This study aimed to optimise the treatment of early breast cancer in older patients. It tested the hypothesis that comprehensive geriatric assessment (CGA) could be used to predict two-year survival in older breast cancer patients. Based on the CGA scoring a treatment algorithm was devised that could help in recommending whether primary endocrine treatment (PET) or surgery plus endocrine treatment would be best indicated in individual patients. Methods: The study included women >70 years of age with early breast cancer, seen in a dedicated Leicester clinic between 01/2005 and 04/2007. All patients had comprehensive assessment including documentation of Satariano Index of Co-morbidities (SIC), Mini-Mental State Examination (MMSE), Geriatric Depression Score (GDS), Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL) and American Society of Anaesthesiologists (ASA) grade. Logistic regression analysis explored any association between these components and two-year survival. Components with positive association were formulated into a Breast Cancer in Elderly Treatment Algorithm (BCETA). Results: 123 patients were included, age range 70-94 (median-82). Twenty-two patients died within two years. Logistic regression analysis found MMSE, ADL, and ASA score to have an independent association with two-year survival. The scores of these components were formulated into a BCETA. Logistic regression revealed a statistically significant association between the BCETA score and two-year survival (p-value 0.00). Other results for the BCETA prognostic model were: sensitivity 89%, specificity 46%, positive predictive value 87%, negative predictive value 52%, odds ratio 7.1 (95% CI 2.5-20.2), and overall accuracy of 81%. C-statistic value (area under ROC curve) for the BCETA score was 0.70. Conclusion: Breast Cancer in Elderly Treatment Algorithm is a new approach to optimise the management of breast cancer in elderly patients. It can help in identifying high-risk patients with expected short-survival who may benefit from PET, if their cancer is hormone receptor positive. Patients with predicted longer life expectancy (lowrisk) may be recommended standard treatment. Further studies are needed to validate it in a larger population.

Background The elderly population in sub-Saharan Africa (SSA) is increasing rapidly, with a consequent rise in noncommunicable disease (NCD). The prevalence of stroke disease is already known to be higher in SSA than in highincome countries (HICs). There are currently no communitybased data on the prevalence of atrial fibrillation (AF) or hypertension (HTN) specifically in elderly SSAs. Design Cross-sectional community-based observational study, with case-control sub-group analysis. Methods Approximately one quarter of the population (n=2232) aged 70 and over of a demographic surveillance site in the rural Hai district of Northern Tanzania underwent screening for AF by 12-lead electrocardiography (ECG), in addition to a subgroup undergoing ambulatory cardiac monitoring looking for paroxysmal AF (n=232). Demographic data were also collected along with disability level, body mass index and blood pressure (BP). The gender-specific prevalence of AF, paroxysmal AF and hypertension in each 5-year age band was determined. ECGs were examined digitally, and P wave indices in this population were described. Results There were only 15/2232 (12 female) participants with AF, giving an age-adjusted prevalence of 0.64%. 6/233 (2.6%) had at least 1 paroxysm of AF, suggesting a total overall prevalence of AF as high as 3.2%.1553/2232 had a BP ≥140/90, giving an age-adjusted prevalence of hypertension of 69.7%. Women had a higher mean systolic (166.0 vs. 154.3mmHg) and diastolic (89.3 vs. 83.1mmHg) BP. Conclusions The prevalence of AF is much lower in this population than elsewhere in the world and points towards potential protective genetic and environmental factors and some differences in risk factor profile. However, the low prevalence of AF is particularly interesting in the setting of a prevalence of hypertension and stroke that is similar to African- Americans in HICs.

Hospital acquired pneumonia (HAP) occurs in 1% of all hospital in-patients, and in around 10% of patients with lower limb fracture, with a mortality of 18- 43%. HAP arises from interactions between three main risk factor groups: resident oral microbiota, aspiration potential (dysphagia, reduced conscious level) and host factors (age, frailty, comorbidity). In this work novel multiplex real time PCR assays were used to study prospectively the oral colonisation dynamics of seven major commensal pathogens over the first fortnight after hospital admission in relation to oral health variables, medical variables and subsequent development of HAP. Of the 93 patients recruited, 10% developed HAP and 60% of in-hospital deaths after lower limb fracture were due to HAP. Persistent oral colonisation with E. coli or S. aureus was significantly associated with HAP or HAP/lower respiratory tract infection in older patients with lower limb fracture. In turn, S. aureus was associated with increased dental plaque at admission and with increased xerostomia indices at 14 days. Other factors such as witnessed aspiration and post-operative cough were also strongly associated with subsequent development of HAP. HAP was associated with increased risk of death and increased length of hospital admission. These findings suggest several potentially modifiable clinical risk factors, and a high risk population for HAP, to whom interventions could be targeted. Given the rise in the older population and the increased costs associated with HAP, early detection and prevention will become increasingly important. Further work is needed to understand the relationships between dental plaque, S. aureus and xerostomia, and also to identify microbial biomarkers which could be used at the start of hospital admission to stratify patients’ risk of HAP.

Aim To determine the prevalence of neurological disorders in the 70 and over population of the Hai district in northern Tanzania through the production and utilisation of a screening questionnaire, and to describe the subtypes, the level of diagnosis, treatment and associated disability. Introduction There are limited data on neurological disorder and disability prevalence from developing countries despite a highlighted need from the World Health Organisation (WHO). This is partly due to the lack of a feasible and valid screening tool. Methods A screening questionnaire was created and validated for use in the elderly population of a developing country. A cross-sectional two phased epidemiological survey was then performed in the Hai district demographic surveillance site (DSS) (n=161,119). 2232 participants (1/4 of the DSS 70+ population) were screened. Positive responders underwent neurological assessment and were questioned regarding health seeking behaviour. Disability assessment was performed using the Barthel Index. Results The screening questionnaire was validated in one randomly selected village (n=277). Further substantiation was performed in a larger population (n=1955). The sensitivity and specificity were 87.8-97.0% and 90.4-94.9% respectively. In 2232 participants, there were 384 neurological diagnoses amongst 349 people. The age adjusted prevalence of ii neurological diagnoses (95% confidence intervals (CI)) was 168.94/1000 (153.39 to 184.48). 58.6% had sought help for their symptoms, 14.6% had been correctly diagnosed and 10.6% were on appropriate treatment. The age adjusted prevalence of severe and moderate disability was 3.7% and 6.2% respectively. Those with neurological disorders had significantly greater odds of disablement. Conclusions This is the first screening instrument to measure the prevalence of neurological disorders specifically in an elderly population in Sub-Saharan Africa (SSA). It is feasible and valid with a high sensitivity and specificity. This is the first community-based neurological disorder prevalence study specifically in the elderly in SSA. It reveals high neurological morbidity and associated disability and low diagnosis and treatment levels.

As humans age, the brain undergoes many changes. This includes loss of the neurotransmitter dopamine, which forms a bridging link between age and the ensuing changes in cognition. However many questions about the precise nature of this relationship with regards to brain structure and function remain unanswered. These questions are important given our expanding aging population, and the answers may help the discovery of new therapeutic interventions for age-related impairments as well as identify mechanisms to promote successful aging. Old age also provides a model for understanding the role of dopamine in many fundamental human behaviours. The aim of my research was to use a multimodal approach to explore the contribution of dopamine to learning and memory in healthy older age. In this thesis I present four studies in which I used a combination of behavioural testing, pharmacological manipulation, structural and functional magnetic resonance imaging in older adults. I show that dopamine boosts delayed episodic memory in a non-linear dose-dependent manner. Using functional MRI, I show this effect is mediated through consolidation rather than encoding by the hippocampus. In two further imaging studies conducted to explore the role of dopamine in reward-based learning, I show that the flexibility of learning depends on the structural integrity of the substantia nigra/ventral tegmental area (the origin of dopamine projections) and that pharmacological enhancement of dopamine levels can remediate abnormal reward processing in the ventral striatum. Individual differences in neural activity associated with reward prediction also relate to anatomical nigro-striatal connectivity, identified using diffusion tensor imaging. Finally, I show that in old age, valence influences decision-making in relation to ones own beliefs about the future, mediated by volume of the anterior cingulate cortex. I conclude this thesis with a brief discussion of the implications of these findings, study limitations and potential future studies.

Introduction Neurocardiovascular instability (NCVI) describes a group of disorders characterised by orthostatic hypotension (OH), carotid sinus hypersensitivity (CSH) and autonomic dysfunction. In cross-sectional studies, NCVI has been associated with cognitive impairment, depression and falls. It is suggested that episodic hypotension causes cerebral hypoperfusion, which in turn causes anoxic brain damage. White matter hyperintensities (WMH) on MRI are thought to represent ischaemic damage due to hypoperfusion and are also associated with cognitive impairment, depression, and falls. Despite these observations, the long-term clinical significance of NCVI remains unclear, particularly in asymptomatic individuals Aims  To examine the associations between NCVI and cognition, depression and falls over a ten-year follow-up  To examine the association between NCVI and WMH volume on MRI  To examine the association between NCVI and ten-year all-cause mortality. Methods Participants were recruited from an established cohort of people aged ≥65 years in 2002. Baseline evaluation of neurocardiovascular function in 2002 included heart rate variability, autonomic function tests and carotid sinus massage. Neuropsychological assessment was performed at baseline and at follow-up. MRI was performed at follow-up (but not at baseline). WMH volume was calculated using FLAIR MRI. Cox regression analysis was used to examine the association between NCVI and mortality. Results In 2002 1000 individuals aged ≥65 years were selected at random from a single GP practice and invited to participate in the study. 353 consented to enrolment in the baseline study. Of whom 104 individuals [median age 79 years (range 74-92)] participated in the year 10 follow-up. Asymptomatic NCVI was not associated with cognition, depression, falls or WMH volume at follow-up. Symptomatic OH was associated with greater decline in CAMCOG memory score [B =1.19, P<0.05] and symptomatic CSH was independently associated with increased WMH volume [P<0.01]. NCVI defined according to standard criteria was not associated with ten-year mortality. However, at baseline it had been identified that the 95th percentile for systolic vasodepression was 76.6 mmHg and the 95th percentile for RR interval post CSM was 7.3 seconds. These thresholds were used to define CSH modified criteria. CSH defined according to modified criteria, derived from the baseline populations’ response to CSM, was associated with increased mortality [HR2.37, P=0.02]. Conclusions NCVI is not associated with adverse outcomes at ten years in asymptomatic older people but symptomatic NCVI is associated with decline in memory and greater WMH volume, suggesting symptoms are of prognostic significance. Modified CSH criteria are better predictors of ten-year mortality than current criteria.

This thesis examines two of the most important issues in the pathophysiology of hypertension in the elderly, disordered cardiovascular neural control and raised peripheral vascular resistance, in clinical studies of hypertensive and normotensive subjects aged over sixty years. Hypertension in elderly subjects is associated with reduced baroreceptor-cardiac reflex sensitivity irrespective of the method used to quantify the reflex. There is no difference in baroreceptor-cardiac reflex sensitivity between elderly subjects with combined systolic-diastolic hypertension and isolated systolic hypertension. Beyond the age of sixty years, baroreflex sensitivity is independently related to the level of systolic blood pressure but not to age. Subjects with isolated systolic hypertension have a greater fall in blood pressure with passive tilt than normotensives despite a greater rise in forearm vascular resistance. Hypertension in elderly subjects is associated with an increased media:lumen ratio in subcutaneous resistance arteries which principally relates to the prevailing level of pulse pressure, particularly when measured by 24-hour ambulatory monitoring. However, there are no differences with hypertension in the contractile behaviour of vascular smooth muscle or in the endothelium-dependent and independent relaxation responses of such resistance arteries. The sympathetic baroreceptor-vascular response is not correlated with the changes observed in the structure of the effector mechanism of the reflex, the resistance artery. However, blood pressure changes with orthostasis are negatively correlated with baroreceptor-cardiac reflex sensitivity, suggesting an aetiological link between hypertension and the postural hypotension with which it is often associated. In conclusion, hypertension in the elderly is associated with reduced baroreflex sensitivity, an impaired blood pressure response to orthostasis and increased resistance artery media:lumen ratio, but no differences in endothelial or vascular smooth muscle function. These findings should help clarify some of the pathophysiological issues in hypertension in the elderly, and guide our approach to the treatment of this common and clinically important condition.

In the period of 1982-1984, a cross sectional, prevalence study of eye disease in the elderly population of Melton Mowbray was carried out. The purpose of the study was to determine the prevalence of the three major blinding conditions in the elderly, namely senile cataract, chronic open-angle glaucoma and age related macular degeneration. The study population was a random sample of the surviving cohort of the Household Survey, which had previously been carried out by the Department of Community Health. Participants were asked to attend a special eye clinic in Melton Mowbray, where each was examined by an Ophthalmologist and an Ophthalmic Optician. The examination included measurement of visual acuity, refraction slit-lamp examination and fundus examination and photography after mydriasis. 529 persons from a study population of 677, participated in the study a response rate of 78%. The prevalence of senile cataract was 55.9%, chronic open angle glaucoma 4.5% and age-related macular degeneration 42%. Only 1.1% of the study participants had diabetic retinopathy. Significant associations for senile cataract were increasing age (p 0.05) and the female sex (p 0.001); for open angle-glaucoma, family history (p0.001) and the absence of arcus senilis (p0.05) and for macular degeneration, increasing age (p0.02) and the absence of arcus senilis (p0.001). A quarter of all participants had a corrected visual acuity of less than 6/18 in their better eye but over 80% had a reading vision of at least N8. The attenders and non-attenders have been compared and an attempt made to assess the amount of potential bias that may have been introduced into the study.

No description available.

This PhD thesis addresses the challenges of social inclusion for older men (65+ years) with dementia in rural England. This applied study used an individually-tailored male-only Technological Initiative, drawing on commercially available computer game technology (e.g. iPad, Nintendo Wii and Microsoft Kinect) to deliver person-centred activities to older men with dementia residing in three rural areas of England over a nine week period. Participatory Action Research (PAR) formed the framework for the conduct of the research. Multiple qualitative methods were employed to explore the perceived impact of the Technological Initiative on the men’s social inclusion. These included focus group discussions, open interviews and extensive reflexive field notes. Twenty two men participated in the research alongside fifteen care partners and five community volunteers. A thematic analysis was undertaken to interpret the data. The research demonstrated that whilst the men enjoyed rural life, aspects of rurality combined with their subjective experiences of dementia to hinder their social inclusion. The Technological Initiative appealed to the men and resulted in their increased social confidence and sense of well-being. Three features were integral to its success: the use of technology; the male-only environment; and the approach adopted. The technology enabled the men to re-engage with their old leisure interests, take part in new activities and so continue their learning and personal growth, and challenge assumptions about their abilities. The male-only environment promoted a sense of familiarity and camaraderie that relaxed the men and encouraged them to speak openly. The approach adopted sought to give voice to the men by situating them as experts in the evolution of the Technological Initiative. The thesis concludes by arguing that community ecopsychosocial initiatives designed to enable male social inclusion would be advised to consider these gendered experiences and promote them through the activities offered, the environment created and the method of delivery.