Background: Alzheimer's disease (AD), the commonest form of dementia, affects people in both industrialised and developing countries. Risk factors for the development of AD include age, the presence of the Apolipoprotein ε4 allele, low vitamin B₁₂ and folate levels, and elevated plasma homocysteine concentrations. Most research involving the associations between these risk factors and AD have been conducted in Europe and North America. We know little about AD and its risk factors in a low to middle income country like South Africa, where nutrition is poor and the background population ApoE ε4 allelic frequency is high. Objective: In this prospective observational study, I wished to determine the relationships between plasma homocysteine, vitamin B₁₂, folate, ApoE ε4 status and cognition in a sample of older persons from the greater Cape Town metropolitan area of the Western Cape region of South Africa. Methods: Cognitively healthy controls and AD participants, diagnosed using NINCDS-ADRDA criteria, were recruited from the community. The study had both cross-sectional and longitudinal components. Cross-sectionally, I related non-fasting plasma homocysteine concentrations, vitamin B₁₂ levels, folate concentrations and the ApoE ε4 genotype to scores from a battery of cognitive tests including the Mini Mental State Examination (MMSE), the Cambridge Cognitive Examination (CAMCOG) and the Learning Subscale score of the CAMCOG. In the longitudinal analysis, I tested whether baseline plasma homocysteine concentrations related to cognitive decline one year after the initial assessment. Results: One hundred and thirteen participants were recruited: 60 controls and 53 AD participants. Plasma homocysteine levels increased with age (rs= 0.418, p<0.001) and were inversely related to cognitive scores in all participants. Homocysteine concentrations were inversely related to vitamin B₁₂ and folate in all study participants (vitamin B₁₂rₛ= -0.47, p<0.001, folaterₛ=-0.33, p=0.001). Homocysteine was inversely related to cognition but, in a regression model, this relation was confounded by the effects of age and years of education. Another regression model showed that vitamin B₁₂ and age independently predicted cognitive scores. There were more ApoE ε4 carriers in the AD group compared with controls and ε4 carrier status was significantly associated with AD. The ApoE ε4 allele modified the relationship between homocysteine and cognition. The association between homocysteine and cognition was strong in ApoE ε4 carriers (e.g. MMSE,rₛ=0.33, p=0.003), but absent in ε4 non-carriers. High baseline homocysteine concentrations did not predict cognitive decline 1 year later. Conclusions: These findings, the first from an African low to middle income country, are consistent with those from studies in industrialised countries. Plasma homocysteine levels increased with age and were inversely related to vitamin B₁₂ and folate. The ApoE ε4 allele strengthened the association between homocysteine and cognition, probably through mechanisms that increase neuronal susceptibility to homocysteine toxicity. My study supports the idea that homocysteine-lowering therapy can reduce the risk of developing AD or slow the progression of the disease.

Background: There are no published longitudinal studies from Africa of people with dementia seen in memory clinics. The aim of this study was to determine the proportions of the different dementia subtypes, rates of cognitive decline, and predictors of survival in patients diagnosed with dementia and seen in a memory clinic. Methods: Data were collected retrospectively from clinic records of patients aged ≥60 seen in the memory clinic at Groote Schuur Hospital, Cape Town, South Africa over a 10-year period. Diagnostic and Statistical Manual of Mental Disorders (DSM–5) criteria were used to identify patients with Major Neurocognitive Disorders (dementia). Additional diagnostic criteria were used to determine the specific subtypes of dementia. Linear regression analysis was used to determine crude rates of cognitive decline, expressed as mini-mental state examination (MMSE) points lost per year. Changes in MMSE scores were derived using mixed effects modelling to curvilinear models of cognitive change, with time as the dependent variable. Multivariable cox survival analysis was used to determine factors at baseline that predicted mortality. Results: Of the 165 patients who met inclusion criteria, 117(70.9%) had Major Neurocognitive Disorder due to Alzheimer's disease (AD), 24(14.6%) Vascular Neurocognitive Disorder (VND), 6(3.6%) Dementia with Lewy Bodies (DLB), 5(3%) Parkinson disease-associated dementia (PDD), 3(1.8%) fronto-temporal dementia, 4(2.4%) mixed dementia and 6(3.6%) other types of dementia. The average annual decline in MMSE points was 2.2(DLB/PDD), 2.1(AD) and 1.3(VND). Cognitive scores at baseline were significantly lower in patients with 8 compared to 13 years of education and in those with VND compared with AD. Factors associated with shorter survival included age at onset greater than 65 (HR=1.82, 95% C.I. 1.11, 2.99, p=0.017), lower baseline MMSE (HR=1.05, 95% C.I. 1.01, 1.10, p=0.029) , Charlson's comorbidity scores of 3 to 4 (HR=1.88, 95% C.I. 1.14, 3.10, p=0.014), scores of 5 or more (HR=1.97, 95% C.I. 1.16, 3.34, p=0.012) and DLB/PDD (HR=3.07, 95% C.I. 1.50, 6.29, p=0.002). Being female (HR=0.59, 95% C.I.0.36, 0.95, p=0.029) was associated with longer survival. Conclusions: Knowledge of dementia subtypes and survival outcomes will help inform decisions about patient selection for potential future therapies and for planning dementia services in resource-poor settings.

No description available.

Introduction: Ageing is a phenomenon that has preoccupied the minds of humankind for generations but it was only in the twentieth century that medical care dedicated to the elderly was created. The field of Geriatric Medicine has grown in South Africa and globally, to be recognized as a subspecialty of Internal Medicine in its own right. Physiological changes in the elderly impact on the increased prevalence of non–communicable diseases and the raised burden of disease in this age group. The altered spectrum of diseases in this age group and atypical manifestations of these conditions make geriatric health care truly unique. In spite of the recognition that the elderly have specific medical conditions, a dedicated health care policy to improve geriatric health care is yet to be developed In South Africa. For such a policy to be created, more needs to be known about the causes of mortality and morbidity that contributes to the burden of disease in this age group. Method: A retrospective chart review was conducted on 218 admissions of persons aged 60 years and over to the medical wards of King Edward VIII Hospital. This is a regional facility in Durban, South Africa, that provides mainly secondary and tertiary levels of care. An ethical waiver was obtained from the Biomedical Research Ethics Committee of the University of KwaZulu- Natal and all data sheets were de-identified. A structured data extraction sheet was used to record demographic and clinical data, including the admission diagnoses, presence of concomitant diseases, management and complications of some of these diseases, length of hospitalization and outcome of admission. Results: The study population comprised 191 patients aged 60 years and over, with a mean age of 70.5 ± 7.4 years (range 60 – 90 years). The patients were predominantly female (61.3%) and Black African (83.8%). While the majority of patients had only 1 admission, most were admitted with multiple diagnoses. Four or more diagnoses were recorded for 58.1% of the patients, with 50 patients (26.2%) having four diagnoses and 38 patients (19.9%) having five diagnoses. A history of current smoking was recorded in 38% of males and 7.2% females. Respiratory disease was the most common admission diagnosis (42.7%), followed by cardiac (42.2%) and renal disease (40.4%). An infection was present in 116 cases (53.2%) on admission, the commonest being pneumonia in 71 (61.2%), followed by urinary tract infection in 34 (28%) and septicaemia in 11 (9.5%). Cardiovascular disease was the most common underlying chronic disease, with hypertension being present in 150 patients (68.8%) and cardiomyopathy in 60 patients (25.5%). Of the patients with hypertension, evidence of end organ damage was present in 128 patients (85.3%), with hypertensive heart disease in 97 patients (75.8%), renal disease in 61 patients (47.7%), cerebrovascular disease in 37 patients (28.91%), hypertensive retinopathy in 11 patients (8.6%) and peripheral vascular disease in 5 patients (3.91%). The most common risk factors for congestive cardiomyopathy were hypertension in 55 cases (67%) and diabetes mellitus in 24 cases (40%). In addition, infection was the most common identifiable precipitating factor for cardiac failure in 40 % of cardiac failure cases Eleven patients were on anticoagulant therapy, of which three (27.3%) presented with overwarfarinization. More importantly, eight of the 17 patients (47%) with atrial fibrillation were not on anticoagulants. Neurological disease was present in 27.5% of the admissions with cerebrovascular disease being the most common (75% of all neurological cases) A diagnosis of malignancy was recorded in 13.1% of admissions with the most common primary site being the lung. In eight patients (32 % of those with malignancy) there was evidence of metastatic disease. Men were more likely than women to be admitted with respiratory disease (22.8% vs. 2.2%, p < 0.0001) such as chronic obstructive airways disease (57% vs. 34.5%, p = 0.001). Although pneumonia was more common in men than in women, this did not reach clinical significance (40.5% vs. 28.8%, p = 0.053). In contrast, more women were admitted with arrhythmias (16.5% vs. 6.3%, p = 0.03), congestive cardiac failure (30.2% vs. 15.2%, p = 0.013) and endocrine diseases (23.7% vs. 12.7%, p = 0.048). Renal disease was more common in women than in men, but did not reach statistical significance (44.6% vs. 32.9%, p = 0.060) In the 191 patients, 64 deaths (33.7%) were recorded during hospitalization. The mortality rate was found to be significantly higher in patients with 15 cerebrovascular accidents, acute renal failure, diabetes mellitus, and infection (including pneumonias). Conclusion: This study confirms the high prevalence and disease burden of non-communicable diseases in older patients, with the majority of patients having multiple diagnoses on admission. Hypertension and other cardiovascular diseases were identified as being most common with a high prevalence of target organ damage. Furthermore, in the patients with malignancy metastatic disease was common. These findings suggest that older patients may present late due to a lack of awareness, limited access to appropriate health care, or lack of adequate treatment and screening programmes. In addition to the burden of non-communicable diseases (NCD), infection (particularly pneumonia) emerged as a common cause for admission and mortality. These findings confirm the high burden of non-communicable diseases and their complications in the older population and highlight the need screening programs to improve detection and better management of these conditions. Furthermore the association of a high mortality with infections, finding underscores the need for implementation and adherence to treatment guidelines, and to develop and adhere to vaccination guidelines. Furthermore, training of health care personnel at all levels should be intensified in an attempt to decrease the burden of disease in older persons and to improve their quality of life. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2011.

The aging process is associated with disease states that may be painful, disabling and life-threatening. Elderly patients frequently have more than one disorder and appropriate pharmacotherapy may result in polypharmacy (treatment with multiple drugs). This situation, combined with age-related alterations in the handling of and sensitivity to drugs, predisposes older patients to adverse drug reactions (ADR's). This study was undertaken to assess the actual risks and potential benefits of long-term polypharmacy in the management of elderly hospital out-patients. A particular aim was to get some indication of whether or not polypharmacy was justifiable in the study population. Accordingly, the medical records of 132 ambulatory patients, 70 years of age and over, who had been attending the general out-patient department of a large teaching hospital for a period of twelve months or longer, were retrospectively examined. The patient's age, diagnoses, prescribed medication, ADR's and clinical therapeutic benefit were assessed, recorded and analyzed. The average patient age in the sample studied was 77,6 years. 71% of the sample were females. 419 disorders were identified, giving an average of 3,17 per patient. 603 drugs were prescribed in total, giving an average of 4, 57 per patient. There was no statistically significant association between increasing age and the number of diagnoses per patient or the number of drugs prescribed. Medication was felt to be therapeutically effective in 63% of the patients, whilst an ADR was noted in 14% of the sample. There was no statistically significant difference in the age, number of diseases or number of drugs prescribed between the total group, the ADR group and the non-ADR group. These parameters were therefore not useful in identifying those patients more likely to experience an ADR. The apparent effectiveness of the medication prescribed and the relatively low incidence of ADR' s in the group studied suggests that appropriate and judicious multiple drug therapy can benefit many elderly ambulatory patients and therefore polypharmacy could be regarded as permissible in this context. Apart from these observations, this dissertation also includes recommendations on ways to minimize the incidence of ADRs in the elderly, and areas for ongoing research in this field are identified.

No description available.

Acute hospitals have seen unprecedented demographic changes, where older age, frailty and cognitive impairment now characterise the majority of health service users. Delirium is very common in this setting, and adverse outcomes are well described. However, studies investigating cognitive outcomes after delirium in unselected samples have been lacking. This thesis had four objectives: (1) To estimate the prevalence of delirium in the general population (2) To assess the association of delirium with cognitive outcomes (3) To investigate how these associations relate to underlying dementia pathology (4) To develop novel methods for retrospectively ascertaining delirium. Methods: Data from three population-based neuropathology cohort studies were used: Vantaa 85+; Cambridge City over-75s Cohort (CC75C); MRC Cognitive Function and Ageing Study (CFAS). (1) To ascertain the prevalence of delirium in the general population, a measure of delirium was developed using data recorded in standardised interview schedules, with criterion validity evaluated through the association with mortality and dementia risk. (2) The association with cognitive outcomes was tested in a series of logistic regression models, where delirium was the exposure and dementia (or worsening dementia severity) was the outcome. In addition, the association with change in Mini-Mental Status Examination (MMSE) score was assessed using random-effects linear regression. (3) In brain donors from all three cohorts, the independent effects of delirium, dementia pathology, and their interaction, were investigated using the same approach. (4) A chart-based method for deriving a retrospective diagnosis for delirium was developed, validated against bedside psychiatrist diagnosis. Vignettes from the medical record were abstracted and delirium status decided by expert consensus panel. Results: (1) Age-specific prevalence in CFAS increased with age from 1.8% in the 65-69 year age group to 13.5% in the ≥90 age group (p<0.01 for trend). (2) Delirium was consistently associated with adverse cognitive outcomes: new dementia (OR 8.7, 95% CI 2.1 to 35); worsening dementia severity (OR 3.1, 95% CI 1.5 to 6.3); faster change in Mini-Mental Status Examination (MMSE) score (1.0 additional points/year, p<0.01) (3) In the neuropathology analyses, decline attributable to delirium was -0.37 MMSE points/year (p<0.01). Decline attributable to dementia pathology was -0.39 MMSE points/year (p<0.01). However, the combination of delirium and dementia pathology resulted in the greatest decline, where the interaction contributed a further -0.16 MMSE points/year (p=0.01), suggesting that delirium worsened cognitive trajectories in dementia, but through distinct pathophysiological pathways not accounted for by Alzheimer’s, vascular or Lewy body pathology. (4) The chart abstraction method yielded a sensitivity of 0.88 and specificity 0.75 for ‘possible delirium’, with lower sensitivity (0.58) and higher specificity (0.93) for ‘probable delirium’ (AUC 0.86, 95% CI 0.82 to 0.89). This thesis adds to the small body of work on delirium in prospective studies, with the first ever analyses conducted in whole populations. The findings suggest new possibilities regarding the pathology of cognitive impairment, positioning delirium and/or its precipitants as a critically inter-related mechanism.

This century will bring an explosion in the geriatric population aged 65 and older, with those over 80 the fastest growing group. Falls, vehicle collisions, burns, and abuse are traumatic events that our geriatric patients may be susceptible to and from which they may not recover. Primary care providers should enhance their understanding of the complex issues of geriatric trauma to facilitate prevention and to assist the patient's recovery to normal function, addressing barriers such as immobility, pain, malnutrition, and acute confusion. Improved outcomes require combined efforts of disciplines and specialties intervening for optimal management for older trauma patients from pre-hospital care through rehabilitation or end-of-life issues.

Abstract Older adults with complex memory problems benefit when they have the opportunity to consult with a specialist for a comprehensive cognitive assessment. Specialists such as geriatricians, psychogeriatricians or neurologists often work in major cities or large metropolitan towns. Travelling to see a specialist either alone or with a carer is complicated for an older person because of medical issues or disability. The use of videoconferencing may provide a way to link a specialist with a patient without the need for the patient, or the specialist, to travel long distances. Two literature reviews were carried out. The initial review identified studies of the diagnosis of cognition via telemedicine. Thirty-two studies were identified which assessed cognition via telephone or video conference. The focus of the study was either the administration of a standardised cognitive assessment tool (n=30) or an unstructured comprehensive cognitive assessment interview (all via video conference) (n=2). The sample sizes were small but the levels of agreement were high, suggesting that further work in this area may identify that diagnosis of dementia via video conference is reliable. There has been limited work in the area of diagnostic agreement when a specialist is assessing a patient for the first time via video conference, even less work in the area of mental health assessment of older people. The second literature review identified 19 studies of diagnostic agreement using video conference with a sample size of 20 or more. The fields of research were: Dermatology (n=10); Mental Health (n=4); Minor Injuries (n=2); Neurology (n=2); and Rheumatology (n=1). Of the four studies in the area of mental health, one focused on the diagnosis of dementia with the publication of a protocol for assessing Alzheimer’s disease (AD) via video conference. The review highlighted that diagnosis via video conference in other medical fields had been shown to be reliable but that limited work was evident regarding the reliability of diagnosing dementia via video conference. A range of statistical analyses have been used to measure agreement in studies of diagnosis via VC. Overall Proportional Agreement (Po) and Cohen’s kappa (K) are the two most common calculations. There was little uniformity of reporting in the studies identified in the literature review. The variation in reporting made it difficult to compare results or provide data for a meta-analysis of similar studies. Consideration of the methods for analysing diagnostic agreement was undertaken using the approaches identified in the literature review as a starting point. The aim of this research was to identify if a diagnosis of the presence of dementia in an older adult by a specialist is reliable when the assessment interview occurs via video conference. A pilot study was carried out prior to the implementation of a National Health and Medical Research Council (NHMRC) funded multi-site project to test inter-rater agreement for the diagnosis of dementia and subsidiary questions. The candidate is a Chief Investigator (CI) on the NHMRC project grant and participated in writing the grant submission. A pilot study was completed for the purpose of refining the research protocol and establishing preliminary data for the calculation of sample size. A geriatrician carried out a cognitive assessment via video conference with the patient and the carer. The doctor had access to the patient’s chart and the results of a battery of standardised cognitive assessments administered face-to-face (FTF) by the clinic nurse earlier in the day. A second interview was carried out, face-to-face, by a second doctor on the same day. Inter-rater reliability was assessed between doctors. To place the level of agreement in context, inter-rater reliability between paired face-to-face assessments was also measured. Forty-two participants were divided into two groups: paired face-to-face assessments (FF, n=22) or paired video conference and face-to-face assessments (FV/VF, n=20). Twenty-two participants were male. Their average age was 70 years (SD=11.1, Range 50-90). The mean Standardised Mini-Mental State Examination (SMMSE) score was 23.93 (SD=5.42, Range 8-30)[1]. The outcome of agreement was measured using PO and Cohen’s K. FF group (PO=0.636; K=0.430, p=0.005) and the FV/VF group (PO=0.650; K=0.650, p=0.004) showed similar levels of agreement. The main study was a non-inferiority, prospective cohort study following a similar format as the pilot. Patients were randomised to two groups. The first group participated in two interviews; one via VC, the other was face-to-face (FV/VF). The second group was subjected to dual face-to-face assessments (FF). The video conference interview consisted of real-time video conference with the doctor interacting with both the carer and the patient. A battery of standardised assessments, a medical history, imaging and blood tests were prepared before hand and available to the doctor for use in the interview. One hundred and fifty-five participants were divided into two groups: paired face-to-face assessments (FF, n=73) or paired video conference and face-to-face assessments (FV or VF, n=82). Seventy-five of the participants were male. The average age was 76-years (SD=9, Range 54-95). The mean SMMSE was 23.8 (SD=4.4, Range 8-30). Overall proportional agreement (Po) and Weighted K were calculated as a measure of agreement for the presence of dementia. The FF group (Po=0.740; K=0.57, p<0.0001) and the FV/VF group (Po=0.780; K=0.64, p<0.0001) showed similar levels of agreement. Using the same study cohort, additional data were collected to identify the significance of the physical examination (PE) for diagnosing dementia. One of two doctors was allocated the task of completing a physical examination of the patient following initial assessment interview and after the diagnosis decisions had been recorded. Following the physical examination a second record of diagnosis decisions were recorded by the same doctor. The doctor was asked to identify if the diagnosis, formulation, treating options or additional investigations had altered as a result of the in-person physical examination. The physical examination supported clarity of the diagnosis particularly if a vascular element was involved. This dissertation provides evidence of the reliability of a diagnosis of dementia obtained via video conference. Furthermore, the work detailed in this dissertation represents the largest international study on assessing diagnostic accuracy of cognition and makes a significant contribution to the work in telemedicine in the area of mental health. This dissertation provides generalisations that can impact the use of video conference for diagnosis across a range of specialities, with the ultimate goal of improving access to specialist advice for people living in rural areas.

No abstract available. / Thesis (M.Med.)-University of Natal, 1986.