| 1. |
- Karalija, Nina, 1984-, et al.
(författare)
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A common polymorphism in the dopamine transporter gene predicts working memory performance and in vivo dopamine integrity in aging
- 2021
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 245
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Tidskriftsartikel (refereegranskat)abstract
- Dopamine (DA) integrity is suggested as a potential cause of individual differences in working memory (WM) performance among older adults. Still, the principal dopaminergic mechanisms giving rise to WM differences remain unspecified. Here, 61 single-nucleotide polymorphisms, located in or adjacent to various dopamine-related genes, were assessed for their links to WM performance in a sample of 1313 adults aged 61–80 years from the Berlin Aging Study II. Least Absolute Shrinkage and Selection Operator (LASSO) regression was conducted to estimate associations between polymorphisms and WM. Rs40184 in the DA transporter gene, SLC6A3, showed allelic group differences in WM, with T-carriers performing better than C homozygotes (p<0.01). This finding was replicated in an independent sample from the Cognition, Brain, and Aging study (COBRA; baseline: n = 181, ages: 64–68 years; 5-year follow up: n = 129). In COBRA, in vivo DA integrity was measured with 11C-raclopride and positron emission tomography. Notably, WM as well as in vivo DA integrity was higher for rs40184 T-carriers at baseline (p<0.05 for WM and caudate and hippocampal D2-receptor availability) and at the 5-year follow-up (p<0.05 for WM and hippocampal D2 availability). Our findings indicate that individual differences in DA transporter function contribute to differences in WM performance in old age, presumably by regulating DA availability.
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| 2. |
- Karalija, Nina, 1984-, et al.
(författare)
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Longitudinal Dopamine D2 Receptor Changes and Cerebrovascular Health in Aging
- 2022
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Ingår i: Neurology. - 1526-632X .- 0028-3878. ; 99, s. e1278-e1289
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Cross-sectional studies suggest marked dopamine (DA) decline in aging, but longitudinal evidence is lacking. The aim of this study was to estimate within-person decline rates for DA D2-like receptors (DRD2) in aging and examine factors that may contribute to individual differences in DRD2 decline rates. METHODS: We investigated 5-year within-person changes in DRD2 availability in a sample of older adults. At both occasions, PET with 11C-raclopride and MRI were used to measure DRD2 availability in conjunction with structural and vascular brain integrity. RESULTS: Longitudinal analyses of the sample (baseline: n = 181, ages: 64-68 years, 100 men and 81 women; 5-year follow-up: n = 129, 69 men and 60 women) revealed aging-related striatal and extrastriatal DRD2 decline, along with marked individual differences in rates of change. Notably, the magnitude of striatal DRD2 decline was ∼50% of past cross-sectional estimates, suggesting that the DRD2 decline rate has been overestimated in past cross-sectional studies. Significant DRD2 reductions were also observed in select extrastriatal regions, including hippocampus, orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC). Distinct profiles of correlated DRD2 changes were found across several associative regions (ACC, dorsal striatum, and hippocampus) and in the reward circuit (nucleus accumbens and OFC). DRD2 losses in associative regions were associated with white matter lesion progression, whereas DRD2 losses in limbic regions were related to reduced cortical perfusion. DISCUSSION: These findings provide the first longitudinal evidence for individual and region-specific differences of DRD2 decline in older age and support the hypothesis that cerebrovascular factors are linked to age-related dopaminergic decline.
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| 3. |
- Karalija, Nina, 1984-, et al.
(författare)
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Longitudinal support for the correlative triad among aging, dopamine D2-like receptor loss, and memory decline
- 2024
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Ingår i: NEUROBIOLOGY OF AGING. - 0197-4580 .- 1558-1497. ; 136, s. 125-132
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Tidskriftsartikel (refereegranskat)abstract
- Dopamine decline is suggested to underlie aging -related cognitive decline, but longitudinal examinations of this link are currently missing. We analyzed 5 -year longitudinal data for a sample of healthy, older adults (baseline: n = 181, age: 64-68 years; 5 -year follow-up: n = 129) who underwent positron emission tomography with 11C- raclopride to assess dopamine D2 -like receptor (DRD2) availability, magnetic resonance imaging to evaluate structural brain measures, and cognitive tests. Health, lifestyle, and genetic data were also collected. A datadriven approach (k -means cluster analysis) identified groups that differed maximally in DRD2 decline rates in age -sensitive brain regions. One group (n = 47) had DRD2 decline exclusively in the caudate and no cognitive decline. A second group (n = 72) had more wide -ranged DRD2 decline in putamen and nucleus accumbens and also in extrastriatal regions. The latter group showed significant 5 -year working memory decline that correlated with putamen DRD2 decline, along with higher dementia and cardiovascular risk and a faster biological pace of aging. Taken together, for individuals with more extensive DRD2 decline, dopamine decline is associated with memory decline in aging.
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| 4. |
- Korkki, Saana M., et al.
(författare)
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Fronto-striatal dopamine D2 receptor availability is associated with cognitive variability in older individuals with low dopamine integrity
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Within-person, moment-to-moment, variability in behavior increases with advancing adult age, potentially reflecting the influence of reduced structural and neurochemical brain integrity, especially that of the dopaminergic system. We examined the role of dopamine D2 receptor (D2DR) availability, grey-, and white-matter integrity, for between-person differences in cognitive variability in a large sample of healthy older adults (n = 181; 64–68 years) from the Cognition, Brain, and Aging (COBRA) study. Intra-individual variability (IIV) in cognition was measured as across-trial variability in participants’ response times for tasks assessing perceptual speed and working memory, as well as for a control task of motor speed. Across the whole sample, no associations of D2DR availability, or grey- and white-matter integrity, to IIV were observed. However, within-person variability in cognition was increased in two subgroups of individuals displaying low mean-level cognitive performance, one of which was characterized by low subcortical and cortical D2DR availability. In this latter group, fronto-striatal D2DR availability correlated negatively with within-person variability in cognition. This finding suggests that the influence of D2DR availability on cognitive variability may be more easily disclosed among individuals with low dopamine-system integrity, highlighting the benefits of large-scale studies for delineating heterogeneity in brain-behavior associations in older age.
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| 5. |
- Lill, Christina M., et al.
(författare)
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The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:12, s. 1407-1416
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Tidskriftsartikel (refereegranskat)abstract
- A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent. These data were combined with those from 28 published data sets by meta-analysis. Furthermore, we tested whether rs75932628 shows association with amyloid beta (Ab42) and total-tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment. Our data show that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (odds ratio or OR = 2.71, P = 4.67 x 10(-25)). No consistent evidence for association was found between this marker and the risk of FTLD (OR = 2.24, P = .0113 across 2673 cases/9283 controls), PD (OR 5 1.36, P = .0767 across 8311 cases/79,938 controls) and ALS (OR 5 1.41, P = .198 across 5544 cases/7072 controls). Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF-total-tau (P = .0110) but not Ab42 suggesting that TREM2's role in AD may involve tau dysfunction. (C) 2015 The Alzheimer's Association.
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| 6. |
- Lövdén, Martin, 1972, et al.
(författare)
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Education and Cognitive Functioning Across the Life Span
- 2020
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Ingår i: Psychological Science in the Public Interest. - : SAGE Publications. - 1529-1006 .- 2160-0031 .- 1539-6053. ; 21:1, s. 6-41
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Forskningsöversikt (refereegranskat)abstract
- © The Author(s) 2020. Cognitive abilities are important predictors of educational and occupational performance, socioeconomic attainment, health, and longevity. Declines in cognitive abilities are linked to impairments in older adults’ everyday functions, but people differ from one another in their rates of cognitive decline over the course of adulthood and old age. Hence, identifying factors that protect against compromised late-life cognition is of great societal interest. The number of years of formal education completed by individuals is positively correlated with their cognitive function throughout adulthood and predicts lower risk of dementia late in life. These observations have led to the propositions that prolonging education might (a) affect cognitive ability and (b) attenuate aging-associated declines in cognition. We evaluate these propositions by reviewing the literature on educational attainment and cognitive aging, including recent analyses of data harmonized across multiple longitudinal cohort studies and related meta-analyses. In line with the first proposition, the evidence indicates that educational attainment has positive effects on cognitive function. We also find evidence that cognitive abilities are associated with selection into longer durations of education and that there are common factors (e.g., parental socioeconomic resources) that affect both educational attainment and cognitive development. There is likely reciprocal interplay among these factors, and among cognitive abilities, during development. Education–cognitive ability associations are apparent across the entire adult life span and across the full range of education levels, including (to some degree) tertiary education. However, contrary to the second proposition, we find that associations between education and aging-associated cognitive declines are negligible and that a threshold model of dementia can account for the association between educational attainment and late-life dementia risk. We conclude that educational attainment exerts its influences on late-life cognitive function primarily by contributing to individual differences in cognitive skills that emerge in early adulthood but persist into older age. We also note that the widespread absence of educational influences on rates of cognitive decline puts constraints on theoretical notions of cognitive aging, such as the concepts of cognitive reserve and brain maintenance. Improving the conditions that shape development during the first decades of life carries great potential for improving cognitive ability in early adulthood and for reducing public-health burdens related to cognitive aging and dementia.
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| 7. |
- Lövdén, Martin, 1972, et al.
(författare)
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Human Skill Learning: Expansion, Exploration, Selection, and Refinement
- 2020
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Ingår i: Current Opinion in Behavioral Sciences. - : Elsevier BV. - 2352-1546. ; 36, s. 163-168
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Forskningsöversikt (refereegranskat)abstract
- © 2020 The Authors Learning, or the process of acquiring knowledge and skill, allows humans to shape and adapt to their environments during development. Researchers have long theorized that the principal brain processes behind learning resemble a recruitment process. The brain initially explores an expanded pool of candidate neural circuits. Based on outcomes, the most promising candidate circuit is selected for refinement. Partly fuelled by new methods, the last decade of research on learning-related functional and structural changes in rodents has supported this theory, and, more recently, related evidence has started to emerge from human studies. We emphasize the need for formal theories and neurocomputational modelling of cortical plasticity to guide work on open issues, such as the link between functional and structural changes.
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| 8. |
- Lövdén, Martin, 1972, et al.
(författare)
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No moderating influence of education on the association between changes in hippocampus volume and memory performance in aging
- 2023
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Ingår i: Aging Brain. - : Elsevier. - 2589-9589. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Contemporary accounts of factors that may modify the risk for age-related neurocognitive disorders highlight education and its contribution to a cognitive reserve. By this view, individuals with higher educational attainment should show weaker associations between changes in brain and cognition than individuals with lower educational attainment. We tested this prediction in longitudinal data on hippocampus volume and episodic memory from 708 middle-aged and older individuals using local structural equation modeling. This technique does not require categorization of years of education and does not constrain the shape of relationships, thereby maximizing the chances of revealing an effect of education on the hippocampus-memory association. The results showed that the data were plausible under the assumption that there was no influence of education on the association between change in episodic memory and change in hippocampus volume. Restricting the sample to individuals with elevated genetic risk for dementia (APOE ε4 carriers) did not change these results. We conclude that the influence of education on changes in episodic memory and hippocampus volume is inconsistent with predictions by the cognitive reserve theory.
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| 9. |
- Nyberg, Lars, 1966-, et al.
(författare)
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Longitudinal stability in working memory and frontal activity in relation to general brain maintenance
- 2022
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive functions are well-preserved for some older individuals, but the underlying brain mechanisms remain disputed. Here, 5-year longitudinal 3-back in-scanner and offline data classified individuals in a healthy older sample (baseline age = 64–68 years) into having stable or declining working-memory (WM). Consistent with a vital role of the prefrontal cortex (PFC), WM stability or decline was related to maintained or reduced longitudinal PFC functional responses. Subsequent analyses of imaging markers of general brain maintenance revealed higher levels in the stable WM group on measures of neurotransmission and vascular health. Also, categorical and continuous analyses showed that rate of WM decline was related to global (ventricles) and local (hippocampus) measures of neuronal integrity. Thus, our findings support a role of the PFC as well as general brain maintenance in explaining heterogeneity in longitudinal WM trajectories in aging.
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| 10. |
- Schmiedek, Florian, et al.
(författare)
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Practice-Related Changes in Perceptual Evidence Accumulation Correlate With Changes in Working Memory
- 2023
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Ingår i: Journal of Experimental Psychology: General. - : American Psychological Association (APA). - 0096-3445 .- 1939-2222. ; 152:3
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Tidskriftsartikel (refereegranskat)abstract
- It has been proposed that evidence accumulation determines not only the speed and accuracy of simple perceptual decisions but also influences performance on tasks assessing higher-order cognitive abilities, such as working memory (WM). Accordingly, estimates of evidence accumulation based on diffusion decision modeling of perceptual decision-making tasks have been found to correlate with WM performance. Here we use diffusion decision modeling in combination with latent factor modeling to test the stronger prediction that practice-induced changes in evidence accumulation correlate with changes in WM performance. Analyses are based on data from the COGITO Study, in which 101 young adults practiced a battery of cognitive tasks, including three simple two-choice reaction time tasks and three WM tasks, in 100 day-to-day training sessions distributed over 6 months. In initial analyses, drift rates were found to correlate across the three choice tasks, such that latent factors of evidence accumulation could be established. These latent factors of evidence accumulation were positively correlated with latent factors of practiced and unpracticed WM tasks, both before and after practice. As predicted, individual differences in changes of evidence accumulation correlated positively with changes in WM performance. Our findings support the proposition that decision making and WM both rely on the active maintenance of task-relevant internal representations
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