Determinants of clinical progress in Alzheimer's disease

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).; 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 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.; 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 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 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.; 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 MM...