Memory impairment in Amyloidß-status Alzheimer's disease is associated with a reduction in CA1 and dentate gyrus volume: In vivo MRI at 7T.

INTRODUCTION: In Alzheimer's disease (AD), early diagnosis facilitates treatment options and leads to beneficial outcomes for patients, their carers and the healthcare system. The neuropsychological battery of the Uniform Data Set (UDSNB3.0) assesses cognition in ageing and dementia, by measuring scores across different cognitive domains such as attention, memory, processing speed, executive function and language. However, its neuroanatomical correlates have not been investigated using 7 Tesla MRI (7T MRI). METHODS: We used 7T MRI to investigate the correlations between hippocampal subfield volumes and the UDSNB3.0 in 24 individuals with Amyloidß-status AD and 18 age-matched controls, with respective age ranges of 60 (42-76) and 62 (52-79) years. AD participants with a Medial Temporal Atrophy scale of higher than 2 on 3T MRI were excluded from the study. RESULTS: A significant difference in the entire hippocampal volume was observed in the AD group compared to healthy controls (HC), primarily influenced by CA1, the largest hippocampal subfield. Notably, no significant difference in whole brain volume between the groups implied that hippocampal volume loss was not merely reflective of overall brain atrophy. UDSNB3.0 cognitive scores showed significant differences between AD and HC, particularly in Memory, Language, and Visuospatial domains. The volume of the Dentate Gyrus (DG) showed a significant association with the Memory and Executive domain scores in AD patients as assessed by the UDSNB3.0.. The data also suggested a non-significant trend for CA1 volume associated with UDSNB3.0 Memory, Executive, and Language domain scores in AD. In a reassessment focusing on hippocampal subfields and MoCA memory subdomains in AD, associations were observed between the DG and Cued, Uncued, and Recognition Memory subscores, whereas CA1 and Tail showed associations only with Cued memory. DISCUSSION: This study reveals differences in the hippocampal volumes measured using 7T MRI, between individuals with early symptomatic AD compared with healthy controls. This highlights the potential of 7T MRI as a valuable tool for early AD diagnosis and the real-time monitoring of AD progression and treatment efficacy. CLINICALTRIALS: GOV: ID NCT04992975 (Clinicaltrial.gov 2023).

Neuropsychological tests associated with symptomatic HIV-associated neurocognitive disorder (HAND) in a cohort of older adults in Tanzania.

OBJECTIVE: Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) prevalence is expected to increase in East Africa as treatment coverage increases, survival improves, and this population ages. This study aimed to better understand the current cognitive phenotype of this newly emergent population of older combination antiretroviral therapy (cART)-treated people living with HIV (PLWH), in which current screening measures lack accuracy. This will facilitate the refinement of HAND cognitive screening tools for this setting. METHOD: This is a secondary analysis of 253 PLWH aged ≥50 years receiving standard government HIV clinic follow-up in Kilimanjaro, Tanzania. They were evaluated with a detailed locally normed low-literacy neuropsychological battery annually on three occasions and a consensus panel diagnosis of HAND by Frascati criteria based on clinical evaluation and collateral history. RESULTS: Tests of verbal learning and memory, categorical verbal fluency, visual memory, and visuoconstruction had an area under the receiver operating characteristic curve >0.7 for symptomatic HAND (s-HAND) (0.70-0.72; p < 0.001 for all tests). Tests of visual memory, verbal learning with delayed recall and recognition memory, psychomotor speed, language comprehension, and categorical verbal fluency were independently associated with s-HAND in a logistic mixed effects model (p < 0.01 for all). Neuropsychological impairments varied by educational background. CONCLUSIONS: A broad range of cognitive domains are affected in older, well-controlled, East African PLWH, including those not captured in widely used screening measures. It is possible that educational background affects the observed cognitive impairments in this setting. Future screening measures for similar populations should consider assessment of visual memory, verbal learning, language comprehension, and executive and motor function.

The prevalence and outcomes of depression in older HIV-positive adults in Northern Tanzania: a longitudinal study.

Studies of depression and its outcomes in older people living with HIV (PLWH) are currently lacking in sub-Saharan Africa. This study aims to investigate the prevalence of psychiatric disorders in PLWH aged ≥ 50 years in Tanzania focussing on prevalence and 2-year outcomes of depression. PLWH aged ≥ 50 were systematically recruited from an outpatient clinic and assessed using the Mini-International Neuropsychiatric Interview (MINI). Neurological and functional impairment was assessed at year 2 follow-up. At baseline, 253 PLWH were recruited (72.3% female, median age 57, 95.5% on cART). DSM-IV depression was highly prevalent (20.9%), whereas other DSM-IV psychiatric disorders were uncommon. At follow-up (n = 162), incident cases of DSM-IV depression decreased from14.2 to 11.1% (χ2: 2.48, p = 0.29); this decline was not significant. Baseline depression was associated with increased functional and neurological impairment. At follow-up, depression was associated with negative life events (p = 0.001), neurological impairment (p < 0.001), and increased functional impairment (p = 0.018), but not with HIV and sociodemographic factors. In this setting, depression appears highly prevalent and associated with poorer neurological and functional outcomes and negative life events. Depression may be a future intervention target.

Sex-disease dimorphism underpins enhanced motion sickness susceptibility in primary adrenal insufficiency: a cross-sectional observational study.

Environmental motion can induce physiological stress and trigger motion sickness. In these situations, lower-than-normal levels of adrenocorticotropic hormone (ACTH) have been linked with increased susceptibility to motion sickness in healthy individuals. However, whether patients with primary adrenal insufficiency, who typically have altered ACTH levels compared to the normal population, exhibit alterations in sickness susceptibility remains unknown. To address this, we recruited 78 patients with primary adrenal insufficiency and compared changes in the motion sickness susceptibility scores from 10 years prior to diagnosis (i.e. retrospective sickness rating) with the current sickness measures (post-diagnosis), using the validated motion sickness susceptibility questionnaire (MSSQ). Group analysis revealed that motion sickness susceptibility pre-diagnosis did not differ between controls and patients. We observed that following treatment, current measures of motion sickness were significantly increased in patients and subsequent analysis revealed that this increase was primarily in female patients with primary adrenal insufficiency. These observations corroborate the role of stress hormones in modulating sickness susceptibility and support the notion of a sexually dimorphic adrenal cortex as we only observed selective enhancement in females. A potential mechanism to account for our novel observation remains obscure, but we speculate that it may reflect a complex sex-disease-drug interaction.

Prevalence and 1-year incidence of HIV-associated neurocognitive disorder (HAND) in adults aged ≥50 years attending standard HIV clinical care in Kilimanjaro, Tanzania.

OBJECTIVES: HIV-associated neurocognitive disorders (HANDs) are prevalent in older people living with HIV (PLWH) worldwide. HAND prevalence and incidence studies of the newly emergent population of combination antiretroviral therapy (cART)-treated older PLWH in sub-Saharan Africa are currently lacking. We aimed to estimate HAND prevalence and incidence using robust measures in stable, cART-treated older adults under long-term follow-up in Tanzania and report cognitive comorbidities. DESIGN: Longitudinal study. PARTICIPANTS: A systematic sample of consenting HIV-positive adults aged ≥50 years attending routine clinical care at an HIV Care and Treatment Centre during March-May 2016 and followed up March-May 2017. MEASUREMENTS: HAND by consensus panel Frascati criteria based on detailed locally normed low-literacy neuropsychological battery, structured neuropsychiatric clinical assessment, and collateral history. Demographic and etiological factors by self-report and clinical records. RESULTS: In this cohort (n = 253, 72.3% female, median age 57), HAND prevalence was 47.0% (95% CI 40.9-53.2, n = 119) despite well-managed HIV disease (Mn CD4 516 (98-1719), 95.5% on cART). Of these, 64 (25.3%) were asymptomatic neurocognitive impairment, 46 (18.2%) mild neurocognitive disorder, and 9 (3.6%) HIV-associated dementia. One-year incidence was high (37.2%, 95% CI 25.9 to 51.8), but some reversibility (17.6%, 95% CI 10.0-28.6 n = 16) was observed. CONCLUSIONS: HAND appear highly prevalent in older PLWH in this setting, where demographic profile differs markedly to high-income cohorts, and comorbidities are frequent. Incidence and reversibility also appear high. Future studies should focus on etiologies and potentially reversible factors in this setting.

Preliminary evaluation of a smartphone application (DelApp) for identification of delirium in sub-Saharan Africa.

OBJECTIVE: In sub-Saharan Africa, there are no validated screening tools for delirium in older adults, despite the known vulnerability of older people to delirium and the associated adverse outcomes. This study aimed to assess the effectiveness of a brief smartphone-based assessment of arousal and attention (DelApp) in the identification of delirium amongst older adults admitted to the medical department of a tertiary referral hospital in Northern Tanzania. METHOD: Consecutive admissions were screened using the DelApp during a larger study of delirium prevalence and risk factors. All participants subsequently underwent detailed clinical assessment for delirium by a research doctor. Delirium and dementia were identified against DSM-5 criteria by consensus. RESULTS: Complete data for 66 individuals were collected of whom 15 (22.7%) had delirium, 24.5% had dementia without delirium, and 10.6% had delirium superimposed on dementia. Sensitivity and specificity of the DelApp for delirium were 0.87 and 0.62, respectively (AUROC 0.77) and 0.88 and 0.73 (AUROC 0.85) for major cognitive impairment (dementia and delirium combined). Lower DelApp score was associated with age, significant visual impairment (<6/60 acuity), illness severity, reduced arousal and DSM-5 delirium on univariable analysis, but on multivariable logistic regression only arousal remained significant. CONCLUSION: In this setting, the DelApp performed well in identifying delirium and major cognitive impairment but did not differentiate delirium and dementia. Performance is likely to have been affected by confounders including uncorrected visual impairment and reduced level of arousal without delirium. Negative predictive value was nevertheless high, indicating excellent 'rule out' value in this setting.

Interplay of Ferritin Accumulation and Ferroportin Loss in Ageing Brain: Implication for Protein Aggregation in Down Syndrome Dementia, Alzheimer's, and Parkinson's Diseases.

Iron accumulates in the ageing brain and in brains with neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Down syndrome (DS) dementia. However, the mechanisms of iron deposition and regional selectivity in the brain are ill-understood. The identification of several proteins that are involved in iron homeostasis, transport, and regulation suggests avenues to explore their function in neurodegenerative diseases. To uncover the molecular mechanisms underlying this association, we investigated the distribution and expression of these key iron proteins in brain tissues of patients with AD, DS, PD, and compared them with age-matched controls. Ferritin is an iron storage protein that is deposited in senile plaques in the AD and DS brain, as well as in neuromelanin-containing neurons in the Lewy bodies in PD brain. The transporter of ferrous iron, Divalent metal protein 1 (DMT1), was observed solely in the capillary endothelium and in astrocytes close to the ventricles with unchanged expression in PD. The principal iron transporter, ferroportin, is strikingly reduced in the AD brain compared to age-matched controls. Extensive blood vessel damage in the basal ganglia and deposition of punctate ferritin heavy chain (FTH) and hepcidin were found in the caudate and putamen within striosomes/matrix in both PD and DS brains. We suggest that downregulation of ferroportin could be a key reason for iron mismanagement through disruption of cellular entry and exit pathways of the endothelium. Membrane damage and subsequent impairment of ferroportin and hepcidin causes oxidative stress that contributes to neurodegeneration seen in DS, AD, and in PD subjects. We further propose that a lack of ferritin contributes to neurodegeneration as a consequence of failure to export toxic metals from the cortex in AD/DS and from the substantia nigra and caudate/putamen in PD brain.

Informal Caregiving and Alzheimer's Disease: The Psychological Effect.

Background and Objectives: People with Alzheimer's disease and dementia in general benefit from home-based care as demonstrated via their better quality of life, increased lifespan, and delayed disease progression. Since currently nearly half of the dementia care is being provided by informal and unpaid caregiving, the health, wellbeing and quality of life of informal dementia caregivers is extremely important. Materials and Methods: We used a systematic review process with searches based upon the six elements from the "Quality of Life Scale for Informal Carers of Older Adults" with additional items on traditional and non-traditional caregiving ideologies, as well as caregivers' experiences. Results: We identified 19 studies with primary data. Informal caregivers of older adults with Alzheimer's Disease experience significant emotional strain, documented through increased levels of anxiety and depression, as well as increased caregiver burden and poorer quality of life, primarily due to caregiving ideologies, financial strain and a lack of support. Conclusions: Our findings suggest that caregiving should be a normative component of adult education to better prepare individuals with the mental and physical skills required for undertaking informal caregiving. They should also help inform policy makers to develop novel programs and services to both assist and reduce informal caregivers' strain, whilst considering their different social and cultural contexts.

Low levels of frailty in HIV-positive older adults on antiretroviral therapy in northern Tanzania.

There are over 3 million people in sub-Saharan Africa (SSA) aged 50 and over living with HIV. HIV and combined antiretroviral therapy (cART) exposure may accelerate the ageing in this population, and thus increase the prevalence of premature frailty. There is a paucity of data on the prevalence of frailty in an older HIV + population in SSA and screening and diagnostic tools to identify frailty in SSA. Patients aged ≥ 50 were recruited from a free Government HIV clinic in Tanzania. Frailty assessments were completed, using 3 diagnostic and screening tools: the Fried frailty phenotype (FFP), Clinical Frailty Scale (CFS) and Brief Frailty Instrument for Tanzania (B-FIT 2). The 145 patients recruited had a mean CD4 + of 494.84 cells/µL, 99.3% were receiving cART and 72.6% were virally suppressed. The prevalence of frailty by FFP was 2.758%. FFP frailty was significantly associated with female gender (p = 0.006), marital status (p = 0.007) and age (p = 0.038). Weight loss was the most common FFP domain failure. The prevalence of frailty using the B-FIT 2 and the CFS was 0.68%. The B-FIT 2 correlated with BMI (r = - 0.467, p = 0.0001) and CD4 count in females (r = - 0.244, p = 0.02). There is an absence of frailty in this population, as compared to other clinical studies. This may be due to the high standard of HIV care at this Government clinic. Undernutrition may be an important contributor to frailty. It is unclear which tool is most accurate for detecting the prevalence of frailty in this setting as levels of correlation are low.

Screening for HIV-Associated Neurocognitive Disorder (HAND) in Adults Aged 50 and Over Attending a Government HIV Clinic in Kilimanjaro, Tanzania. Comparison of the International HIV Dementia Scale (IHDS) and IDEA Six Item Dementia Screen.

Validated screening tools for HIV-associated neurocognitive disorders (HAND) are lacking for the newly emergent ageing population of people living with HIV (PLWH) in sub-Saharan Africa (SSA). We aimed to validate and compare diagnostic accuracy of two cognitive screening tools, the International HIV dementia scale (IHDS), and the Identification and Interventions for Dementia in Elderly Africans (IDEA) screen, for identification of HAND in older PLWH in Tanzania. A systematic sample of 253 PLWH aged ≥ 50 attending a Government clinic in Tanzania were screened with the IHDS and IDEA. HAND were diagnosed by consensus American Academy of Neurology (AAN) criteria based on detailed clinical neuropsychological assessment. Strict blinding was maintained between screening and clinical evaluation. Both tools had limited diagnostic accuracy for HAND (area under the receiver operating characteristic (AUROC) curve 0.639-0.667 IHDS, 0.647-0.713 IDEA), which was highly-prevalent (47.0%). Accurate HAND screening tools for older PLWH in SSA are needed.

RESUMEN: Faltan pruebas cognitivas válidas para los trastornos neurocognitivos asociados al VIH (según sus siglas en inglés, HIV-Associated Neurocognitive Disorder (HAND) en la población emergente de personas mayores que viven con el VIH en el África subsahariana. Nuestro objetivo era validar y comparar la precisión diagnóstica de dos pruebas cognitivas, la escala internacional de demencia por VIH (según sus siglas en ingles International HIV dementia scale (IHDS) y la prueba 'IDEA', para el cribado de trastornos neurocognitivos asociados al VIH (HAND) en personas mayores viviendo con VIH en Tanzania. Una muestra sistemática de 253 personas de ≥50 años que asistieron a una clínica gubernamental en Tanzania se examinó con el IHDS y la IDEA. HAND fueron diagnosticados por consenso según los criterios de la Academia Americana de Neurología (AAN) basados en una detallada evaluación neuropsicológica y clínica. Las fases de cribado y de evaluación clínica se realizaron de forma independiente y a ciegas. Ambas herramientas tenían una precisión de diagnóstico limitada para HAND (área bajo la característica de funcionamiento del receptor (AUROC) curva 0.639 ­ 0.667 IHDS, 0.647-0.713 IDEA). HAND era altamente frecuente (47%). Se necesitan pruebas cognitivas por cribado de deterioro cognitivo en personas mayores con VIH en el África subsahariana.

Risk factors for symptomatic HIV-associated neurocognitive disorder in adults aged 50 and over attending a HIV clinic in Tanzania.

OBJECTIVES: HIV-associated neurocognitive disorder (HAND), although prevalent, remains a poorly researched cause of morbidity particularly in sub-Saharan Africa (SSA). We aimed to explore the risk factors for HAND in people aged 50 and over under regular follow-up at a government HIV clinic in Tanzania. METHODS: HIV-positive adults aged 50 years and over were approached for recruitment at a routine HIV clinic appointment over a 4-month period. A diagnostic assessment for HAND was implemented, including a full medical/neurological assessment and a collateral history from a relative. We investigated potential risk factors using a structured questionnaire and by examination of clinic records. RESULTS: Of the cohort (n = 253), 183 (72.3%) were female and the median age was 57 years. Fifty-five individuals (21.7%) met the criteria for symptomatic HAND. Participants were at a greater risk of having symptomatic HAND if they lived alone [odds ratio (OR) = 2.566, P = .015], were illiterate (OR 3.171, P = .003) or older at the time of HIV diagnosis (OR = 1.057, P = .015). Age was correlated with symptomatic HAND in univariate, but not multivariate analysis. CONCLUSIONS: In this setting, HIV-specific factors, such as nadir CD4 count, were not related to symptomatic HAND. The "legacy theory" of early central nervous system damage prior to initiation of anti-retroviral therapy initiation may contribute, only in part, to a multifactorial aetiology of HAND in older people. Social isolation and illiteracy were associated with symptomatic HAND, suggesting greater cognitive reserve might be protective.

The Prevalence of Diabetes in Autistic Persons: A Systematic Review.

BACKGROUND: It has been proposed that autistic individuals are at an increased risk of type 1 and type 2 diabetes. Improved understanding of diabetes prevalence in autistic persons will help inform resource allocation for diabetes-related public health measures for this patient group. OBJECTIVE: To conduct a systematic review of published literature pertaining to type 1 and type 2 diabetes prevalence in autistic individuals, including comparison with their non-autistic peers. METHODS: Eligibility criteria included studies investigating the prevalence of diabetes in autistic individuals, as well as having been published in the English language. A systematic search of online databases (MEDLINE, PsycINFO, CINAHL, EMBASE and PubMed) was conducted on 4th April 2020. Additional approaches included the ancestry method, grey literature searches and expert consultation. Studies were qualitatively analysed with reporting quality appraised. RESULTS: 19 eligible studies were identified, 7 of which provided type-specific diabetes prevalence data. Of 15 studies that included a non-autistic control group, 9 reported a higher diabetes prevalence among autistic persons, with a statistically significant difference in 4 studies. Studies demonstrating a higher diabetes prevalence in autistic groups had higher average study population sizes and reporting quality ratings. CONCLUSION: It is uncertain whether diabetes is significantly more prevalent in autistic persons relative to their non-autistic peers, though larger studies suggest a trend in this direction. Nevertheless, diabetes is a significant public health issue for the autistic community, which may require a tailored approach for identification and management. Prospero database registration number: CRD42019122176.

The therapeutic 'make-over' of dementias-an introduction.

The online themed collection of 15 papers recently published provides an update on the advances of pharmacological and non-pharmacological interventions in dementia over the last 15 years. The published studies reflect the efficacy of the current anti-dementia treatments, preventive treatments of cardio and cerebrovascular incidents (known to be risk factors for dementia), alongside the use of antidepressant medication and non-pharmacological interventions for treatment of behavioural and psychopathological symptoms of dementia. We also address the future preventative steps and therapeutic strategies currently in development to combat the devastating consequences of dementia.

Risk Factors for Delirium in Older Medical Inpatients in Tanzania.

BACKGROUND: The risk factors for prevalent delirium in older hospitalised adults in Sub-Saharan Africa (SSA) remain poorly characterised. METHODS: A total of 510 consecutive admissions of adults aged ≥60 years to acute medical wards of Kilimanjaro Christian Medical Centre in northern Tanzania were recruited. Patients were assessed within 24 h of admission with a risk factor questionnaire, physiological observations, neurocognitive assessment, and informant interview. Delirium and dementia diagnoses were made according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM V) and DSM IV respectively, by an expert panel. RESULTS: Being male, current alcohol use, dementia, and physiological markers of illness severity were significant independent risk factors for delirium on multivariable analysis. CONCLUSIONS: The risk factors for prevalent delirium in older medical inpatients in SSA include pre-existing dementia, and are similar to those identified in high-income countries. Our data could help inform the development of a delirium risk stratification tool for older adults in SSA.

Electrochemical Detection of Plasma Immunoglobulin as a Biomarker for Alzheimer's Disease.

The clinical diagnosis and treatment of Alzheimer's disease (AD) represent a challenge to clinicians due to the variability of clinical symptomatology as well as the unavailability of reliable diagnostic tests. In this study, the development of a novel electrochemical assay and its potential to detect peripheral blood biomarkers to diagnose AD using plasma immunoglobulins is investigated. The immunosensor employs a gold electrode as the immobilizing substrate, albumin depleted plasma immunoglobulin as the biomarker, and polyclonal rabbit Anti-human immunoglobulin (against IgA, IgG, IgM) as the receptor for plasma conjugation. The assay showed good response, sensitivity and reproducibility in differentiating plasma immunoglobulin from AD and control subjects down to 10-9 dilutions of plasma immunoglobulin representing plasma content concentrations in the pg mL-1 range. The newly developed assay is highly sensitive, less time consuming, easy to handle, can be easily modified to detect other dementia-related biomarkers in blood samples, and can be easily integrated into portable devices.

Evaluation of the delirium early monitoring system (DEMS).

BACKGROUND: Despite awareness of the negative health and financial outcomes of delirium, systems to routinely assess and manage the condition are absent in clinical practice. We report the development and pilot evaluation of a Delirium Early Monitoring System (DEMS), designed to be completed by non-medical staff to influence clinical processes within inpatient settings. Two versions of the DEMS are described based on a modified Confusion Assessment Method (DEMS-CAM) and Delirium Observation Screening Scale (DEMS-DOSS). METHODS: Both versions of DEMS were piloted on a 20-bedded Psychogeriatric ward over 6 weeks. Training was administered to ward staff on the use of each version of the DEMS and data were collected via electronic medical records and completed assessment sheets. The primary outcome was patterns of DEMS use and the secondary outcome was the initiation of delirium management protocols. Data regarding the use of the DEMS DOSS and DEMS CAMS were analyzed using χ 2 tests. RESULTS: Completion rates for the DEMS CAM and DEMS DOSS were 79% and 68%, respectively. Non-medical staff were significantly more likely to use the DEMS-CAM as part of daily practice as opposed to the DEMS-DOSS (p<0.001). However, there was no difference between the use of the DEMS-CAM and DEMS-DOSS in triggering related actions such as documentation of assessment scores in patients' medical records and implementation of delirium management protocols. CONCLUSIONS: This real world evaluation revealed that non-medical staff were able to incorporate delirium monitoring into their practice, on the majority of occasions, as part of their daily working routine. Further research is necessary to determine if the routine use of the DEMS can lead to improved understandings and practice of non-medical staff regarding delirium detection.

Plasma and platelet clusterin ratio is altered in Alzheimer's disease patients with distinct neuropsychiatric symptoms: findings from a pilot study.

BACKGROUND: Clusterin protein in plasma has been found to differentiate between people with and without cognitive changes. However, these findings are not conclusive, despite the clusterin gene variations repeatedly being linked to increased risk for dementia, in particular Alzheimer's disease (AD). METHOD: We analysed the level of clusterin in platelet and plasma in 25 subjects with a clinical diagnosis of AD and 26 subjects with no cognitive impairment. RESULTS: In the current study, we report that the levels of both plasma and platelet clusterin are similar between AD and cognitively intact individuals. Clusterin plasma and platelet levels, as well as the plasma/platelet clusterin ratio, were not affected by age, gender, cognitive impairment and/or overt behavioural symptomatology, including presence of hallucinations and delusions, as well as depression. However, the plasma/platelet clusterin ratio was positively associated in with the Neuropsychiatric Inventory measures of agitation, apathy, irritability and motor aberrant behaviour in AD subjects. CONCLUSION: Previous inconsistencies in reported blood clusterin levels may be a result of underlying non-cognitive symptoms in people with AD. Our findings need now to be replicated in larger group of dementia subjects.

Molecular imaging biomarkers for dementia with Lewy bodies: an update.

BACKGROUND: Dementia with Lewy body (DLB) is considered to be the second most common form of neurodegenerative disorders after Alzheimer's disease (AD), affecting as many as 100,000 people in the UK and up to 1.3 million in the USA. However, nearly half of patients with DLB remain undiagnosed thus depriving many of them from an early and adequate treatment of their distressing symptoms. Accurate and early diagnosis of DLB is important for both patients and their caregivers, since the neuropsychiatric symptoms require specific management. METHODS: In the current study, we review the most recent developments in the field of molecular nuclear imaging to diagnose DLB. RESULTS: The review addresses, the neurotransmitter based (dopaminergic, cholinergic, and glutamatergic) nuclear imaging techniques, role of the autonomic dysfunction and its visualization in DLB with myocardial sympathetic imaging and vesicular catecholamine uptake, as well as the use of amyloid polypeptides and glial markers as molecular imaging probes in the clinical diagnosis of DLB. CONCLUSIONS: Most of the above nuclear imaging methods are restricted to highly specialized clinical centers, and thus not applicable to a large number of patients requiring dementia (e.g. DLB) diagnosis in routine clinical setting. Validating them against more readily accessible peripheral biomarkers, e.g. CSF and blood biomarkers linked to the DLB process, may facilitate their use in wider clinical settings.

Deconstructing dementia and delirium hospital practice: using cultural historical activity theory to inform education approaches.

Older patients with dementia and delirium receive suboptimal hospital care. Policy calls for more effective education to address this though there is little consensus on what this entails. The purpose of this clarification study is to explore how practice gaps are constructed in relation to managing the confused hospitalised older patient. The intent is to inform educational processes in the work-place beyond traditional approaches such as training. Adopting grounded theory as a research method and working within a social constructionist paradigm we explored the practice gaps of 15 healthcare professionals by interview and conducted five focus groups with patients, carers and Liaison mental health professionals. Data were thematically analysed by constant comparison and theoretical sampling was undertaken until saturation reached. Categories were identified and pragmatic concepts developed grounded within the data. Findings were then further analysed using cultural historical activity theory as a deductive lens. Practice gaps in relation to managing the confused older patient are determined by factors operating at individual (knowledge and skill gaps, personal philosophy, task based practice), team (leadership, time and ward environmental factors) and organisational (power relationships, dominance of medical model, fragmentation of care services) levels. Conceptually, practice appeared to be influenced by socio-cultural ward factors and compounded by a failure to join up existing "patient" knowledge amongst professionals. Applying cultural historical activity theory to further illuminate the findings, the central object is defined as learning about the patient and the mediating artifacts are the care relationships. The overarching medical dominance emerges as an important cultural historical factor at play and staff rules and divisions of labour are exposed. Lastly key contradictions and tensions in the system that work against learning about the patient are identified. Cultural historical activity theory can be used to advance understanding of practice gaps in order to develop a broader transformative approach to dementia and delirium practice and education. Structural changes at an individual, team and systems level resulting from this novel understanding of practice complexity are proposed. Contradictions can be used as foci for expansive learning. Lastly, interprofessional education (formal and informal) is advocated to further knotwork and improve the care of the older confused patient.