Optimization of Statistical Single Subject Analysis of Brain FDG PET for the Prognosis of Mild Cognitive Impairment-to-Alzheimer’s Disease Conversion

Lange, Catharina; Suppa, Per; Frings, Lars; Brenner, Winfried; Spies, Lothar; Buchert, Ralph

doi:10.3233/jad-150814

Cited by 57 publications

(54 citation statements)

References 47 publications

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“…2 Striatal hypometabolism in mHD subjects with respect to control group, controlling for the effect of atrophy (p < 0.001 uncorrected, k = 50 voxel). Prefrontal and Temporal hypometabolism in mHD subjects with respect to control group (p < 0.001 uncorrected, k = 50 voxel) [24]. Then, they were spatially normalized to MNI space using the SPM PET template and smoothed using a Gaussian kernel of 12 × 12 × 12 mm FWHM.…”

Section: Qualitative and Quantitative Analysismentioning

confidence: 99%

Striatal hypometabolism in premanifest and manifest Huntington’s disease patients

López-Mora

Camacho

Pérez‐Pérez

et al. 2016

Eur J Nucl Med Mol Imaging

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F-FDG PET/CT might be a helpful tool to identify patterns of glucose metabolism in the striatum across the stages of HD and might be relevant in assessing the clinical status of gene-expanded HD carriers due to the fact that dysfunctional glucose metabolism begins at early preHD stages of the disease. F-FDG PET/CT appears as a promising method to monitor the response to disease-modifying therapies even if applied in premanifest subjects.

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Section: Qualitative and Quantitative Analysismentioning

confidence: 99%

Striatal hypometabolism in premanifest and manifest Huntington’s disease patients

López-Mora

Camacho

Pérez‐Pérez

et al. 2016

Eur J Nucl Med Mol Imaging

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“…The optimal dEQ score threshold to predict MCI2AD conversion appeared to be moderately sensitive and specific to that outcome. Its AUC of 0.86 is as good [35] or better than previous psychometric and neuroimaging biomarkers [36][37][38]. The combination of psychometrics and biomarkers may have incremental advantages over our approach [39,40], but ours is obtainable with much less expense and effort.…”

Section: Discussionmentioning

confidence: 80%

δ scores predict mild cognitive impairment and Alzheimer's disease conversions from nondemented states

Royall

Palmer²

2017

Alz & Dem Diag Ass & Dis Mo

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IntroductionWe tested the latent variable “δ” (for “dementia”)'s ability to predict conversion to “mild cognitive impairment” (MCI) and Alzheimer's disease (AD).MethodsAn ethnicity equivalent d homolog (“dEQ”) was constructed in n = 1113 Mexican- American (MA) and n = 1958 non-Hispanic white (NHW) participants in the Texas Alzheimer's Research and Care Consortium. “Normal Controls” (NC) (n = 1276) and MCI cases (n = 611) were followed annually for up to 6 years [m = 4.7(0.6)].Results22.0% (n = 281) of NC converted to “MCI” or “AD”. 17.3%( n = 106) of MCI converted to “AD.” Independently of covariates, each quintile increase in the dEQ scores of NC increased the odds of conversion by 52%. Each quintile increase in the dEQ scores of MCI cases increased the odds of conversion to AD almost three-fold.DiscussionBaseline δ scores predict MCI and AD conversions from nondemented states in MA and NHW.

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“…Interestingly, a moderate positive relationship between plasma cortisol levels and FDG uptake was found in the small group of cognitively normal individuals (n = 26), selectively within the pre-defined FDG AD signature 32 . The unexpected result could potentially reflect neural compensation or aberrant neural activation in the face of neurotoxic insults.…”

Section: Relationship Between Plasma Cortisol and Cerebral Glucose Mementioning

confidence: 94%

“…For structural MRI, we assessed bilateral hippocampal volume according HarP 30 , corrected for TIV using a simple ratio method. For FDG, we examined the mean SUVr in the combined AD ROI described above 32 .…”

Section: Regions-of Interest Analysismentioning

confidence: 99%

Cortisol associated with hypometabolism across the Alzheimer’s disease spectrum

Wirth

Lange

Huijbers

2019

Preprint

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Equal contribution (*) †Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: AbstractObjective: Hypothalamic-pituitary-adrenal (HPA) dysregulation is proposed as a risk factor for Alzheimer's disease (AD). This cross-sectional study assessed relationships between plasma cortisol levels and neuroimaging biomarkers, specifically brain glucose metabolism and gray matter volume, across the AD spectrum.Methods: Cognitively normal older adults and patients with mild cognitive impairment (MCI) and AD dementia were included from the Alzheimer's Disease Neuroimaging Initiative. Participants (n = 556) were selected based on availability of baseline measures of plasma cortisol levels and gray matter volume, as estimated with magnetic resonance imaging. Within a subsample (n = 288), we examined brain glucose metabolism (n = 288) as with positron emission tomography. Relationships between plasma cortisol and AD neuroimaging biomarkers were assessed using regions-of-interest and voxel-wise analyses.Results: Across the entire cohort, higher plasma cortisol was also related to lower gray matter volume, most notably in the left lateral temporal-parietal-occipital regions.Importantly, higher plasma cortisol concentration was also related to hypometabolism, especially in lateral temporo-parietal and medial parietal regions. When stratified by diagnosis, these negative associations were most pronounced in MCI and AD patients.Interpretation: High plasma cortisol was associated with hypometabolism predominantly in AD-sensitive regions. Our results indicate that HPA axis activation could influence brain metabolism and exacerbate existing AD pathological processes. This is consistent with a notion that stress is a conceivable target for intervention to slow down AD Plasma cortisol and cerebral glucose metabolism Wirth, Lange, and Huijbers; p. 3 progression. Future studies should delineate underlying pathological mechanisms and investigate if clinical or lifestyle interventions could alleviate negative actions of stress on AD.

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Optimization of Statistical Single Subject Analysis of Brain FDG PET for the Prognosis of Mild Cognitive Impairment-to-Alzheimer’s Disease Conversion

Abstract: The prognostic value of voxel-based single subject analysis of brain FDG PET in MCI subjects can be improved considerably by optimizing the processing pipeline.

Cited by 57 publications

References 47 publications

Striatal hypometabolism in premanifest and manifest Huntington’s disease patients

Striatal hypometabolism in premanifest and manifest Huntington’s disease patients

δ scores predict mild cognitive impairment and Alzheimer's disease conversions from nondemented states

Cortisol associated with hypometabolism across the Alzheimer’s disease spectrum

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