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| 2. |
- M. Gavelin, Hanna, 1982-, et al.
(författare)
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Cognitive function in clinical burnout: A systematic review and meta-analysis
- 2022
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Ingår i: Work & Stress. - : Taylor & Francis. - 0267-8373 .- 1464-5335. ; 36:1, s. 86-104
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Forskningsöversikt (refereegranskat)abstract
- Clinical burnout has been associated with impaired cognitive functioning; however, inconsistent findings have been reported regarding the pattern and magnitude of cognitive deficits. The aim of this systematic review and multivariate meta-analysis was to assess cognitive function in clinical burnout as compared to healthy controls and identify the pattern and severity of cognitive dysfunction across cognitive domains. We identified 17 studies encompassing 730 patients with clinical burnout and 649 healthy controls. Clinical burnout was associated with impaired performance in episodic memory (g = −0.36, 95% CI −0.57 to −0.15), short-term and working memory (g = −0.36, 95% CI −0.52 to −0.20), executive function (g = −0.39, 95% CI −0.55 to −0.23), attention and processing speed (g = −0.43, 95% CI −0.57 to −0.29) and fluency (g = −0.53, 95% CI −1.04 to −0.03). There were no differences between patients and controls in crystallized (k = 6 studies) and visuospatial abilities (k = 4). Our findings suggest that clinical burnout is associated with cognitive impairment across multiple cognitive domains. Cognitive dysfunction needs to be considered in the clinical and occupational health management of burnout to optimise rehabilitation and support return-to-work.
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| 3. |
- M. Gavelin, Hanna, 1982-, et al.
(författare)
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Computerized cognitive training in Parkinson’s disease : A systematic review and meta-analysis
- 2022
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Ingår i: Ageing Research Reviews. - : Elsevier. - 1568-1637 .- 1872-9649. ; 80
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive impairment is a central non-motor symptom of Parkinson’s disease (PD), and there are no established treatments. Computerized cognitive training (CCT) is a safe and efficacious strategy but its efficacy in PD is unclear. We aimed to investigate the efficacy of CCT on cognitive, psychosocial and daily function, and assess potential effect moderators in people with PD without dementia. Randomized controlled trials of CCT were included in multivariate meta-analyses and meta-regressions. Seventeen studies (16 trials) encompassing 679 participants were included. The pooled effect of CCT relative to control was small and statistically significant for overall cognitive function (g=0.16; 95% CI 0.02–0.29). There was robust evidence for benefit on clinical measures of global cognition across 10 trials (g=0.33; 95% CI 0.19–0.48), especially in PD with mild cognitive impairment (PD-MCI), as well as on individual cognitive domains. Greater CCT dose and PD-MCI population were associated with larger effect sizes, but no statistically significant differences were found between subgroups. There was no significant difference in the efficacy of home-based compared to supervised training. Our findings suggest that CCT is associated with cognitive benefits in PD, including when delivered remotely. Larger, well-powered trials are warranted to examine what specific CCT regimens are most likely to promote cognitive and everyday functioning in the long-term.
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| 5. |
- Ninou, AH, et al.
(författare)
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PFKFB3 Inhibition Sensitizes DNA Crosslinking Chemotherapies by Suppressing Fanconi Anemia Repair
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:14
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Tidskriftsartikel (refereegranskat)abstract
- Replicative repair of interstrand crosslinks (ICL) generated by platinum chemotherapeutics is orchestrated by the Fanconi anemia (FA) repair pathway to ensure resolution of stalled replication forks and the maintenance of genomic integrity. Here, we identify novel regulation of FA repair by the cancer-associated glycolytic enzyme PFKFB3 that has functional consequences for replication-associated ICL repair and cancer cell survival. Inhibition of PFKFB3 displays a cancer-specific synergy with platinum compounds in blocking cell viability and restores sensitivity in treatment-resistant models. Notably, the synergies are associated with DNA-damage-induced chromatin association of PFKFB3 upon cancer transformation, which further increases upon platinum resistance. FA pathway activation triggers the PFKFB3 assembly into nuclear foci in an ATR- and FANCM-dependent manner. Blocking PFKFB3 activity disrupts the assembly of key FA repair factors and consequently prevents fork restart. This results in an incapacity to replicate cells to progress through S-phase, an accumulation of DNA damage in replicating cells, and fork collapse. We further validate PFKFB3-dependent regulation of FA repair in ex vivo cultures from cancer patients. Collectively, targeting PFKFB3 opens up therapeutic possibilities to improve the efficacy of ICL-inducing cancer treatments.
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| 6. |
- Nordvall, Olov, 1980-
(författare)
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Cognition in interned adolescents : aspects of executive functions and training
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This doctoral thesis examines adolescents with a history of antisocial behavior with a focus on investigating executive functioning, impulsivity and experiences of everyday executive problems. The thesis further investigates the associations between self-reported and performance-based measures. Finally, it investigates whether processed-based executive function training can influence trained and non-trained executive functions and related scholastic abilities.Antisocial behavior is a complex concept, associated with high costs of personal, interpersonal and societal nature. In general, people implement the majority of their life´s share of delinquent and antisocial behaviors around the adolescent years, as described by the so-called age-crime curve. This period is associated with rapid cognitive development, and deficits in this period of time have been associated with an increased susceptibility to partake in antisocial behavior. Also, larger impairments are associated with more severe behaviors. In many western countries, there exist a duality of both welfare and judicial considerations in the case of antisocial individuals who are minors. As compared to adults, persons under the age of criminal responsibility typically face a different combination of rehabilitative and penal consequences from maladaptive, delinquent or antisocial behaviors. In this context, increased understanding of the cognitive underpinnings of antisocial behavior, and how best to support sound cognitive development are therefore relevant to the furthering of rehabilitative practice. This thesis expands on existing knowledge by examining interned adolescents from an executive functions framework and also investigates how it relate to other constructs of clinical relevance.This is done in three empirical studies. The first two are cross-sectional and aimed at assessing a number of cognitive constructs and associated behaviors. The third study is aimed at examining the effects of a training intervention on said constructs. The studies indicated poorer pre-test performance by the interned adolescents as compared to their non-interned counterparts. However, no deficits specific to any one executive function was discernable. The results also showed that the internees self-reports expressed more perceived problems with inhibiting behaviors and managing unplanned prompts to shift from a planned activity. They also indicated it harder to resist impulsive behaviors related to negative affect, lower premeditative ability, and had more issues with persevering in prolonged tasks. In addition, there were a few connections between the performance-based and the self-reported accounts of executive functioning. Of particular interest was that the majority of group effects in self-reported constructs was related to the specific executive function updating, a finding not previously reported. This executive function has previously been suggested to be antecedent of antisocial behavior though. As for the training, the only substantial improvement was to perceptual speed, which occurred irrespective of training progression or experimental condition. This was mirrored by the posttest self-reports whose rather modest gains were also unrelated to both experimental conditions and training improvements.In conclusion, executive functioning and trait-based cognition are related to some degree, and both associate to antisocial behavior as operationalized by internment status. Process-based cognitive training can however not feasibly be determined to affect or alter these relations.
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| 7. |
- Sindi, S., et al.
(författare)
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Multimodal Preventive Trial for Alzheimer’s Disease : MIND-ADmini Pilot Trial Study Design and Progress
- 2022
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Ingår i: The Journal of Prevention of Alzheimer's Disease. - : Serdi-Editions. - 2274-5807 .- 2426-0266. ; 9:1, s. 30-39
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Tidskriftsartikel (refereegranskat)abstract
- Background: Interventions simultaneously targeting multiple risk factors and mechanisms are most likely to be effective in preventing cognitive impairment. This was indicated in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) testing a multidomain lifestyle intervention among at-risk individuals. The importance of medical food at the early symptomatic disease stage, prodromal Alzheimer’s disease (AD), was emphasized in the LipiDiDiet trial. The feasibility and effects of multimodal interventions in prodromal AD are unclear. Objectives: To evaluate the feasibility of an adapted FINGER-based multimodal lifestyle intervention, with or without medical food, among individuals with prodromal AD. Methods: MIND-ADmini is a multinational proof-of-concept 6-month randomized controlled trial (RCT), with four trial sites (Sweden, Finland, Germany, France). The trial targeted individuals with prodromal AD defined using the International Working Group-1 criteria, and with vascular or lifestyle-related risk factors. The parallel-group RCT includes three arms: 1) multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); 2) multimodal lifestyle intervention+medical food (Fortasyn Connect); and 3) regular health advice/ care (control group). Primary outcomes are feasibility and adherence. Secondary outcomes are adherence to the individual intervention domains and healthy lifestyle changes. Results: Screening began on 28 September 2017 and was completed on 21 May 2019. Altogether 93 participants were randomized and enrolled. The intervention proceeded as planned. Conclusions: For the first time, this pilot trial tests the feasibility and adherence to a multimodal lifestyle intervention, alone or combined with medical food, among individuals with prodromal AD. It can serve as a model for combination therapy trials (non-pharma, nutrition-based and/or pharmacological interventions).
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