AbstractBackground and main objective: Impaired insight is highly frequent in frontotemporal dementia (FTD) and especially prominent in its behavioural variant (bvFTD). The intrinsic complexity of this symptom seems to have hampered the accurate study of its underlying neuroanatomical substrates. The overarching goal of the present investigation was to explore the neural correlates of altered insight in FTD in order to determine whether broad and more specific objects of insight are underpinned by different or the same brain areas in this disease.
Methods: A systematic review on the matter was conducted to set the theoretical background of this thesis. A sample made up of 15 FTD patients (11 bvFTD and 4 language variant FTD -lvFTD-), 12 Alzheimer’s disease patients (AD), 6 motor neuron disease (MND)/amyotrophic lateral sclerosis patients (ALS) and 34 cognitively healthy controls (HC) was evaluated with an extensive battery of insight assessment methods, neuropsychological tests, and self-administered and informant-based neuropsychiatric/behavioural scales. Several analyses were conducted in this research project, including an examination of the psychometric properties of different insight assessment approaches, a characterization of the cohort in terms of levels of insight, neuropsychological performances, neuropsychiatric symptoms and functionality in activities of daily living (ADL), an effort to identify neuropsychological/behavioural predictors of insight and an evaluation of the caregiver burden associated with all those variables. 3 Tesla high resolution Magnetic Resonance Imaging (MRI) brain anatomical scans were acquired from a part of the sample. A voxel-based morphometry (VBM) analysis was carried out to find correlations between altered insight into broad and specific objects and gray matter densities.
Results: Literature suggests that different modalities of insight are mediated by distinct brain areas in FTD. Participant-informant level of agreement and clinical judgement are valid and reliable insight assessment methods to be used in dementia. The same applies to self-appraisal accuracy, although this approach appears to be a measure of metacognition instead. Levels of insight into health condition (broad object) and insight into memory, social cognition and functionality in ADL (specific objects) in bvFTD were significantly worse than those observed in the other neurodegenerative diseases under analysis and HC. Also, compared to HC, FTD and AD patients exhibited significantly worse scores in several insight, neuropsychological and neuropsychiatric measures. It was not possible to identify neuropsychological or behavioural predictors in the cohort with the analysis conducted. Caregiver burden for FTD and AD patients did not differ significantly. The VBM analysis did not show statistically significant correlations between different forms of insight and distinctive gray matter volumes in FTD using a conservative statistical approach.
Discussion and conclusions: Although insight seems to be conceptually and neuroanatomically differentiated into broad and specific objects of insight according to the literature, the present investigation found inconclusive results to support that different modalities of insight are underpinned by distinct brain areas in FTD. Further research is needed to elucidate the neuroanatomical substrates of this highly elusive concept in FTD and other types of dementia such as AD focusing on how insight can be broken down into broad and specific objects.
|Date of Award||25 Jan 2022|
|Supervisor||Jade Thai-Goodson (Supervisor), E J Coulthard (Supervisor) & Catherine Pennington (Supervisor)|