Background: Several studies have linked type 2 diabetes (T2D) to an increased risk of developing Alzheimer’s disease (AD). This has led to an interest in using antidiabetic treatments for the ...prevention of AD. However, the underlying mechanisms explaining the relationship between T2D and AD have not been completely elucidated. Objective: Our objective was to examine cerebral 18F-fluorodeoxyglucose (FDG) uptake during normal aging and in AD patients in regions associated with diabetes genetic risk factors expression in order to highlight which genes may serve as potential targets for pharmaceutical intervention. Methods: We calculated regional glucose metabolism differences in units of standardized uptake values (SUVR) for 386 cognitively healthy adults and 335 clinically probable AD patients. We then proceeded to extract gene-expression data from the publicly available Allen Human Brain Atlas (HBA) database. We used the nearest genes to 46 AD- and T2D-associated SNPs previously identified in the literature, and mapped their expression to the same 34 cortical regions in which we calculated SUVRs, to derive. SNPs with a donor consistency of 0.40 or greater were selected for further analysis. We evaluated the associations between SUVR and gene-expression across the brain. Results: Of the 46 risk-factor genes, 15 were found to be significantly correlated with FDG-PET brain metabolism in healthy adults and probable AD patients after correction for multiple comparisons. Using multiple regression, we found that five genes explained a total of 72.5 percent of the SUVR variance across the healthy adult group regions, while four genes explained a total of 79.3 percent of the SUVR variance across the probable AD group regions. There were significant differences in whole-brain SUVR as a function of allele frequencies for two genes. Conclusions: These results highlight the association between risk factor genes for T2D and regional glucose metabolism during both normal aging and in probable AD. Highlighted genes were associated with mitochondrial stability, vascular maintenance, and glucose intolerance. Pharmacological intervention of these pathways has the potential to improve glucose metabolism during normal again as well as in AD patients.
Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are part of a spectrum of Lewy body disorders, who exhibit a range of cognitive and gait impairments. Cognitive-motor interactions can be ...examined by performing a cognitive task while walking and quantified by a dual task cost (DTC). White matter hyperintensities (WMH) on magnetic resonance imaging have also been associated with both gait and cognition. Our goal was to examine the relationship between DTC and WMH in the Lewy body spectrum, hypothesizing DTC would be associated with increased WMH volume.
Seventy-eight participants with PD, PD with mild cognitive impairment (PD-MCI), PD with dementia or DLB (PDD/DLB), and 20 cognitively unimpaired participants were examined in a multi-site study. Gait was measured on an electronic walkway during usual gait, counting backward, animal fluency, and subtracting sevens. WMH were quantified from magnetic resonance imaging using an automated pipeline and visual rating. A median split based on DTC was performed. Models included age as well as measures of global cognition and cardiovascular risk.
Compared to cognitively unimpaired participants, usual gait speed was lower and DTC was higher in PD-MCI and PDD/DLB. Low DTC participants had higher usual gait speed. WMH burden was greater in high counting DTC participants. Frontal WMH burden remained significant after adjusting for age, cardiovascular risk and global cognition.
Increased DTC was associated with higher frontal WMH burden in Lewy body disorders after adjusting for age, cardiovascular risk, and global cognition. Higher DTC was associated with age.
Manual segmentation from magnetic resonance imaging (MR) is the gold standard for evaluating hippocampal atrophy in Alzheimer's disease (AD). Nonetheless, different segmentation protocols provide up ...to 2.5-fold volume differences. Here we surveyed the most frequently used segmentation protocols in the AD literature as a preliminary step for international harmonization. The anatomical landmarks (anteriormost and posteriormost slices, superior, inferior, medial, and lateral borders) were identified from 12 published protocols for hippocampal manual segmentation (Abbreviation first author, publication year: B Bartzokis, 1998; C Convit, 1997; dTM deToledo-Morrell, 2004; H Haller, 1997; J Jack, 1994; K Killiany, 1993; L Lehericy, 1994; M Malykhin, 2007; Pa Pantel, 2000; Pr Pruessner, 2000; S Soininen, 1994; W Watson, 1992). The hippocampi of one healthy control and one AD patient taken from the 1.5T MR ADNI database were segmented by a single rater according to each protocol. The accuracy of the protocols' interpretation and translation into practice was checked with lead authors of protocols through individual interactive web conferences. Semantically harmonized landmarks and differences were then extracted, regarding: (a) the posteriormost slice, protocol B being the most restrictive, and H, M, Pa, Pr, S the most inclusive; (b) inclusion C, dTM, J, L, M, Pr, W or exclusion B, H, K, Pa, S of alveus/fimbria; (c) separation from the parahippocampal gyrus, C being the most restrictive, B, dTM, H, J, Pa, S the most inclusive. There were no substantial differences in the definition of the anteriormost slice. This survey will allow us to operationalize differences among protocols into tracing units, measure their impact on the repeatability and diagnostic accuracy of manual hippocampal segmentation, and finally develop a harmonized protocol.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract Background Hippocampal volumetry on magnetic resonance imaging is recognized as an Alzheimer's disease (AD) biomarker, and manual segmentation is the gold standard for measurement. However, ...a standard procedure is lacking. We operationalize and quantitate landmark differences to help a Delphi panel converge on a set of landmarks. Methods One hundred percent of anatomic landmark variability across 12 different protocols for manual segmentation was reduced into four segmentation units (the minimum hippocampus, the alveus/fimbria, the tail, and the subiculum), which were segmented on magnetic resonance images by expert raters to estimate reliability and AD-related atrophy. Results Intra- and interrater reliability were more than 0.96 and 0.92, respectively, except for the alveus/fimbria, which were 0.86 and 0.77, respectively. Of all AD-related atrophy, the minimum hippocampus contributed to 67%; tail, 24%; alveus/fimbria, 4%; and the subiculum, 5%. Conclusions Anatomic landmark variability in available protocols can be reduced to four discrete and measurable segmentation units. Their quantitative assessment will help a Delphi panel to define a set of landmarks for a harmonized protocol.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Major hardware/software changes to MRI platforms, either planned or unplanned, will almost invariably occur in longitudinal studies. Our objective was to assess the resulting variability on relevant ...imaging measurements in such context, specifically for three Siemens Healthcare Magnetom Trio upgrades to the Prisma
platform. We report data acquired on three healthy volunteers scanned before and after three different platform upgrades. We assessed differences in image signal contrast-to-noise ratio (CNR) on T1-weighted images (T1w) and fluid-attenuated inversion recovery images (FLAIR); brain morphometry on T1w image; and small vessel disease (white matter hyperintensities; WMH) on FLAIR image. Prisma
upgrade resulted in higher (30%) and more variable neocortical CNR and larger brain volume and thickness mainly in frontal areas. A significant relationship was observed between neocortical CNR and neocortical volume. For FLAIR images, no significant CNR difference was observed, but WMH volumes were significantly smaller (-68%) after Prisma
upgrade, when compared to results on the Magnetom Trio. Together, these results indicate that Prisma
upgrade significantly influenced image signal, brain morphometry measures and small vessel diseases measures and that these effects need to be taken into account when analyzing results from any longitudinal study undergoing similar changes.
Introduction
Brain activation is hypothesized to form an inverse U‐shape in prodromal Alzheimer's disease (AD), with hyperactivation in the early phase, followed by hypoactivation.
Methods
Using ...task‐related functional magnetic resonance imaging (fMRI), we tested the inverse U‐shape hypothesis with polynomial regressions and between‐group comparisons in individuals with subjective cognitive decline plus (SCD+; smaller hippocampal volumes compared to a group of healthy controls without SCD and/or apolipoprotein E APOE ε4 allele) or mild cognitive impairment (MCI).
Results
A quadratic function modeled the relationship between proxies of disease severity (neurodegeneration, memory performance) and left superior parietal activation. Linear negative functions modeled the relationship between neurodegeneration and left hippocampal/right inferior temporal activation. Group comparison indicated presence of hyperactivation in SCD+ and hypoactivation in MCI in the left superior parietal lobule, relative to healthy controls.
Discussion
These findings support the presence of an inverse U‐shape model of activation and suggest that hyperactivation might represent a biomarker of the early AD stages.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
We aimed to longitudinally assess the relationship between changing brain energy metabolism (glucose and acetoacetate) and cognition during healthy aging. Participants aged 71 ± 5 year underwent ...cognitive evaluation and quantitative positron emission tomography (PET) and magnetic resonance imaging (MRI) scans at baseline (
= 25) and two (
= 25) and four (
= 16) years later. During the follow-up, the rate constant for brain extraction of glucose (K
) declined by 6%-12% mainly in the temporo-parietal lobes and cingulate gyri (
≤ 0.05), whereas brain acetoacetate extraction (Kacac) and utilization remained unchanged in all brain regions (
≥ 0.06). Over the 4 years, cognitive results remained within the normal age range but an age-related decline was observed in processing speed. K
in the caudate was directly related to performance on several cognitive tests (
= +0.41 to +0.43,
≤ 0.04). Peripheral insulin resistance assessed by the homeostasis model assessment of insulin resistance (HOMA-IR) was significantly inversely related to K
in the thalamus (
= -0.44,
= 0.04) and in the caudate (
= -0.43,
= 0.05), and also inversely related to executive function, attention and processing speed (
= -0.45 to -0.53, all
≤ 0.03). We confirm in a longitudinal setting that the age-related decline in K
is directly associated with declining performance on some tests of cognition but does not significantly affect Kacac.
Proper normative data of anatomical measurements of cortical regions, allowing to quantify brain abnormalities, are lacking. We developed norms for regional cortical surface areas, thicknesses, and ...volumes based on cross-sectional MRI scans from 2713 healthy individuals aged 18 to 94 years using 23 samples provided by 21 independent research groups. The segmentation was conducted using FreeSurfer, a widely used and freely available automated segmentation software. Models predicting regional cortical estimates of each hemisphere were produced using age, sex, estimated total intracranial volume (eTIV), scanner manufacturer, magnetic field strength, and interactions as predictors. The explained variance for the left/right cortex was 76%/76% for surface area, 43%/42% for thickness, and 80%/80% for volume. The mean explained variance for all regions was 41% for surface areas, 27% for thicknesses, and 46% for volumes. Age, sex and eTIV predicted most of the explained variance for surface areas and volumes while age was the main predictors for thicknesses. Scanner characteristics generally predicted a limited amount of variance, but this effect was stronger for thicknesses than surface areas and volumes. For new individuals, estimates of their expected surface area, thickness and volume based on their characteristics and the scanner characteristics can be obtained using the derived formulas, as well as Z score effect sizes denoting the extent of the deviation from the normative sample. Models predicting normative values were validated in independent samples of healthy adults, showing satisfactory validation R2. Deviations from the normative sample were measured in individuals with mild Alzheimer's disease and schizophrenia and expected patterns of deviations were observed.
•Normative data for morphometric estimates of cortical brain regions are provided.•Segmentation was performed using FreeSurfer 5.3 with Desikan-Killiany atlas.•Models include age, sex, eTIV and scanner's OEM and strength.•Normative Z scores can be automatically computed using supplemental material.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract Background A globally harmonized protocol (HarP) for manual hippocampal segmentation based on magnetic resonance has been recently developed by a task force from European Alzheimer's Disease ...Consortium (EADC) and Alzheimer's Disease Neuroimaging Initiative (ADNI). Our aim was to produce benchmark labels based on the HarP for manual segmentation. Methods Five experts of manual hippocampal segmentation underwent specific training on the HarP and segmented 40 right and left hippocampi from 10 ADNI subjects on both 1.5 T and 3 T scans. An independent expert visually checked segmentations for compliance with the HarP. Descriptive measures of agreement between tracers were intraclass correlation coefficients (ICCs) of crude volumes and similarity coefficients of three-dimensional volumes. Results Two hundred labels have been provided for the 20 magnetic resonance images. Intra- and interrater ICCs were >0.94, and mean similarity coefficients were 1.5 T, 0.73 (95% confidence interval CI, 0.71–0.75); 3 T, 0.75 (95% CI, 0.74–0.76). Conclusion Certified benchmark labels have been produced based on the HarP to be used for tracers' training and qualification.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
40.
FreeSurfer subcortical normative data Potvin, Olivier; Mouiha, Abderazzak; Dieumegarde, Louis ...
Data in brief,
12/2016, Volume:
9, Issue:
C
Journal Article
Peer reviewed
Open access
This article contains a spreadsheet computing estimates of the expected subcortical regional volumes of an individual based on its characteristics and the scanner characteristics, in addition to ...supplementary results related to the article “Normative data for subcortical regional volumes over the lifetime of the adult human brain” (O. Potvin, A. Mouiha, L. Dieumegarde, S. Duchesne, 2016) 1 on normative data for subcortical volumes. Data used to produce normative values was obtained by anatomical magnetic resonance imaging from 2790 healthy individuals aged 18–94 years using 23 samples provided by 21 independent research groups. The segmentation was conducted using FreeSurfer. The spreadsheet includes formulas in order to compute for a new individual, significance test for volume abnormality, effect size and estimated percentage of the normative population with a smaller volume while taking into account age, sex, estimated intracranial volume (eTIV), and scanner characteristics. Detailed R-squares of each predictor for all formula are also reported as well as the difference of subcortical volumes segmented by FreeSurfer on two different computer hardware setups.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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