| 1. |
- Almkvist, Ove, et al.
(författare)
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Predicting Cognitive Decline across Four Decades in Mutation Carriers and Non-carriers in Autosomal-Dominant Alzheimer's Disease
- 2017
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Ingår i: Journal of the International Neuropsychological Society. - : CAMBRIDGE UNIV PRESS. - 1355-6177 .- 1469-7661. ; 23:3, s. 195-203
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this study was to investigate cognitive performance including preclinical and clinical disease course in carriers and non-carriers of autosomal-dominant Alzheimer's disease (adAD) in relation to multiple predictors, that is, linear and non-linear estimates of years to expected clinical onset of disease, years of education and age. Methods: Participants from five families with early-onset autosomal-dominant mutations (Swedish and Arctic APP, PSEN1 M146V, H163Y, and I143T) included 35 carriers (28 without dementia and 7 with) and 44 non-carriers. All participants underwent a comprehensive clinical evaluation, including neuropsychological assessment at the Memory Clinic, Karolinska University Hospital at Huddinge, Stockholm, Sweden. The time span of disease course covered four decades of the preclinical and clinical stages of dementia. Neuropsychological tests were used to assess premorbid and current global cognition, verbal and visuospatial functions, short-term and episodic memory, attention, and executive function. Results: In carriers, the time-related curvilinear trajectory of cognitive function across disease stages was best fitted to a formulae with three predictors: years to expected clinical onset (linear and curvilinear components), and years of education. In non-carriers, the change was minimal and best predicted by two predictors: education and age. The trajectories for carriers and non-carriers began to diverge approximately 10 years before the expected clinical onset in episodic memory, executive function, and visuospatial function. Conclusions: The curvilinear trajectory of cognitive functions across disease stages was mimicked by three predictors in carriers. In episodic memory, executive and visuospatial functions, the point of diverging trajectories occurred approximately 10 years ahead of the clinical onset compared to non-carriers.
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| 2. |
- Persson, Ninni, et al.
(författare)
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A principal component model of medical health : Implications for cognitive deficits and decline among adults in a population-based sample
- 2013
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Ingår i: Journal of Health Psychology. - : SAGE Publications. - 1359-1053 .- 1461-7277. ; 18:10, s. 1268-1287
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Tidskriftsartikel (refereegranskat)abstract
- Longitudinal blood- and cognitive data from 879 adults were analyzed to extract a multidimensional health structure for prediction of cognitive change. Six health components were identified and replicated at two waves. Following, cognitive outcomes were regressed on the health components. Large proportions of cognitive age related variations were accounted for by baseline health in both cross-sectional and prospective analyses. Less variation was accounted for when health change and cognitive change were contrasted. Cardiovascular health was particularly important for prediction of cognitive change. Our study underlines causal relations between health and cognitive functions, and suggests that some effects are long term.
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| 3. |
- Schöll, Michael, et al.
(författare)
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Time Course of Glucose Metabolism in Relation to Cognitive Performance and Postmortem Neuropathology in Met146Val PSEN1 Mutation Carriers
- 2011
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 24:3, s. 495-506
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Tidskriftsartikel (refereegranskat)abstract
- Studies in carriers of mutations that cause early-onset familial Alzheimer's disease (eoFAD) are of significant interest. We showed previously that regional glucose hypometabolism could be detected many years before disease onset in presenilin 1 (PSEN1) mutation carriers. Here we studied four members of a family with a Met146Val PSEN1 mutation, two symptomatic carriers and two non-carriers, longitudinally with (18)F-FDG PET over a period of about two and four years, respectively. The two mutation carriers showed global cortical glucose hypometabolism over time with the most distinct decline occurring in the posterior cingulate, the parietal and parietotemporal cortex, which was also observed when compared with a group of 23 healthy controls and a group of 27 sporadic Alzheimer's disease (sAD) patients. This decline correlated with cognitive deterioration over time as measured by neuropsychological tests. Postmortem examination of brain tissue revealed substantially elevated levels of AD type neuropathology in terms of neuritic plaques and neurofibrillary tangles in the two mutation carriers compared with a reference group of 249 sAD patients. In the mutation carriers, the amount of neuritic plaques but not neurofibrillary tangles correlated hereby significantly with regional glucose metabolism as measured by (18)F-FDG on the last scanning occasions, which were performed four and approximately five years before death, respectively. We here show that FDG PET can depict in vivo the aggressive disease progression in eoFAD mutation carriers in relationship to neuropathology.
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| 4. |
- Vannini, Patrizia, et al.
(författare)
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Failure to modulate neural response to increased task demand in mild Alzheimer's disease : fMRI study of visuospatial processing
- 2008
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961 .- 1095-953X. ; 31:3, s. 287-297
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is characterized by disturbances of visuospatial cognition. Given that these impairments are closely related to metabolic and neuropathological changes, our study aimed to investigate the functional competency of brain regions in the visuospatial networks responsible for early clinical symptoms in AD using event-related functional magnetic resonance imaging (fMRI). Participants (13AD patients with mild symptoms and 13 age- and education-matched controls) performed an angle discrimination task with varying task demand. Using a novel approach that modeled the dependency of the blood oxygenation level-dependent (BOLD) signal on the subject's reaction time allowed us to investigate task demand-dependent signal changes between the groups. Both groups demonstrated overlapping neural networks engaged in angle discrimination, including the parieto-occipital and frontal regions. In several network regions, AD patients showed a significantly weaker and sometimes no BOLD signal due to increased task demand compared with controls, demonstrating failure to modulate the neural response to increased task demand. A general task demand-independent increase of activation in AD patients compared with controls was found in right middle temporal gyrus. This latter finding may indicate an attempt to compensate for dysfunctional areas in the dorsal visual pathway. These results confirm deficits in visuospatial abilities, which occur early in AD, and offer new insights into the neural mechanisms underlying this impairment.
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