Distinct patterns of hippocampal subfield volumes predict coping strategies, emotion regulation, and impulsivity in healthy adults.

BACKGROUND: Recent studies have suggested that the hippocampus (HC) is involved in cognitive and behavioral functions beyond memory. We aimed to investigate how the volume of each subfield of the HC is associated with distinct patterns of coping strategies, emotion regulation, and impulsivity in a healthy population. METHODS: We studied a total of 218 healthy subjects using the Leipzig mind-brain-body dataset. Participants were assessed for coping strategies, emotion regulation, and impulsivity using the Cognitive Emotion Regulation Questionnaire (CERQ), Coping Orientations to Problems Experienced (COPE), Impulsive Behavior Scale (UPPS), and Behavioral Activation and Inhibition System (BAS/BIS). The associations between HC subfield volumes including CA1, CA2/3, CA4/DG, SR-SL-SM, and subiculum, and behavioral scores were examined using multiple linear regression models adjusted for possible confounders, including age, sex, years of education, handedness, total intracranial volume (ICV), and HC volume. RESULTS: The use of emotional support, venting, and positive reframing coping strategies were significantly and positively correlated with total, total right, and total left HC volumes. Venting was significantly associated with CA1 after adjusting for age, sex, handedness, and education (P=0.001, B = 0.265, P-FDR = 0.005). No significant association was observed between CERQ subscales and HC subfield volumes after controlling for confounders and multiple analyses. However, sensation-seeking subscale of the UPPS-P was positively correlated with total and right CA2-CA3 volumes after adjustments for age, sex, handedness, ICV, and HC volumes (P=0.002, B = 0.266, P-FDR = 0.035). BAS and BIS subscales did not show significant relationship with HC subfield volumes. CONCLUSION: Patterns of HC subfields volumes are associated with coping strategies, impulsivity, and emotion regulation. In particular, using emotional support, positive reframing, venting, and sensation seeking are significantly associated with certain HC subfield volumes. These findings suggest that the hippocampus may play a crucial role in modulating emotional responses and behavioral adaptations, offering potential targets for therapeutic interventions.

Polygenic hazard score predicts synaptic and axonal degeneration and cognitive decline in Alzheimer's disease continuum.

BACKGROUND: Growth associated protein-43 (GAP-43) and neurofilaments light (NFL) are biomarkers of synaptic and axonal injury, and are associated with cognitive decline in Alzheimer's disease (AD) contiuum. We investigated whether Polygenic Hazard Score (PHS) is associated with specific biomarkers and cognitive measures, and if it can predict the relationship between GAP-43, NFL, and cognitive decline in AD. METHOD: We enrolled 646 subjects: 93 with AD, 350 with mild cognitive impairment (MCI), and 203 cognitively normal controls. Variables included GAP-43, plasma NFL, and PHS. A PHS of 0.21 or higher was considered high risk while a PHS below this threshold was considered low risk. A subsample of 190 patients with MCI with four years of follow-up cognitive assessments were selected for longitudinal analysis . We assessed the association of the PHS with AD biomarkers and cognitive measures, as well as the predictive power of PHS on cognitive decline and the conversion of MCI to AD. RESULTS: PHS showed high diagnostic accuracy in distinguishing AD, MCI, and controls. At each follow-up point, high risk MCI patients showed higher level of cognitive impairment compared to the low risk group. GAP-43 correlated with all follow-up cognitive tests in high risk MCI patients which was not detected in low risk MCI patients. Moreover, high risk MCI patients progressed to dementia more rapidly compared to low risk patients. CONCLUSION: PHS can predict cognitive decline and impacts the relationship between neurodegenerative biomarkers and cognitive impairment in AD contiuum. Categorizing patients based on PHS can improve the prediction of cognitive outcomes and disease progression.

Altered brain connectivity in mild cognitive impairment is linked to elevated tau and phosphorylated tau, but not to GAP-43 and Amyloid-ß measurements: a resting-state fMRI study.

Mild Cognitive Impairment (MCI) is a neurological condition characterized by a noticeable decline in cognitive abilities that falls between normal aging and dementia. Along with some biomarkers like GAP-43, Aß, tau, and P-tau, brain activity and connectivity are ascribed to MCI; however, the link between brain connectivity changes and such biomarkers in MCI is still being investigated. This study explores the relationship between biomarkers like GAP-43, Aß, tau, and P-tau, and brain connectivity. We enrolled 25 Participants with normal cognitive function and 23 patients with MCI. Levels of GAP-43, Aß1-42, t-tau, and p-tau181p in the CSF were measured, and functional connectivity measures including ROI-to-voxel (RV) correlations and the DMN RV-ratio were extracted from the resting-state fMRI data. P-values below 0.05 were considered significant. The results showed that in CN individuals, higher connectivity within the both anterior default mode network (aDMN) and posterior DMN (pDMN) was associated with higher levels of the biomarker GAP-43. In contrast, MCI individuals showed significant negative correlations between DMN connectivity and levels of tau and P-tau. Notably, no significant correlations were found between Aß levels and connectivity measures in either group. These findings suggest that elevated levels of GAP-43 indicate increased functional connectivity in aDMN and pDMN. Conversely, elevated levels of tau and p-tau can disrupt connectivity through various mechanisms. Thus, the accumulation of tau and p-tau can lead to impaired neuronal connectivity, contributing to cognitive decline.

Depression is associated with the nonmotor symptoms of Parkinson's disease: A comparative analysis.

Background and aims: The nonmotor symptoms (NMS) of Parkinson's disease (PD) and their potential role in early diagnosis are recent debates. Herein, we aimed to investigate the association between depression and NMS of PD including sleep disorders, hyposexuality, hyposmia, constipation, and orthostatic hypotension. Methods: A total of 93 PD patients with depression and 67 PD patients without depression were included in the study, and NMS were compared between the two groups. Furthermore, the possible associations between depression severity measured by Beck Depression Inventory (BDI) and NMS were investigated using linear regression or binary logistic regression models controlled for possible confounders. Eventually, we performed a subgroup analysis in each mild, moderate, and severe depression group. Results: Orthostatic hypotension, constipation, and hyposexuality showed a significant difference between PD patients with and without depression (p < 0.001, p = 0.029, and p < 0.001, respectively). The BDI score was significantly associated with hyposexuality, Montreal cognitive assessment (MoCA), and Pittsburgh Sleep Quality (p = 0.016, p = 0.010, and p = 0.011, respectively); however, after adjustments for possible confounders, the associations of the BDI score with the MoCA score and hyposexuality remained significant (p = 0.015 and p = 0.019, respectively). Considering subgroup analysis, a similar pattern of significant results was observed particularly in the severe group. Conclusions: This study suggests a possible association between depression in PD patients and some NMS observed in the course of PD. These findings could be beneficial for early diagnosis of the disease, which eventually could make a considerable difference in the management of PD patients. Additional interventional longitudinal studies are warranted to explore how controlling depression could impact the NMS of patients with PD.

The Therapeutic Role of Intermittent Theta Burst Stimulation in Schizophrenia: A Systematic Review and Meta-analysis.

ABSTRACT: Schizophrenia affects approximately 1% of the population worldwide. Multifactorial reasons, ranging from drug resistance to adverse effects of medications, have necessitated exploring further therapeutic options. Intermittent theta burst stimulation (iTBS) is a novel high-frequency form of transcranial magnetic stimulation, a safe procedure with minor adverse effects with faster and longer-lasting poststimulation effects with a potential role in treating symptoms; however, the exact target brain regions and symptoms are still controversial. Therefore, we aimed to systematically investigate the current literature regarding the therapeutic utilities of iTBS using Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Twelve studies were included among which 9 found iTBS effective to some degree. These studies targeted the dorsolateral prefrontal cortex and the midline cerebellum. We performed a random-effects meta-analysis on studies that compared the effects of iTBS on schizophrenia symptoms measured by the Positive and Negative Syndrome Scale (PANSS) to sham treatment. Our results showed no significant difference between iTBS and sham in PANSS positive and negative scores, but a trend-level difference in PANSS general scores ( k = 6, P = 0.07), and a significant difference in PANSS total scores ( k = 6, P = 0.03). Analysis of the studies targeting the dorsolateral prefrontal cortex showed improvement in PANSS negative scores ( k = 5, standardized mean difference = -0.83, P = 0.049), but not in PANSS positive scores. Moderators (intensity, pulse, quality, sessions) did not affect the results. However, considering the small number of studies included in this meta-analysis, future works are required to further explore the effects of these factors and also find optimum target regions for positive symptoms.

Psychosis of Epilepsy: A 10-Year Iranian Clinical Survey.

Objective: Psychoses of epilepsy usually have an acute onset, accompanied by brief symptom duration and a risk of recurrence. Managing these conditions can be challenging due to the potential for seizures associated with certain antipsychotic medications, as well as exacerbating psychosis resulting from some antiepileptic medications. Our objective in this study was to assess the occurrence of psychosis among patients with epilepsy, as well as identify the factors linked to the presence and severity of psychosis in this population. Method : In this study, we included a total of 514 subjects diagnosed with epilepsy referring to our neuropsychiatry clinic affiliated with Tehran University of Medical Sciences from April 2011 to December 2021, among whom 57 patients showed psychotic presentations. We compared baseline and clinical characteristics between patients with psychosis of epilepsy and non-psychosis patients who also had epilepsy. Results: Marital status was the sole demographic factor that displayed a statistically significant difference between the psychosis and non-psychosis groups (P = 0.019). There was no significant difference observed between the two groups regarding family history of epilepsy and age at the onset of the epilepsy. Patients with psychosis experienced significantly more frequent seizures and generalized type (P < 0.001). Participants were matched for demographics and other clinical factors between the refractory and controlled psychosis groups, except for the psychosis frequency (P = 0.007). The type of epilepsy was significantly associated with psychosis when adjusted for the covariates (P < 0.001). Conclusion: Patients with psychosis of epilepsy experienced more episodes of epilepsy than non-psychotics. We identified generalized epilepsy as an independent risk factor for the development of psychosis. Additional cohorts are warranted to explore the factors associated with epilepsy-related psychosis across diverse populations.

A Comprehensive Investigation of the Potential Role of Lipoproteins and Metabolite Profile as Biomarkers of Alzheimer's Disease Compared to the Known CSF Biomarkers.

Introduction: While cerebrospinal fluid (CSF) core biomarkers have been considered diagnostic biomarkers for a long time, special attention has been recently dedicated to lipoproteins and metabolites that could be potentially associated with Alzheimer's disease (AD) neurodegeneration. Herein, we aimed to investigate the relationship between the levels of CSF core biomarkers including Aß-42, TAU, and P-TAU and plasma lipoproteins and metabolites of patients with AD from the baseline cohort of the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Method: Using the ADNI database, fourteen subclasses of lipoproteins as well as a number of lipids and fatty acids and low-molecular metabolites including amino acids, ketone bodies, and glycolysis-related metabolites in blood samples were measured as potential noninvasive markers, and their association with the CSF core biomarkers was statistically investigated controlling for age and gender. Results: A total number of 251 AD subjects were included, among whom 71 subjects were negative for the Apo-E ε4 allele and 150 were positive. There was no significant difference between the two groups regarding cognitive assessments, CSF core biomarkers, and lipoproteins and metabolites except the level of Aß-42 (p < 0.001) and phenylalanine (p = 0.049), which were higher in the negative group. CSF TAU and P-TAU were significantly correlated with medium and small HDL in the negative group, and with extremely large VLDL in the positive group. Our results also indicated significant correlations of metabolites including unsaturated fatty acids, glycerol, and leucine with CSF core biomarkers. Conclusion: Based on our findings, a number of lipoproteins and metabolites were associated with CSF core biomarkers of AD. These correlations showed some differences in Apo-E ε4 positive and negative groups, which reminds the role of Apo-E gene status in the pathophysiology of AD development. However, further research is warranted to explore the exact association of lipoproteins and other metabolites with AD core biomarkers and pathology.

White matter tracts alterations underpinning reward and conflict processing.

BACKGROUND: Reinforcement sensitivity theory (RST) is proposed as a neurobiological system that eventually led to emotion and motivation-based constructs of personality. Traditionally segmented into the behavioral activation system (BAS) and the behavioral inhibition system (BIS), RST is commonly used to describe personality and behavior. Although there have been studies linking gray matter alterations with BIS/BAS subscales, the role of white matter (WM) alterations is yet controversial. We aimed to investigate the specific WM tracts associated with BIS/BAS scores. METHODS: 220 healthy participants (mean age = 39.14 ± 20.23, 80 (35.7 %) females) were evaluated using the BIS/BAS questionnaire from the LEMON database. Diffusion MRI connectometry (DMRI) was used to investigate the WM correlates of BIS/BAS subscales in each gender group. Multiple regression models with the covariates of age, handedness, and education were fitted to address the correlation of local connectomes with BIS/BAS components. RESULTS: DMRI connectometry revealed that the quantitative anisotropy (QA) value of the splenium of the corpus callosum, right cerebellum, middle cerebellar peduncle, and superior cerebellar peduncle, had a significant negative correlation with each BIS/BAS subscale. In contrast, the QA value in the body of the corpus callosum and bilateral cingulum showed a positive correlation with BIS/BAS subscales. CONCLUSION: The integrity of WM in certain tracts is associated with behavioral activation and inhibition. This finding expands our knowledge of the neural networks associated with risk-taking and reward-seeking behaviors.

CSF-Targeted Proteomics Indicate Amyloid-Beta Ratios in Patients with Alzheimer's Dementia Spectrum.

Background: According to recent studies, amyloid-ß (Aß) isoforms as cerebrospinal fluid (CSF) biomarkers have remarkable predictive value for cognitive decline in the early stages of Alzheimer's disease (AD). Herein, we aimed to investigate the correlations between several targeted proteomics in CSF samples with Aß ratios and cognitive scores in patients in AD spectrum to search for potential early diagnostic utility. Methods: A total of 719 participants were found eligible for inclusion. Patients were then categorized into cognitively normal (CN), mild cognitive impairment (MCI), and AD and underwent an assessment of Aß and proteomics. Clinical Dementia Rating (CDR), Alzheimer's Disease Assessment Scale (ADAS), and Mini Mental State Exam (MMSE) were used for further cognitive assessment. The Aß42, Aß42/Aß40, and Aß42/38 ratios were considered as means of comparison to identify those peptides corresponding significantly to these established biomarkers and cognitive scores. The diagnostic utility of the IASNTQSR, VAELEDEK, VVSSIEQK, GDSVVYGLR, EPVAGDAVPGPK, and QETLPSK was assessed. Results: All investigated peptides corresponded significantly to Aß42 in controls. In those with MCI, VAELEDEK and EPVAGDAVPGPK were significantly correlated with Aß42 (p value < 0.001). Additionally, IASNTQSR, VVSSIEQK, GDSVVYGLR, and QETLPSK were significantly correlated with Aß42/Aß40 and Aß42/38 (p value < 0.001) in this group. This group of peptides similarly corresponded to Aß ratios in those with AD. Eventually, IASNTQSR, VAELEDEK, and VVSSIEQK were significantly associated with CDR, ADAS-11, and ADAS-13, particularly in MCI group. Conclusion: Our research suggests potential early diagnostic and prognostic utilities for certain peptides extracted from CSF-targeted proteomics research. The ethical approval of ADNI is available at ClinicalTrials.gov with Identifier: NCT00106899.

The glucocerebrosidase mutations and uric acid levels in Parkinson's disease: A 3-years investigation of a potential biomarker".

Background: Blood uric acid level indicates an emerging biomarker in Parkinson's disease (PD). This study aimed to evaluate longitudinal uric acid levels among different kinds of glucocerebrosidase (GBA) mutations and to compare it among sporadic PD, genetic cohort Parkinson's disease (GENPD), genetic cohort unaffected (GENUN), and healthy control (HC) patients. Methods: We conducted a study on 654 individuals from the Parkinson's progression markers initiative (PPMI) database. Baseline characteristics, uric acid levels, movement disorder society unified Parkinson's disease rating scale III (MDS-UPDRS III), Hoehn and Yahr Parkinson stage (H&Y stage), and DaT scan specific binding ratio (SBR) data were obtained. Different GBA mutations were collected and categorized into three groups. Longitudinal measurements of uric acid and MDS-UPDRS III score were evaluated during 3-years of follow-up. Result: GENPD cohort exhibited a greater MDS-UPDRS III score, H&Y stage, and lower SBR in the right caudate, left caudate, and right putamen compared to sporadic PD. Baseline uric acid level was similar among all groups and different GBA variants. After adjustment for age, sex, and body mass index, the uric acid level was significantly lower in the GENPD group than in HC during year 2 (P-value: 0.009). No significant longitudinal differences were detected for the MDS-UPDRS III score and three groups of GBA mutations. Conclusion: This is the first study to assess uric acid levels and MDS-UPDRS III scores among different GBA mutation variants within 3 years of follow-up. We found similar clinical characteristics among different subtypes of GBA mutations.

Valproic acid-induced hyperammonemia in neuropsychiatric disorders: a 2-year clinical survey.

INTRODUCTION: Valproic acid (VPA)-induced hyperammonemia (HA) is a rare adverse effect reported even at therapeutic VPA levels. The present study aimed to investigate the characteristics of VPA-induced HA and its association with the total dose, duration, and level of VPA. This study also investigated whether the use of VPA in combination with other medications has any effect on elevating serum ammonia levels. METHODS: A total of 316 patients with a history of VPA prescribed for underlying neuropsychiatric disorders were found eligible for the study. Data including demographic information, medical history and diagnosis, VPA dosage, VPA treatment duration, VPA level, and ammonia serum level were extracted and reviewed from our hospital records. The history of other neuropsychiatric medications was also included. RESULTS: Among 316 patients receiving VPA, HA was observed in 54 (17%) patients, and 15 patients were symptomatic among them. There was no significant difference in demographics between symptomatic and asymptomatic HA groups except for the number of co-administrated medications (p = 0.044). Besides, VPA duration and dose did not show a significant difference between the two groups. Additionally, the VPA level was significantly higher in patients who used risperidone in addition to VPA (p = 0.019). Eventually, VPA level showed a significant association with ammonia level (p = 0.025) and symptomatic HA (p = 0.033) after adjusting for possible confounders. CONCLUSION: VPA level showed a significant association with ammonia level and symptomatic HA. Moreover, co-administrated medications such as risperidone might have an impact on the serum level of VPA. Further studies are recommended to confirm these findings.

Trait anger representation in microstructural white matter tracts: A diffusion MRI study.

BACKGROUND: Understanding the microstructure of the brain that underlies emotions is of pivotal importance for psychology and psychiatry. Herein, we investigated white matter (WM) tracts associated with anger using the diffusion magnetic resonance imaging (DMRI) connectometry approach while exploring potential sex differences. METHODS: 225 healthy participants from the LEMON database were evaluated using the State-Trait Anger Expression Inventory (STAXI). WM images were prepared and analyzed with DMRI. Multiple regression models were fitted to address the correlation of local connectomes with STAXI components with age and handedness as covariates. RESULTS: There were no statistically significant differences in state anger and trait anger between males and females (p = 0.55 and 0.30, respectively). DMRI connectometry revealed that quantitative anisotropy (QA) values in the bilateral corticospinal tract (CST), splenium of corpus callosum (SCC), middle cerebellar peduncle, left inferior cerebellar peduncle, left cingulum, and left fornix were negatively correlated with trait anger and trait anger temperament (TAT) in males. In contrast, the QA values in the bilateral CST and SCC showed a positive correlation with trait anger and TAT in females, which, however, did not reach statistical significance. LIMITATIONS: The cross-sectional design and self-reported measures of anger limit the generalizability of our results. CONCLUSIONS: This is the first DMRI connectometry study to investigate WM circuits involved in anger. We found that the pathways associated with the limbic system and movement-related regions were involved in trait anger and anger expression in men, while no brain pathways showed a significant relationship with anger in women.

Isolated schwannoma originating from the infraorbital nerve: A case report.

As a benign isolated and encapsulated tumor originating from the nerve sheaths, schwannomas rarely appear on the cranial nerves, among which infraorbital nerve schwannomas are highly uncommon. We report a case of isolated infraorbital nerve schwannoma in a 58-year-old male patient with a clinical manifestation of proptosis in the affected eye.

White matter tracts associated with alexithymia and emotion regulation: A diffusion MRI study.

BACKGROUND: Alexithymia is a cognitive-affective impairment, suggested to be associated with emotion regulation. Herein, we investigated white matter (WM) tracts with Diffusion Magnetic Resonance Imaging (DMRI) connectometry approach using quantitative anisotropy (QA) tractography to discover possible associations between the emotion identification and regulation patterns and WM tracts. METHODS: DMRI data were acquired from 218 healthy subjects aging 39.15 ± 20.19 who filled the Toronto Alexithymia Scale (TAS) and emotion regulation questionnaire (ERQ) from the LEMON dataset. Connectometry analysis was applied on WM tracts in DMRI images. RESULTS: DMRI connectometry analysis revealed a significant correlation between TAS identification score and increased microstructural connectivity in WM pathways, including the body of corpus callosum (CC), bilateral fornix, and left arcuate fasciculus (AF) in males (FDR = 0.028), and corticospinal and cingulum tracts in females (FDR = 0.026). Furthermore, we found a significant positive correlation between overall TAS score and fornix properties in men (FDR = 0.026) and corticospinal tracts in women (FDR = 0.028). Middle cerebellar peduncle negatively correlated with describing emotion (FDR = 0.025) and the splenium of the CC and corticospinal tracts negatively correlated with this subscale (FDR = 0.049) in male group. However, the splenium of the CC, corticospinal tracts, and left AF positively associated with this subscale (FDR = 0.029). The splenium of the CC was negatively related to externally-oriented thinking among men (FDR = 0.038). Our results showed marginally associations between ERQ and similar WM tracts. CONCLUSION: Certain WM microstructures significantly correlate with emotion identification and regulation. These tracts are associated with specific somatosensory areas, language processing areas, and limbic area.

Memantine administration in patients with optic neuritis: a double blind randomized clinical trial.

INTRODUCTION: As an inflammatory phenomenon, optic neuritis (ON) that causes demyelination in the optic nerve damages the retinal cells, and leads to visual impairment. Herein, we aimed to investigate the potential therapeutic effects of memantine on ON. METHODS: In this double-blinded randomized clinical trial, participants with the first episode of acute ON meeting the inclusion criteria were enrolled and were randomly divided into memantine group (MG; N = 20) and placebo group (PG; N = 18). Patients of MG received memantine for 6 weeks. The thickness of the retinal nerve fiber layer (RNFL), visual evoked potential (VEP), and visual acuity (VA) was measured in both groups at baseline and 3-month follow-up. RESULTS: Thirty-eight patients with ON were enrolled. In the follow-up, mean RNFL thickness of both groups significantly decreased in all quadrants (P < 0.001). Also, RNFL thickness of all but temporal quadrants were significantly higher in the MG than placebo. The reduction in RNFL thickness difference was insignificant between two groups in all but the inferior quadrant which was significantly lower in MG (P = 0.024). In follow-up, mean-to-peak of P100 of the affected eye were significantly lowered (P < 0.001). The changes in VEP were insignificant. Originally, the mean VA was 0.15 ± 0.08 and 0.17 ± 0.09 in MG and PG, respectively, but was improved significantly to 0.92 ± 0.06 and 0.91 ± 0.06 in MG and PG, respectively, in follow-up. CONCLUSION: Memantine can reduce the RNFL thinning in three quadrants by blocking NMD receptors. However, visual acuity did not show a significant difference between the two groups.

The potential role of the cardiac MIBG scan in differentiating the drug-induced Parkinsonism from Parkinson's disease.

INTRODUCTION: Considering the difficulties of differentiating Parkinson's disease (PD) from drug-induced Parkinsonism (DIP) in patients receiving antipsychotics, developing robust diagnostic tools is essential. Herein, we used the metaiodobenzylguanidine (MIBG) scan to assess its diagnostic accuracy for this purpose. METHODS: 44 DIP patients and 32 patients with PD as controls were enrolled. All the participants underwent a cardiac 131I-MIBG scan. Statistical analysis was conducted to determine the significance of the results, and accuracy analyses were conducted to calculate the related sensitivity and specificity of the MIBG scan. RESULTS: The mean age of PD and DIP groups were 62.6 ± 5.9 and 51.5 ± 10.8 years, respectively. The mean duration of drug consumption in the DIP group was 52.2 ± 29.4 days (the mean interval between drug initiation and DIP onset was 28.5 ± 20.5). Symptoms relief occurred 40 ± 24.2 days after drug discontinuation. In the PD group, 15.6% showed negative and 84.4% positive results on the MIBG scan. In the DIP group, 86.4% were negative, and the remaining were positive. The difference in MIBG uptake between the two groups was statistically significant (P-value < 0.001). The sensitivity and specificity of the MIBG scan were 84.4% (CI: 84.0-84.8) and 86.36% (CI: 86.0-86.7) for the diagnosis of PD, respectively. CONCLUSION: Our results indicated more positive MIBG scans in the PD group than the DIP. Also, the MIBG scan's sensitivity and specificity in differentiating the PD are acceptable. Future works should assess these findings and the role of the MIBG scan in prognosis assessment of DIP and better allocation of the patients to related disciplines.

Alterations of the serum and CSF ferritin levels and the diagnosis and prognosis of amyotrophic lateral sclerosis.

BACKGROUND: The ALS diagnostic challenges necessitate more robust diagnostic and prognostic methods. A potential biomarker in this regard is the alterations of ferritin levels in the serum and CSF of patients compared to controls. METHODS: The CSF and serum ferritin levels were measured in 50 ALS cases and 50 control patients with predefined exclusion criteria. The ELISA method was utilized for laboratory measurement and was statistically analyzed using the SPSS. RESULTS: Heightened serum ferritin levels in cases were not statistically significant. However, CSF ferritin levels were significantly higher in ALS patients (P < 0.001). Serum ferritin levels were significantly negatively correlated with the disease duration (P = 0.015) and were significantly positively correlated with the disease progression rate (DPR) (P = 0.012). CONCLUSION: Heightened CSF ferritin levels can be used for the diagnosis of ALS. The correlation between the serum ferritin levels with the DPR and its correlation with the disease duration suggests potential prognostic utilities.

A Systematic Review of the Association between Amyloid-ß and τ Pathology with Functional Connectivity Alterations in the Alzheimer Dementia Spectrum Utilizing PET Scan and rsfMRI.

The association between functional connectivity (FC) alterations with amyloid-ß (Aß) and τ protein depositions in Alzheimer dementia is a subject of debate in the current literature. Although many studies have suggested a declining FC accompanying increased Aß and τ concentrations, some investigations have contradicted this hypothesis. Therefore, this systematic review was conducted to sum up the current literature in this regard. The PROSPERO guideline for systematic reviews was applied for development of a research protocol, and this study was initiated after getting the protocol approval. Studies were screened, and those investigating FC measured by resting-state functional MRI and Aß and τ protein depositions using amyloid and τ positron emission tomography were included. We categorized the included studies into 3 groups methodologically, addressing the question using global connectivity analysis (examining all regions of interest across the brain based on a functional atlas), seed-based connectivity analysis, or within-networks connectivity analysis. The quality of the studies was assessed using the Newcastle-Ottawa Scale. Among 31 included studies, 14 found both positive and negative correlations depending on the brain region and stage of the investigated disease, while 7 showed an overall negative correlation, 8 indicated an overall positive correlation, and 2 found a nonsignificant association between protein deposition and FC. The investigated regions were illustrated using tables. The posterior default mode network, one of the first regions of amyloid accumulation, and the temporal lobe, the early τ deposition region, are the 2 most investigated regions where inconsistencies exist. In conclusion, our study indicates that transneuronal spreading of τ and the amyloid hypothesis can justify higher FC related to higher protein depositions when global connectivity analysis is applied. However, the discrepancies observed when investigating the brain locally could be due to the varying manifestations of the amyloid and τ overload compensatory mechanisms in the brain at different stages of the disease with hyper- and hypoconnectivity cycles that can occur repeatedly. Nevertheless, further studies investigating both amyloid and τ deposition simultaneously while considering the stage of Alzheimer dementia are required to assess the accuracy of this hypothesis.

Pathogenesis and promising therapeutics of Alzheimer disease through eIF2α pathway and correspondent kinases.

Eukaryotic initiation factor 2 (eIF2α) pathway is overactivated in Alzheimer disease and is probably associated with synaptic and memory deficiencies. EIF2α protein is principally in charge of the regulation of protein synthesis in eukaryotic cells. Four kinases responsible for eIF2α phosphorylation at ser-51 are: General control non-derepressible-2 kinase (GCN2), double-stranded RNA-activated protein kinase (PKR), PKR-like endoplasmic reticulum kinase (PERK), and heme-regulated inhibitor kinase (HRI) are the four kinases. They lead to reduced levels of general translation and paradoxical increase of stress-responsive mRNAs expression including the B-secretase (BACE1) and the transcriptional modulator activating transcription factor 4 (ATF4), which in turn accelerates the beta-amyloidogenesis, tau phosphorylation, proapoptotic pathway induction and autophagy elements formation leading to the main pathological hallmarks of AD. Findings suggest that genetic or pharmacological inhibition of correspondent kinases can restore memory and prevent neurodegeneration. This implies that inhibition of eIF2α phosphorylation through respondent kinases is indeed a feasible prospect of clinical application. This review discusses recent therapeutic approaches targeting eIF2α pathway and provides an overview of the links between correspondent kinases overactivation with neurodegeneration in AD.

Cytokines in narcolepsy: A systematic review and meta-analysis.

BACKGROUND: Narcolepsy is a sleep disorder characterized by a loss of hypocretin neurons in the hypothalamus. Inflammation is proposed as a mechanism for neurodegeneration in narcolepsy. Numerous studies have investigated peripheral cytokine measures in narcoleptic patients, though the results are not conclusive. The current systematic review and meta-analysis aims to address the question of how do serum/plasma cytokine levels change in narcolepsy. METHODS: A systematic search of the literature to July 2019, was conducted to identify studies that measured cytokine levels in patients with narcolepsy, compared with those in controls without narcolepsy. RESULTS: Twelve studies were included in the meta-analysis: ten for interleukin (IL)-6, five for IL-8, three for IL-10, and ten for tumor necrosis factor alpha (TNF-α). Compared with controls, patients with narcolepsy had higher plasma levels of IL-6 (95% CI [0.22, 3.74]; P = 0.03) and TNF-α (95% CI [0.53, 4.18]; P = 0.01), while did not significantly differ in plasma IL-8 (95% CI [-1.64, 2.08]; P = 0.82) and IL-10 (95% CI [-1.29, 0.72]; P = 0.57) as well as serum IL-6 (95% CI [-1.48, 0.32], P = 0.21) and TNF-α (95% CI [-3.14, 0.19], P = 0.08) and CSF IL-8 (95% CI [-1.16, 0.41]; P = 0.35) levels. Patients with narcolepsy exhibited lower CSF IL-6 (95% CI [-0.66, 0.06]; P = 0.02) levels comparing with controls. CONCLUSIONS: Patients with narcolepsy had elevated plasma levels of IL-6 and TNF-α and lower levels of CSF IL-6 than non-narcoleptic controls. Our results support the role of inflammation in the pathophysiology of narcolepsy. However, plasma levels of IL-8 and IL-10, serum levels of IL-6 and TNF-α and CSF IL-8 did not significantly differ between patients and controls.