A Cochrane review on brain [18F]FDG PET in dementia: limitations and future perspectives

Morbelli, Silvia; Garibotto, Valentina; Giessen, Elsmarieke van de; Arbizu, Javier; Chételat, Gaël; Drezgza, Alexander; Hesse, Swen; Lammertsma, Adriaan A.; Law, Ian; Pappatà, Sabina; Payoux, Pierre; Pagani, Marco

doi:10.1007/s00259-015-3098-2

Cited by 59 publications

(33 citation statements)

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“…In all between-group comparisons except hippocampus volume, the EMCI subjects were similar to the healthy CN controls, underscoring the heterogeneity of this clinical concept. The lack of difference in PCC metabolism dissociates EMCI from the classical MCI concept in which PCC hypometabolism has been shown as a robust finding [50]. Third, effect sizes for the significant effects of hippocampus volume on PCC metabolism were small, particularly in CN and EMCI subjects.…”

Section: Discussionmentioning

confidence: 99%

Does posterior cingulate hypometabolism result from disconnection or local pathology across preclinical and clinical stages of Alzheimer’s disease?

Teipel

Grothe

2015

Eur J Nucl Med Mol Imaging

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Purpose Posterior cingulate cortex (PCC) hypometabolism as measured by FDG PET is an indicator of Alzheimer’s disease (AD) in prodromal stages, such as in mild cognitive impairment (MCI), and has been found to be closely associated with hippocampus atrophy in AD dementia. We studied the effects of local and remote atrophy and of local amyloid load on the PCC metabolic signal in patients with different preclinical and clinical stages of AD. Methods We determined the volume of the hippocampus and PCC grey matter based on volumetric MRI scans, PCC amyloid load based on AV45 PET, and PCC metabolism based on FDG PET in 667 subjects participating in the Alzheimer’s Disease Neuroimaging Initiative spanning the range from cog-nitively normal ageing through prodromal AD to AD dementia. Results In cognitively normal individuals and those with early MCI, PCC hypometabolism was exclusively associated with hippocampus atrophy, whereas in subjects with late MCI it was associated with both local and remote effects of atrophy as well as local amyloid load. In subjects with AD dementia, PCC hypometabolism was exclusively related to local atrophy. Conclusion Our findings suggest that the effects of remote pathology on PCC hypometabolism decrease and the effects of local pathology increase from preclinical to clinical stages of AD, consistent with a progressive disconnection of the PCC from downstream cortical and subcortical brain regions.

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Section: Discussionmentioning

confidence: 99%

Does posterior cingulate hypometabolism result from disconnection or local pathology across preclinical and clinical stages of Alzheimer’s disease?

Teipel

Grothe

2015

Eur J Nucl Med Mol Imaging

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“…However, a limited accuracy of prediction by 18 F-FDG PET of conversion from MCI to AD was reported in some studies (6)(7)(8). Likewise, a Cochrane review did not recommend using 18 F-FDG PET for this purpose (9), although this recommendation has been a matter of controversy (10).…”

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confidence: 99%

Principal Components Analysis of Brain Metabolism Predicts Development of Alzheimer Dementia

Blazhenets

Sörensen

et al. 2018

J Nucl Med

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The value of 18 F-FDG PET for predicting conversion from mild cognitive impairment (MCI) to Alzheimer dementia (AD) is currently under debate. We used a principal components analysis (PCA) to identify a metabolic AD conversion-related pattern (ADCRP) and investigated the prognostic value of the resulting pattern expression score (PES). Methods: 18 F-FDG PET scans of 544 MCI patients were obtained from the Alzheimer Disease Neuroimaging Initiative database and analyzed. We implemented voxel-based PCA and standard Statistical Parametric Mapping analysis (as a reference) to disclose cerebral metabolic patterns associated with conversion from MCI to AD. By Cox proportional hazards regression, we examined the prognostic value of candidate predictors. Also, we constructed prognostic models with clinical, imaging, and clinical and imaging variables in combination. Results: PCA revealed an ADCRP that involved regions with relative decreases in metabolism (temporoparietal, frontal, posterior cingulate, and precuneus cortices) and relative increases in metabolism (sensorimotor and occipital cortices, cerebellum, and left putamen). Among the predictor variables age, sex, Functional Activities Questionnaire, Mini-Mental State Examination, apolipoprotein E, PES, and normalized 18 F-FDG uptake (regions with significant hypo-and hypermetabolism in patients with conversion vs. those without conversion), PES was the best independent predictor of conversion (hazard ratio, 1.77, per z score increase; 95% CI, 1.24-2.52; P , 0.001). Moreover, adding PES to the model including the clinical variables significantly increased its prognostic value. Conclusion: The ADCRP expression score was a valid predictor of conversion. A combination of clinical variables and PES yielded a higher accuracy than each single tool in predicting conversion from MCI to AD, underlining the incremental utility of 18 F-FDG PET. Principal Components Analysis of Brain Metabolism PredictsDevelopment of http://jnm.snmjournals.org/content/60/6/837 This article and updated information are available at: http://jnm.snmjournals.org/site/subscriptions/online.xhtml Information about subscriptions to JNM can be found at: http://jnm.snmjournals.org/site/misc/permission.xhtml

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“…Values for sensitivity and specificity are quite variable, depending on disease severity as well as on the specific metric used, but the overall performance of the test is good, with a median sensitivity and specificity of 80 and 72.5%, respectively [9, 10]. …”

Section: Introductionmentioning

confidence: 99%

Education-Adjusted Normality Thresholds for FDG-PET in the Diagnosis of Alzheimer Disease

et al. 2018

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Background: A corollary of the reserve hypothesis is that what is regarded as pathological cortical metabolism in patients might vary according to education. Objective: The aim of this study is to assess the incremental diagnostic value of education-adjusted over unadjusted thresholds on the diagnostic accuracy of FDG-PET as a biomarker for Alzheimer disease (AD). Methods: We compared cortical metabolism in 90 healthy controls and 181 AD patients from the Alzheimer Disease Neuroimaging Initiative (ADNI) database. The AUC of the ROC curve did not differ significantly between the whole group and the higher-education patients or the lower-education subjects. Results: The threshold of wMetaROI values providing 80% sensitivity was lower in higher-education patients and higher in the lower-education patients, compared to the standard threshold derived over the whole AD collective, without, however, significant changes in sensitivity and specificity. Conclusion: These data show that education, as a proxy of reserve, is not a major confounder in the diagnostic accuracy of FDG-PET in AD and the adoption of education-adjusted thresholds is not required in daily practice.

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A Cochrane review on brain [18F]FDG PET in dementia: limitations and future perspectives

Cited by 59 publications

References 50 publications

Does posterior cingulate hypometabolism result from disconnection or local pathology across preclinical and clinical stages of Alzheimer’s disease?

Does posterior cingulate hypometabolism result from disconnection or local pathology across preclinical and clinical stages of Alzheimer’s disease?

Principal Components Analysis of Brain Metabolism Predicts Development of Alzheimer Dementia

Education-Adjusted Normality Thresholds for FDG-PET in the Diagnosis of Alzheimer Disease

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