Memory precision across space and time in Alzheimer's disease


This thesis aimed to deepen current understanding of the mechanisms underlying visual short-term memory (VSTM) impairments in Alzheimer’s Disease (AD). The mixture model of working memory (WM) was deployed to dissect the differential contributions of distinct VSTM processes: ability to detect a target, swapping an item with another item in memory (misbinding), random guessing and precision of item representation (memory precision). Proficiency in filtering an unwanted item out (filtering ability), whether presented simultaneously with the to-be-remembered stimuli (encoding) or during the retention phase (maintenance) was also studied. In addition, measures of overall task performance, spatial localisation errors and reaction times were analysed.
Chapter 2 showed that healthy ageing was associated with a decline in VSTM memory precision, while in AD patients higher guessing and lower target detection were the main sources of memory errors. AD patients were also particularly affected when a distractor was presented during maintenance (filtering at maintenance), but not at encoding. As a comparator, patients with Parkinson’s Disease (PD) showed higher guessing rates, but preserved filtering abilities. In Chapter 3 the “What was where” Oxford Memory Task (OMT), was used to assess VSTM performance in people at risk of developing AD dementia, i.e., patients with subjective cognitive impairment (SCI) and mild cognitive impairment (MCI), compared to patients with established AD dementia. Apart from reaction time measures, most metrics derived from the OMT task were able to discriminate between healthy controls and patients with MCI, and between MCI and AD dementia. Mixture model metrics and spatial localization error also differed significantly between people with SCI and MCI. All metrics were correlated with hippocampal atrophy.
Chapter 4 showed that OMT metrics clustered into four specific spatial patterns of atrophy in the grey matter across a cohort of healthy controls and AD patients, with the Precuneus being associated only with metrics that carried spatial information. In Chapter 5 a key white matter region encompassing three tracts (Optic radiation, Forceps Major and Middle Longitudinal Fasciculus) was identified to be associated with VSTM performance on OMT in the left hemisphere in AD patients, but in the right hemisphere in healthy controls.
Finally, In Chapter 6 OMT metrics and several other cognitive measures derived from an online battery testing VSTM, executive functions, processing speed, long-term memory and visuospatial abilities, were related to plasma biomarkers of AD; phospotau (pTau)181, Glial fibrillary acidic protein (GFAP), Neurofilament Light Chain (NfL), and amyloid β 42/40 ratio (Aβ42/40 ratio). The results showed that of these biomarkers, pTau181 was most closely correlated to cognitive performance. However, cognitive measures and plasma biomarkers had different degrees of test-retest reliability, with pTau181 showing the highest degree of variability among plasma biomarkers in this sample.

Keywords: digital assessments
Alzheimer's disease
experimental psychology
plasma biomarkers
neuroimaging
Advisor: Husain, M
Mackay, C