| 1. |
- Josefsson, Maria, 1979-, et al.
(författare)
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Genetic and Lifestyle Predictors of 15-Year Longitudinal Change in Episodic Memory
- 2012
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Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 60:12, s. 2308-2312
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To reveal distinct longitudinal trajectories in episodic memory over 15 years and to identify demographic, lifestyle, health-related, and genetic predictors of stability or decline. Design: Prospective cohort study. Setting: The Betula Project, Umeå, Sweden. Participants: One thousand nine hundred fifty-four healthy participants aged 35 to 85 at baseline. Measurements: Memory was assessed according to validated episodic memory tasks in participants from a large population-based sample. Data were analyzed using a random-effects pattern-mixture model that considered the effect of attrition over two to four longitudinal sessions. Logistic regression was used to determine significant predictors of stability or decline relative to average change in episodic memory. Results: Of 1,558 participants with two or more test sessions, 18% were classified as maintainers and 13% as decliners, and 68% showed age-typical average change. More educated and more physically active participants, women, and those living with someone were more likely to be classified as maintainers, as were carriers of the met allele of the catechol-O-methyltransferase gene. Less educated participants, those not active in the labor force, and men were more likely to be classified as decliners, and the apolipoprotein E ɛ4 allele was more frequent in decliners. Conclusion: Quantitative, attrition-corrected assessment of longitudinal changes in memory can reveal substantial heterogeneity in aging trajectories, and genetic and lifestyle factors predict such heterogeneity.
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| 2. |
- Nyberg, Lars, et al.
(författare)
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Age-related and genetic modulation of frontal cortex efficiency
- 2014
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Ingår i: Journal of cognitive neuroscience. - : MIT Press. - 0898-929X .- 1530-8898. ; 26:4, s. 746-754
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Tidskriftsartikel (refereegranskat)abstract
- The dorsolateral pFC (DLPFC) is a key region for working memory. It has been proposed that the DLPFC is dynamically recruited depending on task demands. By this view, high DLPFC recruitment for low-demanding tasks along with weak DLPFC upregulation at higher task demands reflects low efficiency. Here, the fMRI BOLD signal during working memory maintenance and manipulation was examined in relation to aging and catechol-O-methyltransferase (COMT) Val(158)Met status in a large representative sample (n = 287). The efficiency hypothesis predicts a weaker DLPFC response during manipulation, along with a stronger response during maintenance for older adults and COMT Val carriers compared with younger adults and COMT Met carriers. Consistent with the hypothesis, younger adults and met carriers showed maximal DLPFC BOLD response during manipulation, whereas older adults and val carriers displayed elevated DLPFC responses during the less demanding maintenance condition. The observed inverted relations support a link between dopamine and DLPFC efficiency.
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| 3. |
- Nyberg, Lars, et al.
(författare)
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Longitudinal evidence for diminished frontal-cortex function in aging
- 2010
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 107:52, s. 22682-22686
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Tidskriftsartikel (refereegranskat)abstract
- Cross-sectional estimates of age-related changes in brain structure and function were compared with 6-y longitudinal estimates. The results indicated increased sensitivity of the longitudinal approach as well as qualitative differences. Critically, the cross-sectional analyses were suggestive of age-related frontal overrecruitment, whereas the longitudinal analyses revealed frontal underrecruitment with advancing age. The cross-sectional observation of overrecruitment reflected a select elderly sample. However, when followed over time, this sample showed reduced frontal recruitment. These findings dispute inferences of true age changes on the basis of age differences, hence challenging some contemporary models of neurocognitive aging, and demonstrate age-related decline in frontal brain volume as well as functional response.
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| 4. |
- Persson, Jonas, et al.
(författare)
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Longitudinal assessment of default-mode brain function in aging
- 2014
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 35:9, s. 2107-2117
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Tidskriftsartikel (refereegranskat)abstract
- Age-related changes in the default-mode network (DMN) have been identified in prior cross-sectional functional magnetic resonance imaging studies. Here, we investigated longitudinal change in DMN activity and connectivity. Cognitively intact participants (aged 49-79 years at baseline) were scanned twice, with a 6-year interval, while performing an episodic memory task interleaved with a passive control condition. Longitudinal analyses showed that the DMN (control condition > memory task) could be reliably identified at both baseline and follow-up. Differences in the magnitude of task-induced deactivation in posterior DMN regions were observed between baseline and follow-up indicating reduced deactivation in these regions with increasing age. Although no overall longitudinal changes in within-network connectivity were found across the whole sample, individual differences in memory change correlated with change in connectivity. Thus, our results show stability of whole-brain DMN topology and functional connectivity over time in healthy older adults, whereas within-region DMN analyses show reduced deactivation between baseline and follow-up. The current findings provide novel insights into DMN functioning that may assist in identifying brain changes in patient populations, as well as characterizing factors that distinguish between normal and pathologic aging.
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| 5. |
- Persson, Jonas, et al.
(författare)
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Longitudinal structure – function correlates in elderly reveal MTL dysfunction with cognitive decline
- 2012
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Ingår i: Cerebral Cortex. - New York, NY : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 22:10, s. 2297-2304
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Tidskriftsartikel (refereegranskat)abstract
- By integrating behavioral measures and imaging data, previous investigations have explored the relationship between biological markers of aging and cognitive functions. Evidence from functional and structural neuroimaging has revealed that hippocampal volume and activation patterns in the medial temporal lobe (MTL) may predict cognitive performance in old age. Most past demonstrations of age-related differences in brain structure–function were based on cross-sectional comparisons. Here, the relationship between 6-year intraindividual change in functional magnetic resonance imaging (fMRI) signal and change in memory performance over 2 decades was examined. Correlations between intraindividual change in fMRI signal during episodic encoding and change in memory performance measured outside of scanning were used as an estimate for relating brain–behavior changes. The results revealed a positive relationship between activation change in the hippocampus (HC) and change in memory performance, reflecting reduced hippocampal activation in participants with declining performance. Using a similar analytic approach as for the functional data, we found that individuals with declining performance had reduced HC volume compared with individuals with intact performance. These observations provide a strong link between cognitive change in older adults and MTL structure and function and thus provide insights into brain correlates of individual variability in aging trajectories.
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| 6. |
- Pudas, Sara, et al.
(författare)
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Brain characteristics of individuals resisting age-related cognitive decline over two decades
- 2013
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 33:20, s. 8668-8677
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Tidskriftsartikel (refereegranskat)abstract
- Some elderly appear to resist age-related decline in cognitive functions, but the neural correlates of successful cognitive aging are not well known. Here, older human participants from a longitudinal study were classified as successful or average relative to the mean attrition-corrected cognitive development across 15-20 years in a population-based sample (n = 1561). Fifty-one successful elderly and 51 age-matched average elderly (mean age: 68.8 years) underwent functional magnetic resonance imaging while performing an episodic memory face-name paired-associates task. Successful older participants had higher BOLD signal during encoding than average participants, notably in the bilateral PFC and the left hippocampus (HC). The HC activation of the average, but not the successful, older group was lower than that of a young reference group (n = 45, mean age: 35.3 years). HC activation was correlated with task performance, thus likely contributing to the superior memory performance of successful older participants. The frontal BOLD response pattern might reflect individual differences present from young age. Additional analyses confirmed that both the initial cognitive level and the slope of cognitive change across the longitudinal measurement period contributed to the observed group differences in BOLD signal. Further, the differences between the older groups could not be accounted for by differences in brain structure. The current results suggest that one mechanism behind successful cognitive aging might be preservation of HC function combined with a high frontal responsivity. These findings highlight sources for heterogeneity in cognitive aging and may hold useful information for cognitive intervention studies.
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| 7. |
- Pudas, Sara, et al.
(författare)
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Maintenance and Manipulation in Working Memory : Differential Ventral and Dorsal Frontal Cortex fMRI Activity
- 2009
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Ingår i: Acta Psychologica Sinica. - : Science Press. - 0439-755X. ; 41:11, s. 1054-1062
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Tidskriftsartikel (refereegranskat)abstract
- A verbal working memory protocol was designed and evaluated on a group of healthy younger adults in preparation for a large-scale functional magnetic resonance (fMRI) study on aging and memory. Letters were presented in two critical conditions: (i) maintenance, in which letters were to be memorized and kept in mind over a four second interval, and (ii) manipulation, in which letters were shifted forward in alphabetical order, and the new order was kept in mind. Analyses of fMRI data showed that the protocol elicited reliable activation in the frontal cortex, with manipulation producing more extensive activation patterns, both in whole-brain analyses and in predefined regions of interest (ROIs). There was also a distinction between dorsal and ventral lateral prefrontal regions, such that manipulation elicited more dorsolateral prefrontal activation. The protocol also elicited activation in various subcortical areas, previously associated with working-memory tasks. It was concluded that this working memory protocol is appropriate for investigating age-related changes in frontal-cortex functioning.
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| 8. |
- Pudas, Sara, 1983-, et al.
(författare)
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Midlife memory ability accounts for brain activity differences in healthy aging
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Cross-sectional neuroimaging studies suggest that hippocampal and prefrontal cortex (PFC) functions underlie individual differences in memory ability in elderly individuals, but it is unclear how individual differences in cognitive ability in youth contribute to cognitive and neuroimaging measures in older age. Here, a sample from a longitudinal population-based study (N = 201, aged 55-80) was used to investigate the relative influence of midlife memory ability and age-related memory change on memory-related BOLD-signal variability in healthy elderly. Hierarchical regression analyses showed that midlife memory ability, assessed 15-20 years earlier, explained at least as much variance as memory change in clusters in the left inferior PFC and the bilateral hippocampus, during memory encoding. Memory change estimates, however, were found to be more sensitive in detecting bilateral frontal regions specifically diagnostic of age-related memory change. These finding highlight challenges in interpreting individual differences in neurocognitive measures as age-related changes in the absence of longitudinal data, and also demonstrates the improved sensitivity of longitudinal measures.
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| 9. |
- Pudas, Sara, et al.
(författare)
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Midlife memory ability accounts for brain activity differences in healthy aging
- 2014
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 35:11, s. 2495-2503
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Tidskriftsartikel (refereegranskat)abstract
- Cross-sectional neuroimaging studies suggest that hippocampal and prefrontal cortex functions underlie individual differences in memory ability in older individuals, but it is unclear how individual differences in cognitive ability in youth contribute to cognitive and neuroimaging measures in older age. Here, we investigated the relative influences of midlife memory ability and age-related memory change on memory-related BOLD-signal variability at one time point, using a sample from a longitudinal population-based aging study (N = 203, aged 55–80 years). Hierarchical regression analyses showed that midlife memory ability, assessed 15–20 years earlier, explained at least as much variance as memory change in clusters in the left inferior prefrontal cortex and the bilateral hippocampus, during memory encoding. Furthermore, memory change estimates demonstrated higher sensitivity than current memory levels in identifying distinct frontal regions where activity was selectively related to age-related memory change, as opposed to midlife memory. These findings highlight challenges in interpreting individual differences in neurocognitive measures as age-related changes in the absence of longitudinal data and also demonstrate the improved sensitivity of longitudinal measures.
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