Cerebral Small Vessel Disease in Sporadic and Familial Alzheimer Disease.

Alzheimer disease (AD) is the most common cause of dementia. Biological definitions of AD are limited to the cerebral burden of amyloid ß plaques, neurofibrillary pathology, and neurodegeneration. However, current evidence suggests that various features of small vessel disease (SVD) are part of and covertly modify both sporadic and familial AD. Neuroimaging studies suggest that white matter hyperintensities explained by vascular mechanisms occurs frequently in the AD spectrum. Recent advances have further emphasized that frontal periventricular and posterior white matter hyperintensities are associated with cerebral amyloid angiopathy in familial AD. Although whether SVD markers precede the classically recognized biomarkers of disease is debatable, post-mortem studies show that SVD pathology incorporating small cortical and subcortical infarcts, microinfarcts, microbleeds, perivascular spacing, and white matter attenuation is commonly found in sporadic as well as in mutation carriers with confirmed familial AD. Age-related cerebral vessel pathologies such as arteriolosclerosis and cerebral amyloid angiopathy modify progression or worsen risk by shifting the threshold for cognitive impairment and AD dementia. The incorporation of SVD as a biomarker is warranted in the biological definition of AD. Therapeutic interventions directly reducing the burden of brain amyloid ß have had no major impact on the disease or delaying cognitive deterioration, but lowering the risk of vascular disease seems the only rational approach to tackle both early- and late-onset AD dementia.

Dementia in Africa: Current evidence, knowledge gaps, and future directions.

In tandem with the ever-increasing aging population in low and middle-income countries, the burden of dementia is rising on the African continent. Dementia prevalence varies from 2.3% to 20.0% and incidence rates are 13.3 per 1000 person-years with increasing mortality in parts of rapidly transforming Africa. Differences in nutrition, cardiovascular factors, comorbidities, infections, mortality, and detection likely contribute to lower incidence. Alzheimer's disease, vascular dementia, and human immunodeficiency virus/acquired immunodeficiency syndrome-associated neurocognitive disorders are the most common dementia subtypes. Comprehensive longitudinal studies with robust methodology and regional coverage would provide more reliable information. The apolipoprotein E (APOE) ε4 allele is most studied but has shown differential effects within African ancestry compared to Caucasian. More candidate gene and genome-wide association studies are needed to relate to dementia phenotypes. Validated culture-sensitive cognitive tools not influenced by education and language differences are critically needed for implementation across multidisciplinary groupings such as the proposed African Dementia Consortium.

Brain arteriolosclerosis.

Brain arteriolosclerosis (B-ASC), characterized by pathologic arteriolar wall thickening, is a common finding at autopsy in aged persons and is associated with cognitive impairment. Hypertension and diabetes are widely recognized as risk factors for B-ASC. Recent research indicates other and more complex risk factors and pathogenetic mechanisms. Here, we describe aspects of the unique architecture of brain arterioles, histomorphologic features of B-ASC, relevant neuroimaging findings, epidemiology and association with aging, established genetic risk factors, and the co-occurrence of B-ASC with other neuropathologic conditions such as Alzheimer's disease and limbic-predominant age-related TDP-43 encephalopathy (LATE). There may also be complex physiologic interactions between metabolic syndrome (e.g., hypertension and inflammation) and brain arteriolar pathology. Although there is no universally applied diagnostic methodology, several classification schemes and neuroimaging techniques are used to diagnose and categorize cerebral small vessel disease pathologies that include B-ASC, microinfarcts, microbleeds, lacunar infarcts, and cerebral amyloid angiopathy (CAA). In clinical-pathologic studies that factored in comorbid diseases, B-ASC was independently associated with impairments of global cognition, episodic memory, working memory, and perceptual speed, and has been linked to autonomic dysfunction and motor symptoms including parkinsonism. We conclude by discussing critical knowledge gaps related to B-ASC and suggest that there are probably subcategories of B-ASC that differ in pathogenesis. Observed in over 80% of autopsied individuals beyond 80 years of age, B-ASC is a complex and under-studied contributor to neurologic disability.

Vascular dysfunction-The disregarded partner of Alzheimer's disease.

Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging-Alzheimer's Association describes a biomarker-based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood-brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for >50% of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts.

Small vessels, dementia and chronic diseases - molecular mechanisms and pathophysiology.

Cerebral small vessel disease (SVD) is a major contributor to stroke, cognitive impairment and dementia with limited therapeutic interventions. There is a critical need to provide mechanistic insight and improve translation between pre-clinical research and the clinic. A 2-day workshop was held which brought together experts from several disciplines in cerebrovascular disease, dementia and cardiovascular biology, to highlight current advances in these fields, explore synergies and scope for development. These proceedings provide a summary of key talks at the workshop with a particular focus on animal models of cerebral vascular disease and dementia, mechanisms and approaches to improve translation. The outcomes of discussion groups on related themes to identify the gaps in knowledge and requirements to advance knowledge are summarized.

Progress toward standardized diagnosis of vascular cognitive impairment: Guidelines from the Vascular Impairment of Cognition Classification Consensus Study.

INTRODUCTION: Progress in understanding and management of vascular cognitive impairment (VCI) has been hampered by lack of consensus on diagnosis, reflecting the use of multiple different assessment protocols. A large multinational group of clinicians and researchers participated in a two-phase Vascular Impairment of Cognition Classification Consensus Study (VICCCS) to agree on principles (VICCCS-1) and protocols (VICCCS-2) for diagnosis of VCI. We present VICCCS-2. METHODS: We used VICCCS-1 principles and published diagnostic guidelines as points of reference for an online Delphi survey aimed at achieving consensus on clinical diagnosis of VCI. RESULTS: Six survey rounds comprising 65-79 participants agreed guidelines for diagnosis of VICCCS-revised mild and major forms of VCI and endorsed the National Institute of Neurological Disorders-Canadian Stroke Network neuropsychological assessment protocols and recommendations for imaging. DISCUSSION: The VICCCS-2 suggests standardized use of the National Institute of Neurological Disorders-Canadian Stroke Network recommendations on neuropsychological and imaging assessment for diagnosis of VCI so as to promote research collaboration.

Deposition of amyloid ß in the walls of human leptomeningeal arteries in relation to perivascular drainage pathways in cerebral amyloid angiopathy.

Deposition of amyloid ß (Aß) in the walls of cerebral arteries as cerebral amyloid angiopathy (CAA) suggests an age-related failure of perivascular drainage of soluble Aß from the brain. As CAA is associated with Alzheimer's disease and with intracerebral haemorrhage, the present study determines the unique sequence of changes that occur as Aß accumulates in artery walls. Paraffin sections of post-mortem human occipital cortex were immunostained for collagen IV, fibronectin, nidogen 2, Aß and smooth muscle actin and the immunostaining was analysed using Image J and confocal microscopy. Results showed that nidogen 2 (entactin) increases with age and decreases in CAA. Confocal microscopy revealed stages in the progression of CAA: Aß initially deposits in basement membranes in the tunica media, replaces first the smooth muscle cells and then the connective tissue elements to leave artery walls completely or focally replaced by Aß. The pattern of development of CAA in the human brain suggests expansion of Aß from the basement membranes to progressively replace all tissue elements in the artery wall. Establishing this full picture of the development of CAA is pivotal in understanding the clinical presentation of CAA and for developing therapies to prevent accumulation of Aß in artery walls. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.

Vascular cognitive impairment neuropathology guidelines (VCING): the contribution of cerebrovascular pathology to cognitive impairment.

There are no generally accepted protocols for post-mortem assessment in cases of suspected vascular cognitive impairment. Neuropathologists from seven UK centres have collaborated in the development of a set of vascular cognitive impairment neuropathology guidelines (VCING), representing a validated consensus approach to the post-mortem assessment and scoring of cerebrovascular disease in relation to vascular cognitive impairment. The development had three stages: (i) agreement on a sampling protocol and scoring criteria, through a series of Delphi method surveys; (ii) determination of inter-rater reliability for each type of pathology in each region sampled (Gwet's AC2 coefficient); and (iii) empirical testing and validation of the criteria, by blinded post-mortem assessment of brain tissue from 113 individuals (55 to 100 years) without significant neurodegenerative disease who had had formal cognitive assessments within 12 months of death. Fourteen different vessel and parenchymal pathologies were assessed in 13 brain regions. Almost perfect agreement (AC2 > 0.8) was found when the agreed criteria were used for assessment of leptomeningeal, cortical and capillary cerebral amyloid angiopathy, large infarcts, lacunar infarcts, microhaemorrhage, larger haemorrhage, fibrinoid necrosis, microaneurysms, perivascular space dilation, perivascular haemosiderin leakage, and myelin loss. There was more variability (but still reasonably good agreement) in assessment of the severity of arteriolosclerosis (0.45-0.91) and microinfarcts (0.52-0.84). Regression analyses were undertaken to identify the best predictors of cognitive impairment. Seven pathologies-leptomeningeal cerebral amyloid angiopathy, large infarcts, lacunar infarcts, microinfarcts, arteriolosclerosis, perivascular space dilation and myelin loss-predicted cognitive impairment. Multivariable logistic regression determined the best predictive models of cognitive impairment. The preferred model included moderate/severe occipital leptomeningeal cerebral amyloid angiopathy, moderate/severe arteriolosclerosis in occipital white matter, and at least one large infarct (area under the receiver operating characteristic curve 77%). The presence of 0, 1, 2 or 3 of these features resulted in predicted probabilities of vascular cognitive impairment of 16%, 43%, 73% or 95%, respectively. We have developed VCING criteria that are reproducible and clinically predictive. Assuming our model can be validated in an independent dataset, we believe that this will be helpful for neuropathologists in reporting a low, intermediate or high likelihood that cerebrovascular disease contributed to cognitive impairment.10.1093/brain/aww214_video_abstractaww214_video_abstract.

The Vascular Impairment of Cognition Classification Consensus Study.

INTRODUCTION: Numerous diagnostic criteria have tried to tackle the variability in clinical manifestations and problematic diagnosis of vascular cognitive impairment (VCI) but none have been universally accepted. These criteria have not been readily comparable, impacting on clinical diagnosis rates and in turn prevalence estimates, research, and treatment. METHODS: The Vascular Impairment of Cognition Classification Consensus Study (VICCCS) involved participants (81% academic researchers) from 27 countries in an online Delphi consensus study. Participants reviewed previously proposed concepts to develop new guidelines. RESULTS: VICCCS had a mean of 122 (98-153) respondents across the study and a 67% threshold to represent consensus. VICCCS redefined VCI including classification of mild and major forms of VCI and subtypes. It proposes new standardized VCI-associated terminology and future research priorities to address gaps in current knowledge. DISCUSSION: VICCCS proposes a consensus-based updated conceptualization of VCI intended to facilitate standardization in research.

APOE associations with severe CAA-associated vasculopathic changes: collaborative meta-analysis.

OBJECTIVES: Cerebral amyloid angiopathy (CAA) is associated with lobar intracerebral haemorrhage (ICH). While only the ε4 allele of the apolipoprotein E (APOE) gene is associated with the presence of CAA, both APOE-ε4 and ε2 are associated with lobar ICH. The generally accepted explanation is that APOE-ε4 promotes vascular amyloid deposition, while APOE-ε2 promotes progression to severe CAA with associated vasculopathic changes that cause vessel rupture and ICH. We assessed the evidence for these allele-specific effects. METHODS: We systematically identified published studies with data on APOE genotype and histopathological assessment of postmortem brains for CAA severity. We obtained unpublished data from these for meta-analyses of the effects of ε4-containing (ε4+) and ε2-containing (ε2+) genotypes on progression to severe CAA. RESULTS: Of six eligible studies (543 eligible participants), data were available from 5 (497 participants, 353 with CAA). Meta-analyses showed a possible association of ε4+ genotypes with severe CAA (ε4+ vs ε4-: severe vs mild/moderate CAA, OR 2.5, 95% CI 1.4 to 4.5, p=0.002; severe vs moderate CAA, OR 1.7, 95% CI 0.9 to 3.1, p=0.11). For ε2+ versus ε2- genotypes, there was no significant association, but the very small number of participants with ε2+ genotypes (22) precluded reliable estimates. CONCLUSIONS: We found a possible association of severe CAA with APOE-ε4 but not APOE-ε2. However, our findings do not exclude a biologically meaningful association between APOE-ε2 and severe CAA. Further work is needed to elucidate fully the allele-specific associations of APOE with CAA and their mechanisms.

Lack of Association of Vascular Risk Factors with HIV-Associated Neurocognitive Disorders in cART-Treated Adults Aged ≥ 50 Years in Tanzania.

HIV-associated neurocognitive disorders (HAND) are highly prevalent in those ageing with HIV. High-income country data suggest that vascular risk factors (VRFs) may be stronger predictors of HAND than HIV-disease severity, but data from sub-Saharan Africa are lacking. We evaluated relationships of VRFs, vascular end-organ damage and HAND in individuals aged ≥ 50 in Tanzania. c-ART-treated individuals were assessed for HAND using consensus criteria. The prevalence of VRFs and end organ damage markers were measured. The independent associations of VRFs, end organ damage and HAND were examined using multivariable logistic regression. Data were available for 153 individuals (median age 56, 67.3% female). HAND was highly prevalent (66.7%, 25.5% symptomatic) despite well-managed HIV (70.5% virally suppressed). Vascular risk factors included hypertension (34%), obesity (10.5%), hypercholesterolemia (33.3%), diabetes (5.3%) and current smoking (4.6%). End organ damage prevalence ranged from 1.3% (prior myocardial infarction) to 12.5% (left ventricular hypertrophy). Measured VRFs and end organ damage were not independently associated with HAND. The only significant association was lower diastolic BP (p 0.030, OR 0.969 (0.943-0.997). Our results suggest that vascular risk factors are not major drivers of HAND in this setting. Further studies should explore alternative aetiologies such as chronic inflammation.

Biomarkers and Risk Assessment of Alzheimer's Disease in Low- and Middle-Income Countries.

Dementia is a chronic syndrome which is common among the elderly and is associated with significant morbidity and mortality for patients and their caregivers. Alzheimer's disease (AD), the most common form of clinical dementia, is biologically characterized by the deposition of amyloid-ß plaques and neurofibrillary tangles in the brain. The onset of AD begins decades before manifestation of symptoms and clinical diagnosis, underlining the need to shift from clinical diagnosis of AD to a more objective diagnosis using biomarkers. Having performed a literature search of original articles and reviews on PubMed and Google Scholar, we present this review detailing the existing biomarkers and risk assessment tools for AD. The prevalence of dementia in low- and middle-income countries (LMICs) is predicted to increase over the next couple of years. Thus, we aimed to identify potential biomarkers that may be appropriate for use in LMICs, considering the following factors: sensitivity, specificity, invasiveness, and affordability of the biomarkers. We also explored risk assessment tools and the potential use of artificial intelligence/machine learning solutions for diagnosing, assessing risks, and monitoring the progression of AD in low-resource settings. Routine use of AD biomarkers has yet to gain sufficient ground in clinical settings. Therefore, clinical diagnosis of AD will remain the mainstay in LMICs for the foreseeable future. Efforts should be made towards the development of low-cost, easily administered risk assessment tools to identify individuals who are at risk of AD in the population. We recommend that stakeholders invest in education, research and development targeted towards effective risk assessment and management.

Transcriptomic Profiling Reveals Discrete Poststroke Dementia Neuronal and Gliovascular Signatures.

Poststroke dementia (PSD) is associated with pathology in frontal brain regions, in particular dorsolateral prefrontal cortex (DLPFC) neurons and white matter, remote from the infarct. We hypothesised that PSD results from progressive DLPFC neuronal damage, associated with frontal white matter gliovascular unit (GVU) alterations. We investigated the transcriptomic profile of the neurons and white matter GVU cells previously implicated in pathology. Laser-capture microdissected neurons, astrocytes and endothelial cells were obtained from the Cognitive Function After Stroke cohort of control, PSD and poststroke non-dementia (PSND) human subjects. Gene expression was assessed using microarrays and pathway analysis to compare changes in PSD with controls and PSND. Neuronal findings were validated using NanoString technology and compared with those in the bilateral common carotid artery stenosis (BCAS) mouse model. Comparing changes in PSD compared to controls with changes in PSND compared to controls identified transcriptomic changes associated specifically with dementia. DLPFC neurons showed defects in energy production (tricarboxylic acid (TCA) cycle, adenosine triphosphate (ATP) binding and mitochondria), signalling and communication (MAPK signalling, Toll-like receptor signalling, endocytosis). Similar changes were identified in neurons isolated from BCAS mice. Neuronal findings accompanied by altered astrocyte communication and endothelium immune changes in the frontal white matter, suggesting GVU dysfunction. We propose a pathogenic model in PSD whereby neuronal changes are associated with frontal white matter GVU dysfunction leading to astrocyte failure in supporting neuronal circuits resulting in delayed cognitive decline associated with PSD. Therefore, targeting these processes could potentially ameliorate the dementia seen in PSD.

Neuropathology of microbleeds in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

Cerebral microbleeds (CMBs) detected on magnetic resonance imaging are common in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The neuropathologic correlates of CMBs are unclear. In this study, we characterized findings relevant to CMBs in autopsy brain tissue of 8 patients with genetically confirmed CADASIL and 10 controls within the age range of the CADASIL patients by assessing the distribution and extent of hemosiderin/iron deposits including perivascular hemosiderin leakage (PVH), capillary hemosiderin deposits, and parenchymal iron deposits (PID) in the frontal cortex and white matter, basal ganglia and cerebellum. We also characterized infarcts, vessel wall thickening, and severity of vascular smooth muscle cell degeneration. CADASIL subjects had a significant increase in hemosiderin/iron deposits compared with controls. This increase was principally seen with PID. Hemosiderin/iron deposits were seen in the majority of CADASIL subjects in all brain areas. PVH was most pronounced in the frontal white matter and basal ganglia around small to medium sized arterioles, with no predilection for the vicinity of vessels with severe vascular changes or infarcts. CADASIL subjects have increased brain hemosiderin/iron deposits but these do not occur in a periarteriolar distribution. Pathogenesis of these lesions remains uncertain.

Capacity-Building for Stroke Genomic Research Data Collection: The African Neurobiobank Ethical, Legal, and Social Implications Project Experience.

Background: The fields of stroke genomics, biobanking, and precision medicine are rapidly expanding in sub-Saharan Africa. However, the ethical, legal, and social implications (ELSI) of emerging neurobiobanking and genomic data resources are unclear in an emerging African scientific landscape with unique cultural, linguistic, and belief systems. Objective: This article documents capacity-building experiences of researchers during the development, pretesting, and validation of data collection instruments of the African Neurobiobank for Precision Stroke Medicine-(ELSI) Project. Methods: The African Neurobiobank for Precision Stroke Medicine-ELSI project is a transnational, multicenter project implemented across seven sites in Ghana and Nigeria. Guided by the Community-Based Participatory Research framework, we conducted three workshops with key stakeholders to review the study protocol, ensure uniformity in implementation; pretest, harmonize, and integrate context-specific feedback to ensure validity and adaptability of data collection instruments. Workshop impact was assessed using an open-ended questionnaire, which included questions on experience with participation in any of the workshops, building capacity in Genetic and Genomic Research (GGR), level of preparedness toward GGR, the genomic mini-dictionary developed by the team, and its impact in enhancing understanding in GGR. Data were analyzed qualitatively using a thematic framework approach. Results: Findings revealed the usefulness of the workshop in improving participants' knowledge and capacity toward GGR implementation. It further identified local, context-specific concerns regarding quality data collection, the need to develop culturally acceptable, genomic/biobanking data collection tools, and a mini-dictionary. Participants-reported perceptions were that the mini-dictionary enhanced understanding, participation, and data collection in GGR. Overall, participants reported increased preparedness and interest in participating in GGR. Conclusion: Capacity-building is a necessary step toward ELSI-related genomic research implementation in African countries where scholarship of ELSI of genomics research is emerging. Our findings may be useful to the design and implementation of ELSI-GGR projects in other African countries.

Research participants' perception of ethical issues in stroke genomics and neurobiobanking research in Africa.

Background: There is a growing interest in stroke genomics and neurobiobanking research in Africa. These raise several ethical issues, such as consent, re-use, data sharing, storage, and incidental result of biological samples. Despite the availability of ethical guidelines developed for research in Africa, there is paucity of information on how the research participants' perspectives could guide the research community on ethical issues in stroke genomics and neurobiobanking research. To explore African research participants' perspectives on these issues, a study was conducted at existing Stroke Investigation Research and Education Network (SIREN) sites in Nigeria and Ghana. Method: Using an exploratory design, twenty-eight Focus Group Discussions (FGDs) sessions were conducted with stroke survivors (n=7), caregivers(n=7), stroke - free controls(n=7), and Community Advisory Board members(n=7). Data were collected using an interview guide. Interviews were conducted in English and indigenous languages of the community, audio recorded, and transcribed verbatim. Data were analyzed using NVivo (March, 2020) Software. Result: Results revealed that stroke genomics and neurobiobanking research in Africa require researchers' direct attention to ethical issues. Concerns were raised about understanding, disclosure and absence of coercion as components of true autonomous decision making in research participation. Participants argued that the risk and benefits attached to participation should be disclosed at the time of recruitment. Fears around data sharing were voiced as adherence to the principle of privacy and confidentiality were of paramount importance to participants. The preference was to receive the results of incidental findings with no stigma attached from society. Conclusion: Research participants' perspectives are a vital aspect of community engagement in stroke genomics and neurobiobanking research. Findings from this study suggest that research participants are interested in these fields of research in Africa if their concerns about ethical issues are appropriately addressed within the research framework.

Non-Communicable Neurological Disorders and Neuroinflammation.

Traumatic brain injury, stroke, and neurodegenerative diseases represent a major cause of morbidity and mortality in Africa, as in the rest of the world. Traumatic brain and spinal cord injuries specifically represent a leading cause of disability in the younger population. Stroke and neurodegenerative disorders predominantly target the elderly and are a major concern in Africa, since their rate of increase among the ageing is the fastest in the world. Neuroimmunology is usually not associated with non-communicable neurological disorders, as the role of neuroinflammation is not often considered when evaluating their cause and pathogenesis. However, substantial evidence indicates that neuroinflammation is extremely relevant in determining the consequences of non-communicable neurological disorders, both for its protective abilities as well as for its destructive capacity. We review here current knowledge on the contribution of neuroinflammation and neuroimmunology to the pathogenesis of traumatic injuries, stroke and neurodegenerative diseases, with a particular focus on problems that are already a major issue in Africa, like traumatic brain injury, and on emerging disorders such as dementias.

Nox2 underpins microvascular inflammation and vascular contributions to cognitive decline.

Chronic microvascular inflammation and oxidative stress are inter-related mechanisms underpinning white matter disease and vascular cognitive impairment (VCI). A proposed mediator is nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (Nox2), a major source of reactive oxygen species (ROS) in the brain. To assess the role of Nox2 in VCI, we studied a tractable model with white matter pathology and cognitive impairment induced by bilateral carotid artery stenosis (BCAS). Mice with genetic deletion of Nox2 (Nox2 KO) were compared to wild-type (WT) following BCAS. Sustained BCAS over 12 weeks in WT mice induced Nox2 expression, indices of microvascular inflammation and oxidative damage, along with white matter pathology culminating in a marked cognitive impairment, which were all protected by Nox2 genetic deletion. Neurovascular coupling was impaired in WT mice post-BCAS and restored in Nox2 KO mice. Increased vascular expression of chemoattractant mediators, cell-adhesion molecules and endothelial activation factors in WT mice post-BCAS were ameliorated by Nox2 deficiency. The clinical relevance was confirmed by increased vascular Nox2 and indices of microvascular inflammation in human post-mortem subjects with cerebral vascular disease. Our results support Nox2 activity as a critical determinant of VCI, whose targeting may be of therapeutic benefit in cerebral vascular disease.

Biological sample donation and informed consent for neurobiobanking: Evidence from a community survey in Ghana and Nigeria.

INTRODUCTION: Genomic research and neurobiobanking are expanding globally. Empirical evidence on the level of awareness and willingness to donate/share biological samples towards the expansion of neurobiobanking in sub-Saharan Africa is lacking. AIMS: To ascertain the awareness, perspectives and predictors regarding biological sample donation, sharing and informed consent preferences among community members in Ghana and Nigeria. METHODS: A questionnaire cross-sectional survey was conducted among randomly selected community members from seven communities in Ghana and Nigeria. RESULTS: Of the 1015 respondents with mean age 39.3 years (SD 19.5), about a third had heard of blood donation (37.2%, M: 42.4%, F: 32.0%, p = 0.001) and a quarter were aware of blood sample storage for research (24.5%; M: 29.7%, F: 19.4%, p = 0.151). Two out of ten were willing to donate brain after death (18.8%, M: 22.6%, F: 15.0%, p<0.001). Main reasons for unwillingness to donate brain were; to go back to God complete (46.6%) and lack of knowledge related to brain donation (32.7%). Only a third of the participants were aware of informed consent (31.7%; M: 35.9%, F: 27.5%, p<0.001). Predictors of positive attitude towards biobanking and informed consent were being married, tertiary level education, student status, and belonging to select ethnic groups. CONCLUSION: There is a greater need for research attention in the area of brain banking and informed consent. Improved context-sensitive public education on neurobiobanking and informed consent, in line with the sociocultural diversities, is recommended within the African sub region.