The 2022 symposium on dementia and brain aging in low- and middle-income countries: Highlights on research, diagnosis, care, and impact.

Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. HIGHLIGHTS: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs.

Overlapping Neuroimmune Mechanisms and Therapeutic Targets in Neurodegenerative Disorders.

Many potential immune therapeutic targets are similarly affected in adult-onset neurodegenerative diseases, such as Alzheimer's (AD) disease, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), as well as in a seemingly distinct Niemann-Pick type C disease with primarily juvenile onset. This strongly argues for an overlap in pathogenic mechanisms. The commonly researched immune targets include various immune cell subsets, such as microglia, peripheral macrophages, and regulatory T cells (Tregs); the complement system; and other soluble factors. In this review, we compare these neurodegenerative diseases from a clinical point of view and highlight common pathways and mechanisms of protein aggregation, neurodegeneration, and/or neuroinflammation that could potentially lead to shared treatment strategies for overlapping immune dysfunctions in these diseases. These approaches include but are not limited to immunisation, complement cascade blockade, microbiome regulation, inhibition of signal transduction, Treg boosting, and stem cell transplantation.

Radial and ulnar approach for carotid artery stenting with Roadsaver™ double layer micromesh stent: Early and long-term follow-up.

AIMS: We aimed to evaluate the feasibility and safety of carotid artery stenting (CAS) with a newly designed double-layer micromesh stent using wrist approach in patients with significant carotid disease. MATERIALS AND METHODS: Between January 2016 and December 2021, 105 patients undergoing CAS with Roadsaver™ stent were enrolled in a single center prospective study. Follow-up assessments included neurological exams, duplex ultrasound (DUS), and 12-lead ECG. The primary endpoint was the 30-day composite rate of stroke, death, and myocardial infarction. Secondary endpoints included procedure success, access site complications, device success, target lesion revascularization, and in-stent restenosis evaluated with DUS. Long-term outcomes up to 72 months of follow-up were assessed in all eligible patients. RESULTS: The study population was predominantly male (69.5%) with a median age of 68 ± 8 years. Patients were symptomatic in 80% of the cases, and 35% fulfilled the high-risk criteria for surgical endarterectomy. The right internal carotid artery was the target artery in 56 (53.4%), and the left in 49 (46.6%) of the cases. All procedures were successfully completed from the right wrist, with right radial access in 94 (89.5%) cases and ulnar artery access with previous radial artery occlusion in 11 (10.5%) cases. All patients were treated successfully with the study device. The primary endpoint was met with a 30-day major adverse event rate of 0.9% (1/105). Up to 72 months of follow-up (median 30 ± 20 months) there were no strokes, neurological deaths, or target lesion revascularization of the treated lesion. Doppler ultrasound examination revealed nonsignificant in-stent restenosis in two asymptomatic patients. There was no hand ischemia detected in any patient. CONCLUSION: Results from this study demonstrate the radial and ulnar access for CAS with double layer micromesh Roadsaver™ stent is safe and feasible and associated with favorable early and long-term follow-up.

Psychopathology in psychotic disorders: Congruency between self-reported and observer-rated measures highest for affective symptoms and lowest for negative symptoms.

Considering that both observer ratings and patient self-reports on severity of psychopathological symptoms are being used in research and clinical settings, this paper aims to explore the degree of congruence between these two sources. Eighty-two adult outpatients diagnosed with psychotic disorders rated their symptoms using the Brief Symptom Inventory (BSI). Observers assessed patients' functioning using the Brief Psychiatry Rating Scale (BPRS). Self-ratings (overall BSI) were strongly correlated to observers' evaluations (overall BPRS). Anxiety/depression symptoms dimension of the BPRS were significantly associated with all nine symptom dimensions of the BSI, while positive symptoms dimension and unusual and withdrawal behavior in the BPRS showed a significant relationship to seven symptom dimensions as measured with the BSI. Mania/activation in the BPRS was significantly and negatively related only to phobic anxiety in BSI. Eight symptom dimensions of the BSI (interpersonal sensitivity was an exception), as well as unusual and withdrawal behavior and positive symptoms in the BPRS were rated as more severe in unemployed study participants. Self-rated paranoid ideation was higher in less educated participants. No sex or marital status differences were found in the BSI and BPRS dimensions. The obtained pattern of correlations implied that congruence was highest in regards to affective symptomatology, followed by positive symptoms, and lowest for disorganization and withdrawal behavior.

Psychometric Characteristics of the Macedonian Version of Clinical Assessment Interview for Negative Symptoms (CAINS).

BACKGROUND: Despite the importance of effective assessment and treatment of negative symptoms among patients with psychosis, no validated instruments are available in the Republic of North Macedonia. The aim of this paper was to explore psychometric properties, namely factorial structure, internal consistency, convergent and discriminant validity of the Clinical Assessment Interview for Negative Symptoms (CAINS). SUBJECTS AND METHODS: In this cross-sectional study 82 outpatients diagnosed with psychosis (64 with schizophrenia and 18 with bipolar disorder; female=34, mean age=41.05±10.09) were assessed. RESULTS: The exploratory factor analysis revealed two factorial structure of the negative symptoms as measured by the CAINS, i.e. 'expression and motivation' and 'pleasure'. Two items aimed to measure motivation for family relations and motivation for work/school activities loaded on the expression factor instead on motivation and pleasure factor which differs from the original version of the CAINS. Convergent validity was proven by positive relationship to negative symptoms as measured by the BPRS. Positive, but weak correlation with BPRS positive symptoms demonstrated its discriminant validity. Internal consistency of overall CAINS scale and its two subscales was very high. CONCLUSION: The CAINS can be used to assess negative symptoms in individuals with psychosis in the Macedonian clinical context. Consequently, this work can provide a foundation for further clinical advancement and research of negative symptoms in Macedonian healthcare.

Evaluation of APOE Genotype and Vascular Risk Factors As Prognostic and Risk Factors for Alzheimer's Disease and Their Influence On Age of Symptoms Onset.

BACKGROUND: Alzheimer's disease (AD), the most common cause of dementia, is evolving to become a threatening epidemy of the 21st century. Only 21% of the predicted number of AD patients in Macedonia have been diagnosed and treated, which means that almost 80% are underdiagnosed or misdiagnosed. Apolipoprotein E gene (APOE) is recognised as the strongest genetic risk factor for sporadic AD. Whether and when Alzheimer's disease develops, depends on the very complex interaction between genetic and modifiable risk factors. It has been known that vascular factors like hypertension, diabetes mellitus, hypercholesterolemia and obesity increase the risk of developing both AD, vascular dementia and mixed AD and vascular pathology. AIM: This study aims to evaluate the influence of APOEε4 allele presence and modifiable vascular risk factors (hypertension, diabetes mellitus and dyslipidemia) as prognostic and risk factors for AD and their influence on the age of onset of AD symptoms among 144 AD patients from Macedonia. MATERIAL AND METHODS: Study group of a total of 144 patients diagnosed with AD was evaluated. APOE genotyping was performed using APOE haplotype-specific sequence specific-primer (SSP)-PCR (Polymerase Chain Reaction) methodology. The non-standardized questionnaire was used to obtain information about demographics, lifestyle and modifiable risk factors that could influence disease onset and phenotype. RESULTS: Statistically significant association was found between the presences of APOEε4 allele in AD group versus controls. The presence of APOEε4 allele increases the risk of developing AD in a 3-fold manner. The average age of disease onset in the ε4 carrier group was 67.2 ± 8.3 and in the ε4 non-carrier group 69.7 ± 9.4. This confirms that the presence of APOEε4 allele shifts towards earlier disease onset, though the difference is not statistically significant. Out of the vascular risk factors, only hypertension was significantly associated with earlier AD onset. Out of total 144 patients, in 22.9% the first symptom onset was before the age of 65, that can be considered as early onset Alzheimer's Disease (EOAD), which is much higher than 5% for EOAD as most of the studies report. CONCLUSIONS: The average age of disease onset of 68.4 years could be considered earlier than the average age of AD onset worldwide. Out of all the vascular risk factors analysed in this study, only hypertension and dyslipidemia were found to significantly increase the risk for developing AD and only the presence of hypertension influences the age of onset, shifting towards earlier disease onset. Public awareness campaigns should be organised to influence general population knowledge about Alzheimer's disease, early recognition and the influence of modifiable vascular risk factors.

Myasthenia Gravis and Associated Diseases.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease caused by the action of specific antibodies to the postsynaptic membrane of the neuromuscular junction, leading to impaired neuromuscular transmission. Patients with MG have an increased incidence of other autoimmune diseases. AIM: to determine the presence of other associated diseases in patients with MG. METHOD: A group of 127 patients with MG followed in 10 years period, in which the presence of other associated diseases has been analysed. RESULTS: The sex ratio is in favour of the female sex, the average age of the initial manifestation of the disease is less than 50 years, 65.4% of the patients with MG have another disease. 15.0% patients have associated another autoimmune disease. Thyroid disease is the most common associated with MG, rarely rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and other autoimmune diseases. Other diseases include hypertension, heart disease, diabetes, respiratory diseases, dyslipidemia. 10.2% of the patients are diagnosed with extrathymic tumours of various origins. CONCLUSION: Associated diseases are common in patients with MG, drawing attention to the possible common basis for their coexistence, as well as their impact on the intensity and treatment of the disease.

Mental health law in the Former Yugoslav Republic of Macedonia.

Psychiatrists are often confronted with the problem of non-consensual treatment. This paper focuses on the rights of patients with mental health disorders in the Former Yugoslav Republic of Macedonia in relation to non-consensual treatment and deprivation of liberty. The current mental health legislation and its implementation in local services is described with an emphasis on the assessment and treatment of patients with mental disorders.