| 1. |
- Pudas, Sara, et al.
(author)
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Maintenance and Manipulation in Working Memory : Differential Ventral and Dorsal Frontal Cortex fMRI Activity
- 2009
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In: Acta Psychologica Sinica. - : Science Press. - 0439-755X. ; 41:11, s. 1054-1062
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Journal article (peer-reviewed)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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| 2. |
- Lind, Johanna, et al.
(author)
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Reduced functional brain activity response in cognitively intact apolipoprotein E ε4 carriers
- 2006
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In: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 129:5, s. 1240-1248
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Journal article (peer-reviewed)abstract
- The apolipoprotein E epsilon4 (APOE epsilon4) is the main known genetic risk factor for Alzheimer's disease. Genetic assessments in combination with other diagnostic tools, such as neuroimaging, have the potential to facilitate early diagnosis. In this large-scale functional MRI (fMRI) study, we have contrasted 30 APOE epsilon4 carriers (age range: 49-74 years; 19 females), of which 10 were homozygous for the epsilon4 allele, and 30 non-carriers with regard to brain activity during a semantic categorization task. Test groups were closely matched for sex, age and education. Critically, both groups were cognitively intact and thus symptom-free of Alzheimer's disease. APOE epsilon4 carriers showed reduced task-related responses in the left inferior parietal cortex, and bilaterally in the anterior cingulate region. A dose-related response was observed in the parietal area such that diminution was most pronounced in homozygous compared with heterozygous carriers. In addition, contrasts of processing novel versus familiar items revealed an abnormal response in the right hippocampus in the APOE epsilon4 group, mainly expressed as diminished sensitivity to the relative novelty of stimuli. Collectively, these findings indicate that genetic risk translates into reduced functional brain activity, in regions pertinent to Alzheimer's disease, well before alterations can be detected at the behavioural level.
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| 3. |
- Lind, Johanna, et al.
(author)
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Reduced hippocampal volume in non-demented carriers fo the apolipoprotein E ε4 : Relation to chronological age and recognition memory
- 2006
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In: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 396:1, s. 23-27
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Journal article (peer-reviewed)abstract
- Apolipoprotein E ε4 (APOE ε4) is the main known genetic risk factor for Alzheimer's disease (AD). Some previous studies have reported structural brain changes as well as cognitive deficits in non-demented APOE ε4 carriers, but the pattern of results is inconsistent and studies with larger sample sizes have been called for. Here we compared hippocampal volume and recognition–memory performance between AD-symptom-free carriers (N = 30) and non-carriers (N = 30) of the APOE ε4 (age range: 49–79 years). We observed reduced right hippocampal volume in APOE ε4 carriers, and found that the difference was most pronounced before the age of 65. Further, the APOE ε4 carriers made significantly more false alarms in the recognition–memory test, and the number of false alarms correlated significantly with right hippocampus volume. These results indicate that relatively young individuals at genetic risk for AD have smaller hippocampal volume and lower performance on hippocampal-dependent cognitive tasks. A question for the future is whether smaller hippocampal volume represents early-onset hippocampal volume reduction or an inherent trait.
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| 4. |
- Nyberg, Lars, et al.
(author)
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Age-related and genetic modulation of frontal cortex efficiency
- 2014
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In: Journal of cognitive neuroscience. - : MIT Press. - 0898-929X .- 1530-8898. ; 26:4, s. 746-754
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Journal article (peer-reviewed)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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| 5. |
- Nyberg, Lars, et al.
(author)
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Longitudinal evidence for diminished frontal-cortex function in aging
- 2010
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In: 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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Journal article (peer-reviewed)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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| 6. |
- Persson, Jonas, et al.
(author)
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Altered deactivation in individuals with genetic risk for Alzheimer's disease
- 2008
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In: Neuropsychologia. - : Elsevier BV. - 0028-3932 .- 1873-3514. ; 46:6, s. 1679-1687
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Journal article (peer-reviewed)abstract
- Regions that show task-induced deactivations may be part of a default-mode network related to processes that are more engaged during passive than active task conditions. Alteration of task-induced deactivations with age and dementia is indicated by atypical engagement of default-mode network regions. Genetic studies show a relation between the apolipoprotein E4 (APOE4) allele and the common form of Alzheimer’s disease (AD), and altered functional brain activation has been observed in non-demented APOE4 carriers compared to non-carriers. Here we investigate the hypothesis of altered default-mode network brain responses in individuals with genetic risk for AD. Functional MRI was used to assess task-induced deactivation in 60 subjects of which 30 carried at least one copy of the APOE4 allele, and 30 non-carriers. Subjects were scanned while performing a semantic categorization task shown to promote episodic memory encoding. The results show patterns of deactivation consistent with the default-mode network. We also found reduced deactivation in non-demented APOE4 carriers compared to non-carriers, suggesting alterations in the default-mode network in the absence of dementia. These results implicate possibilities for investigatin altered properties of task-induced deactivations in individuals with genetic risk for AD, and may prove useful for pre-clinical identification of individuals susceptible to memory problems and AD.
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| 7. |
- Persson, Jonas, et al.
(author)
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Herbal extracts and memory enhancement : Response to Scholey et al.
- 2005
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In: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 179:3, s. 708-709
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Journal article (peer-reviewed)abstract
- Reply by the current author to the comments made by Scholey et al. (see record 2005-04969-023) on the original article (see record 2004-13858-010). The letter by Scholey et al. contains several accounts of criticism. The principal claim that they make is that, although negative findings of cognition-enhancing effects have been found in several studies, this is not enough evidence to conclude that these products do not improve cognitive performance. The authors emphasize that the methods used in these studies need careful examination and they identify a number of criteria that, preferably, should be met for these studies to be "adequately powered". The problem is (and this is also discussed by Scholey et al.) that even if these criteria are met, there are still negative findings.
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| 8. |
- Persson, Jonas, et al.
(author)
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Longitudinal assessment of default-mode brain function in aging
- 2014
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In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 35:9, s. 2107-2117
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Journal article (peer-reviewed)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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| 9. |
- Persson, Jonas, et al.
(author)
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Longitudinal structure – function correlates in elderly reveal MTL dysfunction with cognitive decline
- 2012
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In: Cerebral Cortex. - New York, NY : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 22:10, s. 2297-2304
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Journal article (peer-reviewed)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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| 10. |
- Persson, Jonas, et al.
(author)
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Preserved Hippocampus Activation in Normal Aging as Revealed by fMRI
- 2011
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In: Hippocampus. - : Wiley. - 1050-9631 .- 1098-1063. ; 21:7, s. 753-766
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Journal article (peer-reviewed)abstract
- The hippocampus is deteriorated in various pathologies such as Alzheimer's disease (AD) and such deterioration has been linked to memory impairment. By contrast, the structural and functional effects of normal aging on the hippocampus is a matter of debate, with some findings suggesting deterioration and others providing evidence of preservation. This constitutes a crucial question since many investigations on AD are based on the assumption that the deterioration of the hippocampus is the breaking point between normal and pathological aging. A growing number of fMRI studies specifically aimed at investigating hippocampal engagement in various cognitive tasks, notably memory tasks, but the results have been inconclusive. Here, we optimized the episodic face-name paired-associates task in order to test the functioning of the hippocampus in normal aging. Critically, we found no difference in the activation of the hippocampus between the young and a group of older participants. Analysis of individual patterns of activation substantiated this impression. Collectively, these findings provide evidence of preserved hippocampal functioning in normal aging.
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