Enhancing cognitive and functional assessment for Alzheimer’s disease

One major challenge recently recognised by a EU consensus conference is the need of brief, reliable, simple methods to assess Alzheimer’s Disease (AD). There is an emphasis on the need for cognitive, behavioural and functional measures that are sensitive and specific for detecting the cognitive impairment earlier of the course of the disease. In my thesis I explore what are these measures. This thesis sought to explore two themes: the first, where I enhance the existing knowledge about Visual Short-Term Memory Binding as a sensitive, specific and early cognitive marker for AD. The second theme is to look at which everyday functional abilities decline first in the trajectory from the healthy ageing to dementia. I argue that everyday financial decline is the earliest functional impairment in the course of the disease. There are evidences indicating that the Temporal Memory Binding (TMB) reliably detects asymptomatic carriers of the Presenil-1 gene mutation E280A that leads to familial AD and amnestic Mild Cognitive Impairment (aMCI) patients who are at a high risk of conversion to dementia; the test is not affected by healthy ageing and chronic depression; it has been proved culturally unbiased. All these factors make the test a perfect marker for AD. The TMB test has been developed as a computer version. This poses several limitation of using the test globally: it has low mobility, difficulty testing on the older population and patients with AD who have preferences more to conventional paper-and-pencil tests. Therefore, one of the main aims of the thesis was to create a more clinically and user-friendly version of the test. I created a Flash-Card version of the test that contained several modifications from the standard computer version to make the test more clinically oriented: all participants were presented only with two items and the test was presented as a recognition task. The alternative version of the test was presented in the form of the Tablet PC. The first series of experiments (Experiments 1-7) reported in this thesis were dedicated to compare these three formats of testing. I showed that all three methods of testing are equivalent to each other. In these experiments I also have confirmed that the test is unaffected by age in order to serve as a baseline performance on the Flash-Cards and Tablet PC to measure AD performance. In the following Chapter 3, I focused on addressing the question, what is the neurological reason for older adults to perform as well as younger participants. For that I employed a mobile low-density EEG system that has advantages in its mobility and user-friendliness, which is important in clinical setting and in research with frail older participants. The results of the study showed increased activity over all electrodes sites suggesting that older participants recruited more neural resources to achieve levels of performance similar to those observed in younger adults. To show that my Flash-cards TMB task still holds specificity to only AD I recruited patients with aMCI, AD patients and Parkinson’s disease (PD) patients with and without cognitive deterioration (Chapter 4). The results of the study showed that only patients with AD presented impaired performance on the TMB task. On the contrary, compared to either cognitively healthy older individuals or PD patients with normal cognition, patients with PD dementia did not show impairment on the TMB. The other main aim of this thesis was to investigate what functional abilities decline first on the course of the disease and what are those “minimal functional problems”. As part of this thesis I conducted a literature review (Chapter 7) that showed that everyday financial abilities represent the most complex and multidimensional functional activities. I coined a term Acreemagnosia to highlight the specificity of the symptom. In order to assess this specific symptom I developed The Acreemagnosia Measurement (TAM) that is a multi-items measure that inquiries about a person’s awareness of financial abilities and examines actual performance on the broad range of everyday financial tasks. On the groups of healthy middle-aged and older people I validated TAM (Chapter 8). I used a two-parameter IRT model to analyse the psychometric properties of TAM and established the best items that would describe financial abilities of participants in different age and gender groups. The analysis suggests that TAM is measuring most reliably at low to average levels of financial ability, meaning that TAM is potentially a good financial measure for people with limited financial proficiency, which is in keeping with the design and intended use of the instrument with elderly retired people and people with cognitive impairment. The results did not reveal any differential item functioning across different gender and age groups in the scale that indicates that tendency to endorse the item reflects the ability level and are not affected by variables such as gender and age. As TAM is intended for patients with cognitive impairment, I recruited patients with amnestic-MCI and mild-AD (Chapter 9). In this feasibility study I showed that patients with amnestic-MCI are already present with some problems in everyday financial abilities and are unaware of these problems demonstrating that they present with Acreemagnosia, thus confirming the sensitivity of TAM to capture such impairments. The general findings of this thesis indicate that TMB task and TAM can enhance the assessment of dementia and potentially serve in the detection of cognitive impairment at the pre-clinical level