-Beta-Knock-In Mouse Model of Late-Onset Alzheimer's Disease.

The purpose of our study is to investigate early cellular, molecular, morphological and behavioral changes in humanized amyloid-beta-knock-in (hAbKI) mice. Using seven-month-old homozygous hAbKI mice, we studied behavioral phenotype parameters, including spatial learning and memory (Morris Water Maze), locomotor activity (open field), working memory (Y-maze) and motor coordination (rotarod); mRNA abundance, protein levels, soluble amyloid-beta 40 and 42 levels and regional immunoreactivities of key markers of mitochondrial dynamics, mitochondrial biogenesis, synaptic health, mitophagy and autophagy; mitochondrial function and using transmission electron microscopy & Golgi–Cox staining, we assessed mitochondrial morphology and dendritic spines. Our extensive behavioral analysis revealed that seven-month-old hAbKI mice showed impairments in motor coordination, reduced locomotor and exploration activities, impairments in working memory and spatial learning and memory. Our mRNA and protein analyses revealed the increased expression of mitochondrial-fission genes and reduced expression of mitochondrial-fusion, mitochondrial-biogenesis, synaptic, autophagy and mitophagy genes in seven-month-old hAbKI mice. An immunofluorescence analysis revealed altered immunoreactivities and agreed with the immunoblot results. Transmission-electron-microscopy data revealed increased mitochondrial fragmentation and reduced mitochondrial length in both hippocampal and cortical tissues of seven-month-old hAbKI mice and mitochondrial function defective. A Golgi–Cox-staining analysis revealed reduced dendritic spines in both cerebral cortices and hippocampi of hAbKI mice. Soluble amyloid-beta (1–40 and 1–42) were detected in three-month-old hAbKI mice and progressively increased in seven-month-old mice. These observations suggest that the human amyloid-beta peptide is sufficient to cause behavioral, mitochondrial, synaptic and ultrastructural changes in seven-month-old hAbKI mice. Our study findings also suggest that hAbKI mice might serve as a model for preclinical studies of preventive therapies.

The behavioral variant of Alzheimer\u2019s disease does not show a selective loss of Von Economo and phylogenetically related neurons in the anterior cingulate cortex

BackgroundThe neurobiological origins of the early and predominant behavioral changes seen in the behavioral variant of Alzheimer’s disease (bvAD) remain unclear. A selective loss of Von Economo neurons (VENs) and phylogenetically related neurons have been observed in behavioral variant frontotemporal dementia (bvFTD) and several psychiatric diseases. Here, we assessed whether these specific neuronal populations show a selective loss in bvAD.MethodsVENs and GABA receptor subunit theta (GABRQ)-immunoreactive pyramidal neurons of the anterior cingulate cortex (ACC) were quantified in post-mortem tissue of patients with bvAD (n = 9) and compared to typical AD (tAD, n = 6), bvFTD due to frontotemporal lobar degeneration based on TDP-43 pathology (FTLD, n = 18) and controls (n = 13) using ANCOVAs adjusted for age and Bonferroni corrected. In addition, ratios of VENs and GABRQ-immunoreactive (GABRQ-ir) pyramidal neurons over all Layer 5 neurons were compared between groups to correct for overall Layer 5 neuronal loss.ResultsThe number of VENs or GABRQ-ir neurons did not differ significantly between bvAD (VENs: 26.0 ± 15.3, GABRQ-ir pyramidal: 260.4 ± 87.1) and tAD (VENs: 32.0 ± 18.1, p = 1.00, GABRQ-ir pyramidal: 349.8 ± 109.6, p = 0.38) and controls (VENs: 33.5 ± 20.3, p = 1.00, GABRQ-ir pyramidal: 339.4 ± 95.9, p = 0.37). Compared to bvFTD, patients with bvAD showed significantly more GABRQ-ir pyramidal neurons (bvFTD: 140.5 ± 82.658, p = 0.01) and no significant differences in number of VENs (bvFTD: 10.9 ± 13.8, p = 0.13). Results were similar when assessing the number of VENs and GABRQ-ir relative to all neurons of Layer 5.DiscussionVENs and phylogenetically related neurons did not show a selective loss in the ACC in patients with bvAD. Our results suggest that, unlike in bvFTD, the clinical presentation in bvAD may not be related to the loss of VENs and related neurons in the ACC.

Psychological Impact and Compliance with Staying at Home of the Public to COVID-19 Outbreak during Chinese Spring Festival

In December 2019, COVID-19 was reported in Wuhan, China. Most of the studies related to the psychological impact and compliance with staying at home due to COVID-19 focused on ten days or one month after the initial “stay-at-home” phase of the COVID-19 pandemic. The early psychological impact and behavior change to COVID-19 during the Chinese Spring Festival (the start time for recommendations to stay at home) is uncertain. In this study, people from 23 provinces in China were recruited to participate in an online survey, using Credamo. Psychological impact and compliance with staying at home were evaluated by a self-designed and validated questionnaire. The results indicated that anxiety was the most often reported feeling (mean: 3.69), followed by sadness (mean: 3.63). Participants employed in foreign-owned companies were most likely to express anxiety and sadness. Overall, 61.8% of participants reported hardly going out, whereas 2.4% said they frequently went out during the initial “stay-at-home” phase of the COVID-19 pandemic. Participants with higher levels of anxiety and sadness were most likely to stay at home against the spread of COVID-19, as were female gender. This survey is an important study of the first reaction to staying at home during the initial “stay-at-home” phase coinciding with Chinese Spring Festival. Our findings identified factors associated with higher level of psychological impact and better compliance with staying at home recommendations during Chinese Spring Festival. The findings can be used to formulate precaution interventions to improve the mental health of vulnerable groups and high uptake of policy during the COVID-19 epidemic.

Clinical subtypes of frontotemporal dementia show different patterns of cortical atrophy

AbstractBackgroundFrontotemporal dementia (FTD) is a progressive neurodegenerative disorder associated with atrophy of the frontal and/or anterior temporal lobes, it is highly heterogeneous and represents about 5% of all cases of dementia and it is one of the most common causes of early‐onset dementia (Onyike and Diehl‐Schmid, 2013). FTD syndromes can be divided into three major groups: the behavioral variant (bvFTD) characterised by prominent early behavioral and personality changes, and the two language variants: the semantic variant (svFTD) and the non‐fluent primary progressive aphasia (pnfaFTD).MethodIn our study we used MRI scans from a frontotemporal lobar degeneration neuroimaging initiative (FTLDNI) database: 133 age and sex matched controls, 70 bvFTD, 36 svFTD and 30 pnfaFTD. Each scan was pre‐processed (Intensity normalization, N3, linear registration, brain masking); tissue classification was performed using BISON (Dadar 2020). All scans were then processed using FALCON (Fonov 2020) to extract its cortical surface anc calculate thickness. Statistical analysis was performed on vertex level.ResultFigure 1 shows relative cortical difference between groups relative to controls, Figure 2 shows areas of significant differences (FDR 1%): the decrease of cortical thickness in the bvFTD group was located in frontal lobes, bilaterally as well as the temporal poles (specially in medial frontal and dorsolateral prefrontal areas). In svFTD, however, cortical thinning is limited to the anterior and lateral temporal lobe, predominantly on the left side. Finally, pnfaFTD shows left sided cortical thinning in prefrontal and Broca’s areas.ConclusionThe identification of predicted patterns of atrophy in each FTD subtype supports the validity of FALCON as an accurate tool to measure cortical changes in neurodegenerative disease. FALCON could be a useful tool for the development of the biomarkers associated with disease and improve understanding of disease progression.

Brain metabolism, amyloid load and neuropsychological correlates in preclinical dementia stages

This multicenter study aimed to investigate the presence of early cognitive, behavioural and brain changes in individuals with subjective cognitive decline (SCD) and pre-Mild Cognitive Impairment (pre-MCI).