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- Bäckman, Lars, et al.
(författare)
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The correlative triad among aging, dopamine, and cognition : current status and future prospects.
- 2006
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Ingår i: Neuroscience and Biobehavioral Review. - : Elsevier BV. - 0149-7634. ; 30:6, s. 791-807
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The brain neuronal systems defined by the neurotransmitter dopamine (DA) have since long a recognized role in the regulation of motor functions. More recently, converging evidence from patient studies, animal research, pharmacological intervention, and molecular genetics indicates that DA is critically implicated also in higher-order cognitive functioning. Many cognitive functions and multiple markers of striatal and extrastriatal DA systems decline across adulthood and aging. Research examining the correlative triad among adult age, DA, and cognition has found strong support for the view that age-related DA losses are associated with age-related cognitive deficits. Future research strategies for examining the DA-cognitive aging link include assessing (a) the generality/specificity of the effects; (b) the relationship between neuromodulation and functional brain activation; and (c) the release of DA during actual task performance.
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| 3. |
- Ekman, Urban, 1968-
(författare)
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Functional brain imaging of cognitive status in Parkinson's disease
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Parkinson’s disease (PD) is next to Alzheimer’s disease (AD) the second most common neurodegenerative disease. PD has traditionally been characterised as a motor disorder, but more recent research has revealed that cognitive impairments are frequent. Cognitive impairments in executive functions, attention, and working memory with reliance on dopaminergic transmission, are often described as dominating the cognitive profile in early-phase PD. However, although knowledge about the neuropathology that underlies the cognitive impairments in PD has increased, its features are complex and knowledge remains insufficient. Therefore, the aim of the current thesis was to improve the understanding of how task-evoked brain responses relate to cognitive status in patients with PD, with and without mild cognitive impairment (MCI), and to evaluate the predictive value of PD-MCI in respect of prodromal Parkinson’s disease dementia (PDD). This was conducted within the “new Parkinsonism in Umeå” (NYPUM) project, which is a prospective cohort study. Patients with idiopathic PD were included in this thesis, and the patients were examined with a comprehensive neuropsychological battery and with a functional MRI (fMRI) working memory protocol. During scanning, patients conducted a verbal two-back task in which they needed to maintain and actively update relevant information, and the primary outcome measure was blood-oxygen-level-dependent (BOLD) signal. This thesis shows that patients with PD-MCI had significantly lower BOLD signal responses than patients without MCI in frontal (anterior cingulate cortex) and striatal (right caudate) regions (Study I). The altered BOLD response in the right caudate was associated with altered presynaptic dopamine binding. The fronto-striatal alterations persisted across time but without any additional change. However, decreased posterior cortical (right fusiform gyrus) BOLD signal responses were observed in patients with PD-MCI relative to patients without MCI across time (Study II). Finally, PD-MCI at baseline examination is highly predictive for prodromal PDD with a six-fold increased risk. Cognitive tests with a posterior cortical basis, to a greater extent, are predictive for prodromal PDD than tests with a fronto-striatal basis. The observed working memory related alterations in patients with PD-MCI suggest that early cognitive impairments in PD are linked to fronto-striatal dopaminergic dysfunction. The longitudinal development of cognitive impairment in PD reflects additional posterior cortical dysfunction. This might reflect a dual syndrome, with dopamine-depleted fronto-striatal alterations that characterise PD-MCI in general, whereas additional posterior cortical cognitive alterations with a non-dopaminergic basis to a greater extent characterise prodromal PDD. If, and how, the two potential syndromes interact, is still unclear. Thus, this thesis provides information on cognitive neuropathological changes in PD that might contribute to more relevant choices of pharmacotherapy and diagnostic accuracy in respect of PDD. However, additional large-scale longitudinal imaging studies are needed to further clarify the neuropatholgogical features of PD-MCI in respect of prodromal PDD.
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| 4. |
- Fischer, Håkan, et al.
(författare)
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Brain activation while forming memories of fearful and neutral faces in women and men
- 2007
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Ingår i: Emotion. - : American Psychological Association (APA). - 1528-3542 .- 1931-1516. ; 7:4, s. 767-773
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Event-related functional MRI (fMRI) was used to assess brain activity during encoding of fearful and neutral faces in 12 women and 12 men. In a subsequent memory analysis, the authors separated successful from unsuccessful encoding of both types of faces, based on whether they were remembered or forgotten in a later recognition memory test. Overall, women and men recruited overlapping neural circuitries. Both sexes activated right-sided medial-temporal regions during successful encoding of fearful faces. Successful encoding of neutral faces was associated with left-sided lateral prefrontal and right-sided superior frontal activation in both sexes. In women, relatively greater encoding related activity for neutral faces was seen in the superior parietal and parahippocampal cortices. By contrast, men activated the left and right superior/middle frontal cortex more than women during successful encoding of the same neutral faces. These findings suggest that women and men use similar neural networks to encode facial information, with only subtle sex differences observed for neutral faces.
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| 5. |
- Frykholm, Erik, 1985-
(författare)
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The relevance and assessment of limb muscle function in individuals with chronic obstructive pulmonary disease
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic obstructive pulmonary disease (COPD) is a disease that is characterised by persistent respiratory symptoms and airflow limitation. Consequences beyond the airways and lungs are common, and include limb muscle dysfunction. Limb muscle dysfunction is treated with exercise training, and should be preceded by assessments to individualise prescriptions. Guidelines recommend assessment of quadriceps strength, but limb muscle dysfunction affects more than strength. Other less investigated assessments may be of interest. During training, direct physiological (cardiorespiratory, metabolic, and biomechanical) and symptomatic responses are important, since they can affect training effectivity, and they may differ depending on whether arms or legs are used. The main aims of this thesis were to investigate the relevance of assessments of quadriceps function, feasibility and reliability of methods to assess quadriceps endurance, and to compare the direct physiological and symptomatic responses during arm and leg activities in people with COPD.Method: This thesis is based on four papers. These include one systematic review with a meta-analysis of studies comparing direct physiological and symptomatic responses to activities performed with the arms versus the legs, and three papers based on an international cross-sectional multicentre study investigating reliability, feasibility, and relevance of three leg extension assessments of quadriceps endurance. Relative and absolute reliability were determined via interclass correlation coefficient (ICC), coefficient of variation (CV %), and limits of agreement (LoA %) for measures of isokinetic total work, isokinetic fatigue index, isometric time to exhaustion, and isotonic repetitions to exhaustion. The relevance of the measures of quadriceps endurance and other quadriceps functions were determined by the association to functional capacity and physical activity with Pearson correlation analyses (r) and multiple linear regression models (R2, adjusted R2, Δ R2, and Δ adjusted R2).Results: Results from the meta-analyses show that leg-cycle ergometer resulted in greater tidal volume (137 mL), minute ventilation (4.8 L/min), and oxygen consumption (164 mL/min) compared to arm cycle ergometer, while symptomatic responses were similar. Physiological responses (e.g., minute ventilation and oxygen consumption) during arm compared to leg resistance training exercises were similar. Results from studies on functional activities depend on the type and intensity of the activity performed. Isokinetic total work was the measurement with the highest relative reliability (ICC = 0.98) and the smallest absolute reliability (e.g., CV% = 6.5). Isokinetic fatigue index, isometric, and isotonic measures demonstrated low-to-high relative reliability (ICC = 0.64, 0.88, 0.91), and absolute reliability was larger (e.g., CV% = 20.3, 14.9, and 15.8%). Participants performed better on the retest for isokinetic total work and isometric measurements (4.8 and 10%, p < 0.001). The feasibility was similar across protocols, with an average time consumption of< 7.5 minutes, limited perceived dyspnoea compared to leg fatigue, and no major adverse advents. The measures of quadriceps function had mostly similar (r = +/- 0.07–0.45) levels of correlations to the functional capacity and physical activity. In multiple regression analyses improved quadriceps power the models to predict functional capacity the most (Δ adjusted R2= 0.10, 0.15, adjusted R2 = 0.60, 0.39). Isotonic endurance was the only muscle function that improved all physical activity models (ΔR2 = 0.04–0.07, p < 0.05, R2 = 0.38–0.49).Conclusions: The results indicate that if the goal of an activity is to maximise physiological responses such as minute ventilation and oxygen consumption, activities involving the legs should be preferred. Symptomatic responses seems task and intensity dependent, which suggest that strategies used to reduce symptoms should be based on relative intensity. In the assessment of quadriceps endurance, isokinetic, isometric and isotonic protocols present low to very high relative reliability. Differences in reliability and the better performance at retest might reflect differences in ability to detect true change. Quadriceps power seems to be more relevant to functional capacity, and isotonic quadriceps endurance seems to be more relevant to physical activity.
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| 10. |
- Jonasson, Lars, 1983-, et al.
(författare)
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Aerobic fitness influences working memory updating via the striatal dopaminergic system in older adults
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- There is much evidence that dopamine is vital for cognitive functioning in aging. Here we tested the hypothesis that aerobic exercise and fitness influences dopaminergic neurotransmission in the striatum as measured by positron emission tomography (PET) and the non-displacable binding potential (BPND ) of [11C]raclopride, and in turn performance on offline working-memory updating tasks. In a sample of 58 older sedentary adults undergoing a six-months exercise intervention, aerobic exercise compared to stretching, toning, and resistance training did not have a differential effect on BPND . At baseline, higher aerobic fitness levels (VO2peak ) were associated with higher BPND in the striatum. Following the intervention, for both forms of training, we found reduced BPND , indicating increased dopamine (DA), in a cluster in the anterior striatum in individuals with larger improvements in VO2peak . This reduction in BPND mediated a positive indirect effect of VO2peak on working-memory updating performance. Collectively these findings implicate DA as a neurocognitive mechanism explaining the positive effects of staying physically active at an old age for working memory.
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