Abstract
With an aging population and an increasing number of individuals with Alzheimer’s disease (AD), a cost-effective, reliable, and non-invasive diagnostic test for AD is needed. The aim of the thesis was to understand how cognitive impairment differs from normal aging, and what the best predictors of AD may be. More specifically, it explored the use of neuropsychological, psychosocial, and biological data in the prediction of AD by examining different stages of aging – normal healthy elderly, individuals with Mild Cognitive Impairment (MCI), and individuals with AD.
In Study 1, a systematic review of the methodologies of 100 articles that looked at MCI, published between the years 2008 and 2010, was conducted to examine how the core clinical criteria of MCI had been interpreted and applied by researchers. The review found large inconsistencies, with a standardised procedure for obtaining objective evidence of impairment lacking, and the process used to make the diagnosis of MCI not well reported.
In Study 2, a longitudinal 10-year follow-up of older adults aged 65 and above (Cohort Study) was conducted to examine the cognitive changes of older adults. Different methods for predicting cognitive impairment was also compared. Normative means were derived from the participants’ performances on a comprehensive list of tests. The data indicated general trends of lowered performance on cognitive tests with age, which were not always uniform. Age and sex influenced some of the cognitive performances, and persons above the age of 80 years showed a faster rate of deterioration. The test of verbal memory appears to be the most sensitive to cognitive changes. Comparison of different prediction methods suggests a more conservative prediction method, which included intra-individual factors may possibly be more reliable.
In Study 3, the Cohort individuals who later developed AD were studied to identify possible predictors. Cognitive and psychosocial factors of ten AD individuals were retrospectively studied as case studies. They were also age and gender-matched with five healthy controls each. Neuropsychological results indicated RAVLT to be the most sensitive in predicting later cognitive impairment and could be used for early diagnosis, however, it lacked reliability at an individuals’ level. The role of APOE genotyping was also indicated as individuals with AD were more likely to be APOE ε4 carriers.
Lastly, in Study 4, biomarkers' role in the prediction of AD was investigated. A systematic review of five articles that used a multiplex immunoassay panel of biomarkers identified 14 overlapping proteins that were expressed significantly different between normal controls and AD individuals. The addition of APOE genotype and transthyretin (TTR) further improved prediction models done by backwards logistic regressions. TTR also showed modest potential diagnostic value by being expressed significantly lower amongst AD patient and normal controls of an independent sample (Concurrent Study). Interestingly, exercise level positively correlated with TTR levels.
Overall, the findings of this thesis enhance current understanding of normal aging and cognitive impairment. Although each neuropsychological, psychosocial, and biological factor showed promising results, none were reliable to be used in isolation as diagnostic tests of AD.