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Machine Learning and Social Robotics for Detecting Early Signs of Dementia [article]

Patrik Jonell, Joseph Mendelson, Thomas Storskog, Goran Hagman, Per Ostberg, Iolanda Leite, Taras Kucherenko, Olga Mikheeva, Ulrika Akenine, Vesna Jelic, Alina Solomon, Jonas Beskow, Joakim Gustafson (+1 others)
2017 arXiv   pre-print
This paper presents the EACare project, an ambitious multi-disciplinary collaboration with the aim to develop an embodied system, capable of carrying out neuropsychological tests to detect early signs of dementia, e.g., due to Alzheimer's disease. The system will use methods from Machine Learning and Social Robotics, and be trained with examples of recorded clinician-patient interactions. The interaction will be developed using a participatory design approach. We describe the scope and method
more » ... the project, and report on a first Wizard of Oz prototype.
arXiv:1709.01613v1 fatcat:bk3udrvhd5b2zmxbje2xd3gbxq

Capillary blood tests may overestimate ketosis: Triangulation between three different measures of beta-hydroxybutyrate

Jakob Norgren, Shireen Sindi, Anna Sandebring-Matton, Ingemar Kåreholt, Ulrika Akenine, Karin Nordin, Staffan Rosenborg, Tiia Ngandu, Miia Kivipelto
2019 American Journal of Physiology. Endocrinology and Metabolism  
The current results are part of a larger study (Norgren J, Sindi S, Sandebring-Matton A, Kåreholt I, Daniilidou M, Akenine U, Nordin K, Rosenborg S, Ngandu T, and Kivipelto M, unpublished observations)  ... 
doi:10.1152/ajpendo.00454.2019 pmid:31821040 fatcat:pdurloavqndbbmnev7pm2udrb4

Ketosis After Intake of Coconut Oil and Caprylic Acid—With and Without Glucose: A Cross-Over Study in Healthy Older Adults

Jakob Norgren, Shireen Sindi, Anna Sandebring-Matton, Ingemar Kåreholt, Makrina Daniilidou, Ulrika Akenine, Karin Nordin, Staffan Rosenborg, Tiia Ngandu, Miia Kivipelto
2020 Frontiers in Nutrition  
Medium-chain-triglycerides (MCT), formed by fatty acids with a length of 6-12 carbon atoms (C6-C12), constitute about two thirds of coconut oil (Coc). MCT have specific metabolic properties which has led them to be described as ketogenic even in the absence of carbohydrate restriction. This effect has mainly been demonstrated for caprylic acid (C8), which constitutes about 6-8% of coconut oil. Our aim was to quantify ketosis and blood glucose after intake of Coc and C8, with and without glucose
more » ... intake. Sunflower oil (Suf) was used as control, expected to not break fasting ketosis, nor induce supply-driven ketosis. Method: In a 6-arm cross-over design, 15 healthy volunteers-age 65-73, 53% women-were tested once a week. After a 12-h fast, ketones were measured during 4 h after intake of coffee with cream, in combination with each of the intervention arms in a randomized order: 1. Suf (30 g); 2. C8 (20 g) + Suf (10 g); 3. C8 (20 g) + Suf (10 g) + Glucose (50 g); 4. Coc (30 g); 5. Coc (30 g) + Glucose (50 g); 6. C8 (20 g) + Coc (30 g). The primary outcome was absolute blood levels of the ketone β-hydroxybutyrate, area under the curve (AUC). ANOVA for repeated measures was performed to compare arms. Results: β-hydroxybutyrate, AUC/time (mean ± SD), for arms were 1: 0.18 ± 0.11; 2: 0.45 ± 0.19; 3: 0.28 ± 0.12; 4: 0.22 ± 0.12; 5: 0.08 ± 0.04; 6: 0.45 ± 0.20 (mmol/L). Differences were significant (all p ≤ 0.02), except for arm 2 vs. 6, and 4 vs. 1 & 3. Blood glucose was stable in arm 1, 2, 4, & 6, at levels slightly below baseline (p ≤ 0.05) at all timepoints hours 1-4 after intake. Conclusions: C8 had a higher ketogenic effect than the other components. Coc was not significantly different from Suf, or C8 with glucose. In addition, we report that a 16-h non-carbohydrate window contributed to a mild ketosis, while blood glucose remained stable. Our results suggest that time-restricted feeding regarding carbohydrates may optimize ketosis from intake of MCT. Clinical Trial Registration: The study was registered as a clinical trial on ClinicalTrials.gov, NCT03904433.
doi:10.3389/fnut.2020.00040 pmid:32351966 pmcid:PMC7175812 fatcat:3mnfy3fqanb33isxfyv2p45s34

Effects of daily L-dopa administration on learning and brain structure in older adults undergoing cognitive training: a randomised clinical trial

Alexander V. Lebedev, Jonna Nilsson, Joanna Lindström, William Fredborg, Ulrika Akenine, Carolina Hillilä, Pia Andersen, Gabriela Spulber, Elizabeth C. M. de Lange, Dirk-Jan van den Berg, Miia Kivipelto, Martin Lövdén
2020 Scientific Reports  
Cognitive aging creates major individual and societal burden, motivating search for treatment and preventive care strategies. Behavioural interventions can improve cognitive performance in older age, but effects are small. Basic research has implicated dopaminergic signalling in plasticity. We investigated whether supplementation with the dopamine-precursor L-dopa improves effects of cognitive training on performance. Sixty-three participants for this randomised, parallel-group, double-blind,
more » ... acebo-controlled trial were recruited via newspaper advertisements. Inclusion criteria were: age of 65-75 years, Mini-Mental State Examination score >25, absence of serious medical conditions. Eligible subjects were randomly allocated to either receive 100/25 mg L-dopa/benserazide (n = 32) or placebo (n = 31) prior to each of twenty cognitive training sessions administered during a four-week period. Participants and staff were blinded to group assignment. Primary outcomes were latent variables of spatial and verbal fluid intelligence. Compared to the placebo group, subjects receiving L-dopa improved less in spatial intelligence (-0.267 SDs; 95%CI [-0.498, -0.036]; p = 0.024). Change in verbal intelligence did not significantly differ between the groups (-0.081 SDs, 95%CI [-0.242, 0.080]; p = 0.323). Subjects receiving L-dopa also progressed slower through the training and the groups displayed differential volumetric changes in the midbrain. No statistically significant differences were found for the secondary cognitive outcomes. Adverse events occurred for 10 (31%) and 7 (23%) participants in the active and control groups, correspondingly. The results speak against early pharmacological interventions in older healthy adults to improve broader cognitive functions by targeting the dopaminergic system and provide no support for learning-enhancing properties of L-dopa supplements in the healthy elderly. The findings warrant closer investigation about the cognitive effects of early dopamine-replacement therapy in neurological disorders. This trial was preregistered at the European Clinical Trial Registry, EudraCT#2016-000891-54 (2016-10-05).
doi:10.1038/s41598-020-62172-y pmid:32251360 fatcat:elt5bbxrjvb3bgsygn3t4zsewq

Integrating nurses' experiences with supporting behaviour change for cardiovascular prevention into a self-management internet platform in Finland and the Netherlands: a qualitative study

Cathrien Rl Beishuizen, Ulrika Akenine, Mariagnese Barbera, Anna Rosenberg, Mandana Fallah Pour, Edo Richard, Hilkka Soininen, Francesca Mangialasche, Miia Kivipelto, A Jeannette Pols, Eric Moll van Charante
2019 BMJ Open  
Global ageing is linked to an increased burden of cardiovascular disease and dementia, which calls for better prevention strategies. Self-management and eHealth applications are regarded as promising strategies to support prevention. The aim of this study was to explore nurses' best practices concerning behaviour change guidance for cardiovascular (CV) prevention in order to learn how to optimally integrate them into a coach-supported internet platform for CV self-management. Qualitative focus
more » ... roup study in Finland and the Netherlands. Discussions were audiotaped and transcribed. Data were thematically analysed following principles of grounded theory. Dutch and Finnish primary care settings. Six Finnish and seven Dutch primary care nurses with experience in CV prevention. Similar best practices were found in both countries and comprised of (1) establishing a relationship of trust, (2) managing awareness and expectations and (3) appropriate timing and monitoring of the process of behaviour change. However, the Finnish and Dutch nurses used different approaches for accomplishment of these practices, which was reflected in their recommendations for online support. Both groups emphasised that online support should be combined with human support and integrated into regular care. Finnish nurses had more confidence in patient self-management and remote communication than Dutch nurses, who emphasised the importance of face-to-face contact and preferred to keep control of medical aspects of prevention. Differences in Dutch and Finnish's nurses' practices for supporting CV prevention appear to reflect their local healthcare practices, which should be taken into account when designing internet platforms for health self-management. Including cognitive health as a goal of CV prevention might stimulate motivation for health behaviour change. ISRCTN48151589; Pre-results.
doi:10.1136/bmjopen-2018-023480 pmid:31175194 pmcid:PMC6577411 fatcat:mq3rpqsqpfc6ripldtadsk7d3u

Effects of daily L-dopa administration on learning and brain structure in older adults undergoing four weeks of cognitive training: a randomised, parallel-group, double-blind, placebo-controlled trial [article]

Alexander V. Lebedev, Jonna Nilsson, Joanna Lindström, William Fredborg, Ulrika Akenine, Carolina Hillilä, Pia Andersen, Gabriela Spulber, Elizabeth CM de Lange, Dirk-Jan van den Berg, Miia Kivipelto, Martin Lövdén
2018 bioRxiv   pre-print
SUMMARYBackgroundCognitive aging creates major individual and societal burden, motivating search for treatment and preventive care strategies. Behavioural interventions can improve cognitive performance in older age, but effects are small. Basic research has implicated dopaminergic signaling in plasticity. We investigated whether transient enhancement of dopaminergic neurotransmission via administration of L-dopa improves effects of cognitive training on performance.MethodsParticipants for this
more » ... randomised, parallel-group, double-blind, placebo-controlled trial were recruited via newspaper advertisements. Inclusion criteria were: age of 65–75 years, Mini-Mental State Examination score >25, absence of serious medical conditions. Eligible subjects were randomly allocated to either receive 100/25mg L-dopa/benserazide or placebo prior to each of twenty cognitive training sessions administered during a four-week period. Participants and staff were masked to group assignment. Primary outcomes were latent variables of spatial and verbal fluid intelligence. This trial was preregistered at the European Clinical Trial Registry, EudraCT#2016-000891-54.FindingsBetween January 1st and October 10th 2017, we screened 235 people from the population in Stockholm, Sweden and randomly assigned 63 eligible subjects to receive L-dopa (n=32) or placebo (n=31) during cognitive training. Compared to the placebo group, subjects receiving L-dopa improved less in spatial intelligence (−0·267 SDs; 95% CI [−0·498, −0·036]; p=0·024). Change in verbal intelligence did not significantly differ between the groups (−0·081 SDs, 95% CI [−0·242, 0·080]; p=0·323). Adverse events occurred for 10 subjects (31%) in the active and for 7 participants (23%) in the control groups.InterpretationThe results speak against early pharmacological interventions in older healthy adults to improve cognitive functions by targeting the dopaminergic system and provide no support for learning-enhancing properties of L-dopa supplements. The findings warrant closer investigation about the cognitive effects of early dopamine-replacement therapy in neurological disorders.FundingEuropean Research Council (ERC Grant agreement #617280–REBOOT), Wallenberg Clinical Scholars, and Stiftelse Stockholms Sjukhem.RESEARCH IN CONTEXTEvidence before this studyWhilst pharmacological treatments have so far been largely unsuccessful in making an impact on age-related cognitive decline, recent findings have suggested small improvements of cognitive performance in older people by combining cognitive training with a healthy diet and aerobic exercises. Both exercise and dietary factors may exhibit plasticity-enhancing properties, and therefore increase effectiveness of cognitive training. In related basic research, dopaminergic signaling has been implicated in brain plasticity. An extensive PubMed search was conducted during the preparatory stage of the study (September 2014–July 2016) to investigate the role of dopamine signaling in neural plasticity and learning, as well as the effects of its deterioration on these characteristics in aging and neurodegenerative disorders. As a result, we found a substantial number of studies reporting acute improvements in cognitive performance and learning by administration of exogenous dopamine precursor L-dopa. A similar search was conducted specifically for this drug to evaluate its pharmacological and safety profile. We found a large body of basic research on both animal models and humans that supported the role of dopamine signaling in learning and plasticity. In addition, two smaller studies reported promising effects of repeated L-dopa administration on learning in the healthy younger population. In all studies, standard small-dose (100mg) L-dopa interventions were safe and well-tolerated.Added value of this studyOur study is the first of its kind to evaluate effects of repeated pro-dopaminergic medication on learning during cognitive training and cognitive performance in healthy older adults. Our results do not support the hypothesis of plasticity- and learning-promoting effects of enhanced dopaminergic neurotransmission by administration of exogenous dopamine precursor L-dopa in the healthy older population. The findings indicate that L-dopa treatment may in fact be detrimental to learning and cognitive performance and lead to structural brain changes within the dopaminergic circuit.Implications of all the available evidenceThe results put constraints on the hypothesis of a key role of the deteriorated dopaminergic system in age-related decline of learning abilities, and speak against early pharmacological interventions in older healthy adults to improve cognitive functions by targeting the dopaminergic system. Our findings also raise concerns about usefulness of novel L-dopa-containing supplements that claim to have neuroprotective and learning-enhancing properties, and present an urgent need to carefully investigate the cognitive outcomes of early pro-dopaminergic interventions in clinical populations often receiving substantially larger doses of L-dopa.
doi:10.1101/482679 fatcat:ezrh53lhcnfrroe7hqvl4ycilq

Attitudes of at-risk older adults about prevention of cardiovascular disease and dementia using eHealth: a qualitative study in a European context

Ulrika Akenine, Mariagnese Barbera, Cathrien Rl Beishuizen, Mandana Fallah Pour, Juliette Guillemont, Anna Rosenberg, Nicola Coley, Francesca Mangialasche, Lotta Salo, Stephanie Savy, A Jeannette Pols, Sandrine Andrieu (+5 others)
2020 BMJ Open  
Downloaded from 7 Akenine U, et al. BMJ Open 2020;10:e037050. doi:10.1136/bmjopen-2020-037050 on November 26, 2020 by guest.  ...  (fg3, Finnish participant) Akenine U, et al. BMJ Open 2020;10:e037050. doi:10.1136/bmjopen-2020-037050 on November 26, 2020 by guest.  ... 
doi:10.1136/bmjopen-2020-037050 pmid:32764085 pmcid:PMC7412614 fatcat:xznuq4wfd5funnyt7dlfkovlay

Positron emission tomography measurement of brain MAO-B inhibition in patients with Alzheimer's disease and elderly controls after oral administration of sembragiline

Stefan Sturm, Anton Forsberg, Stephane Nave, Per Stenkrona, Nicholas Seneca, Andrea Varrone, Robert A. Comley, Patrik Fazio, Candice Jamois, Ryuji Nakao, Zbigniew Ejduk, Nabil Al-Tawil (+4 others)
2016 European Journal of Nuclear Medicine and Molecular Imaging  
Purpose In Alzheimer's disease (AD), increased metabolism of monoamines by monoamine oxidase type B (MAO-B) leads to the production of toxic reactive oxygen species (ROS), which are thought to contribute to disease pathogenesis. Inhibition of the MAO-B enzyme may restore brain levels of monoaminergic neurotransmitters, reduce the formation of toxic ROS and reduce neuroinflammation (reactive astrocytosis), potentially leading to neuroprotection. Sembragiline (also referred as RO4602522, RG1577
more » ... d EVT 302 in previous communications) is a potent, selective and reversible inhibitor of MAO-B developed as a potential treatment for AD. Methods This study assessed the relationship between plasma concentration of sembragiline and brain MAO-B inhibition in patients with AD and in healthy elderly control (EC) subjects. Positron emission tomography (PET) scans using [ 11 C]-L -deprenyl-D 2 radiotracer were performed in ten patients with AD and six EC subjects, who received sembragiline each day for 6-15 days. Results At steady state, the relationship between sembragiline plasma concentration and MAO-B inhibition resulted in an E max of ∼80-90 % across brain regions of interest and in an EC 50 of 1-2 ng/mL. Data in patients with AD and EC subjects showed that near-maximal inhibition of brain MAO-B was achieved with 1 mg sembragiline daily, regardless of the population, whereas lower doses resulted in lower and variable brain MAO-B inhibition. Conclusions This PET study confirmed that daily treatment of at least 1 mg sembragiline resulted in near-maximal inhibition of brain MAO-B enzyme in patients with AD.
doi:10.1007/s00259-016-3510-6 pmid:27633250 pmcid:PMC5281649 fatcat:lieuojdjy5fzje2uee5egzdiwu

Experiences of Participation in a Multimodal Preventive Trial MIND-ADMINI Among Persons with Prodromal Alzheimer's Disease: A Qualitative Study

Ulrika Akenine, Charlotta Thunborg, Miia Kivipelto, Mandana Fallahpour
2022
Multidisciplinary Healthcare 2022:15 https://doi.org/10.2147/JMDH.S345607 DovePress 227 Dovepress https://doi.org/10.2147/JMDH.S345607 DovePress Journal of Multidisciplinary Healthcare 2022:15 228 Akenine  ... 
doi:10.2147/jmdh.s345607 pmid:35125872 pmcid:PMC8811792 fatcat:z4qrg5tzzzbs5agrbswbppf6g4

Clinical Validation of 18F-AZD4694, an Amyloid- -Specific PET Radioligand

Z. Cselenyi, M. E. Jonhagen, A. Forsberg, C. Halldin, P. Julin, M. Schou, P. Johnstrom, K. Varnas, S. Svensson, L. Farde
2012 Journal of Nuclear Medicine  
We thank Britt Marie Swahn for dedicated medicinal chemistry support in radioligand development and Ulrika Lönnqvist-Akenine for excellent patient management.  ... 
doi:10.2967/jnumed.111.094029 pmid:22323782 fatcat:dlgf2v7hxngsjhk3upwhb2c5c4