| 1. |
- Almkvist, Ove, et al.
(författare)
-
Predicting Cognitive Decline across Four Decades in Mutation Carriers and Non-carriers in Autosomal-Dominant Alzheimer's Disease
- 2017
-
Ingår i: Journal of the International Neuropsychological Society. - : CAMBRIDGE UNIV PRESS. - 1355-6177 .- 1469-7661. ; 23:3, s. 195-203
-
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.
|
|
| 3. |
- Vannini, Patrizia, et al.
(författare)
-
Failure to modulate neural response to increased task demand in mild Alzheimer's disease : fMRI study of visuospatial processing
- 2008
-
Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961 .- 1095-953X. ; 31:3, s. 287-297
-
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.
|
|
