| 1. |
- Vikner, Tomas, et al.
(författare)
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5-year associations among cerebral arterial pulsatility, perivascular space dilation, and white matter lesions
- 2022
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Ingår i: Annals of Neurology. - : John Wiley & Sons. - 0364-5134 .- 1531-8249. ; 92:5, s. 871-881
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Tidskriftsartikel (refereegranskat)abstract
- Objective: High cerebral arterial pulsatility index (PI), white matter lesions (WMLs), enlarged perivascular spaces (PVSs), and lacunar infarcts are common findings in the elderly population, and considered indicators of small vessel disease (SVD). Here, we investigate the potential temporal ordering among these variables, with emphasis on determining whether high PI is an early or delayed manifestation of SVD.Methods: In a population-based cohort, 4D flow MRI data for cerebral arterial pulsatility was collected for 159 participants at baseline (age 64–68), and for 122 participants at follow-up 5 years later. Structural MRI was used for WML and PVS segmentation, and lacune identification. Linear mixed-effects (LME) models were used to model longitudinal changes testing for pairwise associations, and latent change score (LCS) models to model multiple relationships among variables simultaneously.Results: Longitudinal 5-year increases were found for WML, PVS, and PI. Cerebral arterial PI at baseline did not predict changes in WML or PVS volume. However, WML and PVS volume at baseline predicted 5-year increases in PI. This was shown for PI increases in relation to baseline WML and PVS volumes using LME models (R (Formula presented.) 0.24; p < 0.02 and R (Formula presented.) 0.23; p < 0.03, respectively) and LCS models ((Formula presented.) = 0.28; p = 0.015 and (Formula presented.) = 0.28; p = 0.009, respectively). Lacunes at baseline were unrelated to PI.Interpretation: In healthy older adults, indicators of SVD are related in a lead–lag fashion, in which the expression of WML and PVS precedes increases in cerebral arterial PI. Hence, we propose that elevated PI is a relatively late manifestation, rather than a risk factor, for cerebral SVD.
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| 2. |
- Johansson, Jarkko, et al.
(författare)
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Longitudinal evidence that reduced hemispheric encoding/retrieval asymmetry predicts episodic-memory impairment in aging
- 2020
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Ingår i: Neuropsychologia. - : Elsevier BV. - 0028-3932 .- 1873-3514. ; 137
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Tidskriftsartikel (refereegranskat)abstract
- The HERA (Hemispheric Encoding/Retrieval Asymmetry) model captures hemispheric lateralization of prefrontal cortex (PFC) brain activity during memory encoding and retrieval. Reduced HERA has been observed in cross-sectional aging studies, but there is no longitudinal evidence, to our knowledge, on age-related changes in HERA and whether maintained or reduced HERA relates to well-preserved memory functioning. In the present study we set out to explore HERA in a longitudinal neuroimaging sample from the Betula study [3 Waves over 10 years; Wave-1: n = 363, W2: n = 227, W3: n = 101]. We used fMRI data from a face-name paired-associates task to derive a HERA index. In support of the HERA model, the mean HERA index was positive across the three imaging waves. The longitudinal age-HERA relationship was highly significant (p < 10(-11)), with a HERA decline occurring after age 60. The age-related HERA decline was associated with episodic memory decline (p < 0.05). Taken together, the findings provide large-scale support for the HERA model, and suggest that reduced HERA in the PFC reflects pathological memory aging possibly related to impaired ability to bias mnemonic processing according to the appropriate encoding or retrieval state.
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| 3. |
- Johansson, Jarkko, et al.
(författare)
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Model of brain maintenance reveals specific change-change association between medial-temporal lobe integrity and episodic memory
- 2022
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Ingår i: Aging Brain. - : Elsevier. - 2589-9589. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Brain maintenance has been identified as a major determinant of successful memory aging. However, the extent to which brain maintenance in support of successful memory aging is specific to memory-related brain regions or forms part of a brain-wide phenomenon is unresolved. Here, we used longitudinal brain-wide gray matter MRI volumes in 262 healthy participants aged 55 to 80 years at baseline to investigate separable dimensions of brain atrophy, and explored the links of these dimensions to different dimensions of cognitive change. We statistically adjusted for common causes of change in both brain and cognition to reveal a potentially unique signature of brain maintenance related to successful memory aging. Critically, medial temporal lobe (MTL)/hippocampal change and episodic memory change were characterized by unique, residual variance beyond general factors of change in brain and cognition, and a reliable association between these two residualized variables was established (r = 0.36, p < 0.01). The present study is the first to provide solid evidence for a specific association between changes in (MTL)/hippocampus and episodic memory in normal human aging. We conclude that hippocampus-specific brain maintenance relates to the specific preservation of episodic memory in old age, in line with the notion that brain maintenance operates at both general and domain-specific levels.
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| 4. |
- Nyberg, Lars, 1966-, et al.
(författare)
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Forecasting memory function in aging : pattern-completion ability and hippocampal activity relate to visuospatial functioning over 25 years
- 2020
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Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 94, s. 217-226
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Tidskriftsartikel (refereegranskat)abstract
- Heterogeneity in episodic memory functioning in aging was assessed with a pattern-completion functional magnetic resonance imaging task that required reactivation of well-consolidated face-name memory traces from fragmented (partial) or morphed (noisy) face cues. About half of the examined individuals (N = 101) showed impaired (chance) performance on fragmented faces despite intact performance on complete and morphed faces, and they did not show a pattern-completion response in hippocampus or the examined subfields (CA1, CA23, DGCA4). This apparent pattern-completion deficit could not be explained by differential hippocampal atrophy. Instead, the impaired group displayed lower cortical volumes, accelerated reduction in mini-mental state examination scores, and lower general cognitive function as defined by longitudinal measures of visuospatial functioning and speed-of-processing. In the full sample, inter-individual differences in visuospatial functioning predicted performance on fragmented faces and hippocampal CA23 subfield activity over 25 years. These findings suggest that visuospatial functioning in middle age can forecast pattern-completion deficits in aging.
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| 5. |
- Nyberg, Lars, 1966-, et al.
(författare)
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Frontal Contribution to Hippocampal Hyperactivity During Memory Encoding in Aging
- 2019
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Ingår i: Frontiers in Molecular Neuroscience. - : Frontiers Media S.A.. - 1662-5099. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Hippocampal hypo- as well as hyper-activation have been reported during memory encoding in older individuals. Prefrontal cortex (PFC) provides top-down state signals to the hippocampus that bias its computation during memory encoding and retrieval, and disturbed top-down signals could contribute to hippocampal hyper-activation. Here, we used >500 cross-sectional and longitudinal observations from a face-name encoding-retrieval fMRI task to examine hippocampal hypo-and hyper-activation in aging. Age-related anterior hippocampal hypo-activation was observed during memory encoding. Next, older individuals who longitudinally dropped-out were compared with those who remained in the study. Older dropouts had lower memory performance and higher dementia risk, and hyper-activated right anterior and posterior hippocampus during memory encoding. During encoding, the dropouts also activated right prefrontal regions that instead were active during retrieval in younger and older remainers. Moreover, the dropouts showed altered frontal-hippocampal functional connectivity, notably elevated right PFC to anterior hippocampus (aHC) connectivity during encoding. In the context of a general pattern of age-related anterior hippocampal hypo-activation during encoding, these findings support a top-down contribution to paradoxically high anterior hippocampal activity in older dropouts who were at elevated risk of pathology.
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| 6. |
- Nyberg, Lars, 1966-, et al.
(författare)
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Individual differences in brain aging : heterogeneity in cortico-hippocampal but not caudate atrophy rates
- 2023
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Ingår i: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 33:9, s. 5075-5081
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Tidskriftsartikel (refereegranskat)abstract
- It is well documented that some brain regions, such as association cortices, caudate, and hippocampus, are particularly prone to age-related atrophy, but it has been hypothesized that there are individual differences in atrophy profiles. Here, we document heterogeneity in regional-atrophy patterns using latent-profile analysis of 1,482 longitudinal magnetic resonance imaging observations. The results supported a 2-group solution reflecting differences in atrophy rates in cortical regions and hippocampus along with comparable caudate atrophy. The higher-atrophy group had the most marked atrophy in hippocampus and also lower episodic memory, and their normal caudate atrophy rate was accompanied by larger baseline volumes. Our findings support and refine models of heterogeneity in brain aging and suggest distinct mechanisms of atrophy in striatal versus hippocampal-cortical systems.
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| 7. |
- Davies, G., et al.
(författare)
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Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
- 2018
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
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| 8. |
- Gorbach, Tetiana, 1991-, et al.
(författare)
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A Hierarchical Bayesian Mixture Model Approach for Analysis of Resting-State Functional Brain Connectivity : An Alternative to Thresholding
- 2020
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Ingår i: Brain Connectivity. - : Mary Ann Liebert. - 2158-0014 .- 2158-0022. ; 10:5, s. 202-211
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Tidskriftsartikel (refereegranskat)abstract
- This article proposes a Bayesian hierarchical mixture model to analyze functional brain connectivity where mixture components represent "positively connected" and "non-connected" brain regions. Such an approach provides a data-informed separation of reliable and spurious connections in contrast to arbitrary thresholding of a connectivity matrix. The hierarchical structure of the model allows simultaneous inferences for the entire population as well as for each individual subject. A new connectivity measure, the posterior probability of a given pair of brain regions of a specific subject to be connected given the observed correlation of regions' activity, can be computed from the model fit. The posterior probability reflects the connectivity of a pair of regions relative to the overall connectivity pattern of an individual, which is overlooked in traditional correlation analyses. This article demonstrates that using the posterior probability might diminish the effect of spurious connections on inferences, which is present when a correlation is used as a connectivity measure. In addition, simulation analyses reveal that the sparsification of the connectivity matrix using the posterior probabilities might outperform the absolute thresholding based on correlations. Therefore, we suggest that posterior probability might be a beneficial measure of connectivity compared with the correlation. The applicability of the introduced method is exemplified by a study of functional resting-state brain connectivity in older adults.
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