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  • 151.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Functional brain imaging of episodic memory decline in ageing2017In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 281, no 1, p. 65-74Article, review/survey (Refereed)
    Abstract [en]

    The episodic long-term memory system supports remembering of events. It is considered to be the most age-sensitive system, with an average onset of decline around 60 years of age. However, there is marked interindividual variability, such that some individuals show faster than average change and others show no or very little change. This variability may be related to the risk of developing dementia, with elevated risk for individuals with accelerated episodic memory decline. Brain imaging with functional magnetic resonance imaging (MRI) of blood oxygen level-dependent (BOLD) signalling or positron emission tomography (PET) has been used to reveal the brain bases of declining episodic memory in ageing. Several studies have demonstrated a link between age-related episodic memory decline and the hippocampus during active mnemonic processing, which is further supported by studies of hippocampal functional connectivity in the resting state. The hippocampus interacts with anterior and posterior neocortical regions to support episodic memory, and alterations in hippocampus–neocortex connectivity have been shown to contribute to impaired episodic memory. Multimodal MRI studies and more recently hybrid MRI/PET studies allow consideration of various factors that can influence the association between the hippocampal BOLD signal and memory performance. These include neurovascular factors, grey and white matter structural alterations, dopaminergic neurotransmission, amyloid-Β and glucose metabolism. Knowledge about the brain bases of episodic memory decline can guide interventions to strengthen memory in older adults, particularly in those with an elevated risk of developing dementia, with promising results for combinations of cognitive and physical stimulation.

  • 152.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Functional imaging studies of intentional and incidental reactiviation: Implications for the bidning problem2006In: Handbook of binding and memory: Perspective from cognitive neuroscience, Oxford: Oxford University Press , 2006, p. 493-515Chapter in book (Other (popular science, discussion, etc.))
  • 153.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Imaging cognition: Recent developments and a tentative hierarchiacal cognitive model2006In: Psychological Science around the world, Psychology Press , 2006Chapter in book (Other (popular science, discussion, etc.))
  • 154.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Impaired and intact cognitive functions in Alzheimer's disease.2008In: American Journal of Psychology, no 49, p. 133-140Article, book review (Other (popular science, discussion, etc.))
  • 155.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Intact frontal memory effect in older age and dementia2004In: Neuron, ISSN 0896-6273, E-ISSN 1097-4199, Vol. 42, no 5, p. 701-702Article in journal (Other academic)
    Abstract [en]

    Older adults and demented patients show preserved functioning on certain tests of implicit memory. In this issue of Neuron, Lustig and Buckner demonstrate that both groups show comparable repetition-based effects on response time and prefrontal activity relative to younger adults.

  • 156.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Introduction to the special section on "cognitive control"2009In: Scandinavian Journal of Psychology, ISSN 0036-5564, E-ISSN 1467-9450, Vol. 50, no 1, p. 3-Article in journal (Refereed)
  • 157.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Kognitiv neurovetenskap: studier av sambandet mellan hjärnaktivitet och mentala processer2009 (ed. 2)Book (Other academic)
  • 158.
    Nyberg, Lars
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    The enactment effect: studies of a memory phenomenon1993Doctoral thesis, comprehensive summary (Other academic)
  • 159.
    Nyberg, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Jakobson Mo, Susanna
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Marklund, Petter
    Nilsson, Lars-Göran
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Bäckman, Lars
    Striatal dopamine D2 binding is related to frontal BOLD response during updating of long-term memory representations.2009In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 46, no 4, p. 1194-1199Article in journal (Refereed)
    Abstract [en]

    Multi-modal brain imaging was used to examine the relation between individual differences in resting-state striatal dopamine D2 binding and the magnitude of prefrontal BOLD activation during updating of long-term memory (LTM) representations. Increased activity in the left prefrontal cortex was observed when LTM updating was required, and there was a positive correlation between striatal D2 activity and the magnitude of left prefrontal activity during updating. These findings support predictions from neurocomputational models of a relation of dopaminergic neurotransmission to transient cognitive operations and related brain activity.

  • 160.
    Nyberg, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Kauppi, Karolina
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Lundquist, Anders
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Persson, Jonas
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Stockholm Brain Institute, Karolinska Institute, Stockholm, Sweden.
    Pudas, Sara
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Karolinska Institute, Stockholm, Sweden.
    Nilsson, Lars-Göran
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Stockholm University, Stockholm Brain Institute.
    Age-related and genetic modulation of frontal cortex efficiency2014In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 26, no 4, p. 746-754Article in journal (Refereed)
    Abstract [en]

    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.

  • 161.
    Nyberg, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Bäckman, Lars
    Cognitive aging: A view from brain imaging2004In: New frontiers in cognitive aging, Oxford University Press, Oxford , 2004, p. 135-159Chapter in book (Other academic)
    Abstract [en]

    The contributions in this volume, and numerous other journal articles and chapters, provide unequivocal evidence that cognitive functions decline across the adult lifespan Importantly, though, some cognitive functions are more affected than others For example, in recent work from the Betula project (Nilsson eta!, 1997), we contrasted episodic and semantic long term memory (Nyberg eta!, 2003) It was found that episodic memory performance deteriorated gradually from middle age through young-old age to old-old age By contrast, semantic memory performance increased from middle-age to young-old age, and the old-old participants performed at a level comparable to the middle aged (Figure 7 la) Furthermore, within the domam of episodic memory, increasing age was associated with a greater reduction of pei form ance on measures of recall compared to measures of recognition (Figure 7 ib) These results provide evidence that episodic long-term memory is more age-sensitive than semantic long-term memory, and that recall is more age-sensitive than recognition.

    These age-related long-term memory changes can be related to patterns of data in working-memory tasks (Gick, Crajic, and Morris, 1988) Working-memory tasks differ with regard to their demand on executive processing and it has been found that age differences are small when the executive demands are low, and substantial wlten such demands are high (see Morris, Gick and Craik, 1988). Many cognitive tasks require working memory functions to a smaller or greater extent, and it has been shown that working memory capacity accounts for a considerable portion of the variance in long-term memory tasks (Hultsch, I-Iertzog, and Dixon, 1990; Park eta!., 1996). Relatedly, the relationship between age and episodic memory has been found to be mediated by proficiency of executive functioning (Troyer, Graves, and Cullum, 1994).

  • 162.
    Nyberg, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Bäckman, Lars
    Influences of Biological and Self-Initiated Factors on Brain and Cognition in Adulthood and Aging2006In: Lifespan Development and the Brain: The Perspective of Biocultural Co-Constructivism / [ed] Paul B. Baltes, Patricia A. Reuter-Lorenz, Frank Rösler, Cambridge: Cambridge University Press, 2006, p. 239-254Chapter in book (Other academic)
    Abstract [en]

    Age-related memory deficits are most pronounced on demanding tests of working memory and episodic memory, and are more pronounced in some older individuals than in others. In this chapter, we review individual-difference factors that influence memory functioning in adulthood and aging. A distinction is drawn between two categories of factors. The first includes biological factors that impose constraints by predisposing the aging brain toward cognitive decline. The second category includes a more heterogeneous collection of factors that are self-initiated and may be seen as offering possibilities rather than imposing constraints. We conclude by presenting some intriguing avenues for future research.

  • 163.
    Nyberg, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Bäckman, Lars
    Memory changes and the aging brain: a multimodal imaging approach2010In: Handbook of the psychology of aging / [ed] K.W Schaie & S L Willis, Elsevier Press , 2010, 7, p. 121-132Chapter in book (Refereed)
  • 164.
    Nyberg, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Dahlin, Erika
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Stigsdotter Neely, Anna
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Bäckman, Lars
    Aging Research Center, Karolinska Institutet, Stockholm.
    Neural correlates of variable working memory load across adult age and skill: dissociative patterns within the fronto-parietal network2009In: Scandinavian Journal of Psychology, ISSN 0036-5564, E-ISSN 1467-9450, Vol. 50, no 1, p. 41-46Article in journal (Refereed)
    Abstract [en]

    We examined neural changes related to variations in working memory load by using an n-back task with three levels and functional magnetic resonance imaging. Younger adults were divided into high- and low-performing groups (Young-High; Young-Low) and compared with older adults. Relative to Young-High, capacity-constraints in working memory were apparent between load 1-2 for the elderly and between load 2-3 for Young-Low. Capacity-constraints in neural activity followed this pattern by showing a monotonically increasing response in parietal cortex and thalamus for Young-High, whereas activity leveled off at 1-back for the elderly and at 2-back for Young-Low. The response in dorsal frontal cortex followed a similar pattern with the addition that the magnitude of activation differed within capacity limitations (Old > Young at 1-back; Young-Low > Young-High at 2-back). These findings indicate that an important determinant of WM capacity is the ability to keep the frontal cortex adequately engaged in relation to current task demands.

  • 165.
    Nyberg, Lars
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Eriksson, Johan
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Working Memory: Maintenance, Updating, and the Realization of Intentions2016In: Cold Spring Harbor Perspectives in Biology, ISSN 1943-0264, E-ISSN 1943-0264, Vol. 8, no 2, article id a021816Article in journal (Refereed)
    Abstract [en]

    "Working memory" refers to avast set of mnemonic processes and associated brain networks, relates to basic intellectual abilities, and underlies many real-world functions. Working-memory maintenance involves frontoparietal regions and distributed representational areas, and can be based on persistent activity in reentrant loops, synchronous oscillations, or changes in synaptic strength. Manipulation of content of working memory depends on the dorsofrontal cortex, and updating is realized by a frontostriatal '"gating" function. Goals and intentions are represented as cognitive and motivational contexts in the rostrofrontal cortex. Different working-memory networks are linked via associative reinforcement-learning mechanisms into a self-organizing system. Normal capacity variation, as well as working-memory deficits, can largely be accounted for by the effectiveness and integrity of the basal ganglia and dopaminergic neurotransmission.

  • 166.
    Nyberg, Lars
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Eriksson, Johan
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Marklund, Petter
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Learning by doing versus learning by thinking: An fMRI study of motor and mental training2006In: Neuropsychologia, Vol. 44, p. 711-717Article in journal (Refereed)
  • 167.
    Nyberg, Lars
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology. Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Habib, R
    Hemispheric Asymmetry of Memory.2008In: Encyclopedia of NeuroscienceArticle in journal (Refereed)
  • 168.
    Nyberg, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Karalija, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Salami, Alireza
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Kaboovand, Neda
    Köhncke, Ylva
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Rieckmann, Anna
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Papenberg, Goran
    Garrett, Douglas D.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Lövdén, Martin
    Lindenberger, Ulman
    Bäckman, Lars
    Dopamine D2 receptor availability is linked to hippocampal-caudate functional connectivity and episodic memory2016In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 113, no 28, p. 7918-7923Article in journal (Refereed)
    Abstract [en]

    D1 and D2 dopamine receptors (D1DRs and D2DRs) may contribute differently to various aspects of memory and cognition. The D1DR system has been linked to functions supported by the prefrontal cortex. By contrast, the role of the D2DR system is less clear, although it has been hypothesized that D2DRs make a specific contribution to hippocampus-based cognitive functions. Here we present results from 181 healthy adults between 64 and 68 y of age who underwent comprehensive assessment of episodic memory, working memory, and processing speed, along with MRI and D2DR assessment with [C-11]raclopride and PET. Caudate D2DR availability was positively associated with episodic memory but not with working memory or speed. Whole-brain analyses further revealed a relation between hippocampal D2DR availability and episodic memory. Hippocampal and caudate D2DR availability were interrelated, and functional MRI-based resting-state functional connectivity between the ventral caudate and medial temporal cortex increased as a function of caudate D2DR availability. Collectively, these findings indicate that D2DRs make a specific contribution to hippocampus-based cognition by influencing striatal and hippocampal regions, and their interactions.

  • 169.
    Nyberg, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Kim, Alice S N
    Rotman Research Institute, University of Toronto, Toronto, ON, Canada M6A 2E1.
    Habib, Reza
    Department of Psychology, Southern Illinois University, Carbondale, IL 62901.
    Levine, Brian
    Rotman Research Institute, University of Toronto, Toronto, ON, Canada M6A 2E1.
    Tulving, Endel
    Rotman Research Institute, University of Toronto, Toronto, ON, Canada M6A 2E1.
    Consciousness of subjective time in the brain2010In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 107, no 51, p. 22356-22359Article in journal (Refereed)
    Abstract [en]

    "Mental time travel" refers to conscious experience of remembering the personal past and imagining the personal future. Little is known about its neural correlates. Here, using functional magnetic resonance imaging, we explored the hypothesis that mental time travel into "nonpresent" times (past and future) is enabled by a special conscious state (chronesthesia). Well-trained subjects repeatedly imagined taking one and the same short walk in a familiar environment, doing so either in the imagined past, present, or future. In an additional condition, they recollected an instance in which they actually performed the same short walk in the same familiar setting. This design allowed us to measure brain activity correlated with "pure" conscious states of different moments of subjective time. The results showed that the left lateral parietal cortex was differentially activated by nonpresent subjective times compared with the present (past and future > present). A similar pattern was observed in the left frontal cortex, cerebellum, and thalamus. There was no evidence that the hippocampal region is involved in subjective time travel. These findings provide support for theoretical ideas concerning chronesthesia and mental time travel.

  • 170.
    Nyberg, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Eriksson, Johan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Sundström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Riklund Åhlström, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Comparing 1,5T and 3T BOLD fMRI imaging of finger tapping with familiar and novel sequences.2007In: Neuroscience Imaging, ISSN 1556-4010, Vol. 2, no 1, p. 53-64Article in journal (Refereed)
    Abstract [en]

    It has been suggested that fMRI at 3T yields stronger and more extensive BOLD activations than fMRI at 1.5T, and that imaging at higher field strengths can reveal unique activations. In the present study we compared, within-subjects, activation patterns during a finger-tapping task at 1.5 and 3T. The data were analyzed with a random-effects model in SPM2. At a strict statistical level (p<0.05, FWE correction for multiple comparisons), ipsilateral cerebellar activation was revealed at 1.5T. At 3T, activation in sensory-motor regions in the contra-lateral cerebrum was identified in addition to the activation in cerebellum. At a less stringent statistical threshold, imaging at 1.5T and 3T revealed overlapping cortical regions with more extensive clusters at 3T. A similar pattern was seen in a comparison of familiar and novel sequences. However, subcortical activations of thalamus and parts of the basal ganglia were uniquely identified at 3T. Analyses at the individual level substantiated the group results by showing that the higher sensitivity of the 3T resulted in images with higher between-individual consistency in activation patterns.

  • 171.
    Nyberg, Lars
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Lövdén, Martin
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Lindenberger, Ulman
    Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany.
    Bäckman, Lars
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Memory aging and brain maintenance2012In: Trends in cognitive sciences, ISSN 1364-6613, E-ISSN 1879-307X, Vol. 16, no 5, p. 292-305Article in journal (Refereed)
    Abstract [en]

    Episodic memory and working memory decline with advancing age. Nevertheless, large-scale population-based studies document well-preserved memory functioning in some older individuals. The influential 'reserve' notion holds that individual differences in brain characteristics or in the manner people process tasks allow some individuals to cope better than others with brain pathology and hence show preserved memory performance. Here, we discuss a complementary concept, that of brain maintenance (or relative lack of brain pathology), and argue that it constitutes the primary determinant of successful memory aging. We discuss evidence for brain maintenance at different levels: cellular, neurochemical, gray- and white-matter integrity, and systems-level activation patterns. Various genetic and lifestyle factors support brain maintenance in aging and interventions may be designed to promote maintenance of brain structure and function in late life.

  • 172.
    Nyberg, Lars
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Marklund, Petter
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Persson, J.
    Cabeza, R.
    Forkstam, C.
    Petersson, K. M.
    Ingvar, M.
    Common prefrontal activations during working memory, episodic memory, and semantic memory.2003In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 41, no 3, p. 371-377Article in journal (Refereed)
  • 173.
    Nyberg, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Pudas, Sara
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Successful Memory Aging2019In: Annual Review of Psychology, ISSN 0066-4308, E-ISSN 1545-2085, Vol. 70, p. 219-243Article, review/survey (Refereed)
    Abstract [en]

    For more than 50 years, psychologists, gerontologists, and, more recently, neuroscientists have considered the possibility of successful aging. How to define successful aging remains debated, but well-preserved age-sensitive cognitive functions, like episodic memory, is an often-suggested criterion. Evidence for successful memory aging comes from cross-sectional and longitudinal studies showing that some older individuals display high and stable levels of performance. Successful memory aging may be accomplished via multiple paths. One path is through brain maintenance, or relative lack of age-related brain pathology. Through another path, successful memory aging can be accomplished despite brain pathology by means of efficient compensatory and strategic processes. Genetic, epigenetic, and lifestyle factors influence memory aging via both paths. Some of these factors can be promoted throughout the life course, which, at the individual as well as the societal level, can positively impact successful memory aging.

  • 174.
    Nyberg, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Pudas, Sara
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lundquist, Anders
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Structural and functional imaging of aging: longitudinal sudies2017In: Cognitive neuroscience of aging: linking cognitive and cerebral aging / [ed] Roberto Cabeza, Lars Nyberg, and Denise C. Park, New York: Oxford University Press, 2017, 2, p. 155-182Chapter in book (Refereed)
    Abstract [en]

    This chapter on longitudinal structural and functional brain imaging examines points of convergence and divergence in findings from neuroimaging studies using cross-sectional versus longitudinal designs. Representative longitudinal age gradients are identified. It presents key methodological issues in longitudinal imaging, including test-retest effects, the influence of attrition, and different kinds of missing data. Various ways of handling data missingness in statistical analyses are also discussed.

  • 175.
    Nyberg, Lars
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Salami, Alireza
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    The APOE epsilon 4 allele in relation to brain white-matter microstructure in adulthood and aging2014In: Scandinavian Journal of Psychology, ISSN 0036-5564, E-ISSN 1467-9450, Vol. 55, no 3, p. 263-267Article in journal (Refereed)
    Abstract [en]

    The Apolipoprotein E (ApoE) epsilon 4 allele is a major genetic risk factor for sporadic Alzheimer's disease and has been associated with structural and functional brain alterations across the adult life span. Recent studies have presented evidence that epsilon 4 affects microstructural properties of brain white matter (WM) in non-demented carriers of the epsilon 4 allele, but conflicting evidence has been presented as well. The main purpose of the present study was therefore to examine ApoE effects on WM in a large sample of middle-aged and older adults (N=273). Diffusion tensor imaging (DTI) data was acquired, and tract-based as well as voxel-wise analyses were conducted. The tract-based analyses revealed no significant ApoE effects, and no significant interactions between genotype and age were observed. Taken together, the findings of the present study suggest that ApoE effects on white-matter microstructure are less abundant than has been suggested in some previous studies.

  • 176.
    Nyberg, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Salami, Alireza
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Andersson, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Eriksson, Johan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Kalpouzos, Grégoria
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Kauppi, Karolina
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Lind, Johanna
    Center for Study of Human Cognition, Department of Psychology, University of Oslo, Norway.
    Pudas, Sara
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Persson, Jonas
    Department of Psychology and Stockholm Brain Institute, Stockholm University, 106 91 Stockholm, Sweden .
    Nilsson, Lars-Göran
    Department of Psychology and Stockholm Brain Institute, Stockholm University, 106 91 Stockholm, Sweden .
    Longitudinal evidence for diminished frontal cortex function in aging2010In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 107, no 52, p. 22682-22686Article in journal (Refereed)
    Abstract [en]

    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.

  • 177. Olofsson, Jonas K
    et al.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Ekström, Ingrid
    Wilson, Donald
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nordin, Steven
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Nordin Adolfsson, Annelie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nilsson, Lars-Göran
    Larsson, Maria
    Long-term episodic memory decline is associated with olfactory deficits only in carriers of ApoE-є42016In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 85, p. 1-9Article in journal (Refereed)
    Abstract [en]

    The ɛ4 allele of the Apolipoprotein E gene is a genetic risk factor for late-onset dementia of the Alzheimers' type (DAT), which is characterized by loss of both episodic memory and olfactory functions. Little is known about the possible role of ɛ4 in the association between ongoing episodic memory decline and olfactory deficits in the general population, but such information is relevant in determining the relevance of olfaction as a marker of DAT risk. The present study was based on a large, population-based sample (n=1087, aged 45-90 years, of which 324 were ɛ4-carriers). Episodic memory change rates were established using data collected every 5 years for a 10-20 year interval leading up to an olfactory assessment using the Scandinavian Odor Identification Test at the last wave of data collection. Participants were classified according to whether or not their episodic memory ability declined more rapidly than the age-typical norm (by > 1SD). Our main result is that only in ɛ4-carriers was episodic memory decline associated with odor identification impairment. In individuals without ɛ4, odor identification was unrelated to episodic memory decline status. Follow-up analyses indicated that this moderation by ɛ4 was due to the olfactory nature of the identification test, and that the effect was not caused by 63 individuals with dementia. Our results suggest that the ɛ4 determines the functional association between ongoing episodic memory decline and olfaction. These findings are consistent with the notion that ɛ4-carriers with DAT, compared to non-carriers, display a cortical atrophy pattern that is more focused on mediotemporal lobe regions supporting olfactory and episodic memory functions. Olfactory and memory assessments might provide complementary information on mediotemporal atrophy prior to clinical dementia onset, but the ɛ4 should be considered when using olfactory assessment as an early-stage indicator.

  • 178. Olofsson, Jonas K.
    et al.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Stanciu, Ingrid
    Wilson, Donald
    Nordin, Steven
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Nilsson, Lars-Goran
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Larsson, Maria
    ApoE-e4 Mediates the Association Between Episodic Memory Decline and Olfactory Identification Deficit2015In: Chemical Senses, ISSN 0379-864X, E-ISSN 1464-3553, Vol. 40, no 7, p. 667-667Article in journal (Other academic)
  • 179.
    Olofsson, Jonas
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Michael, Rönnlund
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Nordin, Steven
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University, 10691 Stockholm, Sweden.
    Larsson, Maria
    Department of Psychology, Stockholm University, 10691 Stockholm, Sweden.
    Odor identification deficit as a predictor of five-year global cognitive change: Interactive effects with age and ApoE-ε42009In: Behavior Genetics, ISSN 0001-8244, E-ISSN 1573-3297, Vol. 39, no 5, p. 496-503Article in journal (Refereed)
    Abstract [en]

    Olfactory impairments are present in common neurodegenerative disorders and predict conversion to dementia in non-demented individuals with cognitive impairment. In cognitively intact elderly, evidence is sparse regarding the role of olfactory deficits in predicting cognitive impairment. The present study investigated predictors of 5-year prospective decline in the Mini-Mental State Examination (MMSE) in a large (n = 501), population-based sample of elderly (65-90 years) individuals. All participants were genotyped for the ApoE gene, assessed for health factors, and were non-demented at the baseline assessment. After partialling out the influences of demographic and health-factors at baseline and dementia at follow-up, poor odor identification ability in combination with older age and the ApoE-epsilon4 allele predicted larger prospective global cognitive decline. This effect could not be produced by a vocabulary test. In sum, the findings suggest that an olfactory deficit can dissociate between benign and malign global cognitive development in non-demented, very old epsilon4-carriers, who are at high risk of developing dementia.

  • 180.
    Olsson, Carl-Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Jonsson, Bert
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Motor representations and practice affect brain systems underlying imagery: an FMRI study of internal imagery in novices and active high jumpers2008In: The Open Neuroimaging Journal, ISSN 1874-4400, E-ISSN 1874-4400, Vol. 2, p. 5-13Article in journal (Refereed)
    Abstract [en]

    This study used functional magnetic resonance imaging (fMRI) to investigate differences in brain activity between one group of active high jumpers and one group of high jumping novices (controls) when performing motor imagery of a high jump. It was also investigated how internal imagery training affects neural activity. The results showed that active high jumpers primarily activated motor areas, e.g. pre-motor cortex and cerebellum. Novices activated visual areas, e.g. superior occipital cortex. Imagery training resulted in a reduction of activity in parietal cortex. These results indicate that in order to use an internal perspective during motor imagery of a complex skill, one must have well established motor representations of the skill which then translates into a motor/internal pattern of brain activity. If not, an external perspective will be used and the corresponding brain activation will be a visual/external pattern. Moreover, the findings imply that imagery training reduces the activity in parietal cortex suggesting that imagery is performed more automatic and results in a more efficient motor representation more easily accessed during motor performance.

  • 181.
    Olsson, Carl-Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Jonsson, Bert
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Internal imagery training in active high jumpers2008In: Scandinavian Journal of Psychology, ISSN 0036-5564, E-ISSN 1467-9450, Vol. 49, no 2, p. 133-140Article in journal (Refereed)
    Abstract [en]

    The main purpose of this study was to examine whether the use of internal imagery would affect high jumping performance for active high jumping athletes. Over a period of six weeks, a group of active high jumpers were trained with an internal imagery program for a total of 72 minutes. This group was compared to a control group consisting of active high jumpers that only maintained their regular work-outs during the same time period. Four variables were measured; jumping height, number of failed attempts, take-off angle, and bar clearance. There was a significant improvement on bar clearance for the group that trained imagery (p < 0.05) but not for the control group. No other differences were found. The results suggest that internal imagery training may be used to improve a component of a complex motor skill. Possible explanations and future recommendations are discussed.

  • 182.
    Olsson, Carl-Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Jonsson, Bert
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Learning by doing and learning by thinking: An fMRI study of combining motor and mental training2008In: Frontiers in human neuroscience, ISSN 1662-5161, Vol. 2, no 5, p. 1-7Article in journal (Refereed)
    Abstract [sv]

    The current study investigated behavioral and neural effects of motor, mental, and combined motor and mental training on a finger tapping task. The motor or mental training groups trained on a finger-sequence for a total of 72 min over six weeks. The motor and mental training group received 72 min motor training and in addition 72 min mental training. Results showed that all groups increased their tapping performance significantly on the trained sequence. After training fMRI data was collected and indicated training specific increases in ventral pre-motor cortex following motor training, and in fusiform gyrus following mental training. Combined motor and mental training activated both the motor and the visual regions. In addition, motor and mental training showed a significant increase in tapping performance on an untrained sequence (transfer). FMRI scanning indicated that the transfer effect involved the cerebellum. Conclusions were that combined motor and mental training recruited both motor and visual systems, and that combined motor and mental training improves motor flexibility via connections from both motor and cognitive systems to the cerebellum.

  • 183.
    Olsson, Carl-Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Brain simulation of action may be grounded in physical experience2011In: Neurocase, ISSN 1355-4794, E-ISSN 1465-3656, Vol. 17, no 6, p. 501-505Article in journal (Refereed)
    Abstract [en]

    An intriguing quality of our brain is that when actions are imagined, corresponding brain regions are recruited as when the actions are actually performed. It has been hypothesized that the similarity between real and simulated actions depends on the nature of motor representations. Here we tested this hypothesis by examining S.D., who never used her legs but is an elite wheel chair athlete. Controls recruited motor brain regions during imagery of stair walking and frontal regions during imagery of wheel chair slalom. S.D. showed the opposite pattern. Thus, brain simulation of actions may be grounded in specific physical experiences.

  • 184.
    Olsson, Carl-Johan
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Motor imagery: if you can't do it, you won't think it2010In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 20, no 5, p. 711-715Article in journal (Refereed)
    Abstract [en]

    Since long, motor imagery has been recognized as a method for studying motor representations. In the last few years, important advances regarding the use of motor imagery have been made. In particular, issues concerning the functional equivalence between imagery and action have been addressed, and how equivalence affects the use of imagery to study motor representations. In this paper, we review recent findings in order to highlight the current state of knowledge about motor imagery and its relation to motor action. Three topics are discussed: (i) the imagery perspective, (ii) task complexity, and (iii) the importance of physical experience. It is shown how theses factors are closely related and how previous studies may have underestimated to what extent these factors affect the interpretation of results. Practical implications for imagery interventions are considered. It is concluded that if you cannot perform an action physically, you cannot imagine it in a way that is necessary for a high degree of functional equivalence.

  • 185. Papenberg, Goran
    et al.
    Karalija, Nina
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Salami, Alireza
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Lindenberger, Ulman
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Bäckman, Lars
    The Influence of Hippocampal Dopamine D2 Receptors on Episodic Memory Is Modulated by BDNF and KIBRA Polymorphisms2019In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 31, no 9, p. 1422-1429Article in journal (Refereed)
    Abstract [en]

    Episodic memory is a polygenic trait influenced by different molecular mechanisms. We used PET and a candidate gene approach to investigate how individual differences at the molecular level translate into between-person differences in episodic memory performance of elderly persons. Specifically, we examined the interactive effects between hippocampal dopamine D2 receptor (D2DR) availability and candidate genes relevant for hippocampus-related memory functioning. We show that the positive effects of high D2DR availability in the hippocampus on episodic memory are confined to carriers of advantageous genotypes of the brain-derived neurotrophic factor (BDNF, rs6265) and the kidney and brain expressed protein (KIBRA, rs17070145) polymorphisms. By contrast, these polymorphisms did not modulate the positive relationship between caudate D2DR availability and episodic memory.

  • 186. Persson, J
    et al.
    Lind, J
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Ingvar, M
    Sleegers, K
    Van Broeckhoven, C
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nilsson, L-G
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Altered deactivation in individuals with genetic risk for Alzheimer's disease.2008In: Neuropsychologia, ISSN 0028-3932, Vol. 46, no 6, p. 1679-1687Article in journal (Refereed)
    Abstract [en]

    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 investigating 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.

  • 187.
    Persson, Jonas
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Bringlöv, Eva
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    The memory-enhancing effects of Ginseng and Ginkgo biloba in healthy volunteers2004In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 172, no 4, p. 430-434Article in journal (Refereed)
    Abstract [en]

    Rationale: The use of herbal remedies, such as Ginkgo biloba and Ginseng, for improving cognitive performance has become increasingly popular during recent years. Several previous studies have indicated that administration of Ginkgo biloba and Ginseng may improve aspects of learning and memory in healthy volunteers. These results, however, are generally not supported by well-controlled clinical studies. Also, positive results have often been reported from studies investigating effects related to short-term, chronic administration of the extract. Nonetheless, both Ginkgo biloba and Ginseng are marketed as having the capacity to enhance cognitive functions, such as memory and learning, in the long term.

    Objective: This study aimed at investigating whether the use of Ginkgo biloba and Ginseng for a long period of time has positive effects on performance on learning and memory.

    Methods: Community-dwelling volunteers ( n=3500) from The Betula prospective cohort study: memory, health, and aging were included in the study.

    Results: It was found that the use of neither Ginkgo biloba ( n=40) nor Ginseng ( n=86) was associated with enhanced memory performance in any of the eight memory tests examined, relative to control groups either using or not using nutritional supplements.

    Conclusions: These findings indicate that use of Ginkgo biloba or Ginseng does not provide any quantifiable beneficial effects on memory performance in the long-term in healthy adult volunteers.

  • 188.
    Persson, Jonas
    et al.
    Department of Psychology, Stockholm University, 106 91 Stockholm, Sweden.
    Kalpouzos, Grégoria
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University, 106 91 Stockholm, Sweden.
    Ryberg, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Preserved hippocampus activation in normal aging as revealed by fMRI.2011In: Hippocampus, ISSN 1050-9631, E-ISSN 1098-1063, Vol. 21, no 7, p. 753-766Article in journal (Refereed)
    Abstract [en]

    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.

  • 189.
    Persson, Jonas
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Lind, Johanna
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Ingvar, Martin
    Cruts, Marc
    Van Broeckhoven, Christine
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nilsson, Lars-Göran
    Nyberg, Lars
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Altered brain white matter integrity in healthy carriers of the APOE epsilon4 allele: A risk for AD?2006In: Neurology, Vol. 66, p. 1029-1033Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Previous research has shown that polymorphisms of apolipoprotein E (APOE) represent genetic risk factors for dementia and for cognitive impairment in the elderly. The neural mechanisms by which these genetic variations influence behavioral performance or clinical severity are not well understood.

    METHODS: The authors used diffusion tensor imaging to investigate ultrastructural properties in brain white matter to detect pathologic processes that modify tissue integrity. Sixty participants were included in the study of which 30 were homozygous for the APOE epsilon3 allele, 10 were homozygous for the APOE epsilon4 allele, and 20 had the APOE epsilon34 allele combination. All individuals were non-demented, and the groups were matched on demographic variables and cognitive performance.

    RESULTS: The results showed a decline in fractional anisotropy, a marker for white matter integrity, in the posterior corpus callosum of epsilon4 carriers compared to non-carriers. Additional sites of altered white matter integrity included the medial temporal lobe.

    CONCLUSIONS: Although the mechanism underlying vulnerability of white matter tracts in APOE epsilon4 carriers is still unknown, these findings suggest that increased genetic risk for developing Alzheimer disease is associated with changes in microscopic white matter integrity well before the onset of dementia.

  • 190. Persson, Jonas
    et al.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Altered brain activity in healthy seniors: what does it mean?2006In: Progress in Brain Research, ISSN 0079-6123, E-ISSN 1875-7855, Vol. 157, p. 45-56Article in journal (Other academic)
    Abstract [en]

    Age-related performance decreases are frequently observed on various memory tasks. Recent brain imaging studies using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) suggest a link between altered patterns of brain activity in older adults and memory performance. Convergent neuroimaging evidence shows that older adults have decreased activity in multiple regions important for memory tasks. Such relative under-activation in older adults is likely related to age-related reductions in cognitive performance. Age-comparative neuroimaging studies have also provided convincing support for regional over-activation by older adults. Such findings indicate that the older brain can re-organize to better cope with cognitive and other challenges. Although over-activation may play a compensatory role when cognitive decline is limited, under-activation seems to be the typical pattern when cognitive impairment is in a more progressed state. This pattern of age-related changes suggests that compensation through over-activation is restricted to the early stages of cognitive impairment in aging.

  • 191.
    Persson, Jonas
    et al.
    Department of Psychology, Stockholm University, Stockholm.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Structure-function correlates of episodic memory in aging2008In: Handbook of Episodic Memory, Elsevier, 2008, p. 521-535Chapter in book (Refereed)
    Abstract [en]

    Normal aging is accompanied by a wide variety of disturbances in the structure and function of the human brain. It is now well established that normal aging is associated with a progressive decline of episodic-memory function, especially in cued and free recall tasks. Although the primary causes of this decline remain elusive, neuroimaging research have presented an avenue for understanding age-related episodic-memory failure. By integrating behavioral measures and imaging data, the relationship between biological markers of aging and cognitive functions can be explored. In this chapter, we review current knowledge about the effects of normal aging, and its neural correlates as revealed by functional and structural neuroimaging. The importance of reliable cognitive measures in aging research, such as longitudinal behavioral assessment, is also highlighted. We also present results that attempt at characterizing cognitive aging at multiple levels by integrating structural, neuroimaging, and episodic-memory measures.

  • 192.
    Persson, Jonas
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Nyberg, Lars
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Lind, Johanna
    MR Research Center, Karolinska Hospital, S-171 76 Stockholm, Sweden.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University, S-106 91 Stockholm, Sweden.
    Ingvar, Martin
    MR Research Center, Karolinska Hospital, S-171 76 Stockholm, Sweden.
    Buckner, Randy L
    Departments of Psychology, Radiology, and Anatomy & Neurobiology, Howard Hughes Medical Institute at Washington University, St Louis, MO 63130, USA.
    Structure-function correlates of cognitive decline in aging2006In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 16, no 7, p. 907-915Article in journal (Refereed)
    Abstract [en]

    To explore neural correlates of cognitive decline in aging, we used longitudinal behavioral data to identify two groups of older adults (n = 40) that differed with regard to whether their performance on tests of episodic memory remained stable or declined over a decade. Analysis of structural and diffusion tensor imaging (DTI) revealed a heterogeneous set of differences associated with cognitive decline. Manual tracing of hippocampal volume showed significant reduction in those older adults with a declining memory performance as did DTI-measured fractional anisotropy in the anterior corpus callosum. Functional magnetic resonance imaging during incidental episodic encoding revealed increased activation in left prefrontal cortex for both groups and additional right prefrontal activation for the elderly subjects with the greatest decline in memory performance. Moreover, mean DTI measures in the anterior corpus callosum correlated negatively with activation in right prefrontal cortex. These results demonstrate that cognitive decline is associated with differences in the structure as well as function of the aging brain, and suggest that increased activation is either caused by structural disruption or is a compensatory response to such disruption.

  • 193.
    Persson, Jonas
    et al.
    Stockholm Univ, Dept Psychol, S-10691 Stockholm, Sweden .
    Pudas, Sara
    Stockholm Univ, Dept Psychol, S-10691 Stockholm, Sweden .
    Lind, Johanna
    Stockholm Univ, Dept Psychol, S-10691 Stockholm, Sweden .
    Kauppi, Karolina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Nilsson, Lars-Göran
    Stockholm Univ, Dept Psychol, S-10691 Stockholm, Sweden .
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Longitudinal structure-function correlates in elderly reveal MTL dysfunction with cognitive decline2012In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 22, no 10, p. 2297-2304Article in journal (Refereed)
    Abstract [en]

    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.

  • 194.
    Persson, Jonas
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Department of Psychology, Aging Research Center (ARC) at Karolinska Institute and Stockholm University, Stockholm, Sweden and Department of Psychology, Stockholm University, Stockholm, Sweden.
    Pudas, Sara
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Department of Psychology, Stockholm University, Stockholm, Sweden.
    Nilsson, Lars-Göran
    Karolinska Inst, Aging Res Ctr ARC, S-11330 Stockholm, Sweden and Stockholm Univ, Dept Psychol, S-11330 Stockholm, Sweden.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Longitudinal assessment of default-mode brain function in aging2014In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 35, no 9, p. 2107-2117Article in journal (Refereed)
    Abstract [en]

    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.

  • 195.
    Pudas, Sara
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Rieckmann, Anna
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Longitudinal evidence for increased functional response in frontal cortex for older adults with hippocampal atrophy and memory decline2018In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 28, no 3, p. 936-948Article in journal (Refereed)
    Abstract [en]

    The functional organization of the frontal cortex is dynamic. Age-related increases in frontal functional responses have been shown during various cognitive tasks, but the cross-sectional nature of most past studies makes it unclear whether these increases reflect reorganization or stable individual differences. Here, we followed 130 older individuals' cognitive trajectories over 20-25 years with repeated neuropsychological assessments every 5th year, and identified individuals with stable or declining episodic memory. Both groups displayed significant gray matter atrophy over 2 successive magnetic resonance imaging sessions 4 years apart, but the decline group also had a smaller volume of the right hippocampus. Only individuals with declining memory demonstrated increased prefrontal functional responses during memory encoding and retrieval over the 4-year interval. Regions with increased functional recruitment were located outside, or on the borders of core task-related networks, indicating an expansion of these over time. These longitudinal findings offer novel insight into the mechanisms behind age-associated memory loss, and are consistent with a theoretical model in which hippocampus atrophy, past a critical threshold, induces episodic-memory decline and altered prefrontal functional organization.

  • 196.
    Pudas, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Persson, Jonas
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    de Luna, Xavier
    Umeå University, Faculty of Social Sciences, Department of Statistics.
    Nilsson, Lars-Göran
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Brain Characteristics of Individuals Resisting Age-Related Cognitive Decline over Two Decades2013In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 33, no 20, p. 8668-8677Article in journal (Refereed)
    Abstract [en]

    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.

  • 197.
    Pudas, Sara
    et al.
    Department of Psychology, Stockholm University, Stockholm, Sweden .
    Persson, Jonas
    Department of Psychology, Stockholm University, Stockholm, Sweden .
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University, Stockholm, Sweden .
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Maintenance and manipulation in working memory: Differential ventral and dorsal frontal cortex fMRI activity2009In: Acta Psychologica Sinica, ISSN 0439-755X, Vol. 41, no 11, p. 1054-1062Article in journal (Refereed)
    Abstract [en]

    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.

  • 198.
    Pudas, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Department of Psychology, Stockholm University, Stockholm.
    Persson, Jonas
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Department of Psychology, Stockholm University, Aging Research Center, Karolinska Institute and Stockholm University, Stockholm.
    Nilsson, Lars-Göran
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Aging Research Center, Karolinska Institute and Stockholm University, Stockholm.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Midlife memory ability accounts for brain activity differences in healthy aging2014In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 35, no 11, p. 2495-2503Article in journal (Refereed)
    Abstract [en]

    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.

  • 199. Ragnarsson, Oskar
    et al.
    Stomby, Andreas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Ryhov County Hospital, Jönköping, Sweden.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Evang, Johan A.
    Ryberg, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Bollerslev, Jens
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Johannsson, Gudmundur
    Decreased prefrontal functional brain response during memory testing in women with Cushing's syndrome in remission2017In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 82, p. 117-125Article in journal (Refereed)
    Abstract [en]

    Neurocognitive dysfunction is an important feature of Cushing's syndrome (CS). Our hypothesis was that patients with CS in remission have decreased functional brain responses in the prefrontal cortex and hippocampus during memory testing. In this cross-sectional study we included 19 women previously treated for CS and 19 commis matched for age, gender, and education. The median remission time was 7 (IQR 6-10) years. Brain activity was studied with functional magnetic resonance imaging during episodic- and working memory tasks. The primary regions of interest were the prefrontal cortex and the hippocampus. A voxel-wise comparison of functional brain responses in patients and controls was performed. During episodic-memory encoding, patients displayed lower functional brain responses in the left and right prefrontal gyrus (p < 0.001) and in the right inferior occipital gyrus (p < 0.001) compared with controls. There was a trend towards lower functional brain responses in the left posterior hippocampus in patients (p = 0.05). During episodic-memory retrieval, the patients displayed lower functional brain responses in several brain areas with the most predominant difference in the right prefrontal cortex (p < 0.001). During the working memory task, patients had lower response in the prefrontal cortices bilaterally (p < 0.005). Patients, but not controls, had lower functional brain response during a more complex working memory task compared with a simpler one. In conclusion, women with CS in long-term remission have reduced functional brain responses during episodic and working memory testing. This observation extends previous findings showing long-term adverse effects of severe hypercortisolaemia on brain function.

  • 200.
    Rieckmann, Anna
    et al.
    Aging Research Center, Department of Neurobiology, Care Sciences & Society, Karolinska Institute, SE-113 30 Stockholm, Sweden.
    Karlsson, Sari
    Aging Research Center, Department of Neurobiology, Care Sciences & Society, Karolinska Institute, SE-113 30 Stockholm, Sweden.
    Karlsson, Per
    Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, SE-171 76 Stockholm, Sweden.
    Brehmer, Yvonne
    Aging Research Center, Department of Neurobiology, Care Sciences & Society, Karolinska Institute, SE-113 30 Stockholm, Sweden.
    Fischer, Håkan
    Aging Research Center, Department of Neurobiology, Care Sciences & Society, Karolinska Institute, SE-113 30 Stockholm, Sweden.
    Farde, Lars
    Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, SE-171 76 Stockholm, Sweden.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Bäckman, Lars
    Aging Research Center, Department of Neurobiology, Care Sciences & Society, Karolinska Institute, SE-113 30 Stockholm, Sweden.
    Dopamine D1 receptor associations within and between dopaminergic pathways in younger and elderly adults: links to cognitive performance2011In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 21, no 9, p. 2023-2032Article in journal (Refereed)
    Abstract [en]

    Age-related dopamine (DA) losses have been extensively demonstrated for the D2 receptor subtype. Comparatively little is known about adult age changes regarding D1 receptors. In this study, we demonstrate marked age-related D1 receptor losses in striatal, limbic, and cortical areas using positron emission tomography and the radioligand [(11)C]SCH23390 in humans. Interregional correlations of binding potential (BP) values were high for areas within DA pathways in younger and elderly adults alike. Furthermore, interregional correlations in D1 BP between DA pathways were uniformly high in younger adults, indicating that D1 receptor densities in striatal, limbic, and cortical areas are not regulated independently, despite dopaminergic innervation from different midbrain areas. For elderly adults, between-pathway correlations of D1 receptor densities were preserved only between mesolimbic and mesocortical areas, whereas striatal BPs were weakly related to those in limbic and neocortical regions. Importantly, weak between-pathway correlations in elderly adults were found only for the slower half of the sample when BP was estimated during a cognitive interference task. These results suggest that D1 receptor densities in different pathways are not regulated independently in younger adults, but segregate in older age, and that this segregation of D1 receptor systems may be related to age-related cognitive slowing.

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