| 1. |
- Motovylyak, Alice, et al.
(författare)
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Age-related differences in white matter microstructure measured by advanced diffusion MRI in healthy older adults at risk for Alzheimer’s disease
- 2022
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Ingår i: Aging Brain. - : Elsevier. - 2589-9589. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Neurite orientation dispersion and density imaging (NODDI) is an advanced diffusion imaging technique, which can detect more distinct microstructural features compared to conventional Diffusion Tensor Imaging (DTI). NODDI allows the signal to be divided into multiple water compartments and derive measures for orientation dispersion index (ODI), neurite density index (NDI) and volume fraction of isotropic diffusion compartment (FISO). This study aimed to investigate which diffusion metric—fractional anisotropy (FA), mean diffusivity (MD), NDI, ODI, or FISO—is most influenced by aging and reflects cognitive function in a population of healthy older adults at risk for Alzheimer’s disease (AD). Age was significantly associated with all but one diffusion parameters and regions of interest. NDI and MD in the cingulate region adjacent to the cingulate cortex showed a significant association with a composite measure of Executive Function and was proven to partially mediate the relationship between aging and Executive Function decline. These results suggest that both DTI and NODDI parameters are sensitive to age-related differences in white matter regions vulnerable to aging, particularly among older adults at risk for AD.
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| 2. |
- Lebedev, Alexander V., et al.
(författare)
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Effects of daily L-dopa administration on learning and brain structure in older adults undergoing cognitive training : a randomised clinical trial
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- 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, 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 100/25 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).
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| 3. |
- Lebedev, Alexander V., et al.
(författare)
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LSD-Induced Entropic Brain Activity Predicts Subsequent Personality Change
- 2016
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Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 37:9, s. 3203-3213
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Tidskriftsartikel (refereegranskat)abstract
- Personality is known to be relatively stable throughout adulthood. Nevertheless, it has been shown that major life events with high personal significance, including experiences engendered by psychedelic drugs, can have an enduring impact on some core facets of personality. In the present, balanced-order, placebo-controlled study, we investigated biological predictors of post-lysergic acid diethylamide ( LSD) changes in personality. Nineteen healthy adults underwent resting state functional MRI scans under LSD ( 75 mu g, I. V.) and placebo ( saline I. V.). The Revised NEO Personality Inventory ( NEO-PI-R) was completed at screening and 2 weeks after LSD/placebo. Scanning sessions consisted of three 7.5-min eyes-closed resting-state scans, one of which involved music listening. A standardized preprocessing pipeline was used to extract measures of sample entropy, which characterizes the predictability of an fMRI time-series. Mixed-effects models were used to evaluate drug-induced shifts in brain entropy and their relationship with the observed increases in the personality trait openness at the 2-week follow-up. Overall, LSD had a pronounced global effect on brain entropy, increasing it in both sensory and hierarchically higher networks across multiple time scales. These shifts predicted enduring increases in trait openness. Moreover, the predictive power of the entropy increases was greatest for the music-listening scans and when ego-dissolution was reported during the acute experience. These results shed new light on how LSD-induced shifts in brain dynamics and concomitant subjective experience can be predictive of lasting changes in personality.
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