| 1. |
- Becker, Nina, et al.
(författare)
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Structure-function associations of successful associative encoding
- 2019
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Ingår i: NeuroImage. - : Elsevier. - 1053-8119 .- 1095-9572. ; 201
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Tidskriftsartikel (refereegranskat)abstract
- Functional magnetic resonance imaging (MRI) studies have demonstrated a critical role of hippocampus and inferior frontal gyrus (IFG) in associative memory. Similarly, evidence from structural MRI studies suggests a relationship between gray-matter volume in these regions and associative memory. However, how brain volume and activity relate to each other during associative-memory formation remains unclear. Here, we used joint independent component analysis (jICA) to examine how gray-matter volume and brain activity would be associated during associative encoding, especially in medial-temporal lobe (MTL) and IFG. T1-weighted images were collected from 27 young adults, and functional MRI was employed during intentional encoding of object pairs. A subsequent recognition task tested participants' memory performance. Unimodal analyses using voxel-based morphometry revealed that participants with better associative memory showed larger gray-matter volume in left anterior hippocampus. Results from the jICA revealed one component that comprised a covariance pattern between gray-matter volume in anterior and posterior MTL and encoding-related activity in IFG. Our findings suggest that gray matter within the MTL modulates distally distinct parts of the associative encoding circuit, and extend previous studies that demonstrated MTL-IFG functional connectivity during associative memory tasks.
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| 2. |
- Gustavsson, Jonatan, et al.
(författare)
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The iron-dopamine D1 coupling modulates neural signatures of working memory across adult lifespan
- 2023
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Ingår i: NeuroImage. - : Elsevier. - 1053-8119 .- 1095-9572. ; 279
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Tidskriftsartikel (refereegranskat)abstract
- Brain iron overload and decreased integrity of the dopaminergic system have been independently reported as brain substrates of cognitive decline in aging. Dopamine (DA), and iron are co-localized in high concentrations in the striatum and prefrontal cortex (PFC), but follow opposing age-related trajectories across the lifespan. DA contributes to cellular iron homeostasis and the activation of D1-like DA receptors (D1DR) alleviates oxidative stress-induced inflammatory responses, suggesting a mutual interaction between these two fundamental components. Still, a direct in-vivo study testing the iron-D1DR relationship and their interactions on brain function and cognition across the lifespan is rare. Using PET and MRI data from the DyNAMiC study (n=180, age=20-79, %50 female), we showed that elevated iron content was related to lower D1DRs in DLPFC, but not in striatum, suggesting that dopamine-rich regions are less susceptible to elevated iron. Critically, older individuals with elevated iron and lower D1DR exhibited less frontoparietal activations during the most demanding task, which in turn was related to poorer working-memory performance. Together, our findings suggest that the combination of elevated iron load and reduced D1DR contribute to disturbed PFC-related circuits in older age, and thus may be targeted as two modifiable factors for future intervention.
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| 3. |
- Kalpouzos, Grégoria, et al.
(författare)
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Higher Striatal Iron Concentration is Linked to Frontostriatal Underactivation and Poorer Memory in Normal Aging
- 2017
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Ingår i: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 27:6, s. 3427-3436
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Tidskriftsartikel (refereegranskat)abstract
- In the brain, intracellular iron is essential for cellular metabolism. However, an overload of free iron is toxic, inducing oxidative stress and cell death. Although an increase of striatal iron has been related to atrophy and impaired cognitive performance, the link between elevated iron and altered brain activity in aging remains unexplored. In a sample of 37 younger and older adults, we examined whether higher striatal iron concentration could underlie age-related differences in frontostriatal activity induced by mental imagery of motor and non-motor scenes, and poorer recall of the scenes. Higher striatal iron concentration was linked to underrecruitment of frontostriatal regions regardless of age and striatal volume, the iron-activity association in right putamen being primarily driven by the older adults. In older age, higher striatal iron was related to poorer memory. Altered astrocytic functions could account for the link between brain iron and brain activity, as astrocytes are involved in iron buffering, neurovascular coupling, and synaptic activity. Our preliminary findings, which need to be replicated in a larger sample, suggest a potential frontostriatal target for intervention to counteract negative effects of iron accumulation on brain function and cognition.
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| 4. |
- Lövdén, Martin, et al.
(författare)
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Changes in perceptual speed and white matter microstructure in the corticospinal tract are associated in very old age
- 2014
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Ingår i: NeuroImage. - : Elsevier. - 1053-8119 .- 1095-9572. ; 102, s. 520-530
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Tidskriftsartikel (refereegranskat)abstract
- The integrity of the brain's white matter is important for neural processing and displays age-related differences, but the contribution of changes in white matter to cognitive aging is unclear. We used latent change modeling to investigate this issue in a sample of very old adults (aged 81-103. years) assessed twice with a retest interval of 2.3. years. Using diffusion-tensor imaging, we probed white matter microstructure by quantifying mean fractional anisotropy and mean diffusivity of six major white matter tracts. Measures of perceptual speed, episodic memory, letter fluency, category fluency, and semantic memory were collected. Across time, alterations of white matter microstructure in the corticospinal tract were associated with decreases of perceptual speed. This association remained significant after statistically controlling for changes in white matter microstructure in the entire brain, in the other demarcated tracts, and in the other cognitive abilities. Changes in brain volume also did not account for the association. We conclude that white matter microstructure is a potent correlate of changes in sensorimotor aspects of behavior in very old age, but that it is unclear whether its impact extends to higher-order cognition.
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| 5. |
- Nordin, Kristin, et al.
(författare)
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DyNAMiC: A prospective longitudinal study of dopamine and brain connectomes : A new window into cognitive aging
- 2022
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Ingår i: Journal of Neuroscience Research. - : Wiley. - 0360-4012 .- 1097-4547. ; 100:6, s. 1296-1320
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Tidskriftsartikel (refereegranskat)abstract
- Concomitant exploration of structural, functional, and neurochemical brain mechanisms underlying age-related cognitive decline is crucial in promoting healthy aging. Here, we present the DopamiNe, Age, connectoMe, and Cognition (DyNAMiC) project, a multimodal, prospective 5-year longitudinal study spanning the adult human lifespan. DyNAMiC examines age-related changes in the brain’s structural and functional connectome in relation to changes in dopamine D1 receptor availability (D1DR), and their associations to cognitive decline. Critically, due to the complete lack of longitudinal D1DR data, the true trajectory of one of the most age-sensitive dopamine systems remains unknown. The first DyNAMiC wave included 180 healthy participants (20–80 years). Brain imaging included magnetic resonance imaging assessing brain structure (white matter, gray matter, iron), perfusion, and function (during rest and task), and positron emission tomography (PET) with the [11C]SCH23390 radioligand. A subsample (n = 20, >65 years) was additionally scanned with [11C]raclopride PET measuring D2DR. Age-related variation was evident for multiple modalities, such as D1DR; D2DR, and performance across the domains of episodic memory, working memory, and perceptual speed. Initial analyses demonstrated an inverted u-shaped association between D1DR and resting-state functional connectivity across cortical network nodes, such that regions with intermediate D1DR levels showed the highest levels of nodal strength. Evident within each age group, this is the first observation of such an association across the adult lifespan, suggesting that emergent functional architecture depends on underlying D1DR systems. Taken together, DyNAMiC is the largest D1DR study worldwide, and will enable a comprehensive examination of brain mechanisms underlying age-related cognitive decline.
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| 6. |
- Nyberg, Lars, et al.
(författare)
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Longitudinal evidence for diminished frontal-cortex function in aging
- 2010
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 107:52, s. 22682-22686
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Tidskriftsartikel (refereegranskat)abstract
- Cross-sectional estimates of age-related changes in brain structure and function were compared with 6-y longitudinal estimates. The results indicated increased sensitivity of the longitudinal approach as well as qualitative differences. Critically, the cross-sectional analyses were suggestive of age-related frontal overrecruitment, whereas the longitudinal analyses revealed frontal underrecruitment with advancing age. The cross-sectional observation of overrecruitment reflected a select elderly sample. However, when followed over time, this sample showed reduced frontal recruitment. These findings dispute inferences of true age changes on the basis of age differences, hence challenging some contemporary models of neurocognitive aging, and demonstrate age-related decline in frontal brain volume as well as functional response.
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| 7. |
- Salami, Alireza, et al.
(författare)
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Elevated Neuroinflammation Contributes to the Deleterious Impact of Iron Overload on Brain Function in Aging
- 2021
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Ingår i: NeuroImage. - : Academic Press. - 1053-8119 .- 1095-9572. ; 230
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Tidskriftsartikel (refereegranskat)abstract
- Intracellular iron is essential for many neurobiological mechanisms. However, at high concentrations, iron may induce oxidative stress and inflammation. Brain iron overload has been shown in various neurodegenerative disorders and in normal aging. Elevated brain iron in old age may trigger brain dysfunction and concomitant cognitive decline. However, the exact mechanism underlying the deleterious impact of iron on brain function in aging is unknown. Here, we investigated the role of iron on brain function across the adult lifespan from 187 healthy participants (20-79 years old, 99 women) who underwent fMRI scanning while performing a working-memory n-back task. Iron content was quantified using R2* relaxometry, whereas neuroinflammation was estimated using myo-inositol measured by magnetic resonance spectroscopy. Striatal iron increased non-linearly with age, with linear increases at both ends of adulthood. Whereas higher frontostriatal activity was related to better memory performance independent of age, the link between brain activity and iron differed across age groups. Higher striatal iron was linked to greater frontostriatal activity in younger, but reduced activity in older adults. Further mediation analysis revealed that, after age 40, iron provided unique and shared contributions with neuroinflammation to brain activations, such that neuroinflammation partly mediated brain-iron associations. These findings promote a novel mechanistic understanding of how iron may exert deleterious effects on brain function and cognition with advancing age.
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| 8. |
- Salami, Alireza, et al.
(författare)
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Functional coherence of striatal resting-state networks is modulated by striatal iron content
- 2018
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 183, s. 495-503
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Tidskriftsartikel (refereegranskat)abstract
- Resting-state spontaneous fluctuations have revealed individual differences in the functional architecture of brain networks. Previous research indicates that the striatal network shows alterations in neurological conditions but also in normal aging. However, the neurobiological mechanisms underlying individual differences in striatal resting-state networks (RSNs) have been less explored. One candidate that may account for individual differences in striatal spontaneous activity is the level of local iron accumulation. Excessive iron in the striatum has been linked to a loss of structural integrity and reduced brain activity during task performance in aging. Using independent component analysis in a sample of 42 younger and older adults, we examined whether higher striatal iron content, quantified using relaxometry, underlies individual differences in spontaneous fluctuations of RSNs in general, and of the striatum in particular. Higher striatal iron content was linked to lower spontaneous coherence within both caudate and putamen RSNs regardless of age. No such links were observed for other RSNs. Moreover, the number of connections between the putamen and other RSNs was negatively associated with iron content, suggesting that iron modulated the degree of cross-talk between the striatum and cerebral cortex. Importantly, these associations were primarily driven by the older group. Finally, a positive association was found between coherence in the putamen and motor performance, suggesting that this spontaneous activity is behaviorally meaningful. A follow-up mediation analysis also indicated that functional connectivity may mediate the link between striatal iron and motor performance. Our preliminary findings suggest that striatal iron potentially accounts for individual differences in spontaneous striatal fluctuations, and might be used as a locus of intervention.
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| 9. |
- Wang, Rui, et al.
(författare)
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Effects of vascular risk factors and APOE epsilon 4 on white matter integrity and cognitive decline
- 2015
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 84:11, s. 1128-1135
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To investigate the effects of vascular risk factors and APOE status on white matter microstructure, and subsequent cognitive decline among older people.Methods:This study included 241 participants (age 60 years and older) from the population-based Swedish National Study on Aging and Care in Kungsholmen in central Stockholm, Sweden, who were free of dementia and stroke at baseline (2001-2004). We collected data through interviews, clinical examinations, and laboratory tests. We measured fractional anisotropy (FA) and mean diffusivity (MD) on diffusion tensor imaging, and estimated volume of white matter hyperintensities using automatic segmentation. We assessed global cognitive function with the Mini-Mental State Examination at baseline and at 3- and/or 6-year follow-up. We analyzed the data using multivariate linear regression and linear mixed models.Results:Heavy alcohol consumption, hypertension, and diabetes were significantly associated with lower FA or higher MD (p < 0.05). When aggregating heavy alcohol consumption, hypertension, and diabetes together with current smoking, having an increasing number of these 4 factors concurrently was associated with decreasing FA and increasing MD (p(trend) < 0.01), independent of white matter hyperintensities. Vascular risk factors and APOE epsilon 4 allele interacted to negatively affect white matter microstructure; having multiple (2) vascular factors was particularly detrimental to white matter integrity among APOE epsilon 4 carriers. Lower tertile of FA and upper tertile of MD were significantly associated with faster Mini-Mental State Examination decline.Conclusions:Vascular risk factors are associated with reduced white matter integrity among older adults, which subsequently predicted faster cognitive decline. The detrimental effects of vascular risk factors on white matter microstructure were exacerbated among APOE epsilon 4 carriers.
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