| 1. |
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| 2. |
- Anjomshoae, Sule, 1985-, et al.
(författare)
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Explaining graph convolutional network predictions for clinicians : an explainable AI approach to Alzheimer’s disease classification
- 2024
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Ingår i: Frontiers in Artificial Intelligence. - : Frontiers Media S.A.. - 2624-8212. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Graph-based representations are becoming more common in the medical domain, where each node defines a patient, and the edges signify associations between patients, relating individuals with disease and symptoms in a node classification task. In this study, a Graph Convolutional Networks (GCN) model was utilized to capture differences in neurocognitive, genetic, and brain atrophy patterns that can predict cognitive status, ranging from Normal Cognition (NC) to Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD), on the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Elucidating model predictions is vital in medical applications to promote clinical adoption and establish physician trust. Therefore, we introduce a decomposition-based explanation method for individual patient classification.Methods: Our method involves analyzing the output variations resulting from decomposing input values, which allows us to determine the degree of impact on the prediction. Through this process, we gain insight into how each feature from various modalities, both at the individual and group levels, contributes to the diagnostic result. Given that graph data contains critical information in edges, we studied relational data by silencing all the edges of a particular class, thereby obtaining explanations at the neighborhood level.Results: Our functional evaluation showed that the explanations remain stable with minor changes in input values, specifically for edge weights exceeding 0.80. Additionally, our comparative analysis against SHAP values yielded comparable results with significantly reduced computational time. To further validate the model's explanations, we conducted a survey study with 11 domain experts. The majority (71%) of the responses confirmed the correctness of the explanations, with a rating of above six on a 10-point scale for the understandability of the explanations.Discussion: Strategies to overcome perceived limitations, such as the GCN's overreliance on demographic information, were discussed to facilitate future adoption into clinical practice and gain clinicians' trust as a diagnostic decision support system.
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| 3. |
- Degerman, Sofie, et al.
(författare)
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Maintained memory in aging is associated with young epigenetic age
- 2017
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Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 55, s. 167-171
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetic alterations during aging have been proposed to contribute to decline in physical and cognitive functions, and accelerated epigenetic aging has been associated with disease and all-cause mortality later in life. In this study, we estimated epigenetic age dynamics in groups with different memory trajectories (maintained high performance, average decline, and accelerated decline) over a 15-year period. Epigenetic (DNA-methylation [DNAm]) age was assessed, and delta age (DNAm age - chronological age) was calculated in blood samples at baseline (age: 55-65 years) and 15 years later in 52 age- and gender-matched individuals from the Betula study in Sweden. A lower delta DNAm age was observed for those with maintained memory functions compared with those with average (p = 0.035) or accelerated decline (p = 0.037). Moreover, separate analyses revealed that DNAm age at follow-up, but not chronologic age, was a significant predictor of dementia (p = 0.019). Our findings suggest that young epigenetic age contributes to maintained memory in aging.
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| 4. |
- Fjell, Anders M., et al.
(författare)
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Poor Self-Reported Sleep is Related to Regional Cortical Thinning in Aging but not Memory Decline-Results From the Lifebrain Consortium
- 2021
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Ingår i: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 31:4, s. 1953-1969
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Tidskriftsartikel (refereegranskat)abstract
- We examined whether sleep quality and quantity are associated with cortical and memory changes in cognitively healthy participants across the adult lifespan. Associations between self-reported sleep parameters (Pittsburgh Sleep Quality Index, PSQI) and longitudinal cortical change were tested using five samples from the Lifebrain consortium (n = 2205, 4363 MRIs, 18-92 years). In additional analyses, we tested coherence with cell-specific gene expression maps from the Allen Human Brain Atlas, and relations to changes in memory performance. "PSQI # 1 Subjective sleep quality" and "PSQI #5 Sleep disturbances" were related to thinning of the right lateral temporal cortex, with lower quality and more disturbances being associated with faster thinning. The association with "PSQI #5 Sleep disturbances" emerged after 60 years, especially in regions with high expression of genes related to oligodendrocytes and S1 pyramidal neurons. None of the sleep scales were related to a longitudinal change in episodic memory function, suggesting that sleep-related cortical changes were independent of cognitive decline. The relationship to cortical brain change suggests that self-reported sleep parameters are relevant in lifespan studies, but small effect sizes indicate that self-reported sleep is not a good biomarker of general cortical degeneration in healthy older adults.
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| 5. |
- Fjell, Anders M., et al.
(författare)
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Self-reported sleep relates to hippocampal atrophy across the adult lifespan : results from the Lifebrain consortium
- 2020
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Ingår i: Sleep. - : Oxford University Press. - 0161-8105 .- 1550-9109. ; 43:5
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Poor sleep is associated with multiple age-related neurodegenerative and neuropsychiatric conditions. The hippocampus plays a special role in sleep and sleep-dependent cognition, and accelerated hippocampal atrophy is typically seen with higher age. Hence, it is critical to establish how the relationship between sleep and hippocampal volume loss unfolds across the adult lifespan.Methods: Self-reported sleep measures and MRI-derived hippocampal volumes were obtained from 3105 cognitively normal participants (18–90 years) from major European brain studies in the Lifebrain consortium. Hippocampal volume change was estimated from 5116 MRIs from 1299 participants for whom longitudinal MRIs were available, followed up to 11 years with a mean interval of 3.3 years. Cross-sectional analyses were repeated in a sample of 21,390 participants from the UK Biobank.Results: No cross-sectional sleep—hippocampal volume relationships were found. However, worse sleep quality, efficiency, problems, and daytime tiredness were related to greater hippocampal volume loss over time, with high scorers showing 0.22% greater annual loss than low scorers. The relationship between sleep and hippocampal atrophy did not vary across age. Simulations showed that the observed longitudinal effects were too small to be detected as age-interactions in the cross-sectional analyses.Conclusions: Worse self-reported sleep is associated with higher rates of hippocampal volume decline across the adult lifespan. This suggests that sleep is relevant to understand individual differences in hippocampal atrophy, but limited effect sizes call for cautious interpretation.
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| 6. |
- Gorbach, Tetiana, et al.
(författare)
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Longitudinal association between hippocampus atrophy and episodic-memory decline
- 2017
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 51, s. 167-176
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Tidskriftsartikel (refereegranskat)abstract
- There is marked variability in both onset and rate of episodic-memory decline in aging. Structural magnetic resonance imaging studies have revealed that the extent of age-related brain changes varies markedly across individuals. Past studies of whether regional atrophy accounts for episodic-memory decline in aging have yielded inconclusive findings. Here we related 15-year changes in episodic memory to 4-year changes in cortical and subcortical gray matter volume and in white-matter connectivity and lesions. In addition, changes in word fluency, fluid IQ (Block Design), and processing speed were estimated and related to structural brain changes. Significant negative change over time was observed for all cognitive and brain measures. A robust brain-cognition change-change association was observed for episodic-memory decline and atrophy in the hippocampus. This association was significant for older (65-80 years) but not middle-aged (55-60 years) participants and not sensitive to the assumption of ignorable attrition. Thus, these longitudinal findings highlight medial-temporal lobe system integrity as particularly crucial for maintaining episodic-memory functioning in older age.
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| 7. |
- Gorbach, Tetiana, 1991-, et al.
(författare)
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Longitudinal association between hippocampus atrophy and episodic-memory decline in non-demented APOE ε4 carriers
- 2020
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Ingår i: Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring. - : John Wiley & Sons. - 2352-8729. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The apolipoprotein E (APOE) ε4 allele is the main genetic risk factor for Alzheimer's disease (AD), accelerated cognitive aging, and hippocampal atrophy, but its influence on the association between hippocampus atrophy and episodic-memory decline in non-demented individuals remains unclear.Methods: We analyzed longitudinal (two to six observations) magnetic resonance imaging (MRI)–derived hippocampal volumes and episodic memory from 748 individuals (55 to 90 years at baseline, 50% female) from the European Lifebrain consortium.Results: The change-change association for hippocampal volume and memory was significant only in ε4 carriers (N = 173, r = 0.21, P = .007; non-carriers: N = 467, r = 0.073,P = .117). The linear relationship was significantly steeper for the carriers [t(629) =2.4, P = .013]. A similar trend toward a stronger change-change relation for carriers was seen in a subsample with more than two assessments.Discussion: These findings provide evidence for a difference in hippocampus-memory association between ε4 carriers and non-carriers, thus highlighting how genetic factors modulate the translation of the AD-related pathophysiological cascade into cognitive deficits.
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| 8. |
- Grydeland, Håkon, et al.
(författare)
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Self-reported sleep relates to microstructural hippocampal decline in beta-amyloid positive Adults beyond genetic risk
- 2021
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Ingår i: Sleep. - : Oxford University Press. - 0161-8105 .- 1550-9109. ; 44:11
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Tidskriftsartikel (refereegranskat)abstract
- Study Objectives: A critical role linking sleep with memory decay and beta-amyloid (A beta) accumulation, two markers of Alzheimer's disease (AD) pathology, may be played by hippocampal integrity. We tested the hypotheses that worse self-reported sleep relates to decline in memory and intra-hippocampal microstructure, including in the presence of A beta.Methods: Two-hundred and forty-three cognitively healthy participants, aged 19-81 years, completed the Pittsburgh Sleep Quality Index once, and two diffusion tensor imaging sessions, on average 3 years apart, allowing measures of decline in intra-hippocampal microstructure as indexed by increased mean diffusivity. We measured memory decay at each imaging session using verbal delayed recall. One session of positron emission tomography, in 108 participants above 44 years of age, yielded 23 A beta positive. Genotyping enabled control for APOE epsilon 4 status, and polygenic scores for sleep and AD, respectively.Results: Worse global sleep quality and sleep efficiency related to more rapid reduction of hippocampal microstructure over time. Focusing on efficiency (the percentage of time in bed at night spent asleep), the relation was stronger in presence of A beta accumulation, and hippocampal integrity decline mediated the relation with memory decay. The results were not explained by genetic risk for sleep efficiency or AD.Conclusions: Worse sleep efficiency related to decline in hippocampal microstructure, especially in the presence of A beta accumulation, and A beta might link poor sleep and memory decay. As genetic risk did not account for the associations, poor sleep efficiency might constitute a risk marker for AD, although the driving causal mechanisms remain unknown.
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| 9. |
- Josefsson, Maria, 1979-, et al.
(författare)
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A Bayesian semiparametric approach for inference on the population partly conditional mean from longitudinal data with dropout
- 2023
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Ingår i: Biostatistics. - : Oxford University Press. - 1465-4644 .- 1468-4357. ; 24:2, s. 372-387
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Tidskriftsartikel (refereegranskat)abstract
- Studies of memory trajectories using longitudinal data often result in highly non-representative samples due to selective study enrollment and attrition. An additional bias comes from practice effects that result in improved or maintained performance due to familiarity with test content or context. These challenges may bias study findings and severely distort the ability to generalize to the target population. In this study we propose an approach for estimating the finite population mean of a longitudinal outcome conditioning on being alive at a specific time point. We develop a flexible Bayesian semi-parametric predictive estimator for population inference when longitudinal auxiliary information is known for the target population. We evaluate sensitivity of the results to untestable assumptions and further compare our approach to other methods used for population inference in a simulation study. The proposed approach is motivated by 15-year longitudinal data from the Betula longitudinal cohort study. We apply our approach to estimate lifespan trajectories in episodic memory, with the aim to generalize findings to a target population.
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| 10. |
- Josefsson, Maria, 1979-, et al.
(författare)
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Genetic and Lifestyle Predictors of 15-Year Longitudinal Change in Episodic Memory
- 2012
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Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 60:12, s. 2308-2312
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To reveal distinct longitudinal trajectories in episodic memory over 15 years and to identify demographic, lifestyle, health-related, and genetic predictors of stability or decline. Design: Prospective cohort study. Setting: The Betula Project, Umeå, Sweden. Participants: One thousand nine hundred fifty-four healthy participants aged 35 to 85 at baseline. Measurements: Memory was assessed according to validated episodic memory tasks in participants from a large population-based sample. Data were analyzed using a random-effects pattern-mixture model that considered the effect of attrition over two to four longitudinal sessions. Logistic regression was used to determine significant predictors of stability or decline relative to average change in episodic memory. Results: Of 1,558 participants with two or more test sessions, 18% were classified as maintainers and 13% as decliners, and 68% showed age-typical average change. More educated and more physically active participants, women, and those living with someone were more likely to be classified as maintainers, as were carriers of the met allele of the catechol-O-methyltransferase gene. Less educated participants, those not active in the labor force, and men were more likely to be classified as decliners, and the apolipoprotein E ɛ4 allele was more frequent in decliners. Conclusion: Quantitative, attrition-corrected assessment of longitudinal changes in memory can reveal substantial heterogeneity in aging trajectories, and genetic and lifestyle factors predict such heterogeneity.
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| 11. |
- Josefsson, Maria, 1979-, et al.
(författare)
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Memory profiles predict dementia over 23–28 years in normal but not successful aging
- 2023
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Ingår i: International psychogeriatrics. - : Cambridge University Press. - 1041-6102 .- 1741-203X. ; 35:7, s. 351-359
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Prospective studies suggest that memory deficits are detectable decades before clinical symptoms of dementia emerge. However, individual differences in long-term memory trajectories prior to diagnosis need to be further elucidated. The aim of the current study was to investigate long-term dementia and mortality risk for individuals with different memory trajectory profiles in a well-characterized population-based sample.Methods: 1062 adults (aged 45–80 years) who were non-demented at baseline were followed over 23–28 years. Dementia and mortality risk were studied for three previously classified episodic memory trajectory groups: maintained high performance (Maintainers; 26%), average decline (Averages; 64%), and accelerated decline (Decliners; 12%), using multistate modeling to characterize individuals’ transitions from an initial non-demented state, possibly to a state of dementia and/or death.Results: The memory groups showed considerable intergroup variability in memory profiles, starting 10–15 years prior to dementia diagnosis, and prior to death. A strong relationship between memory trajectory group and dementia risk was found. Specifically, Decliners had more than a fourfold risk of developing dementia compared to Averages. In contrast, Maintainers had a 2.6 times decreased dementia risk compared to Averages, and in addition showed no detectable memory decline prior to dementia diagnosis. A similar pattern of association was found for the memory groups and mortality risk, although only among non-demented.Conclusion: There was a strong relationship between accelerated memory decline and dementia, further supporting the prognostic value of memory decline. The intergroup differences, however, suggest that mechanisms involved in successful memory aging may delay symptom onset.
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| 12. |
- Kauppi, Karolina, et al.
(författare)
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Effects of polygenic risk for Alzheimer's disease on rate of cognitive decline in normal aging
- 2020
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Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Most people's cognitive abilities decline with age, with significant and partly genetically driven, individual differences in rate of change. Although APOE 4 and genetic scores for late-onset Alzheimer's disease (LOAD) have been related to cognitive decline during preclinical stages of dementia, there is limited knowledge concerning genetic factors implied in normal cognitive aging. In the present study, we examined three potential genetic predictors of age-related cognitive decline as follows: (1) the APOE 4 allele, (2) a polygenic score for general cognitive ability (PGS-cog), and (3) a polygenic risk score for late-onset AD (PRS-LOAD). We examined up to six time points of cognitive measurements in the longitudinal population-based Betula study, covering a 25-year follow-up period. Only participants that remained alive and non-demented until the most recent dementia screening (1-3 years after the last test occasion) were included (n=1087). Individual differences in rate of cognitive change (composite score) were predicted by the PRS-LOAD and APOE 4, but not by PGS-cog. To control for the possibility that the results reflected a preclinical state of Alzheimer's disease in some participants, we re-ran the analyses excluding cognitive data from the last test occasion to model cognitive change up-until a minimum of 6 years before potential onset of clinical Alzheimers. Strikingly, the association of PRS-LOAD, but not APOE 4, with cognitive change remained. The results indicate that PRS-LOAD predicts individual difference in rate of cognitive decline in normal aging, but it remains to be determined to what extent this reflects preclinical Alzheimer's disease brain pathophysiology and subsequent risk to develop the disease.
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| 13. |
- Koch, Elise, et al.
(författare)
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Sex-specific effects of polygenic risk for schizophrenia on lifespan cognitive functioning in healthy individuals
- 2021
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Polygenic risk for schizophrenia has been associated with lower cognitive ability and age-related cognitive change in healthy individuals. Despite well-established neuropsychological sex differences in schizophrenia patients, genetic studies on sex differences in schizophrenia in relation to cognitive phenotypes are scarce. Here, we investigated whether the effect of a polygenic risk score (PRS) for schizophrenia on childhood, midlife, and late-life cognitive function in healthy individuals is modified by sex, and if PRS is linked to accelerated cognitive decline. Using a longitudinal data set from healthy individuals aged 25–100 years (N = 1459) spanning a 25-year period, we found that PRS was associated with lower cognitive ability (episodic memory, semantic memory, visuospatial ability), but not with accelerated cognitive decline. A significant interaction effect between sex and PRS was seen on cognitive task performance, and sex-stratified analyses showed that the effect of PRS was male-specific. In a sub-sample, we observed a male-specific effect of the PRS on school performance at age 12 (N = 496). Our findings of sex-specific effects of schizophrenia genetics on cognitive functioning across the lifespan indicate that the effects of underlying disease genetics on cognitive functioning is dependent on biological processes that differ between the sexes.
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| 14. |
- Nyberg, Lars, et al.
(författare)
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Age-related and genetic modulation of frontal cortex efficiency
- 2014
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Ingår i: Journal of cognitive neuroscience. - : MIT Press. - 0898-929X .- 1530-8898. ; 26:4, s. 746-754
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Tidskriftsartikel (refereegranskat)abstract
- The dorsolateral pFC (DLPFC) is a key region for working memory. It has been proposed that the DLPFC is dynamically recruited depending on task demands. By this view, high DLPFC recruitment for low-demanding tasks along with weak DLPFC upregulation at higher task demands reflects low efficiency. Here, the fMRI BOLD signal during working memory maintenance and manipulation was examined in relation to aging and catechol-O-methyltransferase (COMT) Val(158)Met status in a large representative sample (n = 287). The efficiency hypothesis predicts a weaker DLPFC response during manipulation, along with a stronger response during maintenance for older adults and COMT Val carriers compared with younger adults and COMT Met carriers. Consistent with the hypothesis, younger adults and met carriers showed maximal DLPFC BOLD response during manipulation, whereas older adults and val carriers displayed elevated DLPFC responses during the less demanding maintenance condition. The observed inverted relations support a link between dopamine and DLPFC efficiency.
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| 15. |
- Nyberg, Lars, 1966-, et al.
(författare)
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Biological and environmental predictors of heterogeneity in neurocognitive ageing : Evidence from Betula and other longitudinal studies
- 2020
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Ingår i: Ageing Research Reviews. - : Elsevier. - 1568-1637 .- 1872-9649. ; 64
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Forskningsöversikt (refereegranskat)abstract
- Individual differences in cognitive performance increase with advancing age, reflecting marked cognitive changes in some individuals along with little or no change in others. Genetic and lifestyle factors are assumed to influence cognitive performance in aging by affecting the magnitude and extent of age-related brain changes (i.e., brain maintenance or atrophy), as well as the ability to recruit compensatory processes. The purpose of this review is to present findings from the Betula study and other longitudinal studies, with a focus on clarifying the role of key biological and environmental factors assumed to underlie individual differences in brain and cognitive aging. We discuss the vital importance of sampling, analytic methods, consideration of non-ignorable dropout, and related issues for valid conclusions on factors that influence healthy neurocognitive aging.
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| 16. |
- Nyberg, Lars, et al.
(författare)
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Educational attainment does not influence brain aging
- 2021
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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. ; 118:18
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Tidskriftsartikel (refereegranskat)abstract
- Education has been related to various advantageous lifetime outcomes. Here, using longitudinal structural MRI data (4,422 observations), we tested the influential hypothesis that higher education translates into slower rates of brain aging. Cross-sectionally, education was modestly associated with regional cortical volume. However, despite marked mean atrophy in the cortex and hippocampus, education did not influence rates of change. The results were replicated across two independent samples. Our findings challenge the view that higher education slows brain aging.
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| 17. |
- 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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| 18. |
- 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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| 19. |
- Nyberg, Lars, et al.
(författare)
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Structural and functional imaging of aging : longitudinal sudies
- 2017. - 2
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Ingår i: Cognitive neuroscience of aging. - New York : Oxford University Press. - 9780199372935 ; , s. 155-182
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Bokkapitel (refereegranskat)abstract
- 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.
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| 20. |
- Nyberg, Lars, 1966-, et al.
(författare)
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Successful Memory Aging
- 2019
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Ingår i: Annual Review of Psychology. - : Annual Reviews. - 0066-4308 .- 1545-2085. ; 70, s. 219-243
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Forskningsöversikt (refereegranskat)abstract
- 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.
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| 21. |
- Persson, Jonas, et al.
(författare)
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Longitudinal assessment of default-mode brain function in aging
- 2014
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 35:9, s. 2107-2117
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Tidskriftsartikel (refereegranskat)abstract
- Age-related changes in the default-mode network (DMN) have been identified in prior cross-sectional functional magnetic resonance imaging studies. Here, we investigated longitudinal change in DMN activity and connectivity. Cognitively intact participants (aged 49-79 years at baseline) were scanned twice, with a 6-year interval, while performing an episodic memory task interleaved with a passive control condition. Longitudinal analyses showed that the DMN (control condition > memory task) could be reliably identified at both baseline and follow-up. Differences in the magnitude of task-induced deactivation in posterior DMN regions were observed between baseline and follow-up indicating reduced deactivation in these regions with increasing age. Although no overall longitudinal changes in within-network connectivity were found across the whole sample, individual differences in memory change correlated with change in connectivity. Thus, our results show stability of whole-brain DMN topology and functional connectivity over time in healthy older adults, whereas within-region DMN analyses show reduced deactivation between baseline and follow-up. The current findings provide novel insights into DMN functioning that may assist in identifying brain changes in patient populations, as well as characterizing factors that distinguish between normal and pathologic aging.
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| 22. |
- Persson, Jonas, et al.
(författare)
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Longitudinal structure – function correlates in elderly reveal MTL dysfunction with cognitive decline
- 2012
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Ingår i: Cerebral Cortex. - New York, NY : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 22:10, s. 2297-2304
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Tidskriftsartikel (refereegranskat)abstract
- By integrating behavioral measures and imaging data, previous investigations have explored the relationship between biological markers of aging and cognitive functions. Evidence from functional and structural neuroimaging has revealed that hippocampal volume and activation patterns in the medial temporal lobe (MTL) may predict cognitive performance in old age. Most past demonstrations of age-related differences in brain structure–function were based on cross-sectional comparisons. Here, the relationship between 6-year intraindividual change in functional magnetic resonance imaging (fMRI) signal and change in memory performance over 2 decades was examined. Correlations between intraindividual change in fMRI signal during episodic encoding and change in memory performance measured outside of scanning were used as an estimate for relating brain–behavior changes. The results revealed a positive relationship between activation change in the hippocampus (HC) and change in memory performance, reflecting reduced hippocampal activation in participants with declining performance. Using a similar analytic approach as for the functional data, we found that individuals with declining performance had reduced HC volume compared with individuals with intact performance. These observations provide a strong link between cognitive change in older adults and MTL structure and function and thus provide insights into brain correlates of individual variability in aging trajectories.
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| 23. |
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| 24. |
- Pudas, Sara, et al.
(författare)
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Brain characteristics of individuals resisting age-related cognitive decline over two decades
- 2013
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 33:20, s. 8668-8677
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 25. |
- Pudas, Sara, 1983-
(författare)
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Brain characteristics of memory decline and stability in aging : Contributions from longitudinal observations
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aging is typically associated with declining mental abilities, most prominent for some forms of memory. There are, however, large inter-individual differences within the older population. Some people experience rapid decline whereas others seem almost spared from any adverse effects of aging. This thesis examined the neural underpinnings of such individual differences by using longitudinal observations of episodic memory change across 15-20 years, combined with structural and functional magnetic resonance imaging of the brain. Study I found significant correlations between volume and activity of the hippocampus (HC), and memory change over a 6-year period. That is, individuals with decline in HC function also had declining memory. In contrast, Study II showed that successfully aged individuals, who maintained high memory scores over 15-20 years, had preserved HC function compared to age-matched elderly with average memory change. The successful agers had HC activity levels comparable to those of young individuals, as well as higher frontal activity. Study III revealed that individual differences in memory ability and brain activity of elderly reflect both differential age-related changes, and individual differences in memory ability that are present already in midlife, when age effects are minimal. Specifically, memory scores obtained 15-20 years earlier reliably predicted brain activity in memory-relevant regions such as the frontal cortex and HC. This observation challenges results from previous cross-sectional aging studies that did not consider individual differences in cognitive ability from youth. Collectively the three studies implicate HC and frontal cortex function behind heterogeneity in cognitive aging, both substantiating and qualifying previous results from cross-sectional studies. More generally, the findings highlight the importance of longitudinal estimates of cognitive change for fully understanding the mechanisms of neurocognitive aging.
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