Multimodal studies of brain structureand function in neurodegenerative dementia

Abstract

Alzheimer’s disease (AD) is associated with a prodromal stage of cognitive decline, manifest clinically as mild cognitive impairment (MCI) that progresses ultimately to a stage of dementia. There is an urgent need to recognise AD at its earliest clinical stages, which entails distinguishing AD from other conditions, particularly other neurodegenerative diseases, but at a time when clinical symptoms are non-specific. Investigations such as neuropsychological testing and neuroimaging, using MRI and PET to determine changes in brain structure and metabolism respectively, provide additional useful diagnostic information, the changes associated with these tests now incorporated into diagnostic criteria. These studies aimed to investigate AD and Frontotemporal dementia (FTD) using these investigative tools, with a particular focus on AD in keeping with its central importance as the commonest cause of dementia. Early AD was the focus of the first study. Given the involvement of the hippocampus from the initial stages of AD, and of the role of the hippocampus in spatial memory, the study hypothesis was that a hippocampus-sensitive test of spatial memory would discriminate prodromal AD and mild AD dementia with high sensitivity and specificity. The 4 Mountains Test of spatial memory (4MT) was chosen in view of its potential usability across different cultural settings. The second study focused on dementia due to AD and FTD. Given the diagnostic importance of MRI and PET changes, this study aimed to measure the concordance of atrophy and hypometabolism in six syndromic variants of AD and FTD. The primary hypothesis was that concordance would differ across different AD and FTD syndromes, with a secondary hypothesis that determination of the topographical extent of atrophy and hypometabolism would differ according to the method used to determine imaging changes.

Date of Award	Apr 2016
Original language	English
Awarding Institution	University of Brighton