Alzheimer's disease (AD) is the commonest neurodegenerative disorder that has become increasingly prevalent in most countries. The chronic progressive deteriorating course is characterized by great variations in individual pathways of decline. This abstract summarizes the findings of a prospective study to examine the factors that affect clinical decline in a group of Chinese subjects with Alzheimer's disease (AD). / At the follow up, 19 (18.3%) subjects had died. 74 (71.2%) subjects were alive and were reassessed. Of the subjects reassessed, 49 (66.2%) remained stable at the same CDR, and 25 subjects (33.8%) had deteriorated to a more advanced stage of dementia. A significant deterioration in global cognitive scores (MMSE and DRS) was found (paired t-tests, p<.001). The estimated annual deterioration in MMSE and DRS scores was 1.34 and 4.93. There was a non-significant trend for overall reduction of NP symptoms at the follow up, but a sizable proportion of subjects still exhibited a variety of NP symptoms. / Development of research plan and study objectives is discussed in the third chapter. Due to escalating problem of care for dementia sufferers, a prospective study to examine the clinical factors that affect decline in Chinese elderly people with AD is needed. Four main research objectives are developed. The first objective is to examine the clinical profiles of Chinese subjects with AD. The second objective is to evaluate the relationships between different clinical dimensions of the dementia syndrome. Thirdly, the differences in clinical characteristics between mild and moderate AD would be examined. Finally, significant factors that affect the rate of clinical decline would be determined. / The baseline global cognitive performances were similar among different outcome groups. The 'deteriorated' group had a higher educational level (One way ANOVA, F=4.85, p=.01, Bonferroni comparisons). There was an excess of number of cerebrovascular risk factors (CVRF) in subjects who had deteriorated (Kruskal Wallis test, z=6.6, p=.04). For subjects with CDR 1 at baseline, a significant excess of Apo E4 allele was found in those who had deteriorated at follow up (Pearson chi square 5.72, p=.017; OR = 6.3, CI 1.3 to 30.53). The difference in Apo E4 allele frequency was not significant in subjects with CDR 2 at the baseline. The 'Deceased' group had more advanced age, lower scores in the recognition tests of the Hong Kong List Learning Test (HKLLT) (Kruskal Wallis test, z=8.06, p=.008) and significantly higher scores of 'Parkinsonian signs' (Mann-Whitney U, z=2.99, p=.003). Concerning baseline NP syndromes, 70% of subjects in the 'Affective' groups remained stable at follow up; 31.8% of subjects in the 'Disturbing' groups died, another 31.8% deteriorated at follow up. Logistic regression analysis revealed that a lower score of recognition test of HKLLT, a higher score of 'Parkinsonian signs' and old age were significant predictors for mortality at the 22-month follow up. No significant predictor, apart from a higher premorbid educational level, for the deterioration to a more advanced level of dementia could be identified. / The fifth chapter reports the main research findings. The mean (SD) age at the baseline assessment was 78.18 (5.97) years. The mean (SD) of the Chinese version of the Mini-Mental State Examination (MMSE) and Mattis Dementia Rating Scale (DRS) scores were 16.21(3.69) and 94.88(13.17) respectively. Subjects with moderate AD (Clinical Dementia Rating, CDR=2), compared to subjects with mild AD (CDR=1), performed worse across all cognitive tests. NP symptoms, as evaluated by the Chinese version of the Neuropsychiatric Inventory (NPI), were prevalent and could be classified into 3 subgroups using Latent Class Analysis (LCA): the 'non-disturbing', 'affective' and 'disturbing' groups. The severity of soft neurological signs (SNS) and NP symptoms was more prominent as dementia became more severe. Strong associations between 'Motor coordination' and Sensory integration' signs with cognitive functions were found. The association between NP syndromes and cognitive functions were not as significant. / The following chapter describes the methodology. A group of 104 Chinese subjects with NINCDS-ADRDA criteria for AD were assessed twice in a naturalistic observational study with an average duration of 22 months. Comprehensive evaluation of cognitive, neuropsychiatric (NP), neurological characteristics, cerebrovascular risk and Apolipoprotein E gene polymorphism status was performed at the baseline. The progression of cognitive and clinical decline was compared at the follow up assessment. Baseline and follow up characteristics of cognitive, neuropsychiatric (NP) symptoms and soft neurological signs (SNS) were compared with a group of normal control (NC-FU, CDR=0) and questionable dementia (QD-FU, CDR=0.5). Significant factors influencing progression to a more advanced dementia and mortality were determined. / The introductory chapter outlines the major findings of recent studies on the clinical aspects of AD. Clinical AD is found in 3.6 % of Hong Kong Chinese elders over 70 years old. Literature review suggested that it is a genetically predisposed complex disorder with disease manifestations strongly modulated by health and lifestyle factors. / The last chapter lays out the conclusions of this study. Careful characterization of clinical profile should be emphasized in the management of elderly suffering from AD. This information will be useful for the assessment of prognosis and the formulation of care plan for AD sufferers. / The second chapter focuses on review of recent literature concerning factors that affect cognitive deterioration and clinical decline in AD. The potential determinants of disease progression included genetic predispositions, cognitive and neuropsychiatric profiles, neurological deficits and medical comorbidity. / The sixth Chapter comprises the discussion. The findings of this study provided information about the rate of cognitive and clinical decline in Chinese subjects with AD. The performance characteristics in cognitive tests, inter-subject variations, prevalence of Apo E4 allele and NP symptoms are potential factors that would influence the assessment of cognitive function with time. The universal occurrence of NP symptoms in AD supported a biological explanation for this clinical dimension. The findings also support the notion that cognitive and NP symptoms are relatively independent dimensions of the clinical dementia syndrome. The association between SNS and severity of cognitive impairment suggests that bedside neurological assessment is a feasible way to detect subtle neurological deficits in subjects with very early AD. The presence of 'Parkinsonian signs' predicted mortality, which indicated that the presence of co-morbid subcortical pathology play a significant role in determining the overall outcome. It appeared that trait factors such as the presence of the Apo E4 allele, a higher educational level and pre-existing cerebrovascular diseases, are associated with a faster rate of disease progression, although individual factors may operate differently at different phase of illness. / Lam Chiu Wa. / Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6299. / Thesis (M.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 150-185). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.