Clinical and neuroimaging profiles of a biomarker-confirmed Memory Clinic cohort
File(s)
Author(s)
Loreto, Flavia
Type
Thesis
Abstract
The onset of Alzheimer’s disease (AD) has long been associated with medial temporal lobe (MTL) atrophy and episodic memory impairment. The development of biomarkers of AD neuropathology has led to the discovery of atypical forms of the disease, characterised by highly heterogeneous cognitive presentations and atrophy patterns. Nevertheless, the reasons for such heterogeneity remain poorly understood and are often not captured by the analysis of selected research cohorts using traditional analytical approaches. AD heterogeneity is the main object of interest of this thesis, which examined the cognitive and neuroimaging profiles of a clinical cohort of patients undergoing diagnostic amyloid PET imaging for the assessment of intracerebral amyloid pathology. In line with appropriate use criteria, patients undergoing clinical amyloid PET present with atypical symptoms and relatively young age, representing an ideal group to reappraise the diagnostic value of conventional examinations and study the possible drivers of disease heterogeneity in atypical AD. Chapter 2 of this thesis shows that, impairment in working memory and visuospatial functioning are more strongly associated than episodic memory impairment with Alzheimer’s pathology in this group. Chapter 3 reveals high prevalence of depressive symptoms in patients referred for amyloid PET and proposes depression as a possible driver of both diagnostic uncertainty and the variable clinical presentations observed in this group. Chapters 4 and 5 provide evidence of highly heterogeneous atrophy profiles and of the limited diagnostic utility of MTL volumes assessed through different methods. Finally, Chapter 5 suggests neuroanatomical normative modelling as a promising analytical tool to investigate individual neuroanatomical variation in AD. Altogether, the results of this thesis contribute to knowledge of AD heterogeneous cognitive and neuroimaging profiles, providing insight into the diagnostic utility of these features and highlighting the importance of amyloid assessment in this group to avoid diagnostic delays and errors.
Version
Open Access
Date Issued
2022-09-04
Date Awarded
01/04/2023
License URL
Advisor
Malhotra, Paresh
Perry, Richard
Sponsor
Alzheimer's Society
Grant Number
P75464
Publisher Department
Department of Brain Sciences
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)