Major Disorder Research Articles

Identifying predictive factors for mood recurrence in early-onset major mood disorders: A 4-year, multicenter, prospective cohort study

We investigate the predictive factors of the mood recurrence in patients with early-onset major mood disorders from a prospective observational cohort study from July 2015 to December 2019. A total of 495 patients were classified into three groups according to recurrence during the cohort observation period: recurrence group with (hypo)manic or mixed features (MMR), recurrence group with only depressive features (ODR), and no recurrence group (NR). As a result, the baseline diagnosis of bipolar disorder type 1 (BDI) and bipolar disorder type 2 (BDII), along with a familial history of BD, are strong predictors of the MMR. The discrepancies in wake-up times between weekdays and weekends, along with disrupted circadian rhythms, are identified as a notable predictor of ODR. Our findings confirm that we need to be aware of different predictors for each form of mood recurrences in patients with early-onset mood disorders. In clinical practice, we expect that information obtained from the initial assessment of patients with mood disorders, such as mood disorder type, family history of BD, regularity of wake-up time, and disruption of circadian rhythms, can help predict the risk of recurrence for each patient, allowing for early detection and timely intervention.

Catatonia in patients with dementia: A descriptive study of clinical profiles and treatment response

BackgroundCatatonia is a highly prevalent syndrome in patients presenting with major neurocognitive disorders (dementia). In this study, we aim to provide a comprehensive description of the clinical and therapeutic aspects of catatonia in patients with dementia. MethodThis descriptive study, conducted between September 2015 and June 2022, collected data from 25 patients diagnosed with dementia, out of 143 patients treated for catatonia in our specialized psychiatry department. We collected sociodemographic, clinical and treatment data for each patient. ResultsDementia patients constituted 17% of the catatonic cases. Predominantly female, the cohort had a mean age of 65. Diagnoses included Alzheimer’s (4 patients, 17%) and Parkinson’s (1 patient, 4%) diseases, Lewy body dementia (5 patients, 21%), vascular dementia (4 patients, 17%) and frontotemporal lobar degeneration (10 patients, 41%). The mean Bush-Francis Catatonia Rating Scale score upon admission was 20/69. Overall, complete remission of catatonia was achieved in 75% of patients (n=18), with only 13% (n=3) responding to lorazepam alone, while others required additional interventions such as electroconvulsive therapy (ECT) and/or amantadine. Vascular dementia was predominantly observed in cases resistant to treatment. ConclusionThe findings indicate a frequent co-occurrence of catatonia and dementia, highlighting treatability yet suggesting a potential for resistance to lorazepam, which varies by dementia diagnosis. Investigating the mechanisms underlying this resistance and the variability in treatment response is crucial for developing more precise therapeutic strategies.

Adipocines and longevity: connections and paradoxes

Adipose tissue is an active endocrine organ that regulates energy homeostasis throughout the body by releasing hundreds of biologically active substances called adipokines. Dysregulation of adipokines is a key feature of insulin resistance with the development of metabolic syndrome and type 2 diabetes mellitus, which is an age-dependent pathology. In turn, dysregulation of adipokines and insulin resistance are associated with the development of metabolic deficiency and senile asthenia syndrome in older age groups. Previous studies have shown that the absence of insulin resistance and low prevalence of diabetes among centenarians are metabolic prerequisites for increased lifespan, suggesting a possible role for adipokine homeostasis in healthy longevity. Among numerous adipokines, adiponectin is considered a protective factor, showing a negative correlation with major metabolic disorders associated with age and obesity, and a positive association with life expectancy and insulin sensitivity among centenarians. Despite all the apparent protective effects of adiponectin, large-scale epidemiological studies have revealed the opposite aspect of adiponectin as a predictor of all-cause mortality and cardiovascular disease in patients with heart failure as well as kidney disease. In this review, the clinical significance of adiponectin is considered in centenarians from the point of view of the development of the main geriatric syndrome - senile asthenia, as well as cardiovascular risk and mortality.

Uncovering Cell Cycle Dysregulations and Associated Mechanisms in Cancer and Neurodegenerative Disorders: A Glimpse of Hope for Repurposed Drugs.

The cell cycle is the sequence of events orchestrated by a complex network of cell cycle proteins. Unlike normal cells, mature neurons subsist in a quiescent state of the cell cycle, and aberrant cell cycle activation triggers neuronal death accompanied by neurodegeneration. The periodicity of cell cycle events is choreographed by various mechanisms, including DNA damage repair, oxidative stress, neurotrophin activity, and ubiquitin-mediated degradation. Given the relevance of cell cycle processes in cancer and neurodegeneration, this review delineates the overlapping cell cycle events, signaling pathways, and mechanisms associated with cell cycle aberrations in cancer and the major neurodegenerative disorders. We suggest that dysregulation of some common fundamental signaling processes triggers anomalous cell cycle activation in cancer cells and neurons. We discussed the possible use of cell cycle inhibitors for neurodegenerative disorders and described the associated challenges. We propose that a greater understanding of the common mechanisms driving cell cycle aberrations in cancer and neurodegenerative disorders will open a new avenue for the development of repurposed drugs.

Assessment of Behavioral and Psychological Symptoms in Dementia, Associated Risk Factors and Clinical Correlates

Background: The presence of behavioral and psychological symptoms in dementia (BPSD) are associated with hospitalization, rapid cognitive decline, poor quality of life and higher caregiver burden. Thus, we aim to characterize the BPSD symptoms, its relationship to dementia-related risk factors and their predictive value, if any.Methodology: In 48 adults (mean age: 70.27 ± 10.08) with major neurocognitive disorder (MNCD) as per diagnostic and statistical manual of mental disorders, 5th edition and with Hindi mental status examination scores less than or equal to 23 were recruited. Patients were assessed for cognition by hindi Montreal cognitive assessment (HMOCA) and the clinical dementia rating scale (CDR). BPSD and caregiver burden were assessed using the neuropsychiatric inventory (NPI) and burden assessment schedule (BAS). The correlation of NPI scores with socio-demographic variables and clinical variables was assessed. A forward stepwise linear regression (using p-value < .05) was used to identify possible predictors of the NPI scores.Results: The majority of participants were predominantly males, 25 (52.1%), from urban regions, belonged to middle-class socio-economic status and had severe grading (HMOCA (< 10) of MNCD (25 (52.2%) but had moderate caregiver burden (25 (52.2%)). The most common MNCD type was due to Alzheimer’s disease (22 (45.8%)). Cortical atrophy and ischemic infarcts were the most common neuroimaging abnormalities reported (7 (14.9%)). Mean HMOCA, clinical dementia rating scale (CDR), NPI and BAS scores were 9.13 ± 6.96, 1.50 ± 1.05, 41.79 ± 27.06 and 68.65 ± 22.84, respectively. The most common BPSD domains were sleep disturbance (60.4%) and hallucinations (56.25%). Among the established risk factors, hypertension was present in the highest proportion (21 (43.8%)). As per the stepwise logistic regression model CDR scores, smoking status and HTN were predicted risk factors (R²: 0.452; p = 0.045).Conclusion: Irritability/agitation is most prevalent BPSD. The severity of MNCD, smoking and hypertension may help in the prediction of BPSD and their role may have to be explored in further studies.

Effect of bariatric surgery on obstructive sleep apnea: using the STOP-Bang score as a screening tool

Background Obstructive sleep apnea (OSA), the most prevalent major sleep disorder in the world, has been associated with obesity. Besides reducing weight, bariatric surgery has been reported to improve OSA. Data on the effects of bariatric surgery on OSA are scarce in Egypt. This study aimed to evaluate the short-term effects of bariatric surgery on OSA. Patients and methods This is a prospective study that was conducted on patients who were candidates for bariatric surgery at our institution who completed the STOP-Bang questionnaire before the surgery with a score greater than or equal to 4 and underwent re-evaluation 6 months after surgery. All patients underwent a standardized clinical assessment. The 6-month follow-up data were recorded and analyzed. Results The present study included 30 patients, with a mean baseline BMI of 54.32±9.77 kg/m2. The surgeries performed were Laparoscopic Sleeve Gastrectomy (LSG) (n=21, 70%) and Laparoscopic Roux en Y gastric bypass (LRYGB) (n=9, 30%). The mean baseline STOP-Bang score was 5.3±1.09. At the 6-month follow-up, the mean 6-month postoperative STOP-Bang score was 1.13±1.04 (P<0.001). No statistically significant differences were noted in the BMI or the STOP-Bang score before and after surgery according to the surgery type (P>0.05). There was a statistically significant positive correlation between the 6-month BMI reduction and the Snoring, Tiredness, Observed apnea, Pressure, BMI, Age, Neck, Gender (STOP-Bang) score improvement (r=0.397, P=0.0298). Conclusion This study demonstrated the bariatric surgery-initiated evident improvement and even complete resolution of OSA in patients with obesity, as measured by the STOP-Bang score.

Microglial over-pruning of synapses during development in autism-associated SCN2A-deficient mice and human cerebral organoids.

Autism spectrum disorder (ASD) is a major neurodevelopmental disorder affecting 1 in 36 children in the United States. While neurons have been the focus of understanding ASD, an altered neuro-immune response in the brain may be closely associated with ASD, and a neuro-immune interaction could play a role in the disease progression. As the resident immune cells of the brain, microglia regulate brain development and homeostasis via core functions including phagocytosis of synapses. While ASD has been traditionally considered a polygenic disorder, recent large-scale human genetic studies have identified SCN2A deficiency as a leading monogenic cause of ASD and intellectual disability. We generated a Scn2a-deficient mouse model, which displays major behavioral and neuronal phenotypes. However, the role of microglia in this disease model is unknown. Here, we reported that Scn2a-deficient mice have impaired learning and memory, accompanied by reduced synaptic transmission and lower spine density in neurons of the hippocampus. Microglia in Scn2a-deficient mice are partially activated, exerting excessive phagocytic pruning of post-synapses related to the complement C3 cascades during selective developmental stages. The ablation of microglia using PLX3397 partially restores synaptic transmission and spine density. To extend our findings from rodents to human cells, we established a microglia-incorporated human cerebral organoid model carrying an SCN2A protein-truncating mutation identified in children with ASD. We found that human microglia display increased elimination of post-synapse in cerebral organoids carrying the SCN2A mutation. Our study establishes a key role of microglia in multi-species autism-associated models of SCN2A deficiency from mouse to human cells.

Functional and Therapeutic Potential of Cynara scolymus in Health Benefits.

Dietary supplements enriched with bioactive compounds represent a promising approach to influence physiological processes and enhance longevity and overall health. Cynara cardunculus var. scolymus serves as a functional food supplement with a high concentration of bioactive compounds, which offers various health-promoting benefits. Several chronic diseases have metabolic, genetic, or inflammatory origins, which are frequently interconnected. Pharmacological treatments, although effective, often result in undesirable side effects. In this context, preventive approaches are gaining increased attention. Recent literature indicates that the consumption of bioactive compounds in the diet can positively influence the organism's biological functions. Polyphenols, well-known for their health benefits, are widely recognized as valuable compounds in preventing/combating various pathologies related to lifestyle, metabolism, and aging. The C. scolymus belonging to the Asteraceae family, is widely used in the food and herbal medicine fields for its beneficial properties. Although the inflorescences (capitula) of the artichoke are used for food and culinary purposes, preparations based on artichoke leaves can be used as an active ingredient in herbal medicines. Cynara scolymus shows potential benefits in different domains. Its nutritional value and health benefits make it a promising candidate for improving overall well-being. C. scolymus exhibits anti-inflammatory, antioxidant, liver-protective, bile-expelling, antimicrobial, and lipid-lowering neuroprotective properties. Different studies demonstrate that oxidative stress is the leading cause of the onset and progression of major human health disorders such as cardiovascular, neurological, metabolic, and cancer diseases. The large amount of polyphenol found in C. scolymus has an antioxidant activity, enabling it to neutralize free radicals, preventing cellular damage. This reduces the subsequent risk of developing conditions such as cancer, diabetes, and cardiovascular diseases. Additionally, these polyphenols demonstrate anti-inflammatory activity, which is closely associated with their antioxidant properties. As a result, C. scolymus has the potential to contribute to the treatment of chronic diseases, including intestinal disorders, cardiovascular diseases, and neurodegenerative pathologies. The current review discussed the nutritional profiles, potential benefits, and pharmacological effects of C. scolymus.

Protein-protein Interaction Studies between TSHR Protein in Human and Photosystem II Protein D1 of Ulva fasciata using In silico Protocols

The most prevalent mutation in Hypothyroid Protein, TSHR impacts the course and prognosis of Hypothyroidism in human. We employ 3D in silico drug docking techniques to make the possible mutant TSHR interact with Photosystem II Protein D1 of Ulva fasciata. To carry out drug docking techniques, the translated amino acid sequence and three-dimensional chemical compound were obtained from the NCBI database. The use of sophisticated 3D molecular visualization tools was employed in post-docking experiments. The use of sophisticated 3D molecular visualization tools was employed in post-docking experiments. The docking study results unequivocally show that Photosystem II Protein D1 directly suppresses amino acid mutational sites. TSHR and Photosystem II Protein D1’s electrostatic force is depicted in a three-dimensional manner using notions from molecular dynamics techniques. In the end, we determined that Photosystem II Protein D1, a medicinal component of Ulva fasciata, helps in treating hypothyroidism. Hypothyroidism, being one of the major Endocrinological disorders, our research work helps to prove that the sea weed, Ulva fasciata can effectively act a novel therapeutic agent for treating this disorder.

Mixed Features Specifier in Mood Disorder: The Prevalence and Associated Factors

Introduction: Malaysia’s unique cultural landscape may influence the manifestation of mixed features differently than in global studies. We’ve conducted the first study on the prevalence of the Mixed Feature Specifier (MFS) in mood disorders in Malaysia, addresses crucial research gaps to potentially inform culturally sensitive treatment approaches in Malaysia. Methods: This cross-sectional prevalence study was conducted at a psychiatric hospital in Malaysia, using a researcher administered questionnaire, consisted of five parts which includes sociodemographic factors, clinical characteristics, MADRS score, YMRS score and QoL score. Data was analyzed using SPSS version 24.0. Results: 148 patients were recruited into this study. Overall prevalence of MFS among Major Mood Disorder was 29.8%. There were significant associations between ethnicity (X2=9.063; p=0.028), marital status (X2=18.738; p<0.001) and average monthly income (X2=31.534; p=<0.001) with MFS. In terms of clinical characteristics, there were significant associations between number of hospitalizations (X2=41.026; p<0.001), trials of medications (X2=29.540; p<0.001), total number of medications on (X2=42.338; p<0.001), history of ECT (X2=10.590; p=0.001), family history of mood disorder (X2=20.944; p<0.001), suicidal attempts (X2=26.570; p<0.001), history substance use (X2=19.249; p<0.001), compliance to treatment (X2=4.310; p=0.038), YMRS score (X2=16.799; p=0.001) and MADRS score (X2=43.525; p<0.001) with MFS. Conclusion: We identified predictors associated with MFS, such as amount of income, substance use and number of hospitalizations. Sociodemographic and clinical characteristics are significantly associated with MFS, with significant differences between the QoL of MFS and non-MFS patients. This could foster early detection of cases, hence addressing the psychological needs of both MFS and non-MFS patients.

Anxiety symptoms without depression are associated with cognitive control network (CNN) dysfunction: An fNIRS study.

Anxiety is a common psychological disorder associated with other mental disorders, with depression being the most common comorbidity. Few studies have examined the neural mechanisms underlying anxiety after controlling for depression. This study aimed to explore whether there are differences in cortical activation in anxiety patients with different severities whose depression are normal. In the current study, depression levels were normal for 366 subjects-139 healthy subjects, 117 with mild anxiety, and 110 with major anxiety. Using the Hospital Anxiety and Depression Scale (HADS) and a verbal fluency task (VFT) to test subjects' anxiety and depression and cognitive function, respectively. A 53-channel guided near-infrared spectroscopic imaging technology (fNIRS) detected the concentration of oxyhemoglobin (oxy-Hb). Correlation analysis between anxiety severity and oxy-Hb concentration in the brain cortex was performed, as well as ANOVA analysis of oxy-Hb concentration among the three anxiety severity groups. The results showed that anxiety severity was significantly and negatively correlated with oxy-Hb concentrations in the left frontal eye field (lFEF) and in the right dorsolateral prefrontal area (rDLPFC). The oxy-Hb concentration in the lFEF and the rDLPFC were significantly lower in the major anxiety disorder group than that in the control group. This suggests that decreased cortical activity of the lFEF and rDLPFC may be neural markers of anxiety symptoms after controlling for depression. Anxiety symptoms without depression may be result from the dysfunction of the cognitive control network (CCN) which includes the lFEF and rDLPFC.

Statistical segmentation model for accurate electrode positioning in Parkinson's deep brain stimulation based on clinical low-resolution image data and electrophysiology.

Deep Brain Stimulation (DBS), applying chronic electrical stimulation of subcortical structures, is a clinical intervention applied in major neurologic disorders. In order to achieve a good clinical effect, accurate electrode placement is necessary. The primary localisation is typically based on presurgical MRI imaging, often followed by intra-operative electrophysiology recording to increase the accuracy and to compensate for brain shift, especially in cases where the surgical target is small, and there is low contrast: e.g., in Parkinson's disease (PD) and in its common target, the subthalamic nucleus (STN). We propose a novel, fully automatic method for intra-operative surgical navigation. First, the surgical target is segmented in presurgical MRI images using a statistical shape-intensity model. Next, automated alignment with intra-operatively recorded microelectrode recordings is performed using a probabilistic model of STN electrophysiology. We apply the method to a dataset of 120 PD patients with clinical T2 1.5T images, of which 48 also had available microelectrode recordings (MER). The proposed segmentation method achieved STN segmentation accuracy around dice = 0.60 compared to manual segmentation. This is comparable to the state-of-the-art on low-resolution clinical MRI data. When combined with electrophysiology-based alignment, we achieved an accuracy of 0.85 for correctly including recording sites of STN-labelled MERs in the final STN volume. The proposed method combines image-based segmentation of the subthalamic nucleus with microelectrode recordings to estimate their mutual location during the surgery in a fully automated process. Apart from its potential use in clinical targeting, the method can be used to map electrophysiological properties to specific parts of the basal ganglia structures and their vicinity.

Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders.

Neuroinflammatory and neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), traumatic brain injury (TBI) and Amyotrophic lateral sclerosis (ALS) are chronic major health disorders. The exact mechanism of the neuroimmune dysfunctions of these disease pathogeneses is currently not clearly understood. These disorders show dysregulated neuroimmune and inflammatory responses, including activation of neurons, glial cells, and neurovascular unit damage associated with excessive release of proinflammatory cytokines, chemokines, neurotoxic mediators, and infiltration of peripheral immune cells into the brain, as well as entry of inflammatory mediators through damaged neurovascular endothelial cells, blood-brain barrier and tight junction proteins. Activation of glial cells and immune cells leads to the release of many inflammatory and neurotoxic molecules that cause neuroinflammation and neurodegeneration. Gulf War Illness (GWI) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are chronic disorders that are also associated with neuroimmune dysfunctions. Currently, there are no effective disease-modifying therapeutic options available for these diseases. Human induced pluripotent stem cell (iPSC)-derived neurons, astrocytes, microglia, endothelial cells and pericytes are currently used for many disease models for drug discovery. This review highlights certain recent trends in neuroinflammatory responses and iPSC-derived brain cell applications in neuroinflammatory disorders.

Utility of learning ratio scores from the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Word List Memory Test in distinguishing patterns of cognitive decline in veterans referred for neuropsychological evaluation

Background: The Learning Ratio (LR) is a novel learning score that has shown improved utility over other learning metrics in detecting Alzheimer’s disease (AD) across multiple memory tasks. However, its utility on the Consortium to Establish a Registry for Alzheimer’s Disease Word List Memory Test (CERAD WLMT), a widely used list learning measure sensitive to decline in neurodegenerative disease, is unknown. The goal of the current study was to determine the utility of LR on the CERAD WLMT in differentiating between diagnostic (MiNCD vs MaNCD) and etiologic groups (VaD vs AD) in a veteran sample. Methods: Raw learning slope (RLS) and LR scores were examined in 168 veterans diagnosed with major neurocognitive disorder (MaNCD), mild neurocognitive disorder (MiNCD), or normal aging following neuropsychological evaluation. Patients with MaNCD were further classified by suspected etiology (i.e. microvascular disease vs AD). Results: Whereas RLS scores were not significantly different between MiNCD and MaNCD, LR scores were significantly different between all diagnostic groups (p’s < .05). Those with AD had lower LR scores and RLS scores compared to those with VaD (p’s < .05). LR classification accuracy was acceptable for MiNCD (AUC = .76), excellent for MaNCD (AUC = .86) and VaD (AUC = .81), and outstanding for AD (AUC = .91). Optimal cutoff scores for WLMT LR were derived from Youden’s index. Conclusion: Results support the use of LR scores over RLS when interpreting the CERAD WLMT and highlight the clinical utility of LR in differentiating between diagnostic groups and identifying suspected etiology.

Emerging Evidence of Golgi Stress Signaling for Neuropathies.

The Golgi apparatus is an intracellular organelle that modifies cargo, which is transported extracellularly through the nucleus, endoplasmic reticulum, and plasma membrane in order. First, the general function of the Golgi is reviewed and, then, Golgi stress signaling is discussed. In addition to the six main Golgi signaling pathways, two pathways that have been increasingly reported in recent years are described in this review. The focus then shifts to neurological disorders, examining Golgi stress reported in major neurological disorders, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. The review also encompasses findings related to other diseases, including hypomyelinating leukodystrophy, frontotemporal spectrum disorder/amyotrophic lateral sclerosis, microcephaly, Wilson's disease, and prion disease. Most of these neurological disorders cause Golgi fragmentation and Golgi stress. As a result, strong signals may act to induce apoptosis.

A Hybrid Type 1 trial of a multi-component mHealth intervention to improve post-hospital transitions of care for patients with serious mental illness: Study protocol

BackgroundThe transition from acute (e.g., psychiatric hospitalization) to outpatient care is associated with increased risk for rehospitalization, treatment disengagement, and suicide among people with serious mental illness (SMI). Mobile interventions (i.e., mHealth) have the potential to increase monitoring and improve coping post-acute care for this population. This protocol paper describes a Hybrid Type 1 effectiveness-implementation study, in which a randomized controlled trial will be conducted to determine the effectiveness of a multi-component mHealth intervention (tFOCUS) for improving outcomes for adults with SMI transitioning from acute to outpatient care. MethodsAdults meeting criteria for schizophrenia-spectrum or major mood disorders (n = 180) will be recruited from a psychiatric hospital and randomized to treatment-as-usual (TAU) plus standard discharge planning and aftercare (CHECK-IN) or TAU plus tFOCUS. tFOCUS is a 12-week intervention, consisting of: (a) a patient-facing mHealth smartphone app with daily self-assessment prompts and targeted coping strategies; (b) a clinician-facing web dashboard; and, (c) mHealth aftercare advisors, who will conduct brief post-hospital clinical calls with patients (e.g., safety concerns, treatment engagement) and encourage app use. Follow-ups will be conducted at 6-, 12-, and 24-weeks post-discharge to assess primary and secondary outcomes, as well as target mechanisms. We also will assess barriers and facilitators to future implementation of tFOCUS via qualitative interviews of stakeholders and input from a Community Advisory Board throughout the project. ConclusionsInformation gathered during this project, in combination with successful study outcomes, will inform a potential tFOCUS intervention scale-up across a range of psychiatric hospitals and healthcare systems.Clinicaltrials.govregistration: NCT05703412

Sex-specific neuropsychological correlates of apathy and depression across neurodegenerative disorders.

Apathy and depression are common neuropsychiatric symptoms across neurodegenerative disorders and are associated with impairment in several cognitive domains, yet little is known about the influence of sex on these relationships. We examined the relationship between these symptoms with neuropsychological performance across a combined cohort with mild or major neurodegenerative disorders, then evaluated the impact of sex. We conducted a cohort analysis of participants in the COMPASS-ND study with mild cognitive impairment (MCI), vascular MCI, Alzheimer's disease, mixed dementia, Parkinson's disease, frontotemporal dementia, and cognitively unimpaired (CU) controls. Participants with neurodegenerative disease and CU controls were stratified by the presence (severity ≥1 on Neuropsychiatric Inventory Questionnaire) of either depressive symptoms alone, apathy symptoms alone, both symptoms, or neither. A neuropsychological battery evaluated executive function, verbal fluency, verbal learning, working memory, and visuospatial reasoning. Analysis of covariance was used to assess group differences with age, sex, and education as covariates. Groups included depressive symptoms only (n=70), apathy symptoms only (n=52), both (n=68), or neither (n=262). The apathy and depression+apathy groups performed worse than the neither group on tests of working memory (t(312) =-2.4, p=0.02 and t(328) =-3.8, p=0.001, respectively) and visuospatial reasoning (t(301) =-2.3, p=0.02 and t(321) =-2.6, p=0.01, respectively). The depression, apathy, and depression+apathy groups demonstrated a similar degree of impairment on tests of executive function, processing speed, verbal fluency, and verbal learning when compared to participants without apathy or depression. Sex-stratified analyses revealed that compared to the male neither group, the male apathy and depression+apathy groups were impaired broadly across all cognitive domains except for working memory. Females with depression alone showed deficits on tests of executive function (t(166) =2.4, p=0.01) and verbal learning (t(167) =-4.3, p=0.001) compared to the female neither group. This study demonstrated that in neurodegenerative diseases, apathy with or without depression in males was associated with broad cognitive impairments. In females, depression was associated with deficits in executive function and verbal learning. These findings highlight the importance of effectively treating apathy and depression across the spectrum of neurodegenerative disorders with the goal of optimizing neuropsychological outcomes.

The Relationships between Caregiver Burden, Physical Frailty, Race, Behavioral and Psychological Symptoms (BPSD), and Other Associated Variables: An Exploratory Study.

Background and Objectives: For persons with dementia, the relationships between caregiver burden, physical frailty, race, behavioral and psychological symptoms (BPSD), and other associated variables are poorly understood. Only one prior study examined the relationships among these variables but did not include race, which is an important social determinant of health outcomes in the United States. To examine these interactions, we conducted a cross-sectional exploratory study based on a model by Sugimoto and colleagues. Materials and Methods: The sample comprised 85 patient-caregiver dyads (58% White) seen in four centers in diverse regions of New York State. All patients met DSM5 criteria for a major neurocognitive disorder, had a Clinical Dementia Rating sum score of ≥3, and Mini-Mental State Examination (MMSE) score of 10 to 26. Other measures included the SHARE-Frailty Instrument(FI), the Neuropsychiatric Inventory (NPI) to assess BPSD, Zarit's Caregiver Burden Interview (CBI), Lawton's Activities of Daily Living (ADL) Scale, the MMSE, the Cumulative Illness Rating Scale for Geriatrics (CIRSG), age, and gender. Results: In our sample, 59% met the criteria for prefrail/subsyndromal or frail/syndromal (SSF) on the SHARE-FI. SSF had significant direct effects on the NPI and significant indirect effects on the CBI mediated through the NPI; the NPI had significant direct effects on the CBI. Race (White) had significant direct effects on the CBI (higher) and SSF (lower) but did not have significant indirect effects on the CBI. MMSE, ADL, and CIRSG were not significantly associated with the NPI or the CBI. Conclusions: Our analysis demonstrated that frailty, race, BPSD, and caregiver burden may directly or indirectly influence one another, and therefore should be considered essential elements of dementia assessment, care, and research. These results must be viewed as provisional and should be replicated longitudinally with larger samples.

Peroxisome proliferator-activated receptors and placental function in women with polycystic ovary syndrome.

Adverse pregnancy outcomes in women with polycystic ovary syndrome (PCOS) are frequently associated with abnormal placental functions. This review explores the involvement of proliferator-activated receptors (PPARs) in these processes, to gain molecular insights into abnormal pregnancy conditions associated with PCOS. Polycystic ovary syndrome (PCOS) is one of the major endocrine disorders affecting women during their reproductive ages.Given its association with other pathologies, such as insulin resistance, metabolic syndrome, type 2 diabetes, and obesity, women with PCOS could present high-risk pregnancies, including a high abortion rate, implantation failure, an increased risk of gestational diabetes, preeclampsia, and intrauterine growth restriction. These adverse pregnancy outcomes are often attributed, at least in part, to defects in placental functions. Peroxisome proliferator-activated receptors (PPARs) are important transcription factors that participate in various placental pathways, regulating the expression of genes involved in lipid and glucose metabolism and inflammation. Furthermore, PPARs have been shown to play a role in placental development and function. Taking together this evidence, the present review focuses on the role of PPARs in placental tissue and discusses their implications in the pregnancy outcomes commonly associated with the presence of PCOS. In addition, the main treatments frequently employed have also been discussed.

Neuropsychiatric Symptoms are Related to Blood-biomarkers in Major Neurocognitive Disorders.

Neuropsychiatric symptoms (NPS) are highly prevalent among individuals with major neurocognitive disorders (MNCD). Here, we characterized blood biomarkers (metabolic, inflammatory, neurotrophic profiles and total antioxidant), body composition, physical fitness and quality of life (QoL) in individuals with MNCD according to NPS. The sample comprised 34 older adults (71.4% women; 74.06±6.03 yrs, with MNCD diagnosis) categorized according to 50th percentile [Low (≤12) or High (≥13)] for NPS (Neuropsychiatric Inventory Questionnaire). Sociodemographic, clinical data, body composition, anthropometric, cognitive assessment (ADAS-Cog), physical fitness (Senior Fitness Test), QoL (QoL-Alzheimer's Disease scale) were evaluated, and blood samples were collected for biochemical analysis. Low compared to high NPS group showed higher levels of IL-6, IGF-1and neurotrophic zscore (composite of IGF-1, VEGF-1, BDNF). Additionally, low compared to high NPS group have higher QoL, aerobic fitness and upper body and lower body strength. The severity of NPS seems to be related to modified neurotrophic and inflammatory outcomes, lower physical fitness, and poor QoL. Strategies to counteract NPS development may preserve the physical and mental health of individuals with MNCD.</p>.