Students find cardiovascular physiology challenging. Misunderstandings can be due to the nature of the subject, the way it is taught, and prior knowledge, which impede learning of new concepts. Some misunderstood concepts can be corrected with teaching (i.e., preconceptions), whereas others are resistant to instruction (i.e., misconceptions). A set of questions, specifically created by a panel of physiology experts to probe difficult cardiovascular concepts, was used to identify preconceptions, misconceptions, and the effect of education level on question performance. The introductory cardiovascular lecture used in this study was created based on these questions. In-class polling of medical students’ ( n = 736) performance was performed using the Turning-Point clicker response system during lecture instruction. Results were compared with published data from undergraduates ( n = 1,076) who completed the same questions but without prior instruction. To our knowledge, there have been no studies directly comparing performance using the same instrument and large numbers of undergraduate and medical students. A higher education level was associated with increased performance (preconceptions), whereas several concepts resistant to instruction (misconceptions) were identified. Findings suggest that prior knowledge interfered with the acquisition of medical knowledge. Based on these results, potential causes for these misconceptions and remedial teaching suggestions are discussed.

The medical education system in the United States has gone through a rapid transition to emergency remote teaching as a consequence of the COVID 19 pandemic. For the Engineering Medicine (EnMed) track of the College of Medicine at Texas A&M University, the most challenging aspects are the transition from in-class team-based learning (TBL) to online sessions and virtual facilitation with an interdisciplinary group of faculties. This article outlines the TBL format used in the EnMed curriculum, along with challenges in delivery, student perspective, and strategies for transitioning existing TBL online.

WHAT IS KNOWN ON THE SUBJECT?: People diagnosed with "BPD" often experience crisis and use services "BPD" is a controversial diagnosis, and the experience of crisis and crisis intervention is not well understood WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: People diagnosed with "BPD" have different experiences of crisis, and using the diagnosis alone as a basis for deciding care and treatment is not appropriate There are many human factors which can influence how professionals deliver care to people diagnosed with "BPD" WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The education of staff, views on responsibility, team conflicts and access to clinical supervision can have an impact on how care is delivered, and should be addressed by organizations providing crisis care. Access to care often occurs when a person is self-harming or suicidal, but does not address underlying distress. Crisis care should go beyond managing behaviour and address any underlying needs. ABSTRACT: Introduction "Borderline personality disorder" ("BPD") is associated with frequent use of crisis intervention services. However, no robust evidence base supports specific interventions, and people's experiences are not well understood. Aim To explore the experiences of stakeholders involved in the crisis care of people diagnosed with "BPD." Method Integrative review with nine databases searched January 2000 to November 2017. The search filtered 3,169 titles and abstracts with 46 full-text articles appraised and included. Results Four themes were constructed from thematic analysis: crisis as a recurrent multidimensional cycle, variations and dynamics impacting on crisis intervention, impact of interpersonal dynamics and communication on crisis, and balancing decision-making and responsibility in managing crisis. Discussion Crisis is a multidimensional subjective experience, which also contributes to distress for family carers and professionals. Crisis interventions had limited and subjective benefit. They are influenced by accessibility of services, different understandings of "BPD" and human dynamics in complex decision-making, and can be experienced as helpful or harmful. Implications for practice Subjectivity of crisis experiences shows limitations of the diagnostic model of "BPD," emphasizing that interventions should remain person-centred. While thresholds for intervention are often met after self-harm or suicidality, professionals should review approaches to care and support people with underlying distress.

Medical students have difficulty understanding the mechanisms underlying hyperkalemia-mediated local control of blood flow. Such control mechanisms are crucial in the brain, kidney. and skeletal muscle vasculature. We aimed to identify medical students' misconceptions via assessment of students' in-class knowledge and, subsequently, improve future teaching of this concept. In-class polling was performed with the Turning-Point clicker response system (n = 860) to gauge students' understanding of three physiological concepts related to hyperkalemia: membrane potential (V-m), conductance, and smooth muscle response. V-m includes the concepts of equilibrium potential (V-eq) for specific ions, as well as driving force (DF = V-m - V-eq). Students understood the concept of DF (similar to 70% answered correctly), suggesting their understanding of V-m. However, students misunderstood that hyperkalemia results in depolarization (similar to 52% answered correctly) and leads to an increase in potassium conductance (similar to 31% answered correctly). Clarification of the type of smooth muscle as vascular increased the percentage of correct responses (similar to 51 to 73%). The data indicate that students lacked knowledge of specific potassium conductance in various muscle types, resulting in divergent responses, such as the canonical depolarization in skeletal muscle versus hyperpolarization in smooth muscle cells during hyperkalemia. Misunderstanding of this crucial concept of conductance is directly related to the students' performance. Furthermore, we connected the paradoxical effect of hyperkalemia to pathological acute and chronic hyperkalemia clinical scenarios.

A 25-year-old woman presented a challenging diagnosis of acute rheumatic fever (ARF). Initial symptoms included dry cough and three minor Jones criteria (unabating fever (38.4°C, 0d), elevated acute phase reactants (C-reactive protein, 13d) and joint pain (monoarthralgia) in her neck (0d)). ARF was diagnosed only after presentation of two major Jones criteria (polyarthritis/polyarthralgia (16d) and erythema marginatum (41d)) and positive antistreptolysin O titre (44d). Parotid swelling, peripheral oedema, elevated liver enzymes and diffuse lymphadenopathy complicated the diagnosis. Throat swab, chorea and carditis were negative or absent. Atypical ARF is challenging to recognise. There is no diagnostic test and its presentation is similar to that of other diseases. While the 2015 Jones criteria modification increased specificity of ARF diagnosis, atypical cases may still be missed, especially by physicians in developed countries. Suspicion of atypical ARF, especially after travel to high incidence regions, would allow for earlier treatment and prevention of rheumatic heart disease.

Protein folding is a complex, multisystem process characterized by heavy molecular and cellular footprints. Chaperone machinery enables proper protein folding and stable conformation. Other pathways concomitant with the protein folding process include transcription, translation, post-translational modifications, degradation through the ubiquitin-proteasome system, and autophagy. As such, the folding process can go awry in several different ways. The pathogenic basis behind most neurodegenerative diseases is that the disruption of protein homeostasis (i.e. proteostasis) at any level will eventually lead to protein misfolding. Misfolded proteins often aggregate and accumulate to trigger neurotoxicity through cellular stress pathways and consequently cause neurodegenerative diseases. The manifestation of a disease is usually dependent on the specific brain region that the neurotoxicity affects. Neurodegenerative diseases are age-associated, and their incidence is expected to rise as humans continue to live longer and pursue a greater life expectancy. We presently review the sequelae of protein misfolding and aggregation, as well as the role of these phenomena in several neurodegenerative diseases including Alzheimer’s disease, Huntington’s disease, amyotrophic lateral sclerosis, Parkinson’s disease, transmissible spongiform encephalopathies, and spinocerebellar ataxia. Strategies for treatment and therapy are also conferred with respect to impairing, inhibiting, or reversing protein misfolding.

Physiology is one of the major foundational sciences for the medical curriculum. This discipline has proven challenging for students to master due to ineffective content acquisition and retention. Preliminary data obtained from a survey completed by "low-performance" students (those maintaining a grade average below the passing mark of 70%) at Morehouse School of Medicine reported that students lacked the ability to adequately recognize and extract important physiological concepts to successfully navigate multiple-choice assessments. It was hypothesized that a specially designed, small-group, active learning, physiology in-course enrichment program would minimize course assessment failure rates by enhancing the ability of low-performance students to effectively identify important course content, successfully perform on multiple-choice assessments, and, thereby, improve overall course performance. Using self-report surveys, study skills and test-taking deficiencies limiting successful comprehension of course material and examination performance were identified. Mini-quiz assessments and assignments in formulating multiple-choice examination questions were given to help students recognize and solidify core concepts and improve test-taking ability. Lastly, self-report surveys evaluated the effectiveness of the enrichment program on overall course performance. Results showed a marked improvement in student confidence levels with regards to approaching multiple-choice assessments, and a significant improvement in grades achieved in the physiology component of the first-year curriculum, as 100% of participants achieved a final passing grade average of ≥70%. It was concluded that students became more proficient in identifying, understanding, and applying core physiological concepts and more successful in mastering multiple-choice questions.

Amyloid formation is that the pathological hallmark of type 2 diabetes (T2D) and Alzheimer’s disease (AD). These diseases are marked by extracellular amyloid deposits of islet amyloid polypeptide (IAPP) within the pancreas and amyloid β (Aβ) within the brain. Since it's been shown that IAPP enters the brain which disparate amyloids can cross-seed one another to reinforce amyloid formation, we determined if such crossseeding can occur with the amyloids involved in T2D and AD. We demonstrated that: (1) IAPP promoted oligomerization of Aβ in vitro and in silico, (2) peripheral injection of IAPP increased murine brain IAPP levels, (3) endogenous IAPP localized to Aβ in plaques in mouse models of AD, (4) IAPP was present in and secreted from astrocytes, and (5) IAPP levels were elevated in AD humor (CSF). These observations prompted us to explore a possible mechanism whereby IAPP elevated during metabolic dysfunction enters the brain to cross-seed Aβ and augment AD pathology. We tested this mechanism in both humans and transgenic mice, correlating peripheral levels of IAPP with AD pathology. In African Americans, a gaggle with increased risk for both T2D and AD, peripheral IAPP levels weren't significantly different in samples with no disease, T2D, AD, or both T2D and AD. Furthermore, within the Tg 2576 AD mouse model, IAPP plasma levels weren't significantly elevated at an age where the mice exhibit the glucose intolerance of pre-diabetes. supported this data, it appears unlikely that peripheral IAPP cross-seeds Aβ pathology in the AD brain. However, we offer evidence for a unique association between brain-derived IAPP and AD, which suggests that brain-derived IAPP plays a task in Aβ oligomerization and AD pathology. This potential connection, together with IAPP’s known role in weight and state of mind, requires further research.

Obstructive sleep apnea (OSA) is a sleep disorder characterized by intermittent cessations of breathing due to obstruction of the upper respiratory tract. Obesity and OSA often coexist and obesity may be a major risk factor for worsening OSA. Both are associated with several comorbidities such as hypertension, cardiovascular disease and cerebrovascular accidents. There are biomarkers that are shared between both obesity and OSA with some being more sensitive for OSA. To better understand the relationship of the biomarkers associated specifically with OSA, a more comprehensive review of OSA biomarkers compared to previous literature was conducted with the goal of determining whether OSA is an individual risk factor. Specifically, OSA patients were matched based on BMI to controls with no comorbidities to rule out confounders. Furthermore, it was investigated if continuous positive airway pressure (CPAP) therapy was effective in reducing these biomarkers. OSA was shown to be an individual associated risk factor, compared to obesity, for further changes in biomarkers related to inflammatory changes (Il-8, TNF- a, IL-6, INF-y), epithelial and cellular receptor regulation (ICAM-1, VCAM-1, P-Selectin, TLR-2 and TLR-4), atherosclerosis biomarkers and anatomical changes (increased CIMT, pulse wave velocity, catecholamines, aortic pulse velocity index), diabetes (HbA1c, insulin resistance) and hypertension (sFLT-1, sEng, YKL-40). This review revealed that biomarkers are significantly associated with OSA independent from obesity. CPAP treatment resulted in a reduction of these biomarkers.

The 99.6% failure rate of Alzheimer's disease (AD) drugs suggests flaws in the amyloid hypothesis, and prompts examination of alternative hypotheses. The neurovascular/vascular hypotheses of AD encompass hypoperfusion and metabolic deficits, involve glial, vascular, and neuronal changes, and resulted in identification of AD risk factors (stroke and atherosclerosis). We present substantial new findings and data of our unpublished meta-analysis validation of the neurovascular hypothesis. Using PRISMA guidelines, published data was extracted from publications identified via PubMed and Google scholar searches for the keywords “AD”, “CSF”, and “human”. Selection was for biomarkers measured in both AD and control groups. Sixteen biomarkers were selected: serine, taurine, glycine, methionine, SAM, 5-methyltetrahydrofolate (5- MTHF), cobalamin/B12, thiamine/B1, folate/B9, hFABP, SAP, 24(s)-hydroxycholesterol, VEGF, MCP-1, YKL-40 and homocysteine. Note that homocysteine data was from both CSF and plasma. Ratios of means (RoMs, AD/Control) were calculated and analyzed using random effects meta-analysis; and quality of publications evaluated by a statistical metric. Of 835 publications identified, exclusion and removal of duplicates yielded 112 articles comprising of 6716 AD patients and 8641 control subjects. Significant biomarker differences (AD/control) are as follows: YKL-40 (pooled RoM 1.30, 95% CI 1.25-1.36, p< 0.00001), MCP-1 (1.12, 1.06-1.18, p< 0.00001), 24(s)-hydroxycholesterol (1.27, 1.03-1.57, p=0.02), SAP (1.30, 1.01-1.67, p=0.05), SAM (0.90, 0.83-0.98, p=0.01), 5-MTHF (0.91, 0.85-0.97, p=0.008), and homocysteine: (plasma 1.19, 95% CI 1.11-1.28, p< 0.00001; CSF 1.15, 95% CI 1.10-1.34 p=0.06). The neurovascular hypothesis implicates glial, vascular, and neuronal changes in AD pathology. Glial involvement was suggested by highly significant elevations of glial markers YKL-40 and MCP-1. Vascular (endothelial) dysfunction is not implicated as homocysteine was significantly elevated in blood, but NOT CSF. Vascular involvement via reduced cholesterol clearance is suggested by elevation of CSF 24(s)-hydroxycholesterol levels. Additional data analysis yielded unforeseen results, such as possible dysfunction of methylation reactions in the AD brain (SAM, 5MTHF). Our meta-analysis validates glial involvement in the neurovascular hypothesis, suggest that homocysteine lowering therapies may be ineffective, and compels the investigation of further therapeutic targets.

Background: Alzheimer's disease (AD) is currently incurable and a majority of investigational drugs have failed clinical trials. One explanation for this failure may be the invalidity of hypotheses focusing on amyloid to explain AD pathogenesis. Recently, hypotheses which are centered on synaptic and metabolic dysfunction are increasingly implicated in AD. Objective: Evaluate AD hypotheses by comparing neurotransmitter and metabolite marker concentrations in normal versus AD CSF. Methods: Meta-analysis allows for statistical comparison of pooled, existing cerebrospinal fluid (CSF) marker data extracted from multiple publications, to obtain a more reliable estimate of concentrations. This method also provides a unique opportunity to rapidly validate AD hypotheses using the resulting CSF concentration data. Hubmed, Pubmed and Google Scholar were comprehensively searched for published English articles, without date restrictions, for the keywords “AD”, “CSF”, and “human” plus markers selected for synaptic and metabolic pathways. Synaptic markers were acetylcholine, gamma-aminobutyric acid (GABA), glutamine, and glycine. Metabolic markers were glutathione, glucose, lactate, pyruvate, and 8 other amino acids. Only studies that measured markers in AD and controls (Ctl), provided means, standard errors/deviation, and subject numbers were included. Data were extracted by six authors and reviewed by two others for accuracy. Data were pooled using ratio of means (RoM of AD/Ctl) and random effects meta-analysis using Cochrane Collaboration’s Review Manager software. Results: Of the 435 identified publications, after exclusion and removal of duplicates, 35 articles were included comprising a total of 605 AD patients and 585 controls. The following markers of synaptic and metabolic pathways were significantly changed in AD/controls: acetylcholine (RoM 0.36, 95% CI 0.24-0.53, p<0.00001), GABA (0.74, 0.58-0.94, p<0.01), pyruvate (0.48, 0.24-0.94, p=0.03), glutathione (1.11, 1.01- 1.21, p=0.03), alanine (1.10, 0.98-1.23, p=0.09), and lower levels of significance for lactate (1.2, 1.00-1.47, p=0.05). Of note, CSF glucose and glutamate levels in AD were not significantly different than that of the controls. Conclusion: This study provides proof of concept for the use of meta-analysis validation of AD hypotheses, specifically via robust evidence for the cholinergic hypothesis of AD. Our data disagree with the other synaptic hypotheses of glutamate excitotoxicity and GABAergic resistance to neurodegeneration, given observed unchanged glutamate levels and decreased GABA levels. With regards to metabolic hypotheses, the data supported upregulation of anaerobic glycolysis, pentose phosphate pathway (glutathione), and anaplerosis of the tricarboxylic acid cycle using glutamate. Future applications of meta-analysis indicate the possibility of further in silico evaluation and generation of novel hypotheses in the AD field.

Dementias occur in 10% of the population over 65, with Alzheimer's disease (AD) being the most common, followed by Vascular Dementia (VaD). Mild Cognitive Impairment (MCI) may be prodromal for dementias (AD or VaD). These diseases share several pathological features of altered cognition, metabolic dysfunction, inflammation, and vascular dysfunction, and are currently diagnosed via neurocognitive tests. We hypothesized that meta-analysis of biomarkers for these pathological features would distinguish between MCI, AD and VaD, using Parkinson's disease (PD) as a control disease with markedly different etiogenesis. PubMed and Google Scholar were searched for published articles, without date restrictions, using the keywords “AD”, “CSF”, and “human” and 41 biomarkers for cardiovascular, metabolic, glial, and neuronal pathways or functions. Inclusion criteria were: AD, PD, VaD or MCI diagnoses, and CSF biomarkers measured in both disease and control groups. Ratios of means (RoMs, AD/Control) were calculated and analyzed using random effects meta-analysis. We included 127 publications comprising of 743 diseased and 751 control subjects. RoMs of 10 out of 41 biomarkers were significantly altered in these diseases (Table 1). Despite the limitations of a small number of publications, low power and poor biomarker coverage for MCI, our data suggests differences in functional pathways in these diseases. Acetylcholine, involved in cognition, is lowered in the dementias. Pyruvate, a biomarker of metabolism, was decreased in AD and increased in VaD. Branched chain amino acids, utilized in anaplerosis and glutamate synthesis, were elevated in VaD. VEGF, a biomarker of angiogenesis, was elevated in MCI and VaD. Among inflammatory glial biomarkers, YKL-40 was elevated in MCI, VaD and AD, and MCP-1 was elevated in AD. Notably, PD did not have major overlap in biomarkers. Despite the limitations of this study, pooling of data via meta-analysis results in greater power than the individual publications. Tantalizing results were obtained suggesting that these biomarkers differentiated between these diseases; however, they require further validation. It is clear from our in-silico findings that routine measurement of these CSF biomarkers is advised and can advance the identification of differential or diagnostic biomarkers.

Alzheimer's disease (AD) is currently incurable and a majority of investigational drugs have failed clinical trials. One explanation for this failure is the invalidity of some hypotheses explaining AD pathogenesis. Recently, hypotheses centered on synaptic and metabolic dysfunction are increasingly implicated in AD. Importantly, these hypotheses can readily be validated using neurotransmitter and metabolite biomarkers. Meta-analysis allows for statistical comparison of existing CSF biomarker data extracted from multiple publications, providing a unique opportunity to rapidly validate AD hypotheses in silico. Pubmed and Google Scholar were comprehensively searched for published English articles, without date restrictions, for the keywords “AD”, “CSF”, and “human” plus biomarkers selected for synaptic and metabolic pathways. Synaptic biomarkers were acetylcholine, GABA, glutamine, and glycine. Metabolic biomarkers were glutathione, glucose, lactate, pyruvate, and 8 other amino acids. Only studies that measured biomarkers in both AD and controls, provided means, standard errors/deviation, and subject numbers were included. Data were extracted by six authors and checked by two for accuracy. The data were transformed to log ratio of the means (AD/Control) and analyzed by the random effects model in the meta-analysis software (Cochrane Review Manager). Of 435 identified publications, after exclusion and removal of duplicates, 35 articles were included comprising a total of 605 AD patients and 585 controls. The following biomarkers for synaptic and metabolic pathways were significantly changed in AD/controls: acetylcholine (average ratio 0.36, 95% CI 0.24–0.53, p<0.00001), GABA (0.68, 0.54–0.85, p<0.0008), pyruvate (0.48, 0.24–0.94, p=0.03), glutathione (1.11, 1.01–1.21, p=0.03), alanine (1.10, 0.98–1.23, p=0.09), and lactate (1.17, 0.98–1.39, p=0.09). This study provides proof of concept for the use of meta-analysis validation of AD hypotheses, specifically via robust evidence for the cholinergic hypothesis of AD. Our data disagree with the other synaptic hypotheses of glutamate excitotoxicity (normal glutamate) and GABAergic resistance to neurodegeneration (decreased GABA levels). With regards to metabolic hypotheses, the data supported upregulation of anaerobic glycolysis, pentose phosphate pathway (glutathione), and TCA anaplerosis (several metabolites involved). Future applications of meta-analysis indicate the possibility of further in silico evaluation and generation of novel hypotheses in the AD field.

Alzheimer's disease (AD) is currently incurable and the majority of investigational drugs have failed clinical trials. Thus, there is need to identify novel AD therapeutic targets. Metabolomic analysis of AD CSF has quantified several metabolites. We used meta-analysis to identify the metabolites sginificanlty altered in AD. These metabolites were then correlated to novel or underrepresented AD mechanisms in the literature. Pubmed and Google Scholar were searched for published English articles, without date restrictions, using the keywords “AD”, “CSF”, and “human” plus 41 markers for cardiovascular, metabolic, glial, neuronal, and repair functions. Inclusion criteria were: CSF biomarkers measured in both AD and control groups, with means, standard errors/deviations, and subject numbers reported. Data was extracted by 13 authors and checked by two for accuracy. Data were transformed to log ratio of the means (AD/Control) and analyzed by random effects model in meta-analysis software (Cochrane Review Manager). Of 4,309 publications identified, after exclusion and removal of duplicates, 92 articles were included comprising of 3,492 AD patients and 3,622 control subjects. Markers for neuronal cardiovascular, and glial functions, metabolism, and repair were significantly altered in AD are listed below. Neuronal markers significantly changed in AD/Controls: acetylcholine (average ratio 0.36, 95% CI 0.24–0.53, p<0.00001), GABA (0.68, 0.54–0.85, p<0.0008), and taurine (0.88, 0.77–0.99, p=0.04). Cardiovascular markers: homocysteine (1.19, 1.11–1.28, p< 0.00001), folate/vitamin B9 (0.82, 0.68–0.99, p=0.03), s-adenylmethionine (0.62, 0.40–0.98, p=0.04), cobalamin/B12 (0.90, 0.81–1.0, p=0.04), and 5-methyltetrahydrofolate (0.91, 0.82–1.00, p=0.05). Glial marker: YKL-40 (1.27, 1.22–1.31, p< 0.00001). Metabolic markers: pyruvate (0.48, 0.24–0.94, p=0.03), glutathione (1.11, 1.01–1.21, p=0.03), and lactate (1.17, 0.98–1.39, p=0.09). Markers related to neuronal or wound repair: 24(s)hydroxycholesterol (1.27, 1.03–1.57, p=0.02), and serum amyloid P (SAP: 1.3, 1.01–1.67, p=0.05). Meta-analysis of markers associated with AD identified well known pathways (cholinergic, homocysteine, vitamin B), as well as under-appreciated mechanisms. Examples include a hypoxic-induced response in anaerobic glycolysis (lactate, pyruvate), reduced neuronal inhibition (GABA, taurine decreases), and wound/vascular/glial repair mechanisms (SAP, 24(s)hydroxycholesterol, YKL-40). This meta-analysis of metabolomic data holds promise for in silico evaluation and generation of novel hypotheses in the AD field.

panel of rat (APPsi) and mouse (Tg4-42) biofluids and tissues. This give further help to understand the devastating neurodegenerative disease, related complex biochemical pathways and pathophysiological processes of AD.Conclusions:UsingNMR-basedmetabolic phenotyping we defined a quantitative readout of transgenic animal models in the form of a biomarker panel. These biomarkers not only contribute to the understanding of this devastating neurodegenerative disease and the related pathophysiological processes on a systemic level, but set the base for a wide range of biomedical applications. Our approach can be easily extended to other tissues, matrices, or disease models and translated across species since metabolic pathways are conserved through evolution, and are essentially similar in rodents and humans.

Clear racial differences exist regarding Alzheimer's disease (AD) incidence, with Black individuals 2–3 times more likely to develop AD as White individuals. Compared to Whites, Caribbean Blacks also have increased rates of dementia diagnoses. These disparities may be attributed to increased cardiovascular disease, diabetes risk factors, missed diagnoses, and poor AD knowledge. No AD incidence data is available in Grenada, though a high incidence rate is expected in its predominantly Black population. We hypothesized that lack of AD incidence data may be indicative of a lack of knowledge of AD and related risk factors in Grenada. This study was approved by the Institutional Review Board and conducted from January-April 2015. The validated and published 30-item true/false Alzheimer's Disease Knowledge Scale (ADKS) survey was administered to 183 respondents. The ADKS evaluated several domains of AD knowledge, with an overall ADKS score calculated by summing correct responses. The ADKS also used word matching to yield a Shipley intelligence score. 41.5% of respondents were black, and 64.5% were born in Grenada. The ADKS score was significantly lower in Grenadians compared to the rest of the respondents, but not attributable to gender, race, or age. Grenadians tended to score lower in specific ADKS domains such as risk factors, caregiving, disease symptoms and course. A weak correlation between ADKS and the Shipley intelligence score was observed. Higher education level and affiliation with the SGU School of Medicine correlated with significant increases in the ADKS score, seen in Grenadians, medical students, physicians, and other faculty. Similar published results in survey outcomes were found in US and Australian populations, specifically related to the increased ADKS scores with higher education, and deficits in specific knowledge domains surveyed. Our data suggest that there may be a high incidence of AD in Grenada, influenced by insufficient recognition of AD by lay population, and not due to missed diagnoses. Educational outreach on AD-related risk factors, such as diabetes and high blood pressure, will not only reduce those disease incidences but also likely reduce AD incidence in Grenada.

Dysfunction of the neurovascular unit results in reduced cerebral blood flow, microglial activation and neuronal dysfunction in AD. The significance of mechanistic aspects of the vascular hypothesis can be evaluated by statistical quantification of cardiovascular, glial and neuronal function markers. Furthermore, meta-analysis of these existing CSF marker data, extracted from multiple publications, provides a unique opportunity to rapidly evaluate the importance of these three contributing pathologies. Pubmed and Google scholar were comprehensively searched for published English articles, without date restrictions, for the keywords “AD”, “CSF”, and “human” plus markers selected for cardiovascular, glial, and neuronal functions. Cardiovascular markers used were CRP, hFABP, homocysteine, and VEGF. Glial markers were VKL-40, and MCP-1. Markers of neurological function were vitamins B1and B12, taurine, glycine and 24(s)hydroxycholesterol. Homocysteine pathway markers included methionine, vitamin B9, 5-methyltetrahydrofolate (5-MTHF), serine, and s-adenylmethionine (SAM). Selection criteria for included studies were: CSF biomarkers measured in both AD and control groups, with means, standard errors/deviations, and subject numbers reported. Data was extracted by 6 authors and independently checked by two others for accuracy. The data was transformed to log ratio of the means (AD/Control) and analyzed by random effects model in the meta-analysis software (Cochrane Review Manager). Of 3874 publications identified, after exclusion and removal of duplicates, 67 articles were included comprising of 2,087 AD patients and 1,991 control subjects. The following markers were significantly changed in AD/controls: homocysteine (average ratio 1.19, 95% CI 1.11–1.28, p< 0.00001), YKL-40 (1.27,1.22–1.31, p< 0.00001), 24(s)hydroxycholesterol (1.27,1.03–1.57, p=0.02), folate/vitamin B9 (0.82, 0.68–0.99, p=0.03), SAM (0.62,0.40–0.98, p=0.04), cobalamin/B12 (0.90,0.81–1.0), p=0.04, taurine (0.88,0.77–0.99, p=0.04), and 5-MTHF (0.91,0.82–1.00, p=0.05). This meta-analysis provides support for the vascular hypothesis of AD, and suggests that cardiovascular and glial mechanisms (homocysteine, 24(s)hydroxycholesterol, and YKL-40) play an important role in AD pathogenesis. Reduced perfusion due to atherosclerosis is also suggested (homocysteine and 24(s)hydroxycholersterol). Homocysteine is associated with cognitive decline and brain atrophy. It can be inferred that vitamin B supplementation, and reduction of homocysteine levels prevent cognitive loss.

Oxidative stress is a frequently observed feature of Alzheimer's disease, but its pathological significance is not understood. To explore the relationship between oxidative stress and amyloid plaques, uniformly radiolabeled arachidonate was introduced into transgenic mouse models of Alzheimer's disease via intracerebroventricular injection. Uniform labeling with carbon-14 is used here for the first time, and made possible meaningful quantification of arachidonate oxidative degradation products. The injected arachidonate entered a fatty acid pool that was subject to oxidative degradation in both transgenic and wild-type animals. However, the extent of its degradation was markedly greater in the hippocampus of transgenic animals where amyloid plaques were abundant. In human Alzheimer's brain, plaque-associated proteins were post-translationally modified by hydroxynonenal, a well-known oxidative degradation product of arachidonate. These results suggest that several recurring themes in Alzheimer's pathogenesis, amyloid β proteins, transition metal ions, oxidative stress, and apolipoprotein isoforms, may be involved in a common mechanism that has the potential to explain both neuronal loss and fibril formation in this disease.

Oxidative stress is a frequently observed feature of Alzheimer's disease, but its cause and pathological significance are unclear. Polyunsaturated fatty acids such as arachidonate (omega 6) and docosahexaenoic (omega 3) acids are highly abundant in the brain and are extremely vulnerable to oxidation due to their multiple double bonds. Indeed previously reported in vitro evidence suggests that amyloid beta proteins, in conjunction with transition metal ions, promote the oxidative degradation of polyunsaturated fatty acids into neurotoxic degradation products. Radiolabeled arachidonic acid was introduced via intracerebroventricular injection into mouse models of Alzheimer's disease and the distribution and accumulation of degradation metabolites were monitored. In addition immunohistopathological analysis was performed with antibodies against HNE, an oxidized derivate of arachidonate, in human Alzheimer's disease brains. The oxidative degradation of arachidonate is markedly accelerated in regions of the brain where amyloid plaques are abundant. Studies of human Alzheimer's disease brain show that amyloid plaques co-locate with proteins modified by hydroxynonenal.