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

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

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

Image_1_North Macedonia interprofessional dementia care (NOMAD) – personalized care plans for people with dementia and caregiver psychoeducation delivered at home by interprofessional teams.jpeg

IntroductionThe increasing number of people living with dementia and its burden on families and systems particularly in low- and middle-income countries require comprehensive and efficient post-diagnostic management. This study aimed to explore the acceptability and efficacy of a multi-professional case management and psychoeducation model (North Macedonia Interprofessional Dementia Care, or NOMAD) delivered by mobile teams for people with dementia and their caregivers in North Macedonia.MethodWe conducted a two-arm randomized controlled trial comparing the intervention with treatment as usual. Participants were recruited from 12 general practitioner (GP) offices in the Skopje region. The NOMAD intervention included the delivery of a personalized care plan over four home visits to dyads of people with dementia and their caregivers by a team including a dementia nurse and a social worker, in collaboration with GPs and dementia experts, and the introduction of a caregiver manual. We assessed caregivers' depressive symptoms, burden, and quality of life and the neuropsychiatric symptoms, daily living activities, and service utilization of people with dementia at baseline and follow-up; we also assessed the acceptability of the intervention by analyzing case notes and attendance rates.ResultsOne hundred and twenty dyads were recruited and randomized to either the control (n = 60) or the intervention group (n = 60). At follow-up, caregivers in the intervention group had, on average, scores that were 2.69 lower for depressive symptoms (95% CI [−4.75, −0.62], p = 0.012), and people with dementia had, on average, 11.32 fewer neuropsychiatric symptoms (95% CI [−19.74, −2.90], p = 0.009) and used, on average, 1.81 fewer healthcare services (95% CI [−2.61, −1.00], p DiscussionThe trial showed that it is effective in reducing caregivers' depressive symptoms and neuropsychiatric symptoms in people with dementia and the burden on health and social care services, and it is acceptable for families. Implementing NOMAD in practice will require building primary care capacity and recognizing dementia as a national priority.</p

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

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

Publication status: PublishedFunder: Alzheimer's Association, USAFunder: ICMR: Indian Council for Medical ResearchFunder: GOK: Government of KarnatakaFunder: RBM: Rotary Bangalore MidtownFunder: LSIPL: M/s Lowes Services India Private LimitedFunder: Wellcome Trust, UKFunder: Chinese Neuroscience Society, ChinaFunder: International Society for Neurochemistry; doi: http://dx.doi.org/10.13039/501100008992Funder: AXA Research Fund; doi: http://dx.doi.org/10.13039/501100001961Funder: Appel à Projet des Equipes Émergentes et Labellisées scheme (APREL)Funder: Global Brain Health Institute (GBHI)Funder: Health Professionals Education Partnership Initiative EthiopiaFunder: Rainwater Charitable Foundation – The Bluefield project to cure FTD, and Global Brain Health InstituteFunder: National Research Foundation (NRF)Funder: Michael J. Fox Foundation for Parkinson's Research, USAFunder: National Institute for Health and Care Research, United KingdomFunder: UK National Health Service, Newcastle University,Funder: Alzheimer's Drug Discovery Foundation (ADDF)Funder: Canadian Institute of Health ResearchFunder: National Council for Scientific and Technological Development; doi: http://dx.doi.org/10.13039/501100003593Funder: Bluefield Project, the Olav Thon Foundation, the Erling‐Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, SwedenFunder: Marie Skłodowska‐CurieFunder: National Institute for Health and Care Research University College London Hospitals Biomedical Research CentreTwo 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

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

International audienceTwo 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

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