| 1. |
- Festari, Cristina, et al.
(författare)
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European consensus for the diagnosis of MCI and mild dementia : Preparatory phase
- 2023
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:5, s. 1729-1741
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Etiological diagnosis of neurocognitive disorders of middle-old age relies on biomarkers, although evidence for their rational use is incomplete. A European task force is defining a diagnostic workflow where expert experience fills evidence gaps for biomarker validity and prioritization. We report methodology and preliminary results. Methods: Using a Delphi consensus method supported by a systematic literature review, 22 delegates from 11 relevant scientific societies defined workflow assumptions. Results: We extracted diagnostic accuracy figures from literature on the use of biomarkers in the diagnosis of main forms of neurocognitive disorders. Supported by this evidence, panelists defined clinical setting (specialist outpatient service), application stage (MCI-mild dementia), and detailed pre-assessment screening (clinical-neuropsychological evaluations, brain imaging, and blood tests). Discussion: The Delphi consensus on these assumptions set the stage for the development of the first pan-European workflow for biomarkers’ use in the etiological diagnosis of middle-old age neurocognitive disorders at MCI-mild dementia stages. Highlights: Rational use of biomarkers in neurocognitive disorders lacks consensus in Europe. A consensus of experts will define a workflow for the rational use of biomarkers. The diagnostic workflow will be patient-centered and based on clinical presentation. The workflow will be updated as new evidence accrues.
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| 2. |
- Giannakopoulos, Panteleimon, et al.
(författare)
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Personality Impact on Alzheimer's Disease - Signature and Vascular Imaging Markers : A PET-MRI Study
- 2022
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 85:4, s. 1807-1817
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several studies postulated that personality is an independent determinant of cognitive trajectories in old age. Objective: This study explores the impact of personality on widely used Alzheimer's disease (AD) and vascular imaging markers. Methods: We examined the association between personality and three classical AD imaging markers (centiloid-based-amyloid load, MRI volumetry in hippocampus, and media temporal lobe atrophy), and two vascular MRI parameters (Fazekas score and number of cortical microbleeds) assessed at baseline and upon a 54-month-follow-up. Personality was assessed with the Neuroticism Extraversion Openness Personality Inventory-Revised. Regression models were used to identify predictors of imaging markers including sex, personality factors, presence of APOE epsilon 4 allele and cognitive evolution over time. Results: Cortical GM volumes were negatively associated with higher levels of Conscientiousness both at baseline and follow-up. In contrast, higher scores of Openness were related to better preservation of left hippocampal volumes in these two time points and negatively associated with medial temporal atrophy at baseline. Amyloid load was not affected by personality factors. Cases with higher Extraversion scores displayed higher numbers of cortical microbleeds at baseline. Conclusion: Personality impact on brain morphometry is detected only in some among the routinely used imaging markers. The most robust associations concern the positive role of high levels of Conscientiousness and Openness on AD-signature MRI markers. Higher extraversion levels are associated with increased vulnerability to cortical microbleeds pointing to the fact that the socially favorable traits may have a detrimental effect on brain integrity in old age.
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| 3. |
- Herrmann, Francois R., et al.
(författare)
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Determinants of Cognitive Trajectories in Normal Aging : A Longitudinal PET-MRI Study in a Community-based Cohort
- 2021
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Ingår i: Current Alzheimer Research. - : Bentham Science Publishers. - 1567-2050 .- 1875-5828. ; 18:6, s. 482-491
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Tidskriftsartikel (refereegranskat)abstract
- Background: The determinants of the progressive decrement of cognition in normal aging are still a matter of debate. Alzheimer disease (AD)-signature markers and vascular lesions, but also psychological variables such as personality factors, are thought to have an impact on the longitudinal trajectories of neuropsychological performances in healthy elderly individuals.Objective: The current research aimed to identify the main determinants associated with cognitive trajectories in normal aging.Methods: We performed a 4.5-year longitudinal study in 90 older community-dwellers coupling two neuropsychological assessments, medial temporal atrophy (MTA), number of cerebral microbleeds (CMB), and white matter hyperintensities (WMH) at inclusion, visual rating of amyloid and FDG PET at follow-up, and APOE genotyping. Personality factors were assessed at baseline using the NEO-PIR. Univariate and backward stepwise regression models were built to explore the association between the continuous cognitive score (CCS) and both imaging and personality variables.Results: The number of strictly lobar CMB at baseline (4 or more) was related to a significant increase in the risk of cognitive decrement. In multivariable models, amyloid positivity was associated with a 1.73 unit decrease of the CCS at follow-up. MTA, WMH and abnormal FDG PET were not related to the cognitive outcome. Among personality factors, only higher agreeableness was related to better preservation of neuropsychological performances.Conclusion: CMB and amyloid positivity are the only imaging determinants of cognitive trajectories in this highly selected series of healthy controls. Among personality factors, higher agreeableness confers a modest but significant protection against the decline of cognitive performances.
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| 4. |
- Badoud, Simon, et al.
(författare)
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Distinct spatiotemporal patterns for disease duration and stage in Parkinson's disease
- 2016
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 43:3, s. 509-516
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To assess correlations between the degree of dopaminergic depletion measured using single-photon emission computed tomography (SPECT) and different clinical parameters of disease progression in Parkinson's disease (PD). Methods This retrospective study included 970 consecutive patients undergoing I-123-ioflupane SPECT scans in our institution between 2003 and 2013, from which we selected a study population of 411 patients according to their clinical diagnosis: 301 patients with PD (69.4 +/- 11.0 years, of age, 163 men) and 110 patients with nondegenerative conditions included as controls (72.7 +/- 8.0 years of age, 55 men). Comprehensive and operator-independent data analysis included spatial normalization into standard space, estimation of the mean uptake values in the striatum (caudate nucleus + putamen) and voxel-wise correlation between SPECT signal intensity and disease stage as well as disease duration in order to investigate the spatiotemporal pattern of the dopaminergic nigrostriatal degeneration. To compensate for potential interactions between disease stage and disease duration, one parameter was used as nonexplanatory coregressor for the other. Results Increasing disease stage was associated with an exponential decrease in I-123-ioflupane uptake (R (2) = 0.1501) particularly in the head of the ipsilateral caudate nucleus (p < 0.0001), whereas increasing disease duration was associated with a linear decrease in I-123-ioflupane uptake (p < 0.0001; R (2) = 0.1532) particularly in the contralateral anterior putamen (p < 0.0001). Conclusion We observed two distinct spatiotemporal patterns of posterior to anterior dopaminergic depletion associated with disease stage and disease duration in patients with PD. The developed operator-independent reference database of 411 I-123-ioflupane SPECT scans can be used for clinical and research applications.
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| 5. |
- Boccalini, Cecilia, et al.
(författare)
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Early-Phase 18F-Florbetapir and 18F-Flutemetamol Images as Proxies of Brain Metabolism in a Memory Clinic Setting
- 2023
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Ingår i: Journal of Nuclear Medicine. - : The Society of Nuclear Medicine and Molecular Imaging. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 64:2, s. 266-273
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer disease (AD) neuropathologic changes are 6-amyloid (A6) deposition, pathologic tau, and neurodegeneration. Dual-phase amy-loid PET might be able to evaluate A6 deposition and neurodegenera-tion with a single tracer injection. Early-phase amyloid PET scans provide a proxy for cerebral perfusion, which has shown good correla-tions with neural dysfunction measured through metabolic consump-tion, whereas the late frames depict amyloid distribution. Our study aimed to assess the comparability between early-phase amyloid PET scans and 18F-FDG PET brain topography at the individual level and their ability to discriminate patients. Methods: One hundred sixty-six subjects evaluated at the Geneva Memory Center, ranging from no cognitive impairment to mild cognitive impairment and dementia, underwent early-phase amyloid PET-using either 18F-florbetapir (eFBP) (n = 94) or 18F-flutemetamol (eFMM) (n = 72)-and 18F-FDG PET. A6 status was assessed. SUV ratios (SUVRs) were extracted to evaluate the correlation of eFBP/eFMM and their respective 18F-FDG PET scans. The single-subject procedure was applied to investigate hypometabolism and hypoperfusion maps and their spatial overlap by the Dice coefficient. Receiver-operating-characteristic analyses were performed to compare the discriminative power of eFBP/eFMM and 18F-FDG PET SUVR in AD-related meta-regions of interest between A6-negative healthy controls and cases in the AD continuum. Results: Positive correlations were found between eFBP/eFMM and 18F-FDG PET SUVR independently of A6 status and A6 radiotracer (R> 0.72, P< 0.001). eFBP/eFMM single-subject analysis revealed clusters of significant hypoperfusion with good correspondence to hypometabo-lism topographies, independently of the underlying neurodegenerative patterns. Both eFBP/eFMM and 18F-FDG PET SUVR significantly dis-criminated AD patients from controls in the AD-related meta-regions of interest (eFBP area under the curve [AUC], 0.888; eFMM AUC, 0.801), with 18F-FDG PET performing slightly better, although not sig-nificantly (all P values higher than 0.05), than others (18F-FDG AUC, 0.915 and 0.832 for subjects evaluated with eFBP and eFMM, respec-tively). Conclusion: The distribution of perfusion was comparable to that of metabolism at the single-subject level by parametric analysis, particularly in the presence of a high neurodegeneration burden. Our findings indicate that eFBP and eFMM imaging can replace 18F-FDG PET imaging, as they reveal typical neurodegenerative patterns or allow exclusion of the presence of neurodegeneration. The findings show cost-saving capacities of amyloid PET and support routine use of the modality for individual classification in clinical practice.
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| 6. |
- Giannakopoulos, Panteleimon, et al.
(författare)
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Personality Factors' Impact on the Structural Integrity of Mentalizing Network in Old Age : A Combined PET-MRI Study
- 2020
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Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- The mentalizing network (MN) treats social interactions based on our understanding of other people's intentions and includes the medial prefrontal cortex (mPFC), temporoparietal junction (TPJ), posterior cingulate cortex (PCC), precuneus (PC), and amygdala. Not all elders are equally affected by the aging-related decrease of mentalizing abilities. Personality has recently emerged as a strong determinant of functional connectivity in MN areas. However, its impact on volumetric changes across the MN in brain aging is still unknown. To address this issue, we explored the determinants of volume decrease in MN components including amyloid burden, personality, and APOE genotyping in a previously established cohort of 130 healthy elders with a mean follow-up of 54 months. Personality was assessed with the Neuroticism Extraversion Openness Personality Inventory-Revised. Regression models corrected for multiple comparisons were used to identify predictors of volume loss including time, age, sex, personality, amyloid load, presence of APOE epsilon 4 allele, and cognitive evolution. In cases with higher Agreeableness scores, there were lower volume losses in PCC, PC, and amygdala bilaterally. This was also the case for the right mPFC in elders displaying lower Agreeableness and Conscientiousness. In multiple regression models, the effect of Agreeableness was still observed in left PC and right amygdala and that of Conscientiousness was still observed in right mPFC volume loss (26.3% of variability, significant age and sex). Several Agreeableness (Modesty) and Conscientiousness (order, dutifulness, achievement striving, and self-discipline) facets were positively related to increased volume loss in cortical components of the MN. In conclusion, these data challenge the beneficial role of higher levels of Agreeableness and Conscientiousness in old age, showing that they are associated with an increased rate of volume loss within the MN.
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| 7. |
- Giannakopoulos, Panteleimon, et al.
(författare)
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Prediction of Subtle Cognitive Decline in Normal Aging : Added Value of Quantitative MRI and PET Imaging
- 2021
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media S.A.. - 1663-4365 .- 1663-4365. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Quantitative imaging processing tools have been proposed to improve clinic-radiological correlations but their added value at the initial stages of cognitive decline is still a matter of debate. We performed a longitudinal study in 90 community-dwelling elders with three neuropsychological assessments during a 4.5 year follow-up period, and visual assessment of medial temporal atrophy (MTA), white matter hyperintensities, cortical microbleeds (CMB) as well as amyloid positivity, and presence of abnormal FDG-PET patterns. Quantitative imaging data concerned ROI analysis of MRI volume, amyloid burden, and FDG-PET metabolism in several AD-signature areas. Multiple regression models, likelihood-ratio tests, and areas under the receiver operating characteristic curve (AUC) were used to compare quantitative imaging markers to visual inspection. The presence of more or equal to four CMB at inclusion and slight atrophy of the right MTL at follow-up were the only parameters to be independently related to the worst cognitive score explaining 6% of its variance. This percentage increased to 24.5% when the ROI-defined volume loss in the posterior cingulate cortex, baseline hippocampus volume, and MTL metabolism were also considered. When binary classification of cognition was made, the area under the ROC curve increased from 0.69 for the qualitative to 0.79 for the mixed imaging model. Our data reveal that the inclusion of quantitative imaging data significantly increases the prediction of cognitive changes in elderly controls compared to the single consideration of visual inspection.
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| 8. |
- 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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| 9. |
- Haller, Sven, et al.
(författare)
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PET amyloid in normal aging : direct comparison of visual and automatic processing methods
- 2020
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Ingår i: Scientific Reports. - : NATURE RESEARCH. - 2045-2322. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Assessment of amyloid deposits is a critical step for the identification of Alzheimer disease (AD) signature in asymptomatic elders. Whether the different amyloid processing methods impacts on the quality of clinico-radiological correlations is still unclear. We directly compared in 155 elderly controls with extensive neuropsychological testing at baseline and 4.5 years follow-up three approaches: (i) operator-dependent standard visual reading, (ii) operator-independent automatic SUVR with four different reference regions, and (iii) novel operator and region of reference-independent automatic A beta-index. The coefficient of variance was used to examine inter-individual variability for each processing method. Using visually-established amyloid positivity as the gold standard, the area under the receiver operating characteristic curve (ROC) was computed. Linear regression models were used to assess the association between changes in continuous cognitive score and amyloid uptake values. In SUVR analyses, the coefficient of variance varied from 1.718 to 1.762 according to the area of reference and was of - 3.045 for the A beta-index method. Compared to the visual rating, A beta-index method showed the largest area under the ROC curve [0.9568 (95% CI 0.9252, 0.98833)]. The best cut-off score was of - 0.3359 with sensitivity and specificity values of 0.97 and 0.83, respectively. Only the A beta-index was related to more severe decrement of cognitive performances [regression coefficient: 9.103 (95% CI 1.148, 17.058)]. The A beta-index is considered as preferred option in asymptomatic elders, since it is operator-independent, avoids the selection of reference area, is closer to established visual scoring and correlates with the evolution of cognitive performances.
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| 10. |
- Montandon, Marie-Louise, et al.
(författare)
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Determinants of mesial temporal lobe volume loss in older individuals with preserved cognition : a longitudinal PET amyloid study
- 2020
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Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 87, s. 108-114
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Tidskriftsartikel (refereegranskat)abstract
- Mesial temporal lobe (MTL) is prominently affected in normal aging and associated with neurodegeneration in AD. Whether or not MTL atrophy is dependent on increasing amyloid load before the emergence of cognitive deficits is still disputed. We performed a 4.5-year longitudinal study in 75 older community dwellers (48 women, mean age: 79.3 years) including magnetic resonance imaging at baseline and follow-up, positron emission tomography amyloid during follow-up, neuropsychological assessment at 18 and 55 months, and APOE genotyping. Linear regression models were used to identify predictors of the MTL volume loss. Amyloid load was negatively associated with bilateral MTL volume at baseline explaining almost 10.5% of its variability. In multivariate models including time of follow-up and demographic variables (older age, male gender), this percentage exceeded 35%. The APOE4 allele independently contributed another 6%. Cognitive changes had a modest but still significant negative association with MTL volume loss. Our data support a multifactorial model including amyloid deposition, older age, male gender, APOE4 allele, and slight decline of cognitive abilities as independent predictors of MTL volume loss in brain aging.
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