| 1. |
- Becker, Nina, et al.
(författare)
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Differential Effects of Encoding Instructions on Brain Activity Patterns of Item and Associative Memory
- 2017
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Ingår i: Journal of cognitive neuroscience. - : MIT Press - Journals. - 0898-929X .- 1530-8898. ; 29:3, s. 545-559
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Tidskriftsartikel (refereegranskat)abstract
- Evidence from neuroimaging studies suggests a critical role of hippocampus and inferior frontal gyrus (IFG) in associative relative to item encoding. Here, we investigated similarities and differences in functional brain correlates for associative and item memory as a function of encoding instruction. Participants received either incidental (animacy judgments) or intentional encoding instructions while fMRI was employed during the encoding of associations and items. In a subsequent recognition task, memory performance of participants receiving intentional encoding instructions was higher compared with those receiving incidental encoding instructions. Furthermore, participants remembered more items than associations, regardless of encoding instruction. Greater brain activation in the left anterior hippocampus was observed for intentionally compared with incidentally encoded associations, although activity in this region was not modulated by the type of instruction for encoded items. Furthermore, greater activity in the left anterior hippocampus and left IFG was observed during intentional associative compared with item encoding. The same regions were related to subsequent memory of intentionally encoded associations and were thus task relevant. Similarly, connectivity of the anterior hippocampus to the right superior temporal lobe and IFG was uniquely linked to subsequent memory of intentionally encoded associations. Our study demonstrates the differential involvement of anterior hippocampus in intentional relative to incidental associative encoding. This finding likely reflects that the intent to remember triggers a specific binding process accomplished by this region.
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| 2. |
- Becker, Nina, et al.
(författare)
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Structural brain correlates of associative memory in older adults
- 2015
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 118, s. 146-153
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Tidskriftsartikel (refereegranskat)abstract
- Associative memory involves binding two or more items into a coherent memory episode. Relative to memory for single items, associative memory declines greatly in aging. However, older individuals vary substantially in their ability to memorize associative information. Although functional studies link associative memory to the medial temporal lobe (MTL) and prefrontal cortex (PFC), little is known about how volumetric differences in MTL and PFC might contribute to individual differences in associative memory. We investigated regional gray-matter volumes related to individual differences in associative memory in a sample of healthy older adults (n = 54; age = 60 years). To differentiate item from associative memory, participants intentionally learned face-scene picture pairs before performing a recognition task that included single faces, scenes, and face-scene pairs. Gray-matter volumes were analyzed using voxel-based morphometry region-of-interest (ROI) analyses. To examine volumetric differences specifically for associative memory, item memory was controlled for in the analyses. Behavioral results revealed large variability in associative memory that mainly originated from differences in false-alarm rates. Moreover, associative memory was independent of individuals' ability to remember single items. Older adults with better associative memory showed larger gray-matter volumes primarily in regions of the left and right lateral PFC. These findings provide evidence for the importance of PFC in intentional learning of associations, likely because of its involvement in organizational and strategic processes that distinguish older adults with good from those with poor associative memory.
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| 3. |
- 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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| 4. |
- Brehmer, Yvonne, et al.
(författare)
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Plasticity of brain and cognition in older adults
- 2014
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Ingår i: Psychological Research. - : Springer Science and Business Media LLC. - 0340-0727 .- 1430-2772. ; 78:6, s. 790-802
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Forskningsöversikt (refereegranskat)abstract
- Aging is typically related to changes in brain and cognition, but the aging process is heterogeneous and differs between individuals. Recent research has started investigating the influence of cognitive and physical training on cognitive performance, functional brain activity, and brain structure in old age. The functional relevance of neural changes and the interactions among these changes following interventions is still a matter of debate. Here we selectively review research on structural and functional brain correlates of training-induced performance changes in healthy older adults and present exemplary longitudinal intervention studies sorted by the type of training applied (i.e., strategy-based training, process-specific training, and physical exercise). Although many training studies have been conducted recently, within each task domain, the number of studies that used comparable methods and techniques to assess behavioral and neural changes is limited. We suggest that future studies should include a multimodal approach to enhance the understanding of the relation between different levels of brain changes in aging and those changes that result from training. Investigating inter-individual differences in intervention-induced behavioral and neuronal changes would provide more information about who would benefit from a specific intervention and why. In addition, a more systematic examination of the time course of training-related structural and functional changes would improve the current level of knowledge about how learning is implemented in the brain and facilitate our understanding of contradictory results.
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| 5. |
- Ding, Mozhu, et al.
(författare)
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Cerebral Small Vessel Disease Associated With Atrial Fibrillation Among Older Adults : A Population-Based Study.
- 2021
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Ingår i: Stroke. - : American Heart Association. - 0039-2499 .- 1524-4628. ; 52:8, s. 2685-2689
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Cerebral small vessel disease, as a potential mechanism underlying the association between atrial fibrillation (AF) and dementia, remains poorly investigated. In this cohort study, we sought to examine the association between AF and cerebral small vessel disease markers among older adults.METHODS: Data on 336 participants (age ≥60 years, mean 70.2 years; 60.2% women) free of dementia, disability, and cerebral infarcts were derived from the population-based Swedish National Study on Aging and Care in Kungsholmen. Structural brain magnetic resonance imaging examinations were performed at baseline (2001-2004) and follow-ups (2004-2007 and 2007-2010). Magnetic resonance imaging markers of cerebral small vessel disease included perivascular spaces, lacunes, and volumes of white matter hyperintensities, lateral ventricles, and total brain tissue. AF was assessed at baseline and follow-ups through clinical examinations, electrocardiogram, and medical records. Data were analyzed using linear mixed-effects models.RESULTS: At baseline, 18 persons (5.4%) were identified to have prevalent AF and 17 (5.6%) developed incident AF over the 6-year follow-up. After multivariable adjustment, AF was significantly associated with a faster annual increase in white matter hyperintensities volume (β coefficient=0.45 [95% CI, 0.04-0.86]) and lateral ventricular volume (0.58 [0.13-1.02]). There was no significant association of AF with annual changes in perivascular spaces number (β coefficient=0.53 [95% CI, -0.27 to 1.34]) or lacune number (-0.01 [-0.07 to 0.05]).CONCLUSIONS: Independent of cerebral infarcts, AF is associated with accelerated progression of white matter lesions and ventricular enlargement among older adults.
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| 6. |
- Dintica, Christina S., et al.
(författare)
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Tooth loss is associated with accelerated cognitive decline and volumetric brain differences : a population-based study
- 2018
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 67, s. 23-30
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Tidskriftsartikel (refereegranskat)abstract
- Tooth loss has been related to cognitive impairment; however, its relation to structural brain differences in humans is unknown. Dementia-free participants (n = 2715) of age >= 60 years were followed up for up to 9 years. A subsample (n = 394) underwent magnetic resonance imaging at baseline. Information on tooth loss was collected at baseline, and cognitive function was assessed using the Mini-Mental State Examination at baseline and at follow-ups. Data were analyzed using linear mixed effects models and linear regression models. At baseline, 404 (14.9%) participants had partial tooth loss, and 206 (7.6%) had complete tooth loss. Tooth loss was significantly associated with a steeper cognitive decline (beta: -0.18, 95% confidence interval [CI]: -0.24 to -0.11) and remained significant after adjusting for or stratifying by potential confounders. In cross-sectional analyses, persons with complete or partial tooth loss had significantly lower total brain volume (beta: -28.89, 95% CI: -49.33 to -8.45) and gray matter volume (beta: -22.60, 95% CI: -38.26 to -6.94). Thus, tooth loss may be a risk factor for accelerated cognitive aging.
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| 7. |
- Dong, Yi, et al.
(författare)
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Anosmia, mild cognitive impairment, and biomarkers of brain aging in older adults
- 2023
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:2, s. 589-601
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Tidskriftsartikel (refereegranskat)abstract
- Olfactory impairment is a potential marker for prodromal dementia, but the underlying mechanisms are poorly understood. This population-based study included 4214 dementia-free participants (age ≥65 years). Olfaction was assessed using the 16-item Sniffin’ Sticks identification test. In the subsamples, we measured plasma amyloid beta (Aβ)40, Aβ42, total tau, and neurofilament light chain (NfL; n = 1054); and quantified hippocampal, entorhinal cortex, and white matter hyperintensity (WMH) volumes, and Alzheimer's disease (AD)-signature cortical thickness (n = 917). Data were analyzed with logistic and linear regression models. In the total sample, mild cognitive impairment (MCI) was diagnosed in 1102 persons (26.2%; amnestic MCI, n = 931; non-amnestic MCI, n = 171). Olfactory impairment was significantly associated with increased likelihoods of MCI, amnestic MCI, and non-amnestic MCI. In the subsamples, anosmia was significantly associated with higher plasma total tau and NfL concentrations, smaller hippocampal and entorhinal cortex volumes, and greater WMH volume, and marginally with lower AD-signature cortical thickness. These results suggest that cerebral neurodegenerative and microvascular lesions are common neuropathologies linking anosmia with MCI in older adults.
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| 8. |
- Eriksson, Johan, et al.
(författare)
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Rewiring the brain with repeated retrieval : A parametric fMRI study of the testing effect
- 2011
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Ingår i: Neuroscience Letters. - Amsterdam : Elsevier BV. - 0304-3940 .- 1872-7972. ; 505:1, s. 36-40
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Tidskriftsartikel (refereegranskat)abstract
- The "testing effect" refers to the beneficial effects on memory performance from being tested, a phenomenon of potentially substantial implications in educational settings. While the effect itself is firmly established in previous research, little is known of related brain changes. Here we used fMRI and a parametric design to show that repeated successful retrieval during a memory acquisition phase leads to higher brain activity in the anterior cingulate cortex (ACC) at a subsequent test phase. The extent of ACC activity increase correlated across individuals with memory performance 5 months later. In relation to recent research that associates the ACC with memory consolidation processes, the present results suggest that the testing effect may operate at the systems level by enhancing consolidation of memory representations.
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| 9. |
- Ferencz, Beata, et al.
(författare)
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Promising Genetic Biomarkers of Preclinical Alzheimer's Disease : The Influence of APOE and TOMM40 on Brain Integrity
- 2012
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Ingår i: International Journal of Alzheimer's Disease. - : Hindawi Limited. - 2090-8024 .- 2090-0252. ; 2012
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Forskningsöversikt (refereegranskat)abstract
- Finding biomarkers constitutes a crucial step for early detection of Alzheimer's disease (AD). Brain imaging techniques have revealed structural alterations in the brain that may be phenotypic in preclinical AD. The most prominent polymorphism that has been associated with AD and related neural changes is the Apolipoprotein E (APOE) ε4. The translocase of outer mitochondrial membrane 40 (TOMM40), which is in linkage disequilibrium with APOE, has received increasing attention as a promising gene in AD. TOMM40 also impacts brain areas vulnerable in AD, by downstream apoptotic processes that forego extracellular amyloid beta aggregation. The present paper aims to extend on the mitochondrial influence in AD pathogenesis and we propose a TOMM40-induced disconnection of the medial temporal lobe. Finally, we discuss the possibility of mitochondrial dysfunction being the earliest pathophysiological event in AD, which indeed is supported by recent findings.
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| 10. |
- Ferencz, Beata, et al.
(författare)
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The Benefits of Staying Active in Old Age : Physical Activity Counteracts the Negative Influence of PICALM, BIN1, and CLU Risk Alleles on Episodic Memory Functioning
- 2014
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Ingår i: Psychology and Aging. - : American Psychological Association (APA). - 0882-7974 .- 1939-1498. ; 29:2, s. 440-449
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Tidskriftsartikel (refereegranskat)abstract
- PICALM, BIN1, CLU, and APOE are top candidate genes for Alzheimer's disease, and they influence episodic memory performance in old age. Physical activity, however, has been shown to protect against age-related decline and counteract genetic influences on cognition. The aims of this study were to assess whether (a) a genetic risk constellation of PICALM, BIN1, and CLU polymorphisms influences cognitive performance in old age; and (b) if physical activity moderates this effect. Data from the SNAC-K population-based study were used, including 2,480 individuals (age range = 60 to 100 years) free of dementia at baseline and at 3- to 6-year follow-ups. Tasks assessing episodic memory, perceptual speed, knowledge, and verbal fluency were administered. Physical activity was measured using self-reports. Individuals who had engaged in frequent health-or fitness-enhancing activities within the past year were compared with those who were inactive. Genetic risk scores were computed based on an integration of risk alleles for PICALM (rs3851179 G allele, rs541458 T allele), BIN1 (rs744373 G allele), and CLU (rs11136000 T allele). High genetic risk was associated with reduced episodic memory performance, controlling for age, education, vascular risk factors, chronic diseases, activities of daily living, and APOE gene status. Critically, physical activity attenuated the effects of genetic risk on episodic memory. Our findings suggest that participants with high genetic risk who maintain a physically active lifestyle show selective benefits in episodic memory performance.
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| 11. |
- Ferencz, Beata, et al.
(författare)
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The influence of APOE and TOMM40 polymorphisms on hippocampal volume and episodic memory in old age
- 2013
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Ingår i: Frontiers in Human Neuroscience. - : Frontiers Media SA. - 1662-5161. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial dysfunction is implicated in neurodegenerative disorders, such as Alzheimer's disease (AD). Translocase of outer mitochondrial membrane 40 (TOMM40) may be influential in this regard by influencing mitochondrial neurotoxicity. Little is known about the influence of the TOMM40 gene on hippocampal (HC) volume and episodic memory (EM), particularly in healthy older adults. Thus, we sought to discern the influence of TOMM40 single nucleotide polymorphisms (SNPs), which have previously been associated with medial temporal lobe integrity (rs11556505 and rs2075650), on HC volume and EM. The study sample consisted of individuals from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) who were free of dementia and known neurological disorders, and 6087 years of age (n = 424). EM was measured by using a 16-item word list with a 2-min free recall period and delineation of the HC was performed manually. The influence of Apolipoprotein E (APOE) and TOMM40 was assessed by 2 x 2 ANOVAs and partial correlations. There was no effect of APOE and TOMM40 on EM performance and HC volume. However, partial correlations revealed that HC volume was positively associated with free recall performance (r = 0.21, p < 0.01, r(2) = 0.04). When further stratified for TOMM40, the observed association between HC volume and free recall in APOE epsilon 4 carriers was present in combination with TOMM40 rs11556505 any T (r = 0.28, p < 0.01, R-2 = 0.08) and rs2075650 any G (r = 0.28, p < 0.01, R-2 = 0.08) risk alleles. This pattern might reflect higher reliance on HC volume for adequate EM performance among APOE epsilon 4 carriers with additional TOMM40 risk alleles suggesting that the TOMM40 gene cannot merely be considered a marker of APOE genotype. Nevertheless, neither APOE nor TOMM40 influenced HC volume or EM in this population-based sample of cognitively intact individuals over the age of 60.
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| 12. |
- Ferreira, Daniel, et al.
(författare)
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The interactive effect of demographic and clinical factors on hippocampal volume : A multicohort study on 1958 cognitively normal individuals
- 2017
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Ingår i: Hippocampus. - : Wiley. - 1050-9631 .- 1098-1063. ; 27:6, s. 653-667
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease is characterized by hippocampal atrophy. Other factors also influence the hippocampal volume, but their interactive effect has not been investigated before in cognitively healthy individuals. The aim of this study is to evaluate the interactive effect of key demographic and clinical factors on hippocampal volume, in contrast to previous studies frequently investigating these factors in a separate manner. Also, to investigate how comparable the control groups from ADNI, AIBL, and AddNeuroMed are with five population-based cohorts. In this study, 1958 participants were included (100 AddNeuroMed, 226 ADNI, 155 AIBL, 59 BRC, 295 GENIC, 279 BioFiNDER, 398 PIVUS, and 446 SNAC-K). ANOVA and random forest were used for testing between-cohort differences in demographic-clinical variables. Multiple regression was used to study the influence of demographic-clinical variables on hippocampal volume. ANCOVA was used to analyze whether between-cohort differences in demographic-clinical variables explained between-cohort differences in hippocampal volume. Age and global brain atrophy were the most important variables in explaining variability in hippocampal volume. These variables were not only important themselves but also in interaction with gender, education, MMSE, and total intracranial volume. AddNeuroMed, ADNI, and AIBL differed from the population-based cohorts in several demographic-clinical variables that had a significant effect on hippocampal volume. Variability in hippocampal volume in individuals with normal cognition is high. Differences that previously tended to be related to disease mechanisms could also be partly explained by demographic and clinical factors independent from the disease. Furthermore, cognitively normal individuals especially from ADNI and AIBL are not representative of the general population. These findings may have important implications for future research and clinical trials, translating imaging biomarkers to the general population, and validating current diagnostic criteria for Alzheimer's disease and predementia stages.
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| 13. |
- Gallo, Federico, et al.
(författare)
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Cognitive Trajectories and Dementia Risk : A Comparison of Two Cognitive Reserve Measures.
- 2021
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media S.A.. - 1663-4365. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: Cognitive reserve (CR) is meant to account for the mismatch between brain damage and cognitive decline or dementia. Generally, CR has been operationalized using proxy variables indicating exposure to enriching activities (activity-based CR). An alternative approach defines CR as residual variance in cognition, not explained by the brain status (residual-based CR). The aim of this study is to compare activity-based and residual-based CR measures in their association with cognitive trajectories and dementia. Furthermore, we seek to examine if the two measures modify the impact of brain integrity on cognitive trajectories and if they predict dementia incidence independent of brain status.Methods: We used data on 430 older adults aged 60+ from the Swedish National Study on Aging and Care in Kungsholmen, followed for 12 years. Residual-based reserve was computed from a regression predicting episodic memory with a brain-integrity index incorporating six structural neuroimaging markers (white-matter hyperintensities volume, whole-brain gray matter volume, hippocampal volume, lateral ventricular volume, lacunes, and perivascular spaces), age, and sex. Activity-based reserve incorporated education, work complexity, social network, and leisure activities. Cognition was assessed with a composite of perceptual speed, semantic memory, letter-, and category fluency. Dementia was clinically diagnosed in accordance with DSM-IV criteria. Linear mixed models were used for cognitive change analyses. Interactions tested if reserve measures modified the association between brain-integrity and cognitive change. Cox proportional hazard models, adjusted for brain-integrity index, assessed dementia risk.Results: Both reserve measures were associated with cognitive trajectories [β × time (top tertile, ref.: bottom tertile) = 0.013; 95% CI: -0.126, -0.004 (residual-based) and 0.011; 95% CI: -0.001, 0.024, (activity-based)]. Residual-based, but not activity-based reserve mitigated the impact of brain integrity on cognitive decline [β (top tertile × time × brain integrity) = -0.021; 95% CI: -0.043, 0.001] and predicted 12-year dementia incidence, after accounting for the brain-integrity status [HR (top tertile) = 0.23; 95% CI: 0.09, 0.58].Interpretation: The operationalization of reserve based on residual cognitive performance may represent a more direct measure of CR than an activity-based approach. Ultimately, the two models of CR serve largely different aims. Accounting for brain integrity is essential in any model of reserve.
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| 14. |
- Garzon, Benjamin, et al.
(författare)
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Automated segmentation of midbrain structures with high iron content
- 2018
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 170, s. 199-209
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Forskningsöversikt (refereegranskat)abstract
- The substantia nigra (SN), the subthalamic nucleus (STN), and the red nucleus (RN) are midbrain structures of ample interest in many neuroimaging studies, which may benefit from the availability of automated segmentation methods. The high iron content of these structures awards them high contrast in quantitative susceptibility mapping (QSM) images. We present a novel segmentation method that leverages the information of these images to produce automated segmentations of the SN, STN, and RN. The algorithm builds a map of spatial priors for the structures by non-linearly registering a set of manually-traced training labels to the midbrain. The priors are used to inform a Gaussian mixture model of the image intensities, with smoothness constraints imposed to ensure anatomical plausibility. The method was validated on manual segmentations from a sample of 40 healthy younger and older subjects. Average Dice scores were 0.81 (0.05) for the SN, 0.66 (0.14) for the STN and 0.88 (0.04) for the RN in the left hemisphere, and similar values were obtained for the right hemisphere. In all structures, volumes of manual and automatically obtained segmentations were significantly correlated. The algorithm showed lower accuracy on R-2* and T-2-weighted Fluid Attenuated Inversion Recovery (FLAIR) images, which are also sensitive to iron content. To illustrate an application of the method, we show that the automated segmentations were comparable to the manual ones regarding detection of age-related differences to putative iron content.
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| 15. |
- Garzón, Benjamin, et al.
(författare)
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Can transverse relaxation rates in deep gray matter be approximated from functional and T-2-weighted FLAIR scans for relative brain iron quantification?
- 2017
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Ingår i: Magnetic Resonance Imaging. - : Elsevier BV. - 0730-725X .- 1873-5894. ; 40, s. 75-82
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Tidskriftsartikel (refereegranskat)abstract
- Alterations in iron concentration in certain deep gray matter regions are known to occur in aging and several clinical conditions. In vivo measurements of R-2* transverse relaxation rates and quantitative susceptibility mapping (QSM) have been shown to be strongly correlated with iron concentration in tissue, but their calculation requires the acquisition of a multi-echo gradient recalled echo sequence (MGRE). In the current study, we examined the feasibility of approximating R-2* rates using metrics derived from fMRI-EPI and T-2-weighted FLAIR images, which are widely available. In a sample of 40 healthy subjects, we obtained these metrics (v(EPI) and v(FLAIR)), as well as R-2* rates and QSM estimates, and found significant correlations between v(EPI) and v(FLAIR) and R-2* rates in several subcortical gray matter regions known to accumulate iron, but not in a control corticospinal white matter region. These relationships were preserved after referencing v(EPI) and v(FLAIR) with respect to the values in the control region. Effect sizes (above 0.5 for some of the regions, particularly the largest ones) were calculated and put in relation to those of the correlation between QSM and R-2* rates. We propose that the metrics described here may be applied, possibly in a retrospective fashion, to analyze datasets with available EPI or T-2-weighted FLAIR scans (and lacking a MGRE sequence), to devise new hypotheses regarding links between iron concentration in brain tissue and other variables of interest.
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| 16. |
- Gerritsen, L., et al.
(författare)
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The influence of negative life events on hippocampal and amygdala volumes in old age : a life-course perspective
- 2014
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Ingår i: Psychological Medicine. - 0033-2917 .- 1469-8978. ; 45:6, s. 1219-1228
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Psychosocial stress has been related to changes in the nervous system, with both adaptive and maladaptive consequences. The aim of this study was to examine the relationship of negative events experienced throughout the entire lifespan and hippocampal and amygdala volumes in older adults.METHOD: In 466 non-demented old adults (age range 60-96 years, 58% female), hippocampal and amygdala volumes were segmented using Freesurfer. Negative life events and the age at which these events occurred were assessed by means of a structured questionnaire. Using generalized linear models, hippocampal and amygdala volumes were estimated with life events as independent variables. The statistical analyses were adjusted for age, gender, intracranial volume, lifestyle factors, cardiovascular risk factors, depressive symptoms, and cognitive functioning.RESULTS: Total number of negative life events and of late-life events, but not of early-life, early-adulthood, or middle-adulthood events, was related to larger amygdala volume. There were interactions of early-life events with age and gender. Participants who reported two or more early-life events had significantly smaller amygdala and hippocampal volumes with increasing age. Furthermore, smaller hippocampal volume was found in men who reported two or more early-life events, but not in women.CONCLUSIONS: These results suggest that the effect of negative life events on the brain depends on the time when the events occurred, with the strongest effects observed during the critical time periods of early and late life.
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| 17. |
- Gonneaud, Julie, et al.
(författare)
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Distinct and shared cognitive functions mediate event- and time-based prospective memory impairment in normal ageing
- 2011
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Ingår i: Memory. - : Informa UK Limited. - 0965-8211 .- 1464-0686. ; 19:4, s. 360-377
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Tidskriftsartikel (refereegranskat)abstract
- Prospective memory (PM) is the ability to remember to perform an action at a specific point in the future. Regarded as multidimensional, PM involves several cognitive functions that are known to be impaired in normal ageing. In the present study we set out to investigate the cognitive correlates of PM impairment in normal ageing. Manipulating cognitive load, we assessed event- and time-based PM, as well as several cognitive functions, including executive functions, working memory, and retrospective episodic memory, in healthy participants covering the entire adulthood. We found that normal ageing was characterised by PM decline in all conditions and that event-based PM was more sensitive to the effects of ageing than time-based PM. Whatever the conditions, PM was linked to inhibition and processing speed. However, while event-based PM was mainly mediated by binding and retrospective memory processes, time-based PM was mainly related to inhibition. The only distinction between high- and low-load PM cognitive correlates lies in an additional, but marginal, correlation between updating and the high-load PM condition. The association of distinct cognitive functions, as well as shared mechanisms with event- and time-based PM, confirm that each type of PM relies on a different set of processes.
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| 18. |
- Grande, Giulia, et al.
(författare)
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Brain Changes and Fast Cognitive and Motor Decline in Older Adults
- 2022
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 78:2, s. 326-332
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Tidskriftsartikel (refereegranskat)abstract
- Background: To identify brain magnetic resonance imaging (MRI) signatures characterizing people with different patterns of decline in cognition and motor function.Methods: In the Swedish National Study on Aging and Care in Kungsholmen, Stockholm, 385 participants had available repeated brain MRI examinations, where markers of brain volumes and white matter integrity were assessed. The speed of cognitive and motor decline was estimated as the rate of a Mini-Mental State Examination and gait speed decline over 12 years (linear mixed models), and further dichotomized into the upper (25% fastest rate of decline) versus the lower quartiles. Participants were grouped in slow/no decliners (reference), isolated motor decliners, isolated cognitive decliners, and cognitive and motor decliners. We estimated the associations between changes in brain markers (linear mixed models) and baseline diffusion tensor imaging measures (linear regression model) and the 4 decline patterns.Results: Individuals with concurrent cognitive and motor decline (n = 51) experienced the greatest loss in the total brain (β: −12.3; 95% confidence interval [CI]: −18.2; −6.38) and hippocampal (β: −0.25; 95% CI: −0.34; −0.16) volumes, the steepest accumulation of white matter hyperintensities (β: 1.61; 95% CI: 0.54; 2.68), and the greatest ventricular enlargement (β: 2.07; 95% CI: 0.67; 3.47). Compared to the reference, those only experiencing cognitive decline presented with steeper hippocampal volume loss, whereas those exhibiting only motor decline displayed a greater white matter hyperintensities burden. Lower microstructural white matter integrity was associated with concurrent cognitive and motor decline.Conclusion: Concurrent cognitive and motor decline is accompanied by rapidly evolving and complex brain pathology involving both gray and white matter. Isolated cognitive and motor declines seem to exhibit brain damage with different qualitative features.
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| 19. |
- Gustavsson, Jonatan, et al.
(författare)
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Contributions of the Catechol-O-Methyltransferase Val158Met Polymorphism to Changes in Brain Iron Across Adulthood and Their Relationships to Working Memory
- 2022
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Ingår i: Frontiers in Human Neuroscience. - : Frontiers Media SA. - 1662-5161. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Ageing is associated with excessive free brain iron, which may induce oxidative stress and neuroinflammation, likely causing cognitive deficits. Lack of dopamine may be a factor behind the increase of iron with advancing age, as it has an important role in cellular iron homoeostasis. We investigated the effect of COMT Val 158 Met (rs4680), a polymorphism crucial for dopamine degradation and proxy for endogenous dopamine, on iron accumulation and working memory in a longitudinal lifespan sample (n = 208, age 20-79 at baseline, mean follow-up time = 2.75 years) using structural equation modelling. Approximation of iron content was assessed using quantitative susceptibility mapping in striatum and dorsolateral prefrontal cortex (DLPFC). Iron accumulated in both striatum and DLPFC during the follow-up period. Greater iron accumulation in DLPFC was associated with more deleterious change in working memory. Older (age 50-79) Val homozygotes (with presumably lower endogenous dopamine) accumulated more iron than older Met carriers in both striatum and DLPFC, no such differences were observed among younger adults (age 20-49). In conclusion, individual differences in genetic predisposition related to low dopamine levels increase iron accumulation, which in turn may trigger deleterious change in working memory. Future studies are needed to better understand how dopamine may modulate iron accumulation across the human lifespan.
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| 20. |
- 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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| 21. |
- Heiland, Emerald G, et al.
(författare)
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Cerebral small vessel disease, cardiovascular risk factors, and future walking speed in old age : a population-based cohort study.
- 2021
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Ingår i: BMC Neurology. - : BioMed Central. - 1471-2377. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The purpose of this study was to examine the associations between combined and individual cerebral small vessel disease (cSVD) markers on future walking speed over 9 years; and to explore whether these associations varied by the presence of cardiovascular risk factors (CRFs).METHODS: This population-based cohort study included 331 adults, aged ≥60 years, without limitation in walking speed (≥0.8 m/s). At baseline, cSVD markers, including white matter hyperintensities (WMH), lacunes, and perivascular spaces (PVS), were assessed on magnetic resonance imaging. The modifiable CRFs (physical inactivity, heavy alcohol consumption, smoking, hypertension, high total cholesterol, diabetes, and overweight/obese) were combined into a score. The association between baseline cSVD markers and the decline in walking speed was examined using linear mixed-effects models, whereas Cox proportional hazards models were used to estimate the association with walking speed limitation (defined as < 0.8 m/s) over the follow-up.RESULTS: Over the follow-up period, 76 (23.0%) persons developed walking speed limitation. Participants in the highest tertile of the combined cSVD marker score had a hazard ratio (HR) of 3.78 (95% confidence interval [CI] 1.70-8.45) for walking speed limitation compared with people in the lowest score tertile, even after adjusting for socio-demographics, CRFs, cognitive function, and chronic conditions. When investigating the cSVD markers individually, having the highest burden of WMH was associated with a significantly faster decline in walking speed (β coefficient - 0.020; 95% CI -0.035-0.004) and a greater HR of walking speed limitation (HR 2.78; 95% CI 1.31-5.89) compared with having the lowest WMH burden. Similar results were obtained for the highest tertile of PVS (HR 2.13; 95% CI 1.04-4.36). Lacunes were associated with walking speed limitation, but only in men. Having ≥4 CRFs and high WMH volume simultaneously, showed a greater risk of walking speed limitation compared with having ≥4 CRFs and low WMH burden. CRFs did not modify the associations between lacunes or PVS and walking speed.CONCLUSIONS: Combined cSVD markers strongly predict walking speed limitation in healthy older adults, independent of cognitive function, with WMH and PVS being the strongest contributors. Improving cardiovascular health may help to mitigate the negative effects of WMH on future walking speed.
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| 22. |
- Hooshmand, Babak, et al.
(författare)
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Association of Methionine to Homocysteine Status With Brain Magnetic Resonance Imaging Measures and Risk of Dementia
- 2019
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 76:11, s. 1198-1205
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Impairment of methylation status (ie, methionine to homocysteine ratio) may be a modifiable risk factor for structural brain changes and incident dementia.OBJECTIVE To investigate the association of serum markers of methylation status and sulfur amino acids with risk of incident dementia, Alzheimer disease (AD), and the rate of total brain tissue volume loss during 6 years.DESIGN, SETTING, AND PARTICIPANTS This population-based longitudinal study was performed from March 21, 2001, to October 10, 2010, in a sample of 2570 individuals aged 60 to 102 years from the Swedish Study on Aging and Care in Kungsholmen who were dementia free at baseline and underwent comprehensive examinations and structural brain magnetic resonance imaging (MRI) on 2 to 3 occasions during 6 years. Data analysis was performed from March 1, 2018, to October 1, 2018.MAIN OUTCOMES AND MEASURES Incident dementia, AD, and the rate of total brain volume loss.RESULTS This study included 2570 individuals (mean [SD] age, 73.1 [10.4] years; 1331 [56.5%] female). The methionine to homocysteine ratio was higher in individuals who consumed vitamin supplements (median, 1.9; interquartile range [IQR], 1.5-2.6) compared with those who did not (median, 1.8; IQR, 1.3-2.3; P<.001) and increased per each quartile increase of vitamin B-12 or folate. In the multiadjusted model, an elevated baseline serum total homocysteine level was associated with an increased risk of dementia and AD during 6 years: for the highest homocysteine quartile compared with the lowest, the hazard ratios (HRs) were 1.60 (95% CI, 1.01-2.55) for dementia and 2.33 (95% CI, 1.26-4.30) for AD. In contrast, elevated concentrations of methionine were associated with a decreased risk of dementia (HR, 0.54; 95% CI, 0.36-0.81) for the highest quartile compared with the lowest. Higher values of the methionine to homocysteine ratio were significantly associated with lower risk of dementia and AD: for the fourth methionine-homocysteine quartile compared with the first quartile, the HR was 0.44 (95% CI, 0.27-0.71) for incident dementia and 0.43 (95% CI, 0.23-0.80) for AD. In the multiadjusted linear mixed models, a higher methionine to homocysteine ratio was associated with a decreased rate of total brain tissue volume loss during the study period (beta [SE] per 1-SD increase, 0.038 [0.014]; P=.007).CONCLUSIONS AND RELEVANCE The methionine to homocysteine status was associated with dementia development and structural brain changes during the 6-year study period, suggesting that a higher methionine to homocysteine ratio may be important in reducing the rate of brain atrophy and decreasing the risk of dementia in older adults.
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| 23. |
- Hooshmand, Babak, et al.
(författare)
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Association of Vitamin B-12, Folate, and Sulfur Amino Acids With Brain Magnetic Resonance Imaging Measures in Older Adults A Longitudinal Population-Based Study
- 2016
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 73:6, s. 606-613
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Vitamin B-12, folate, and sulfur amino acids may be modifiable risk factors for structural brain changes that precede clinical dementia. OBJECTIVE To investigate the association of circulating levels of vitamin B-12, red blood cell folate, and sulfur amino acids with the rate of total brain volume loss and the change in white matter hyperintensity volume as measured by fluid-attenuated inversion recovery in older adults. DESIGN, SETTING, AND PARTICIPANTS The magnetic resonance imaging subsample of the Swedish National Study on Aging and Care in Kungsholmen, a population-based longitudinal study in Stockholm, Sweden, was conducted in 501 participants aged 60 years or older who were free of dementia at baseline. A total of 299 participants underwent repeated structural brain magnetic resonance imaging scans from September 17, 2001, to December 17, 2009. MAIN OUTCOMES AND MEASURES The rate of brain tissue volume loss and the progression of total white matter hyperintensity volume. RESULTS In the multi-adjusted linear mixed models, among 501 participants (300 women [59.9%]; mean [SD] age, 70.9 [9.1] years), higher baseline vitamin B-12 and holotranscobalamin levels were associated with a decreased rate of total brain volume loss during the study period: for each increase of 1 SD, beta (SE) was 0.048 (0.013) for vitamin B-12 (P < .001) and 0.040 (0.013) for holotranscobalamin (P = .002). Increased total homocysteine levels were associated with faster rates of total brain volume loss in the whole sample (beta [SE] per 1-SD increase, -0.035 [0.015]; P = .02) and with the progression of white matter hyperintensity among participants with systolic blood pressure greater than 140mmHg (beta [SE] per 1-SD increase, 0.000019 [0.00001]; P = .047). No longitudinal associations were found for red blood cell folate and other sulfur amino acids. CONCLUSIONS AND RELEVANCE This study suggests that both vitamin B-12 and total homocysteine concentrations may be related to accelerated aging of the brain. Randomized clinical trials are needed to determine the importance of vitamin B-12 supplementation on slowing brain aging in older adults.
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| 24. |
- 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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| 25. |
- Kalpouzos, Grégoria, et al.
(författare)
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Impact of negative emotion on the neural correlates of long-term recognition in younger and older adults
- 2012
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Ingår i: Frontiers in Integrative Neuroscience. - : Frontiers Media SA. - 1662-5145. ; 6:74, s. 1-25
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Tidskriftsartikel (refereegranskat)abstract
- Some studies have suggested that the memory advantage for negative emotional information over neutral information (“negativity effect”) is reduced in aging. Besides the fact that most findings are based on immediate retrieval, the neural underpinnings of long-term emotional memory in aging have so far not been investigated. To address these issues, we assessed recognition of neutral and negative scenes after 1- and 3-week retention intervals in younger and older adults using functional magnetic resonance imaging. We further used an event-related design in order to disentangle successful, false, and true recognition. This study revealed four key findings: (1) increased retention interval induced an increased rate of false recognitions for negative scenes, canceling out the negativity effect (present for hit rates only) on discrimination in both younger and older adults; (2) in younger, but not older, adults, reduced activity of the medial temporal lobe was observed over time for neutral scenes, but not for negative scenes, where stable or increased activity was seen; (3) engagement of amygdala (AMG) was observed in older adults after a 3-week delay during successful recognition of negative scenes (hits vs. misses) in comparison with neutral scenes, which may indicate engagement of automatic processes, but engagement of ventrolateral prefrontal cortex was unrelated to AMG activity and performance; and (4) after 3 weeks, but not after 1 week, true recognition of negative scenes was characterized by more activity in left hippocampus and lateral occipito-temporal regions (hits vs. false alarms). As these regions are known to be related to consolidation mechanisms, the observed pattern may indicate the presence of delayed consolidation of true memories. Nonetheless, older adults’ low performance in discrimination of negative scenes could reflect the fact that overall, after long delays of retention, they rely more on general information rather than on perceptual detail in making recognition judgments.
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