Plasma ADAM10 Levels and Their Association with Alzheimer's Disease Diagnosis in Older Adults with Fewer Years of Formal Education.

INTRODUCTION: Low educational attainment is a potential risk factor for Alzheimer's disease (AD) development. Alpha-secretase ADAM10 plays a central role in AD pathology, attenuating the formation of beta-amyloid peptides and, therefore, their aggregation into senile plaques. This study seeks to investigate ADAM10 as a blood-based biomarker in mild cognitive impairment (MCI) and AD in a diverse group of community-dwelling older adults, focusing on those with limited educational attainment. METHODS: Participants were recruited from public health services. Cognition was evaluated using Mini-Mental State Examination (MMSE) and Addenbrooke's Cognitive Examination - Revised (ACE-R) batteries. Blood samples were collected to analyze plasma ADAM10 levels. A logistic regression was conducted to verify the influence of plasma ADAM10 on the AD diagnosis. RESULTS: Significant differences in age, years of education, prescribed medications, and cognitive test scores were found between the MCI and AD groups. Regarding cognitive performance, both ACE-R and MMSE scores displayed significant differences between groups, with post hoc analyses highlighting these distinctions, particularly between AD and cognitively unimpaired individuals. Elevated plasma ADAM10 levels were associated with a 4.5-fold increase in the likelihood of a diagnosis of MCI and a 5.9-fold increase in the likelihood of a diagnosis of AD. These findings suggest ADAM10 levels in plasma as a valuable biomarker for assessing cognitive status in older individuals with low education attainment. CONCLUSION: This study underscores the potential utility of plasma ADAM10 levels as a blood-based biomarker for cognitive status, especially in individuals with low educational backgrounds, shedding light on their relevance in AD development and diagnosis.

A systematic review and meta-analysis on cognitive frailty in community-dwelling older adults: risk and associated factors.

OBJECTIVES: To identify which factors are associated with cognitive frailty (CF), as well as the impact of CF on the incidence of dementia and mortality. METHODS: A systematic review with meta-analysis was carried out using papers that enrolled a total of 75,379 participants and were published up to January 2020. RESULTS: Of the 558 identified records, 28 studies met the inclusion criteria and were included in the review. The meta-analysis of cross-sectional studies showed that CF has a significant association of having an older age and a history of falls. In longitudinal studies, the analysis showed a significant increase in risk of mortality and dementia for those with CF. DISCUSSION: This is the first systematic review and meta-analysis on CF, which addressed a wide variety of factors associated with the theme and which pointed out some as a potential target for prevention or management with different interventions or treatments, showing the clinical importance of its identification in the most vulnerable and susceptible groups.

Lycium barbarum polysaccharide fraction associated with photobiomodulation protects from epithelium thickness and collagen fragmentation in a model of cutaneous photodamage.

Ultraviolet radiation (UVR) is the major etiologic agent of cutaneous photoaging, and different strategies are used to prevent and treat this condition. The polysaccharide fraction (LBPF) isolated from Lycium Barbarum fruits (goji berry) contains several active ingredients with antioxidant, immune system modulation, and antitumor effects. In addition, the photobiomodulation (PBM) is widely applied in photoaging treatment. This study investigated the effects of LBPF and PBM against the UVR-induced photodamage in the skin of hairless mice. The mice were photoaged for 6 weeks in a chronic and cumulative exposure regimen using a 300-W incandescent lamp that simulates the UVR effects. From the third to the sixth week of photoaging induction, the animals received topical applications of LBPF and PBM, singly or combined, in different orders (first LBPF and then PBM and inversely), three times per week after each session of photoaging. After completion of experiments, the dorsal region skin was collected for the analysis of thickness, collagen content, and metalloproteinases (MMP) levels. A photoprotective potential against the increase of the epithelium thickness and the fragmentation of the collagen fibers was achieved in the skin of mice treated with LBPF or PBM singly, as well as their combination. All treatments maintained the skin collagen composition, except when PBM was applied after the LBPF. However, no treatment protected against the UVR-induced MMP increase. Taken together, we have shown that the LBPF and PBM promote a photoprotective effect in hairless mice skin against epidermal thickening and low collagen density. Both strategies, singly and combined, can be used to reduce the UVR-induced cutaneous photoaging.

ADAM10 Plasma and CSF Levels Are Increased in Mild Alzheimer's Disease.

ADAM10 is the main α-secretase that participates in the non-amyloidogenic cleavage of amyloid precursor protein (APP) in neurons, inhibiting the production of ß-amyloid peptide (Aß) in Alzheimer's disease (AD). Strong recent evidence indicates the importance of the localization of ADAM10 for its activity as a protease. In this study, we investigated ADAM10 activity in plasma and CSF samples of patients with amnestic mild cognitive impairment (aMCI) and mild AD compared with cognitively healthy controls. Our results indicated that plasma levels of soluble ADAM10 were significantly increased in the mild AD group, and that in these samples the protease was inactive, as determined by activity assays. The same results were observed in CSF samples, indicating that the increased plasma ADAM10 levels reflect the levels found in the central nervous system. In SH-SY5Y neuroblastoma cells, ADAM10 achieves its major protease activity in the fraction obtained from plasma membrane lysis, where the mature form of the enzyme is detected, confirming the importance of ADAM10 localization for its activity. Taken together, our results demonstrate the potential of plasma ADAM10 to act as a biomarker for AD, highlighting its advantages as a less invasive, easier, faster, and lower-cost processing procedure, compared to existing biomarkers.

Comorbidities predict 30-day hospital mortality of older adults with COVID-19.

We evaluated whether comorbidities predict disease severity and mortality in a cohort of 147 older adults with COVID-19. Patients were divided into three groups according to the Charlson Comorbidity Index (CCI) score. Groups 2 (CCI 4 - 5) and 3 (CCI ≥ 6) had higher 30-day mortality rate as compared to group 1 (CCI ≤ 3). Cox regression showed that even after adding sex, National Early Warning Score (NEWS) 2 score and the need for intensive care unit admission to the model, no significant changes were found in the mortality risk predicted by the CCI score, showing that chronic pathologies are key determinants of short-term survival in COVID-19. This work is important for the geriatric nursing field as it demonstrates that alternative approaches for clinical decision-making that consider the comorbidities, rather than only chronological age, can be especially significant for the management of COVID-19 patients' hospitalization.

[10]-Gingerol-Loaded Nanoemulsion and its Biological Effects on Triple-Negative Breast Cancer Cells.

The apoptotic, cytotoxic, and cytostatic activities for [10]-gingerol in triple-negative breast cancer cells (TNBCs) were already reported. However, despite these important antitumor activities, the compound has the disadvantage to have a hydrophobic characteristic, hindering in vivo administration. To surpass this issue, in this study we have created a [10]-gingerol-loaded nanoemulsion (10GNE) in order to increase the stability and solubility of the compound. The nanoemulsion was characterized and tested for its cytotoxic, cytostatic, and apoptotic effects on a panel of murine and human TNBC cell lines, as well as non-tumor cells, and compared with a [10]-gingerol-free nanoemulsion (NE) and with [10]-gingerol itself. Except for the murine 4T1.13 cell line, the IC50 of the free 10G molecule, after 72 h of incubation, was higher in all cell lines tested, both murine and human, demonstrating therefore the efficacy of the 10GNE regarding cytotoxicity. In murine tumor cells, 60 µM 10GNE was able to arrest cell cycle at sub-G0 phase and induce apoptosis, leading to 48% and 78% of total cell death in 4T1.13 and 4T1Br4 murine tumor cells, respectively. This represents an improvement compared to 10G-free molecule that only induced 74% of total apoptosis at 100 µM in 4T1Br4 cells. Taken together, our results show that nanoformulation preserved the [10]-gingerol cytotoxic and cytostatic properties and improved its apoptotic function on murine TNBC cell lines. These data open new perspectives to a more suitable drug-delivery approach for [10]-gingerol for TNBC treatment that should be further demonstrated using in vivo assays.

Polysaccharide-rich hydrogel formulation combined with photobiomodulation repairs UV-induced photodamage in mice skin.

Prolonged skin exposure to ultraviolet radiation (UVR) induces premature aging in both the epidermis and the dermis. Chronic exposure to UVR induces the activation of mitogen-activated protein kinase (MAPK) signaling pathway, activating c-Jun, c-Fos expression, and transcription factor of AP-1 activating protein. AP-1 activation results in the positive induction of matrix metalloproteinase (MMP) synthesis, which degrade skin collagen fibers. Polysaccharides from the fruit of Lycium barbarum (LBP fraction) have a range of activities and have been demonstrate to repair the photodamage. In different approaches, laser application aims to recover the aged skin without destroying the epidermis, promoting a modulation, called photobiomodulation (PBM), which leads to protein synthesis and cell proliferation, favoring tissue repair. Here we developed a topical hydrogel formulation from a polysaccharide-rich fraction of Lycium barbarum fruits (LBP). This formulation was associated with PBM (red laser) to evaluate whether the isolated and combined treatments would reduce the UVR-mediated photodamage in mice skin. Hairless mice were photoaged for 6 weeks and then treated singly or in combination with LBP and PBM. Histological, immunohistochemistry, and immunofluorescence analyses were used to investigate the levels of c-Fos, c-Jun, MMP-1, -2, and -9, collagen I, III, and FGF2. The combined regimen inhibited UVR-induced skin thickening, decreased the expression of c-Fos and c-Jun, as well as MMP-1, -2, and -9 and concomitantly increased the levels of collagen I, III, and FGF2. The PBM in combination with LBP treatment is a promising strategy for the repair of photodamaged skin, presenting potential clinical application in skin rejuvenation.

Copper(I)-Phosphine Polypyridyl Complexes: Synthesis, Characterization, DNA/HSA Binding Study, and Antiproliferative Activity.

A series of copper(I)-phosphine polypyridyl complexes have been investigated as potential antitumor agents. The complexes [Cu(PPh3)2dpq]NO3 (2), [Cu(PPh3)2dppz]NO3 (3), [Cu(PPh3)2dppa]NO3 (4), and [Cu(PPh3)2dppme]NO3 (5) were synthesized by the reaction of [Cu(PPh3)2NO3] with the respective planar ligand under mild conditions. These copper complexes were fully characterized by elemental analysis, molar conductivity, FAB-MS, and NMR, UV-vis, and IR spectroscopies. Interactions between these copper(I)-phosphine polypyridyl complexes and DNA have been investigated using various spectroscopic techniques and analytical methods, such as UV-vis titrations, thermal denaturation, circular dichroism, viscosity measurements, gel electrophoresis, and competitive fluorescent intercalator displacement assays. The results of our studies suggest that these copper(I) complexes interact with DNA in an intercalative way. Furthermore, their high protein binding affinities toward human serum albumin were determined by fluorescence studies. Additionally, cytotoxicity analyses of all complexes against several tumor cell lines (human breast, MCF-7; human lung, A549; and human prostate, DU-145) and non-tumor cell lines (Chinese hamster lung, V79-4; and human lung, MRC-5) were performed. The results revealed that copper(I)-phosphine polypyridyl complexes are more cytotoxic than the corresponding planar ligand and also showed to be more active than cisplatin. A good correlation was observed between the cytostatic activity and lipophilicity of the copper(I) complexes studied here.

Serotoninergic antidepressants positively affect platelet ADAM10 expression in patients with Alzheimer's disease.

BACKGROUND: Studies have demonstrated a decreased platelet ADAM10 expression in patients with Alzheimer's Disease (AD), classifying this protein as a blood-based AD biomarker. About 50% of the patients with AD are diagnosed with depression, which is commonly treated with tricyclic and tetracyclic antidepressants, monoaminoxidade (MAO) inhibitors and, more preferably, with selective serotonin reuptake inhibitors (SSRIs). Considering that a large proportion of patients with AD takes antidepressant medications during the course of the disease we investigated the influence of this medication on the expression of platelet ADAM10, which is considered the main α-secretase preventing beta-amyloid (ßA) formation. METHODS: Blood was collected for protein extraction from platelets. ADAM10 was analyzed by using western blotting and reactive bands were measured using ß-actin as endogenous control. RESULTS: Platelet ADAM10 protein expression in patients with AD was positively influenced by serotoninergic medication. CONCLUSION: More studies on the positive effects of serotonergic antidepressants on ADAM10 platelet expression should be performed in order to understand its biological mechanisms and to verify whether these effects are reflected in the central nervous system. This work represents an important advance for the study of AD biomarkers, as well as for more effective pharmacological treatment of patients with AD and associated depression.

ADAM10 gene expression in the blood cells of Alzheimer's disease patients and mild cognitive impairment subjects.

ADAM10 is a potential biomarker for Alzheimer's disease (AD). ADAM10 protein levels are reduced in platelets of AD patients. The aim was to verify the total blood and platelet ADAM10 gene expression in AD patients and to compare with mild cognitive impairment (MCI) and healthy subjects. No significant differences in ADAM10 gene expression were observed. Therefore, the decrease of ADAM10 protein in platelets of AD patients is not caused by a reduction in ADAM10 mRNA. Further studies must be performed to investigate other pathways in the down regulation of ADAM10 protein.

Chiral Platinum(II) Complexes Featuring Phosphine and Chloroquine Ligands as Cytotoxic and Monofunctional DNA-Binding Agents.

Chiral molecules in nature are involved in many biological events; their selectivity and specificity make them of great interest for understanding the behavior of bioactive molecules, by providing information about the chiral discrimination. Inspired by these conformational properties, we present the design and synthesis of novel chiral platinum(II) complexes featuring phosphine and chloroquine ligands with the general formula [PtCl(P)2(CQ)]PF6 (where (P)2 = triphenylphosphine (PPh3) (5), 1,3-bis(diphenylphosphine)propane (dppp) (6), 1,4-bis(diphenylphosphine)butane (dppb) (7), 1,1'-bis(diphenylphosphine)ferrocene (dppf) (8), and CQ = chloroquine] and their precursors of the type [PtCl2(P)2] are described. The complexes were characterized by elemental analysis, absorption spectroscopy in the infrared and ultraviolet-visible (UV-vis) regions, multinuclear ((1)H, (13)C, (31)P, (15)N, and (195)Pt) NMR spectroscopy, cyclic voltammetry, and mass spectrometry (in the case of chloroquine complexes). The interactions of the new platinum-chloroquine complexes with both albumin (BSA), using fluorescence spectroscopy, and DNA, by four widely reported methods were also evaluated. These experiments showed that these Pt-CQ complexes interact strongly with DNA and have high affinities for BSA, in contrast to CQ and CQDP (chloroquine diphosphate), which interact weakly with these biomolecules. Additional assays were performed in order to investigate the cytotoxicity of the platinum complexes against two healthy cell lines (mouse fibroblasts (L929) and the Chinese hamster lung (V79-4)) and four tumor cell lines (human breast (MDA-MB-231 and MCF-7), human lung (A549), and human prostate (DU-145)). The results suggest that the Pt-CQ complexes are generally more cytotoxic than the free CQ, showing that they are promising as anticancer drugs.

Platelet a disintegrin and metallopeptidase 10 expression correlates with clock drawing test scores in Alzheimer's disease.

OBJECTIVE: Earlier studies have demonstrated that a disintegrin and metallopeptidase 10 (ADAM10) levels are reduced in Alzheimer's disease (AD) patients compared with healthy subjects. The objective of this study was to evaluate whether platelet ADAM10 levels correlates with the clock drawing test (CDT) scores, which is a simple and a reliable measure of visuospatial ability and executive function in AD patients. METHODS: Thirty elderly patients with probable AD and 25 healthy patients forming the control group, matched by age, gender, and educational level, were evaluated. Platelet proteins were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, and ADAM10 was identified by western blotting. The Spearman's correlation coefficient between ADAM10 and CDT was obtained for each group. The areas under the curves were used to compare the receiver operating characteristic curves. RESULTS: The CDT scores and platelet ADAM10 expression were significantly different between patients with AD and controls and also along the disease's progression. In AD patients, there was a positive correlation between ADAM10 expression and CDT scores. Among non-AD subjects, no correlation was found. The combination of ADAM10 and CDT was significantly better to confirm the AD diagnosis than the AUCs of ADAM10 and CDT separately. CONCLUSIONS: The association of blood-based biomarkers, such as ADAM10, and cognitive tests may be helpful for a more reliable AD diagnosis.

Unraveling the dual role of ADAM10: Bridging the gap between cancer and Alzheimer's disease.

An inverse association between Alzheimer's disease (AD) and cancer has been proposed. Patients with a cancer history have a decreased risk of developing AD, and AD patients have a reduced cancer incidence, which is not seen in vascular dementia patients. Given this association, common molecular and biological mechanisms that could explain this inverse relationship have been proposed before, such as Peptidylprolyl Cis/Trans Isomerase, NIMA-Interacting 1 (Pin1), Wingless and Int-1 (Wnt), and transformation-related protein 53 (p53)-mediated pathways, along with inflammation and oxidative stress-related proteins. A Disintegrin And Metalloprotease 10 (ADAM10) is a protease responsible for the cleavage of key AD- and cancer-related substrates, and it has inverse roles in those diseases: neuroprotective and disease-promoting, respectively. Thus, herein, we review the relevant literature linking AD and cancer and propose how ADAM10 activity might modulate the inverse association between the diseases. Understanding how this protease mediates those two conditions might raise some considerations in the ADAM10 pharmacological modulation for treating AD and cancer.

The effect of light irradiation on a nitro-ruthenium porphyrin complex in the induced death of lung cancer cells in two- and three-dimensional cultures: Insights into the effect of nitric oxide.

Efforts to find compounds selectively affecting cancer cells while sparing normal ones have continued to grow. Nitric oxide (NO) is critical in physiology and pathology, including cancer. It influences cellular processes like proliferation, apoptosis, and angiogenesis. The intricate interaction of NO with cancer cells offers innovative treatment possibilities, but its effects can vary by concentration and site. Ruthenium complexes capable of releasing NO upon stimulation show for this purpose. These versatile compounds can also enhance photodynamic therapy (PDT), a light-activated approach, which induces cellular damage. Ruthenium-based photosensitizers (PSs), delivering NO and producing reactive oxygen species (ROS), offer a novel strategy for improved cancer treatments. In this study, a nitro-ruthenium porphyrin conjugate: {TPyP[Ru(NO2)(bpy)2]4}(PF6)4, designated RuNO2TPyP, which releases NO upon irradiation, was investigated for its effects on lung cells (non-tumor MRC-5 and tumor A549) in 2D and 3D cell cultures. The findings suggest that this complex has potential for PDT treatment in lung cancer, as it exhibits photocytotoxicity at low concentrations without causing cytotoxicity to normal lung cells. Moreover, treatment of cells with RuNO2TPyP followed by light irradiation (4 J cm-2) can induce apoptosis, generate ROS, promote intracellular NO formation, and has anti-migratory effects. Additionally, the complex can modify tumor cell structures and induce photocytotoxicity and apoptosis in a 3D culture. These outcomes are attributed to the internalization of the complex and its subsequent activation upon light irradiation, resulting in NO release and singlet oxygen production.

ADAM10 as a biomarker for Alzheimer's disease: a study with Brazilian elderly.

Alzheimer's disease (AD) is the most common cause of dementia in people above age 65. Platelet studies with ADAM10 have shown that its expression is reduced in AD patients. The aim of this research was to compare the platelet levels of ADAM10 protein in two Brazilian elderly groups, considering the stages of the disease. The SDS-PAGE technique followed by Western blotting was used. Data were analyzed using comparison, correlation and association statistical methods. The results showed reduced platelet ADAM10 levels in AD elderly compared to non-AD subjects. The disease progression intensified this reduction. ADAM10 was the only statistically significant variable (p = 0.01) to increase the AD occurrence probability. The cutoff value of 0.4212 in the receiver operating characteristic curve captured sensitivity and specificity of 70 and 80.77%, respectively. Together with other clinical criteria, ADAM10 seems to be a relevant biomarker tool for early and accurate AD diagnosis.

Protecting cognitive function in older adults with age-related hearing loss: Insights from The Irish Longitudinal Study on Ageing (TILDA) and the role of hearing aids.

BACKGROUND: Age-related hearing loss (ARHL) is prevalent in adults over 70, impairing hearing sensitivity and speech perception. ARHL has been linked to an increased risk of cognitive decline and dementia. However, most affected adults are not receiving adequate treatment, including hearing aids. OBJECTIVE: This study aimed to evaluate the impact of ARHL on cognitive decline in older adults participating in the Irish Longitudinal Study on Aging (TILDA). DESIGN: METHODS: Data from four TILDA waves, a 6-year follow-up, was collected and analyzed using zero-inflated Poisson regression. The primary outcome, cognitive function, was assessed using Mini-Mental State Examination (MMSE) total score and error counts. RESULTS: Our analysis revealed that age, education, use of aids to help with hearing, and history of stroke were significantly associated with error counts at baseline. Additionally, poor hearing was associated with a negative change in MMSE score from wave 4, indicating the potential role of ARHL in cognitive decline. When further adjusted for age, sex, history of stroke, hypertension, any emotional, nervous, or psychiatric problem, polypharmacy, and hearing aids, the zero-inflated Poisson model indicated that poor hearing, use of hearing aids, stroke, hypertension, and polypharmacy all predicted MMSE error counts in follow-up assessments. Moreover, the use of hearing aids was associated with a decreased likelihood of cognitive decline. CONCLUSION: ARHL was independently associated with cognitive decline, underscoring the importance of addressing hearing loss in older adults. Future research should explore the potential of hearing aids to protect cognitive functioning in older adults.

Nanoencapsulation of Ruthenium Complex Ru(ThySMet): A Strategy to Improve Selective Cytotoxicity Against Breast Tumor Cells in 2D and 3D Culture Models.

BACKGROUND: Ruthenium complexes have shown promise in treating many cancers, including breast cancer. Previous studies of our group have demonstrated the potential of the trans-[Ru(PPh3)2(N,N-dimethylN'-thiophenylthioureato-k2O,S)(bipy)]PF6 complex, the Ru(ThySMet), in the treatment of breast tumor cancers, both in 2D and 3D culture systems. Additionally, this complex presented low toxicity when tested in vivo. AIMS: Improve the Ru(ThySMet) activity by incorporating the complex into a microemulsion (ME) and testing its in vitro effects. METHODS: The ME-incorporated Ru(ThySMet) complex, Ru(ThySMet)ME, was tested for its biological effects in two- (2D) and three-dimensional (3D) cultures using different types of breast cells, MDA-MB-231, MCF-10A, 4T1.13ch5T1 and Balb/C 3T3 fibroblasts. RESULTS: An increased selective cytotoxicity of the Ru(ThySMet)ME for tumor cells was found in 2D cell culture, compared with the original complex. This novel compound also changed the shape of tumor cells and inhibited cell migration with more specificity. Additional 3D cell culture tests using the non-neoplastic S1 and the triple-negative invasive T4-2 breast cells have shown that Ru(ThySMet)ME presented increased selective cytotoxicity for tumor cells compared with the 2D results. The morphology assay performed in 3D also revealed its ability to reduce the size of the 3D structures and increase the circularity in T4-2 cells. CONCLUSION: These results demonstrate that the Ru(ThySMet)ME is a promising strategy to increase its solubility, delivery, and bioaccumulation in target breast tumors.

Do the oxidative stress biomarkers predict COVID-19 outcome? An in-hospital cohort study.

In SARSCoV-2 infections, excessive activation of the immune system dramatically elevates reactive oxygen species levels, harms cell structures, and directly increases disease severity and mortality. We aimed to evaluate whether plasma oxidative stress biomarker levels could predict mortality in adults admitted with Coronavirus Disease 2019 (COVID-19), considering potential confounders. We conducted a cohort study of 115 adults (62.1 ± 17.6 years, 65 males) admitted to a Brazilian public hospital for severely symptomatic COVID-19. Serum levels of α-tocopherol, glutathione, superoxide dismutase, 8-hydroxy-2'-deoxyguanosine, malondialdehyde, and advanced oxidation protein products were quantified at COVID-19 diagnosis using real-time polymerase chain reaction. Serum levels of α-tocopherol, glutathione, superoxide dismutase, and advanced oxidation protein products differed significantly between survivors and non-survivors. Serum glutathione levels below 327.2 µmol/mL were associated with a significant risk of death in COVID-19 patients, even after accounting for other factors (adjusted hazard ratio = 3.12 [95% CI: 1.83-5.33]).

The Brain Health Diplomat's Toolkit: supporting brain health diplomacy leaders in Latin America and the Caribbean.

Maintaining and improving brain health, one of the most critical global challenges of this century, necessitates innovative, interdisciplinary, and collaborative strategies to address the growing challenges in Latin America and the Caribbean. This paper introduces Brain Health Diplomacy (BHD) as a pioneering approach to bridge disciplinary and geographic boundaries and mobilize resources to promote equitable brain health outcomes in the region. Our framework provides a toolkit for emerging brain health leaders, equipping them with essential concepts and practical resources to apply in their professional work and collaborations. By providing case studies, we highlight the importance of culturally sensitive, region-specific interventions to address unique needs of vulnerable populations. By encouraging dialogue, ideation, and cross-sector discussions, we aspire to develop new research, policy, and programmatic avenues. The novel BHD approach has the potential to revolutionize brain health across the region and beyond, ultimately contributing to a more equitable global cognitive health landscape.

Apolipoprotein E ε4 allele impairs cortical activity in healthy aging and Alzheimer's disease.

AIM: To investigate the influence of apolipoprotein E (APOE) genotype on cortical activity, using the event-related potential P300 in healthy older adults and individuals with Alzheimer's disease (AD). METHODS: A cohort of 37 healthy older adults and 48 with AD participated in this study and completed an auditory oddball task using electroencephalographic equipment with 21 channels (10-20 system). APOE genotyping was obtained by real-time PCR. RESULTS: AD presented increased P300 latency and lower P300 amplitude, compared to healthy older adults. AD APOE ε4 carriers presented increased P300 latency in F3 (420.7 ± 65.8 ms), F4 (412.0 ± 49.0 ms), C4 (413.0 ± 41.1 ms) and P3 (420.4 ± 55.7 ms) compared to non-carriers (F3 = 382.5 ± 56.8 ms, p < 0.01; F4 = 372.2 ± 56.7 ms, p < 0.01; C4 = 374.2 ± 51.7 ms, p < 0.01; P3 = 384.4 ± 44.4 ms, p < 0.01). Healthy older adults APOE ε4 carriers presented lower Fz amplitude (2.6 ± 1.5 µV) compared to non-carriers (4.9 ± 2.9 µV; p = 0.02). Linear regression analysis showed that being a carrier of APOE ε4 allele remained significantly associated with P300 latency even after adjusting for sex, age, and cognitive grouping. APOE ε4 allele increases P300 latency (95% CI 0.11-0.98; p = 0.02). CONCLUSION: APOE ε4 allele negatively impacts cortical activity in both healthy older adults and AD individuals.