Universität zu Köln

David, Lara-Sophia Isabelle ORCID: 0009-0003-7637-3217 (2024). Relationship Between Grey Matter Volume in Subregions of the Basal Forebrain and the Cortical Acetylcholinesterase Activity in Mild Cognitive Impairment Patients due to Alzheimer’s disease. PhD thesis, Universität zu Köln.

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Abstract

Two thirds of all dementia cases worldwide are due to Alzheimer’s disease (AD). With rising life expectancy AD cases are increasing. Therefore, it has become a focus of research in the past decades. This thesis focuses on the symptomatic “pre-dementia stage” mild cognitive impairment (MCI). AD patients show pathophysiological changes in the brain, such as accumulation of toxic species of amyloid-β (Aβ) and development of neurofibrillary tangles. The basal forebrain (BF) cholinergic neurons, more specifically the nucleus basalis of Meynert (NBM), provide the main source of cholinergic innervation which is essential for different cognitive processes. These neurons have been found to be vulnerable to neuropathologic changes due to AD. Using the existing memory, ageing and the cholinergic system (MACS) dataset 17 MCI due to AD patients (M) and 18 cognitively healthy control subjects (C) were included in the analyses of this project. Each participant received a neuropsychological assessment, a cranial magnetic resonance imaging (MRI) scan and a 11C-N-methyl-4-piperidyl acetate (MP4A) positron emission tomography (PET) scan for quantification of cerebral Acetylcholinesterase (AChE) activity. After processing the MRI and PET images I completed various statistical analyses. The grey matter (GM) volume was calculated using the MRI scans. The hypothesis, based on previous studies is that the degree of atrophy in the BF differs between M and C. I therefore hypothesised that there would be a positive correlation between the GM volume in the NBM and cortical AChE activity. M scored significantly worse on all neuropsychological tests compared to C. The results of this thesis show differences in GM volume between M and C in the posterior nucleus basalis of Meynert (Ch4p), anterior medial and intermediate nucleus basalis of Meynert (Ch4a-i) and the hippocampus. Furthermore, there was a significant positive correlation between GM volume of Ch4p and cortical AChE activity in the hippocampus as well as the temporal lobe without the hippocampus. The atrophic regions in the BF show a significant positive correlation with AChE activity in the temporal and occipital lobe. A significant negative correlation was present between the GM of Ch4p and the “cholinergic deficit” across both groups. Interestingly, there was positive correlation between the GM in the medial septal nuclei and vertical limb of the diagonal band of Broca (Ch1/Ch2) and the “cholinergic deficit”. In conclusion, there is no significant association between the GM in the Ch4p and the cholinergic deficit within the patient group. However, larger Ch1/Ch2 volume was associated with larger “cholinergic deficit” within the M group. The results may help create predictions for the efficacy of the pharmacological treatment of AD patients. The next goal would be to create an individualized therapy plan based on the patients’ “cholinergic deficit”.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code David, Lara-Sophia Isabelle larasophiadavid@googlemail.com orcid.org/0009-0003-7637-3217 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-730832
Date:	2024
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Neurologie > Zentrum für Neurologie
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language Basal forebrain English Acetylcholinesterase English Mild cognitive impairment English
Date of oral exam:	5 April 2024
Referee:	Name Academic Title Kukolja, Juraj Professor Dr. med. Wevers, Andrea K. L. Privatdozentin Dr. rer. nat.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/73083