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Accession . / Number 2807400192 A STUDY OF DEMENTIA IN A RURAL POPULATION Thesis submitted for the degree of Doctor of Medicine (MD) to the University of London by Carol Elspeth Goodeve Brayne, MSc, MBBS, MRCP Academic Department of Community Medicine Cambridge University Medical School Addenbrooke's Hospital Cambridge CB2 2QQ October 1990 ACCESSION . / 0 / NUMBER ProQuest Number: U553023 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a com plete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest ProQuest U553023 Published by ProQuest LLC(2017). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States C ode Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 1 ACKNOWLEDGEMENT S The opportunity to carry out this research was made available to me through a Medical Research Training Fellowship in Epidemiology, and the project itself was supported by the Mental Health Foundation. The project would not have been possible without the help of Professor Gerry Shaper, who advised on the design of the study, Professor Roy Acheson, who supervised me during the study, and Dr. Felicia Huppert, who has provided advice and support throughout. I am grateful to Sir Martin Roth for permission to use an early version of the CAMDEX. I would also like to acknowledge the support of all members of the Department of Community Medicine during the study, particularly Mr. Julian Lipscombe who entered much of the data. I would like to thank Dr Adele Green and Dr Daniel O'Connor who read earlier drafts. Professor Copeland and colleagues kindly trained Dr Paul Calloway in the use of the Geriatric Mental State Examination and provided AGECAT diagnoses. Professor Rod Thompson and Mrs. M. Allsop organised and carried out the analyses of serum for creatine kinase enzymes. Ms Caroline Gill conducted the linear modelling analyses. The comparison of case control methodology is an adaptation of Dr Breteler's tabulation developed for the EURODEM project. The Medical Research Council lent the random zero sphygmomanometers and the Health and Lifestyle the reaction time machines. I would like to express my gratitude to the general practitioners from the Soham health centre and all the staff, who helped make the study possible. Above all, thanks are due to the subjects and their families without whom the study could not have taken place. 2 DECLARATION This study was designed and conducted by the author who personally interviewed and investigated all the subjects. Dr Paul Calloway conducted the Geriatric Mental State interviews on a subsample of the subjects. Mr Julian Lipscombe and Mrs Sue Edmonds entered the data. The assays of thyroid function and creatine kinase isoenzymes were carried out in the Department of Biochemistry and those of auto­ antibodies in the Department of Immunology at Addenbrooke's Hospital, Cambridge. Analyses of haematology and biochemistry samples were performed as part of the routine laboratory service. The term Alzheimer's disease and multi-infarct dementia have been used throughout, rather than a number of other terms used in the literature. ABSTRACT Dementia, in particular Alzheimer's disease, has been widely investigated in clinical settings. Moreover, many epidemiological studies have been carried out to estimate the prevalence and incidence of dementia and, less frequently, Alzheimer's disease. There have also been studies of ageing cohorts to examine mental changes associated with ageing. There has, however, been little research on unselected elderly populations which has been detailed enough to examine the relationship between normal and abnormal mental ageing. The aim of this study was to investigate the distribution of the indices of dementia in a rural population. This allowed investigation of the hypothesis that variables associated with dementia, in particular Alzheimer's disease, are distributed bimodally in the population and allowed investigation of possible associations with these distributions. It also provided prevalence estimates of dementia in a rural population. A population sample of women aged 7 0 to 7 9 was selected from a rural Cambridgeshire health centre. Using the Cambridge Examination for Mental Disorders in the Elderly all aspects required for the diagnosis of dementia and tentative differential diagnosis were collected on 365 women. There was no evidence of bimodality in any of the derived scales, whether cognitive, behavioural or ischaemic. The prevalence of dementia of all types and levels, including mild, was 4.3% in the 70 to 74 age group and 11.7% in the 75 to 79 age group. For more severe dementia a prevalence of 2.8% was found in the 75 to 79 age group, and 0% in the 70 to 74 age group. The rates for more severe dementia were lower than other recent prevalence studies in the UK, whereas the rates for all levels of severity were higher. The tentative diagnosis of Alzheimer's disease accounted for 52% of the diagnoses of dementia and multi-infarct dementia for 31%. Age, social class and education were all significantly and independently associated with scores on the longer cognitive scales (Mini-Mental State Examination and the CAMCOG scale of CAMDEX). Risk factors suggested in the literature for dementia, Alzheimer's disease 4 and cognitive impairment was also investigated. Few factors were associated with either cognitive function or dementia. Age was the only variable associated with both cognitive function and the diagnosis of dementia. Only small proportions of the population were exposed to postulated risk factors and these risk factors, if proven, would account for little population excess risk. In this- study no significant separation of performance on cognitive or , behavioural scales between the demented and the non-demented was found. This could have been due to the small numbers in the tails of the frequency distributions but, if true, it is suggested that this observation might be related to the continuous distribution of underlying neuropathological lesions, such as plaques and tangles, noted in autopsy series of unselected populations. If so, current research into the mechanisms of the dementias may have implications for the understanding of cognitive decline noted in the non-demented elderly over time. 5 CONTENTS Page ne ACKNOWLEDGEMENTS........................... 1 DECLARATION................................ 2 ABSTRACT................................... 3 CONTENTS................................... 5 TABLE CONTENTS............................ 6 FIGURE CONTENTS........................... 8 APPENDIX CONTENTS......................... 9 INTRODUCTION.............................. 10 BACKGROUND................................ 12 DEMOGRAPHIC CHANGES...................... 12 DEMENTIA................................. 12 Diagnostic criteria................... 14 Diagnosis in the community............ 14 Diagnostic accuracy of dementia....... 24 ■ DIFFERENTIAL DIAGNOSIS OF DEMENTIA. .25- Alzheimer's disease 2 6 Multi-infarct dementia................ 32 Accuracy of differential diagnosis 36 DEMENTIA IN THE POPULATION............... 38 Mortality............................. 38 Differential diagnosis in clinical settings.................... 39 Population studies.................... 40 Prevalence studies.................... 4 9 Incidence studies..................... 72 Causation 7 6 CONCLUSIONS.............................. 90 PRESENT STUDY............................. 91 AIMS..................................... 91 METHOD................................... 92 The sample............................ 92 The interview......................... 95 Quality control...................... 102 Data handling........................ 104 RESULTS................................. 106 The sample 10 6 Clinical diagnoses................... 114 Cognitive and other scales........... 121 Quality control...................... 144 Risk factors......................... 148 DISCUSSION............................... 154 METHODOLOGY.......................... 154 DISCUSSION OF RESULTS................ 160 IMPLICATIONS FOR FUTURE RESEARCH..... 179 CONCLUSIONS.............................. 183 APPENDICES............................... 184 BIBLIOGRAPHY............................. 207 TABLE CONTENTS Table number Page n° 1. Diagnostic criteria.......................... 15 2. Post mortem validation studies............... 37 3. Differential diagnosis in clinical settings.... 39 4. Scale validity............................... 45 5. Dementia prevalence - United Kingdom.......... 50 6. Dementia prevalence - Europe................... 51 7. Dementia prevalence - United States........... 52 8. Dementia prevalence in other countries........ 53 9. Prevalence rates by age in women............. 58 10. The ratio of Alzheimer's disease to multi­ infarct dementia.............................. 63 11. The prevalence of dementia and cognitive impairment in institutions....................65 12. a) Incidence studies - community/cohort...... 7 4 12. b) Incidence studies - records/institutions.... 75 13. Summary of case control methodologies........ 77 14. Possible risk factors for dementia and cognitive impairment.......................... 100 15. The sample by age group.......................108
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