| 1. |
- 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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| 2. |
- Emmert, Kirsten, et al.
(författare)
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Influence of Vascular Variant of the Posterior Cerebral Artery (PCA) on Cerebral Blood Flow, Vascular Response to CO2 and Static Functional Connectivity
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The fetal origin of the posterior cerebral artery (fPCA) is a frequent vascular variant in 11-29% of the population. For the fPCA, blood flow in the PCA originates from the anterior instead of the posterior circulation. We tested whether this blood supply variant impacts the cerebral blood flow assessed by arterial spin labeling (ASL), cerebrovascular reserve as well as resting-state static functional connectivity (sFC) in the sense of a systematic confound. Methods The study included 385 healthy, elderly subjects (mean age: 74.18 years [range: 68.9-90.4]; 243 female). Participants were classified into normal vascular supply (n = 296, 76.88%), right fetal origin (n = 23, 5.97%), left fetal origin (n = 16, 4.16%), bilateral fetal origin (n = 4, 1.04%), and intermediate (n = 46, 11.95%, excluded from further analysis) groups. ASL-derived relative cerebral blood flow (relCBF) maps and cerebrovascular reserve (CVR) maps derived from a CO2 challenge with blocks of 7% CO2 were compared. Additionally, sFC between 90 regions of interest (ROIs) was compared between the groups. Results CVR was significantly reduced in subjects with ipsilateral fPCA, most prominently in the temporal lobe. ASL yielded a non-significant trend towards reduced relCBF in bilateral posterior watershed areas. In contrast, conventional atlas-based sFC did not differ between groups. Conclusions In conclusion, fPCA presence may bias the assessment of cerebrovascular reserve by reducing the response to CO2. In contrast, its effect on ASL-assessed baseline perfusion was marginal. Moreover, fPCA presence did not systematically impact resting-state sFC. Taken together, this data implies that perfusion variables should take into account the vascularization patterns.
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| 3. |
- Giannakopoulos, Panteleimon, et al.
(författare)
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Alzheimer resemblance atrophy index, BrainAGE, and normal pressure hydrocephalus score in the prediction of subtle cognitive decline : added value compared to existing MR imaging markers.
- 2022
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Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 32:11, s. 7833-7842
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Established visual brain MRI markers for dementia include hippocampal atrophy (mesio-temporal atrophy MTA), white matter lesions (Fazekas score), and number of cerebral microbleeds (CMBs). We assessed whether novel quantitative, artificial intelligence (AI)-based volumetric scores provide additional value in predicting subsequent cognitive decline in elderly controls.METHODS: A prospective study including 80 individuals (46 females, mean age 73.4 ± 3.5 years). 3T MR imaging was performed at baseline. Extensive neuropsychological assessment was performed at baseline and at 4.5-year follow-up. AI-based volumetric scores were derived from 3DT1: Alzheimer Disease Resemblance Atrophy Index (AD-RAI), Brain Age Gap Estimate (BrainAGE), and normal pressure hydrocephalus (NPH) index. Analyses included regression models between cognitive scores and imaging markers.RESULTS: AD-RAI score at baseline was associated with Corsi (visuospatial memory) decline (10.6% of cognitive variability in multiple regression models). After inclusion of MTA, CMB, and Fazekas scores simultaneously, the AD-RAI score remained as the sole valid predictor of the cognitive outcome explaining 16.7% of its variability. Its percentage reached 21.4% when amyloid positivity was considered an additional explanatory factor. BrainAGE score was associated with Trail Making B (executive functions) decrease (8.5% of cognitive variability). Among the conventional MRI markers, only the Fazekas score at baseline was positively related to the cognitive outcome (8.7% of cognitive variability). The addition of the BrainAGE score as an independent variable significantly increased the percentage of cognitive variability explained by the regression model (from 8.7 to 14%). The addition of amyloid positivity led to a further increase in this percentage reaching 21.8%.CONCLUSIONS: The AI-based AD-RAI index and BrainAGE scores have limited but significant added value in predicting the subsequent cognitive decline in elderly controls when compared to the established visual MRI markers of brain aging, notably MTA, Fazekas score, and number of CMBs.KEY POINTS: • AD-RAI score at baseline was associated with Corsi score (visuospatial memory) decline. • BrainAGE score was associated with Trail Making B (executive functions) decrease. • AD-RAI index and BrainAGE scores have limited but significant added value in predicting the subsequent cognitive decline in elderly controls when compared to the established visual MRI markers of brain aging, notably MTA, Fazekas score, and number of CMBs.
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| 4. |
- Giannakopoulos, Panteleimon, et al.
(författare)
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Less agreeable, better preserved? : A PET amyloid and MRI study in a community-based cohort
- 2020
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Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 89, s. 24-31
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Tidskriftsartikel (refereegranskat)abstract
- The relationship between personality profiles and brain integrity in old age is still a matter of debate. We examined the association between Big Five factor and facet scores and MRI brain volume changes on a 54-month follow-up in 65 elderly controls with 3 neurocognitive assessments (baseline, 18 months, and 54 months), structural brain MRI (baseline and 54 months), brain amyloid PET during follow-up, and APOE genotyping. Personality was assessed with the Neuroticism Extraversion Openness Personality Inventory-Revised. Regression models were used to identify predictors of volume loss including time, age, sex, personality, amyloid load, presence of APOE epsilon 4 allele, and cognitive evolution. Lower agreeableness factor scores (and 4 of its facets) were associated with lower volume loss in the hippocampus, entorhinal cortex, amygdala, mesial temporal lobe, and precuneus bilaterally. Higher openness factor scores (and 2 of its facets) were also associated with lower volume loss in the left hippocampus. Our findings persisted when adjusting for confounders in multivariable models. These data suggest that the combination of low agreeableness and high openness is an independent predictor of better preservation of brain volume in areas vulnerable to neurodegeneration. (C) 2020 Elsevier Inc. All rights reserved.
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| 5. |
- 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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| 6. |
- 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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| 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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Automatic MRI volumetry in asymptomatic cases at risk for normal pressure hydrocephalus
- 2023
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media S.A.. - 1663-4365 .- 1663-4365. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- The occurrence of significant Alzheimer's disease (AD) pathology was described in approximately 30% of normal pressure hydrocephalus (NPH) cases, leading to the distinction between neurodegenerative and idiopathic forms of this disorder. Whether or not there is a specific MRI signature of NPH remains a matter of debate. The present study focuses on asymptomatic cases at risk for NPH as defined with automatic machine learning tools and combines automatic MRI assessment of cortical and white matter volumetry, risk of AD (AD-RAI), and brain age gap estimation (BrainAge). Our hypothesis was that brain aging and AD process-independent volumetric changes occur in asymptomatic NPH-positive cases. We explored the volumetric changes in normal aging-sensitive (entorhinal cortex and parahippocampal gyrus/PHG) and AD-signature areas (hippocampus), four control cortical areas (frontal, parietal, occipital, and temporal), and cerebral and cerebellar white matter in 30 asymptomatic cases at risk for NPH (NPH probability >30) compared to 30 NPH-negative cases (NPH probability <5) with preserved cognition. In univariate regression models, NPH positivity was associated with decreased volumes in the hippocampus, parahippocampal gyrus (PHG), and entorhinal cortex bilaterally. The strongest negative association was found in the left hippocampus that persisted when adjusting for AD-RAI and Brain Age values. A combined model including the three parameters explained 36.5% of the variance, left hippocampal volumes, and BrainAge values, which remained independent predictors of the NPH status. Bilateral PHG and entorhinal cortex volumes were negatively associated with NPH-positive status in univariate models but this relationship did not persist when adjusting for BrainAge, the latter remaining the only predictor of the NPH status. We also found a negative association between bilateral cerebral and cerebellar white matter volumes and NPH status that persisted after controlling for AD-RAI or Brain Age values, explaining between 50 and 65% of its variance. These observations support the idea that in cases at risk for NPH, as defined by support vector machine assessment of NPH-related MRI markers, brain aging-related and brain aging and AD-independent volumetric changes coexist. The latter concerns volume loss in restricted hippocampal and white matter areas that could be considered as the MRI signature of idiopathic forms of NPH.
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| 10. |
- Haller, Sven, et al.
(författare)
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Caffeine impact on working memory-related network activation patterns in early stages of cognitive decline
- 2017
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Ingår i: Neuroradiology. - : Springer. - 0028-3940 .- 1432-1920. ; 59:4, s. 387-395
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Recent evidence indicates that caffeine may have a beneficial effect on cognitive decline and dementia. The current investigation assessed the effect of acute caffeine administration on working memory during the earliest stage of cognitive decline in elderly participants. Methods The study includes consecutive 45 elderly controls and 18 individuals with mild cognitive impairment (MCI, 71.6 +/- 4.7 years, 7 females). During neuropsychological follow-up at 18 months, 24 controls remained stable (sCON, 70.0 +/- 4.3 years, 11 women), while the remaining 21 showed subtle cognitive deterioration (dCON, 73.4 +/- 5.9 years, 14 women). All participants underwent an established 2-back working task in a crossover design of 200 mg caffeine versus placebo. Data analysis included task-related general linear model and functional connectivity tensorial independent component analysis. Results Working memory behavioral performances did not differ between sCON and dCON, while MCI was slower and less accurate than both control groups (p < 0.05). The dCON group had a less pronounced effect of acute caffeine administration essentially restricted to the right hemisphere (p < 0.05 corrected) and reduced default mode network (DMN) deactivation compared to sCON (p < 0.01 corrected). Conclusion dCON cases are characterized by decreased sensitivity to caffeine effects on brain activation and DMN deactivation. These complex fMRI patterns possibly reflect the instable status of these cases with intact behavioral performances despite already existing functional alterations in neocortical circuits.
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