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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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