-
Brain : a Journal of Neurology Jun 2024In frontotemporal lobar degeneration (FTLD), pathological protein aggregation in specific brain regions is associated with declines in human-specialized social-emotional...
In frontotemporal lobar degeneration (FTLD), pathological protein aggregation in specific brain regions is associated with declines in human-specialized social-emotional and language functions. In most patients, disease protein aggregates contain either TDP-43 (FTLD-TDP) or tau (FTLD-tau). Here, we explored whether FTLD-associated regional degeneration patterns relate to regional gene expression of human accelerated regions (HARs), conserved sequences that have undergone positive selection during recent human evolution. To this end, we used structural neuroimaging from patients with FTLD and human brain regional transcriptomic data from controls to identify genes expressed in FTLD-targeted brain regions. We then integrated primate comparative genomic data to test our hypothesis that FTLD targets brain regions linked to expression levels of recently evolved genes. In addition, we asked whether genes whose expression correlates with FTLD atrophy are enriched for genes that undergo cryptic splicing when TDP-43 function is impaired. We found that FTLD-TDP and FTLD-tau subtypes target brain regions with overlapping and distinct gene expression correlates, highlighting many genes linked to neuromodulatory functions. FTLD atrophy-correlated genes were strongly enriched for HARs. Atrophy-correlated genes in FTLD-TDP showed greater overlap with TDP-43 cryptic splicing genes and genes with more numerous TDP-43 binding sites compared with atrophy-correlated genes in FTLD-tau. Cryptic splicing genes were enriched for HAR genes, and vice versa, but this effect was due to the confounding influence of gene length. Analyses performed at the individual-patient level revealed that the expression of HAR genes and cryptically spliced genes within putative regions of disease onset differed across FTLD-TDP subtypes.
PubMed: 38940350
DOI: 10.1093/brain/awae205 -
Brain : a Journal of Neurology Jun 2024Increasing evidence shows that neuroinflammation is a possible modulator of tau spread effects on cognitive impairment in Alzheimer's disease. In this context, plasma...
Increasing evidence shows that neuroinflammation is a possible modulator of tau spread effects on cognitive impairment in Alzheimer's disease. In this context, plasma levels of the glial fibrillary acidic protein (GFAP) have been suggested to have a robust association with Alzheimer's disease pathophysiology. This study aims to assess the correlation between plasma GFAP and Alzheimer's disease pathology, and their synergistic effect on cognitive performance and decline. A cohort of 122 memory clinic subjects with amyloid and tau positron emission tomography, MRI scans, plasma GFAP, and Mini-Mental State Examination (MMSE) was included in the study. A subsample of 94 subjects had a follow-up MMSE score at least one year after baseline. Regional and voxel-based correlations between Alzheimer's disease biomarkers and plasma GFAP were assessed. Mediation analyses were performed to evaluate the effects of plasma GFAP on the association between amyloid and tau PET, and tau PET and cognitive impairment and decline. GFAP was associated with increased tau PET ligand uptake in the lateral temporal and inferior temporal lobes in a strong left-sided pattern independently of age, gender, education, amyloid, and APOE status (β=0.001, p < 0.01). The annual rate of MMSE change was significantly and independently correlated with both GFAP (β=0.006, p < 0.01) and global tau SUVR (β=4.33, p < 0.01), but not with amyloid burden. Partial mediation effects of GFAP were found on the association between amyloid and tau pathology (13.7%), and between tau pathology and cognitive decline (17.4%), but not on global cognition at baseline. Neuroinflammation measured by circulating GFAP is independently associated with tau Alzheimer's disease pathology and with cognitive decline, suggesting neuroinflammation as a potential target for future disease-modifying trials targeting tau pathology. Peretti et al. show that a circulatory marker of neuroinflammation-glial fibrillary acidic protein-is associated with tau pathology in lateral temporal and frontal regions in patients with Alzheimer's disease, independent of amyloid load. Neuroinflammation appears to modulate the association between amyloid and tau biomarkers.
PubMed: 38940331
DOI: 10.1093/brain/awae211 -
Health Care Science Feb 2024Alzheimer's disease (AD) is a progressive brain disorder that impairs cognitive functions, behavior, and memory. Early detection is crucial as it can slow down the...
INTRODUCTION
Alzheimer's disease (AD) is a progressive brain disorder that impairs cognitive functions, behavior, and memory. Early detection is crucial as it can slow down the progression of AD. However, early diagnosis and monitoring of AD's advancement pose significant challenges due to the necessity for complex cognitive assessments and medical tests.
METHODS
This study introduces a data acquisition technique and a preprocessing pipeline, combined with multivariate long short-term memory (M-LSTM) and AdaBoost models. These models utilize biomarkers from cognitive assessments and neuroimaging scans to detect the progression of AD in patients, using The AD Prediction of Longitudinal Evolution challenge cohort from the Alzheimer's Disease Neuroimaging Initiative database.
RESULTS
The methodology proposed in this study significantly improved performance metrics. The testing accuracy reached 80% with the AdaBoost model, while the M-LSTM model achieved an accuracy of 82%. This represents a 20% increase in accuracy compared to a recent similar study.
DISCUSSION
The findings indicate that the multivariate model, specifically the M-LSTM, is more effective in identifying the progression of AD compared to the AdaBoost model and methodologies used in recent research.
PubMed: 38939169
DOI: 10.1002/hcs2.84 -
Frontiers in Human Neuroscience 2024Although memory challenges in autistic individuals have been characterized recently, the functional connectivity of the hippocampus and ventral temporal lobe, two...
INTRODUCTION
Although memory challenges in autistic individuals have been characterized recently, the functional connectivity of the hippocampus and ventral temporal lobe, two structures important for episodic and semantic memory functions, are poorly understood in autistic individuals. Moreover, age-related differences in the functional connectivity associated with these two memory networks are unrevealed.
METHODS
The current study investigated age-related differences in intrinsic connectivity of the hippocampal and ventral temporal lobe (vTL) memory networks in well-matched ASD ( = 73; age range: 10.23-55.40 years old) and Non-ASD groups ( = 74; age range: 10.46-56.20 years old) from the open dataset ABIDE-I. Both theory-driven ROI-to-ROI approach and exploratory seed-based whole-brain approach were used.
RESULTS AND DISCUSSION
Our findings revealed reduced connectivity in ASD compared to Non-ASD peers, as well as an age-related reduction in the connectivity of hippocampal and vTL networks with triple networks, namely, the default mode network (DMN), the central executive network (CEN), and the salience network (SN), potentially underpinning their challenges in memory, language, and social functions. However, we did not observe reliable differences in age-related effects between the ASD and Non-ASD groups. Our study underscores the importance of understanding memory network dysfunctions in ASD across the lifespan to inform educational and clinical practices.
PubMed: 38938289
DOI: 10.3389/fnhum.2024.1394706 -
Trials Jun 2024Cocaine craving is a central symptom of cocaine use disorders (CUD). Virtual reality cue-exposure therapy for craving (VRCET) allows more immersive, realistic, and...
Virtual reality cue-exposure therapy in reducing cocaine craving: the Promoting Innovative COgnitive behavioral therapy for Cocaine use disorder (PICOC) study protocol for a randomized controlled trial.
BACKGROUND
Cocaine craving is a central symptom of cocaine use disorders (CUD). Virtual reality cue-exposure therapy for craving (VRCET) allows more immersive, realistic, and controllable exposure than traditional non-VR cue-exposure therapy (CET), whose efficacy is limited in treating substance use disorders. The purpose of this study is to evaluate the efficacy and acceptability of VRCET, as a stand-alone and add-on intervention (i.e., combined with cognitive therapy), compared to a picture-based CET (PCET), in reducing self-reported cocaine craving in inpatients hospitalized for CUD.
METHODS
Fifty-four inpatients hospitalized for CUD will be randomized in one of two intensive 3-week treatment arms: 10 meetings/2-week treatment of VRCET plus 5 meetings/1-week treatment of memory-focused cognitive therapy (MFCT; experimental arm), or 15 meetings/3-week treatment of PCET (active control arm). The Craving Experience Questionnaire (CEQ - F & S) will be used to assess the primary outcome, i.e., the post-treatment decrease of self-reported cocaine craving frequency (within the past 2 weeks) and intensity scores (in VR exposure to cocaine cues). Secondary endpoints include urinary, physiological, and self-reported cocaine use-related measures. Assessments are scheduled at pretreatment, after 2 weeks of treatment (i.e., VRCET vs. PCET), post-treatment (3 weeks, i.e., VRCET + MFCT vs. PCET), and at 1-month follow-up. Acceptability will be evaluated via (i) the Spatial Presence for Immersive Environments - Cybersickness along VRCET and (ii) the Client Satisfaction Questionnaires after 2 weeks of treatment and post-treatment.
DISCUSSION
This study will be the first to evaluate the acceptability and efficacy of VRCET for CUD, as a psychotherapeutic add-on, to reduce both cocaine craving frequency and intensity. Additionally, this study will provide evidence about the specific interest of VRCET, compared to a non-VR-based CET, as a cue reactivity and exposure paradigm for treating substance use disorders.
TRIAL REGISTRATION
NCT05833529 [clinicaltrials.gov]. Prospectively registered on April 17, 2023.
Topics: Humans; Cocaine-Related Disorders; Craving; Cues; Cognitive Behavioral Therapy; Virtual Reality Exposure Therapy; Treatment Outcome; Randomized Controlled Trials as Topic; Time Factors; Adult; Male; Female
PubMed: 38937824
DOI: 10.1186/s13063-024-08275-7 -
Brain Research Jun 2024Drug addiction may result in sleep problems. Importantly, sleep deprivation (SD) is known as an important risk factor for relapse to drug abuse as SD mimics the effects...
Drug addiction may result in sleep problems. Importantly, sleep deprivation (SD) is known as an important risk factor for relapse to drug abuse as SD mimics the effects of psychostimulants on dopamine system of the brain. Moreover, aging may affect sleep and drug addiction. This study, therefore, set out to assess the effects of methamphetamine (METH) and REM sleep deprivation (RSD) on locomotor activity, anxiety-like behavior and spatial memory in adult and adolescent rats. Adult and adolescent male Wistar rats received a neurotoxic METH regimen; four subcutaneous injections of 6 mg/kg, at 2 h intervals. Five days later, the animals underwent a 48-h RSD episode using the multiple platforms method. They were then examined using the open field (OF), elevated plus maze (EPM) and Y-maze tasks. We found that the METH and RSD paradigms showed synergistic effects to increase locomotion and risk-taking behavior in both adult and adolescent animals, while only adolescent rats revealed RSD-induced anxiety-like behavior. Moreover, adolescent animals revealed greater sensitization for vertical activity following METH plus RSD episode. In addition, METH and RSD paradigms revealed synergistic effects to impair spatial working memory, but neither METH nor RSD alone affected performance of animals in the Y-maze task. Our findings may indicate that there are important relationships between METH and RSD to induce hyperlocomotion, risk-taking behavior and spatial memory impairment, particularly in adolescent animals. Moreover, it seems that adolescent rats may be more susceptible to anxiety-like behavior and hyperlocomotion than adults.
PubMed: 38936532
DOI: 10.1016/j.brainres.2024.149096 -
European Journal of Pharmacology Jun 2024The use of NPS compounds is increasing, and impairment in spatial learning and memory is a growing concern. Alpha-pyrrolidinovalerophenone (α-PVP) consumption, as a...
The use of NPS compounds is increasing, and impairment in spatial learning and memory is a growing concern. Alpha-pyrrolidinovalerophenone (α-PVP) consumption, as a commonly used NPS, can impair spatial learning and memory through brain mitochondrial dysfunction mechanisem. Liraglutide, one of the most well-known Glucagon-like peptide 1 (GLP-1) agonist used as an anti-diabetic and anti-obesity drug. According to current research, Liraglutide likely ameliorate cognitive impairment in neurodegenerative conditions and also substance use disorders. Hence, the purpose of this study is examining the effect of Liraglutide on α-PVP induced spatial learning and memory problems due to brain mitochondrial dysfunction. Wistar rats (8 in each group) received α-PVP (20 mg/kg/d for 10 consecutive days, intraperitoneally (I.P.)). Then, Liraglutide was administered at 47 and 94 μg/kg/d, I.P., for 4 weeks following the α-PVP administration. The Morris Water Maze (MWM) task evaluated spatial learning and memory 24 hours after Liraglutide treatment. Bedside, brain mitochondrial activity parameters including reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), cytochrome c release, mitochondrial outer membrane damage and swelling, and brain ADP/ATP ratio were studied. Our results showed Liraglutide ameliorated α-PVP induced spatial learning and memory impairments through alleviating brain mitochondrial dysfunctions (which is indicated by increasing ROS formation, collapsed MMP, mitochondrial outer membrane damage, cytochrome c release, mitochondrial swelling, and brain ADP/ATP ratio) in rats. This study could be used as a starting point for future studies about the possible role of Liraglutide in mitochondrial dysfunction related to cognitive impairments due to substance use disorder.
PubMed: 38936451
DOI: 10.1016/j.ejphar.2024.176776 -
Behavioural Brain Research Jun 2024Object-location memory (OLM) is a type of declarative memory for spatial information and consists of the individual's ability to establish accurate associations between...
Object-location memory (OLM) is a type of declarative memory for spatial information and consists of the individual's ability to establish accurate associations between objects and their spatial locations. Long-COVID describes the long-term effects of the COVID-19 disease. Long-COVID patients show medial temporal lobe dysfunction and neuropsychological alterations affecting memory. This study aimed to assess OLM in a group of Long-COVID patients, n=66, and a Control group of healthy individuals with similar age and sex composition, n=21, using an immersive virtual reality (iVR)-based OLM task. We also explored associations between the performance in the iVR-based OLM task and general cognitive function (MoCA), and both verbal (VSTM) and visuospatial (SSTM) span. The Long-COVID group showed fewer correct responses, made more task attempts, and invested more time in the iVR-based OLM task than the Control group. Delayed memory was more severely altered than immediate memory in Long-COVID participants. Better MoCA scores of the Long-COVID group were strongly associated with shorter times to complete the immediate recall of the iVR-based OLM task. Besides, the months elapsed since the COVID-19 infection were slightly associated with fewer correct responses in the immediate and 24-hour recalls. These results corroborate previous findings of memory alterations in the Long-COVID syndrome using an iVR-based OLM task, adding new evidence on spatial memory and long-term memory in this population. Implementing spatial iVR tasks to clinical research may improve our understanding of neuropsychological disorders.
PubMed: 38936427
DOI: 10.1016/j.bbr.2024.115127 -
Diabetes Care Jun 2024The impact of age of diabetes diagnosis on dementia risk across the life course is poorly characterized. We estimated the lifetime risk of dementia by age of diabetes...
OBJECTIVE
The impact of age of diabetes diagnosis on dementia risk across the life course is poorly characterized. We estimated the lifetime risk of dementia by age of diabetes diagnosis.
RESEARCH DESIGN AND METHODS
We included 13,087 participants from the Atherosclerosis Risk in Communities Study who were free from dementia at age 60 years. We categorized participants as having middle age-onset diabetes (diagnosis <60 years), older-onset diabetes (diagnosis 60-69 years), or no diabetes. Incident dementia was ascertained via adjudication and active surveillance. We used the cumulative incidence function estimator to characterize the lifetime risk of dementia by age of diabetes diagnosis while accounting for the competing risk of mortality. We used restricted mean survival time to calculate years lived without and with dementia.
RESULTS
Among 13,087 participants, there were 2,982 individuals with dementia and 4,662 deaths without dementia during a median follow-up of 24.1 (percentile 25-percentile 75, 17.4-28.3) years. Individuals with middle age-onset diabetes had a significantly higher lifetime risk of dementia than those with older-onset diabetes (36.0% vs. 31.0%). Compared with those with no diabetes, participants with middle age-onset diabetes also had a higher cumulative incidence of dementia by age 80 years (16.1% vs. 9.4%), but a lower lifetime risk (36.0% vs. 45.6%) due to shorter survival. Individuals with middle age-onset diabetes developed dementia 4 and 1 years earlier than those without diabetes and those with older-onset diabetes, respectively.
CONCLUSIONS
Preventing or delaying diabetes may be an important approach for reducing dementia risk throughout the life course.
PubMed: 38935599
DOI: 10.2337/dc24-0203 -
Probiotics and Antimicrobial Proteins Jun 2024As the population ages, cognitive decline becomes more common. Strategies targeting the gut-brain axis using probiotics are emerging to achieve improvements in...
Cognitive and Emotional Effect of a Multi-species Probiotic Containing Lactobacillus rhamnosus and Bifidobacterium lactis in Healthy Older Adults: A Double-Blind Randomized Placebo-Controlled Crossover Trial.
As the population ages, cognitive decline becomes more common. Strategies targeting the gut-brain axis using probiotics are emerging to achieve improvements in neuropsychiatric and neurological disorders. However, the beneficial role of probiotics on brain function in healthy older adults remains unclear. Our aim was to evaluate a multi-species probiotic formulation as a therapeutic approach to reduce emotional and cognitive decline associated with aging in healthy adults. A randomized double-blind placebo-controlled crossover trial was conducted. The study involved a 10-week intervention where participants consumed the assigned probiotic product daily, followed by a 4-week washout period before the second condition started. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) and the Psychological Experiments Construction Language Test Battery. At the emotional level, the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI) were used. Thirty-three participants, recruited between July 2020 and April 2022, ingested a multispecies probiotic (Lactobacillus rhamnosus and Bifidobacterium lactis). After the intervention, noticeable enhancements were observed in cognitive function (mean difference 1.90, 95% CI 1.09 to 2.70, p < 0.005), memory (mean difference 4.60, 95% CI 2.91 to 6.29, p < 0.005) by MMSE and digit task, and depressive symptoms (mean difference 4.09, 95% CI 1.70 to 6.48, p < 0.005) by BDI. Furthermore, there were significant improvements observed in planning and problem-solving skills, selective attention, cognitive flexibility, impulsivity, and inhibitory ability. Probiotics administration improved cognitive and emotional function in older adults. Limited research supports this, requiring more scientific evidence for probiotics as an effective therapy for cognitive decline. This study has been prospectively registered at ClinicalTrials.gov (NCT04828421; 2020/July/17).
PubMed: 38935259
DOI: 10.1007/s12602-024-10315-2