Effects of daily L-dopa administration on learning and brain structure in older adults undergoing cognitive training: a randomised clinical trial
| العنوان: | Effects of daily L-dopa administration on learning and brain structure in older adults undergoing cognitive training: a randomised clinical trial |
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| المؤلفون: | William Fredborg, Martin Lövdén, Joanna Lindström, Dirk-Jan van den Berg, Jonna Nilsson, Elizabeth C. M. de Lange, Ulrika Akenine, Alexander V. Lebedev, Gabriela Spulber, Pia Andersen, Carolina Hillilä, Miia Kivipelto |
| المصدر: | Scientific Reports, Vol 10, Iss 1, Pp 1-11 (2020) Scientific Reports |
| بيانات النشر: | Nature Publishing Group, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Dopamine Agents, lcsh:Medicine, law.invention, Body Mass Index, Levodopa, Placebos, 0302 clinical medicine, Cognition, Randomized controlled trial, law, Medicine, lcsh:Science, Chromatography, Multidisciplinary, 05 social sciences, Dopaminergic, Brain, Verbal reasoning, Magnetic Resonance Imaging, Cognitive training, 3. Good health, Memory, Short-Term, Randomized controlled trials, Female, medicine.medical_specialty, Placebo, 050105 experimental psychology, Article, 03 medical and health sciences, Double-Blind Method, Humans, Learning, 0501 psychology and cognitive sciences, Effects of sleep deprivation on cognitive performance, Adverse effect, Aged, business.industry, lcsh:R, Working memory, Homovanillic Acid, Clinical trial, Ageing, 030104 developmental biology, Physical therapy, lcsh:Q, business, 030217 neurology & neurosurgery |
| الوصف: | 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 signaling in plasticity. We investigated whether transient enhancement of dopaminergic neurotransmission via administration of L-dopa improves effects of cognitive training on performance.Sixty-three participants for this 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 (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. Adverse events occurred for 10 (31%) and 7 (23%) participants in the active and control groups, correspondingly. No statistically significant differences were found for the secondary cognitive outcomes.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. 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.SignificanceThe 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. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8d57c40b7bcf215f57d00500b2ac27ab http://link.springer.com/article/10.1038/s41598-020-62172-y |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8d57c40b7bcf215f57d00500b2ac27ab |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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