| 1. |
- Haller, Sven, et al.
(författare)
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Amyloid Load, Hippocampal Volume Loss, and Diffusion Tensor Imaging Changes in Early Phases of Brain Aging
- 2019
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Ingår i: Frontiers in Neuroscience. - : FRONTIERS MEDIA SA. - 1662-4548 .- 1662-453X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose Amyloid imaging, gray matter (GM) morphometry and diffusion tensor imaging (DTI) have all been used as predictive biomarkers in dementia. Our objective was to define the imaging profile of healthy elderly controls as a function of their cognitive trajectories and explore whether amyloid burden and white matter (WM) microstructure changes are associated with subtle decrement of neuropsychological performances in old age. Materials and Methods We performed a 4.5-year longitudinal study in 133 elderly individuals who underwent cognitive testing at inclusion and follow-up, amyloid PET, MRI including DTI sequences at inclusion, and APOE epsilon 4 genotyping. All cases were assessed using a continuous cognitive score (CCS) taking into account the global evolution of neuropsychological performances. Data processing included region of interest analysis of amyloid PET analysis, GM densities and tract-based spatial statistics (TBSS)-DTI. Regression models were built to explore the association between the CCS and imaging parameters controlling for significant demographic and clinical covariates. Results Amyloid uptake was not related to the cognitive outcome. In contrast, GM densities in bilateral hippocampus were associated with worst CCS at follow-up. In addition, radial and axial diffusivities in left hippocampus were negatively associated with CCS. Amyloid load was associated with decreased VBM and increased radial and axial diffusivity in the same area. These associations persisted when adjusting for gender and APOE4 genotype. Importantly, they were absent in amygdala and neocortical areas studied. Conclusion The progressive decrement of neuropsychological performances in normal aging is associated with volume loss and WM microstructure changes in hippocampus long before the emergence of clinically overt symptoms. Higher amyloid load in hippocampus is compatible with cognitive preservation in cases with better preservation of GM densities and WM microstructure in this area.
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| 2. |
- Haller, Sven, et al.
(författare)
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Hippocampal Volume Loss, Brain Amyloid Accumulation, and APOE Status in Cognitively Intact Elderly Subjects
- 2019
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Ingår i: Neurodegenerative Diseases. - : S. Karger AG. - 1660-2854 .- 1660-2862. ; 19:3-4, s. 139-147
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hippocampal volume loss (HVL), PET-documented brain amyloid accumulation, and APOE-ε4 status are predictive biomarkers of the transition from mild cognitive impairment to Alzheimer disease (AD). In asymptomatic cases, the role of these biomarkers remains ambiguous. In contrast to the idea that HVL occurs in late phases of neurodegeneration, recent contributions indicate that it might occur before abnormal amyloid PET occurrence in elderly subjects and that its severity could be only marginally related to APOE variants. Using a longitudinal design, we examined the determinants of HVL in our sample, i.e., brain amyloid burden and the presence of APOE-ε4, and made a longitudinal assessment of cognitive functions.METHODS: We performed a 4.5-year longitudinal study on 81 elderly community dwellers (all right-handed;, 48 (59.3%) women; mean age 73.7 ± 3.7 years) including MRI at baseline and follow-up, PET amyloid during follow-up, neuropsychological assessment at 18 and 54 months, and APOE genotyping. All cases were assessed using a continuous cognitive score (CCS) that took into account the global evolution of neuropsychological performance. Linear regression models were used to identify predictors of HVL.RESULTS: There was a negative association between the CCS and HVL bilaterally. In multivariate models adjusting for demographic variables, the presence of APOE-ε4 was related to increased HVL bilaterally. A trend of significance was observed with respect to the impact of amyloid positivity on HVL in the left hemisphere. No significant interaction was found between amyloid positivity and the APOE-ε4 allele.CONCLUSION: The progressive decrement of neuropsychological performance is associated with HVL long before the emergence of clinically overt symptoms. In this cohort of healthy individuals, the presence of the APOE-ε4 allele was shown to be an independent predictor of worst hippocampal integrity in asymptomatic cases independently of amyloid positivity.
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| 3. |
- Herrmann, François R, et al.
(författare)
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Gray Matter Densities in Limbic Areas and APOE4 Independently Predict Cognitive Decline in Normal Brain Aging
- 2019
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Cross-sectional magnetic resonance imaging (MRI) studies reported significant associations between gray matter (GM) density changes in various limbic and neocortical areas and worst cognitive performances in elderly controls. Longitudinal studies in this field remain scarce and led to conflicting data. We report a clinico-radiological investigation of 380 cognitively preserved individuals who undergo neuropsychological assessment at baseline and after 18 months. All cases were assessed using a continuous cognitive score taking into account the global evolution of neuropsychological performances. The vast majority of Mini Mental State Examination (MMSE) 29 and 30 cases showed equal or worst performance at follow-up due to a ceiling effect. GM densities, white matter hyperintensities and arterial spin labeling (ASL) values were assessed in the hippocampus, amygdala, mesial temporal and parietal cortex at inclusion using 3 Tesla MRI Scans. Florbetapir positron emission tomography (PET) amyloid was available in a representative subsample of 64 cases. Regional amyloid uptake ratios (SUVr), mean cortical SUVr values (mcSUVr) and corresponding z-scores were calculated. Linear regression models were built to explore the association between the continuous cognitive score and imaging variables. The presence of an APOE-epsilon 4 allele was negatively related to the continuous cognitive score. Among the areas studied, significant associations were found between GM densities in the hippocampus and amygdala but not mesial temporal and parietal areas and continuous cognitive score. Neither ASL values, Fazekas score nor mean and regional PET amyloid load was related to the cognitive score. In multivariate models, the presence of APOE-epsilon 4 allele and GM densities in the hippocampus and amygdala were independently associated with worst cognitive evolution at follow-up. Our data support the idea that early GM damage in the hippocampus and amygdala occur long before the emergence of the very first signs of cognitive failure in brain aging.
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| 4. |
- Rodriguez, Cristelle, et al.
(författare)
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Structural Correlates of Personality Dimensions in Healthy Aging and MCI.
- 2019
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Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The revised NEO Personality Inventory (NEOPI-R), popularly known as the five-factor model, defines five personality factors: Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness. The structural correlates of these personality factors are still a matter of debate. In this work, we examine the impact of subtle cognitive deficits on structural substrates of personality in the elderly using DTI derived white matter (WM) integrity measure, Fractional Anisotropy (FA). We employed canonical correlation analysis (CCA) to study the relationship between personality factors of the NEOPI-R and FA measures in two population groups: healthy controls and MCI. Agreeableness was the only personality factor to be associated with FA patterns in both groups. Openness was significantly related to FA data in the MCI group and the inverse was true for Conscientiousness. Furthermore, we generated saliency maps using bootstrapping strategy which revealed a larger number of positive correlations in healthy aging in contrast to the MCI status. The MCI group was found to be associated with a predominance of negative correlations indicating that higher Agreeableness and Openness scores were mostly related to lower FA values in interhemispheric and cortico-spinal tracts and a limited number of higher FA values in cortico-cortical and cortico-subcortical connection. Altogether these findings support the idea that WM microstructure may represent a valid correlate of personality dimensions and also indicate that the presence of early cognitive deficits led to substantial changes in the associations between WM integrity and personality factors.
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| 5. |
- van der Thiel, Mere, et al.
(författare)
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Regional Cerebral Perfusion and Cerebrovascular Reactivity in Elderly Controls With Subtle Cognitive Deficits
- 2019
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Ingår i: Frontiers in Aging Neuroscience. - : FRONTIERS MEDIA SA. - 1663-4365. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent studies suggested that arterial spin labeling (ASL)-based measures of cerebral blood flow (CBF) as well as cerebral vasoreactivity to CO2 (CVR CO2) show significant alterations mainly in posterior neocortical areas both in mild cognitive impairment (MCI) and Alzheimer disease. It remains, however, unknown whether similar changes occur in at risk healthy elders without clinically overt symptoms. This longitudinal study investigated patterns of ASL perfusion and CVR CO2 as a function of the cognitive trajectories in asymptomatic elderly individuals.Methods: Seventy-nine community-dwelling subjects (mean age: 78.7 years, 34 male) underwent three neuropsychological assessments during a subsequent 3-year period. Individuals were classified as stable-stable (SS), variable (V), or progressive-progressive (PP). Between-group comparisons were conducted for ASL CBF and transit-time delay maps and beta-maps of CO2 response. Spearman's rho maps assessed the correlation between ASL (respectively, CVR CO2 measures) and Shapes test for working memory, as well as Verbal fluency test for executive functions. Three group-with-continuous-covariate-interaction designs were implemented to investigate group-based differences on the association between neuropsychological scores and ASL or CO2 measures.Results: Comparison of CBF maps demonstrates significantly lower perfusion in the V-group as to PP-cases predominantly in parietal regions, including the precuneus and, to a lesser degree, in temporal and frontal cortex. A stronger CVR CO2 response was found in the PP-group in left parietal areas compared to the V-group. V-cases showed a stronger ASL-Shape value relationship than V-group in right temporoparietal junction and superior parietal lobule. CO2-Shape value correlation was significantly higher in both SS and PP-groups compared to the V-group in right insular and superior perisylvian regions.Conclusion: Our data indicate the presence of decreased ASL and CVR CO2 values mainly in parietal and fronto-temporal areas in cases with the first signs of cognitive instability (V-group). Importantly, the PP-group, at high risk for MCI transition, displays an increase of both parameters in the same areas. Clinicoradiologic correlations also indicate a clear distinction between the V-group and both PP and SS-cases. These data imply the presence of an inverted U-shape pattern of regional blood flow and CVR in old age that might predict subsequent cognitive fate.
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| 6. |
- Zhang, Han, et al.
(författare)
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Inter-Network High-Order Functional Connectivity (IN-HOFC) and its Alteration in Patients with Mild Cognitive Impairment
- 2019
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Ingår i: Neuroinformatics. - : Springer Science and Business Media LLC. - 1539-2791 .- 1559-0089. ; 17:4, s. 547-561
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the high-order interactions among brain regions measured by the similarity of higher-order features (other than the raw blood-oxygen-level-dependent signals) which can characterize higher-level brain functional connectivity (FC). Previously, we proposed FC topographical profile-based high-order FC (HOFC) and found that this metric could provide supplementary information to traditional FC for early Alzheimer's disease (AD) detection. However, whether such findings apply to network-level brain functional integration is unknown. In this paper, we propose an extended HOFC method, termed inter-network high-order FC (IN-HOFC), as a useful complement to the traditional inter-network FC methods, for characterizing more complex organizations among the large-scale brain networks. In the IN-HOFC, both network definition and inter-network FC are defined in a high-order manner. To test whether IN-HOFC is more sensitive to cognition decline due to brain diseases than traditional inter-network FC, 77 mild cognitive impairments (MCIs) and 89 controls are compared among the conventional methods and our IN-HOFC. The result shows that IN-HOFCs among three temporal lobe-related high-order networks are dampened in MCIs. The impairment of IN-HOFC is especially found between the anterior and posterior medial temporal lobe and could be a potential MCI biomarker at the network level. The competing network-level low-order FC methods, however, either revealing less or failing to detect any group difference. This work demonstrates the biological meaning and potential diagnostic value of the IN-HOFC in clinical neuroscience studies.
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