Thesis (Ph.D.)--Aberdeen University, 2009. / Title from web page (viewed on Sep. 2, 2009). Includes bibliographical references.

Diss. (sammanfattning) Stockholm : Stockholms universitet, 2009. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Individuals with Alzheimer Disease (AD) exhibit deficits across multiple cognitive domains years before clinical diagnosis, when they are in the preclinical stages of the disease. Four studies were conducted to (a) examine the preclinical neuropsychological characteristics of English- and French-speaking Alzheimer Disease (AD) participants from the Canadian Study of Health and Aging (CSHA) and (b) determine the utility of select CSHA neuropsychological and demographic measures in predicting AD over a five-year period. Both English- and French-speaking AD participants demonstrated cognitive changes on episodic memory, verbal fluency, and speeded visuomotor processing tasks five years prior to diagnosis, however declines in performance between initial- and re-assessment were not uniform across these domains for either language group. Advanced age and declines in delayed episodic memory were the most significant indicators of progression to AD over a five-year period for both language groups. A validation study was conducted to investigate how well the predictors of AD prognosticate diagnostic outcome for an independent group of at-risk English-speaking participants. The best predictors of AD for the English-speaking group (age, episodic memory, and speeded visuomotor processing) accurately classified close to 70% of individuals from the at-risk sample. The present findings will contribute to diagnostic decisions regarding AD in older English- and French-speaking Canadian adults.

Individuals with Alzheimer Disease (AD) exhibit deficits across multiple cognitive domains years before clinical diagnosis, when they are in the preclinical stages of the disease. Four studies were conducted to (a) examine the preclinical neuropsychological characteristics of English- and French-speaking Alzheimer Disease (AD) participants from the Canadian Study of Health and Aging (CSHA) and (b) determine the utility of select CSHA neuropsychological and demographic measures in predicting AD over a five-year period. Both English- and French-speaking AD participants demonstrated cognitive changes on episodic memory, verbal fluency, and speeded visuomotor processing tasks five years prior to diagnosis, however declines in performance between initial- and re-assessment were not uniform across these domains for either language group. Advanced age and declines in delayed episodic memory were the most significant indicators of progression to AD over a five-year period for both language groups. A validation study was conducted to investigate how well the predictors of AD prognosticate diagnostic outcome for an independent group of at-risk English-speaking participants. The best predictors of AD for the English-speaking group (age, episodic memory, and speeded visuomotor processing) accurately classified close to 70% of individuals from the at-risk sample. The present findings will contribute to diagnostic decisions regarding AD in older English- and French-speaking Canadian adults.

Thesis (M.S.)--University of Missouri--Columbia, 1997. / "December 1997." Typescript. Includes bibliographical references (leaves 34-39). Also available on the Internet.

Diss. (sammanfattning) Stockholm : Stockholms universitet, 2009. / At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Submitted. Paper 4: In progress. Härtill 4 uppsatser.

The present thesis explored a number of topics all linked by their involvement in Alzheimer’s disease (AD). Firstly, hippocampal slices prepared from a new transgenic knock-in mouse model of the disorder PLB1, harbouring human APP (with the Swedish and London mutations), Tau (with the P301L and R406W mutations) and PS1 (with the A246E mutation) genes were characterised electrophysiologically. Data obtained confirm AD-like alterations in PLB1 mice and suggest that these mice are a suitable model of AD and slice electrophysiology is a relevant experimental endpoint. Secondly, the effects of memantine on synaptic transmission and plasticity in the mouse hippocampus were investigated. Memantine was found to inhibit tetanus-induced LTP in the CA1 region at high concentrations (100 μM) while being devoid of such effects at lower (10 μM), therapeutically relevant doses. However, both concentrations acted to enhance baseline synaptic transmission via enhanced muscarinic signalling in a similar fashion to the muscarinic agonist carbachol, suggesting an additional facet to the drugs good clinical utility in AD patients. Thirdly, potential new treatments for AD were investigated in the form of a plant extract from <i>Cassia obtusifolia</i> (COE) and novel synthetic β-secretase (BACE) inhibitors LC25-116, LC25-120 and LC25-184. COE provided significant protection in models of excitotoxicity and mitochondrial dysfunction, both inherently linked to the pathogenesis of AD. The three novel BACE inhibitors significantly reduced Aβ production by an APP-expressing neuroblastoma cell line and reduced the resulting toxicity of its medium to hippocampal cultures. Finally, A1, a risk factor in AD, was investigated by assessing the toxicity of Al.cit.Q (K[A1(C₇H₁₁O₆)₃](OH]4H₂O_.The neuroprotective properties of quinic acid, the ligand attached to A1 in Al.cit.Q., were consequently tested. The results highlight the profound effect the ligand bound to A1 has on the metal’s toxicity and suggest that quinic acid could successfully be employed to combat metal toxicity.

Although a central etiology for Alzheimer disease (AD) has not yet been determined, support has amassed for the notion that oxidative stress may be involved in the pathogenesis of AD. The disruption of iron homeostasis and iron's excessive deposition in AD brain tissues has received increased attention due to the metal's capacity to promote the production of harmful free radicals. Several studies have recently examined whether DNA mutations involved in the iron overload disorder, hemochromatosis, pose an increased risk of acquiring AD. However, the small sample size and low generalizability of previous studies have warranted further investigation. We genotyped 213 AD patients, 106 Mild Cognitively Impaired (MCI) individuals, and 63 Normal Elderly Control (NEC) subjects for the H63D and C282Y HFE mutations to examine whether a relationship exists between HFE gene status and AD presentation in our patient population. DNA analysis was conducted by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP). We did not find any statistically significant associations between HFE gene status and the clinical, demographic, or neuropsychological aspects of AD in our patient population. Interesting trends that fell short of statistical significance included: (a) a deleterious effect of HFE mutations on motor performance, (b) an influence of H63D homozygosity on an earlier onset of cognitive decline, and (c) an influence of H63D homozygosity on an accelerated progression from MCI to AD.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2005. / Härtill 5 uppsatser.