Effects of daily L-dopa administration on learning and brain structure in older adults undergoing cognitive training: a randomised clinical trial
| Autor: | 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 |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
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 |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-11 (2020) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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