Dataset Information

Differential impact of body mass index and leptin on baseline and longitudinal positron emission tomography measurements of the cerebral metabolic rate for glucose in amnestic mild cognitive impairment.

ABSTRACT:

Introduction

Several studies have suggested that greater adiposity in older adults is associated with a lower risk of Alzheimer's disease (AD) related cognitive decline, some investigators have postulated that this association may be due to the protective effects of the adipose tissue-derived hormone leptin. In this study we sought to demonstrate that higher body mass indices (BMIs) are associated with greater baseline FDG PET measurements of the regional cerebral metabolic rate for glucose (rCMRgl), a marker of local neuronal activity, slower rCMRgl declines in research participants with amnestic mild cognitive impairment (aMCI). We then sought to clarify the extent to which those relationships are attributable to cerebrospinal fluid (CSF) or plasma leptin concentrations.

Materials and methods

We used baseline PET images from 716 73 ± 8 years-old aMCI participants from the AD Neuroimaging Initiative (ADNI) of whom 453 had follow up images (≥6 months; mean follow up time 3.3 years). For the leptin analyses, we used baseline CSF samples from 81 of the participants and plasma samples from 212 of the participants.

Results

As predicted, higher baseline BMI was associated with greater baseline CMRgl measurements and slower declines within brain regions preferentially affected by AD. In contrast and independently of BMI, CSF, and plasma leptin concentrations were mainly related to less baseline CMRgl within mesocorticolimbic brain regions implicated in energy homeostasis.

Discussion

While higher BMIs are associated with greater baseline CMRgl and slower declines in persons with aMCI, these associations appear not to be primarily attributable to leptin concentrations.

SUBMITTER: Weise CM

PROVIDER: S-EPMC9782536 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Differential impact of body mass index and leptin on baseline and longitudinal positron emission tomography measurements of the cerebral metabolic rate for glucose in amnestic mild cognitive impairment.

Weise Christopher M CM Chen Kewei K Chen Yinghua Y Devadas Vivek V Su Yi Y Reiman Eric M EM

Frontiers in aging neuroscience 20221122

<h4>Introduction</h4>Several studies have suggested that greater adiposity in older adults is associated with a lower risk of Alzheimer's disease (AD) related cognitive decline, some investigators have postulated that this association may be due to the protective effects of the adipose tissue-derived hormone leptin. In this study we sought to demonstrate that higher body mass indices (BMIs) are associated with greater baseline FDG PET measurements of the regional cerebral metabolic rate for gluc ...[more]

PMID: 36570534

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Project description:ImportancePatients with amnestic mild cognitive impairment (aMCI) may progress to clinical Alzheimer disease (AD), remain stable, or revert to normal. Earlier progression to AD among patients who were β-amyloid positive vs those who were β-amyloid negative has been previously observed. Current research now accepts that a combination of biomarkers could provide greater refinement in the assessment of risk for clinical progression.ObjectiveTo evaluate the ability of flutemetamol F 18 and other biomarkers to assess the risk of progression from aMCI to probable AD.Design, setting, and participantsIn this multicenter cohort study, from November 11, 2009, to January 16, 2014, patients with aMCI underwent positron emission tomography (PET) at baseline followed by local clinical assessments every 6 months for up to 3 years. Patients with aMCI (365 screened; 232 were eligible) were recruited from 28 clinical centers in Europe and the United States. Physicians remained strictly blinded to the results of PET, and the standard of truth was an independent clinical adjudication committee that confirmed or refuted local assessments. Flutemetamol F 18-labeled PET scans were read centrally as either negative or positive by 5 blinded readers with no knowledge of clinical status. Statistical analysis was conducted from February 19, 2014, to January 26, 2018.InterventionsFlutemetamol F 18-labeled PET at baseline followed by up to 6 clinical visits every 6 months, as well as magnetic resonance imaging and multiple cognitive measures.Main outcomes and measuresTime from PET to probable AD or last follow-up was plotted as a Kaplan-Meier survival curve; PET scan results, age, hippocampal volume, and aMCI stage were entered into Cox proportional hazards logistic regression analyses to identify variables associated with progression to probable AD.ResultsOf 232 patients with aMCI (118 women and 114 men; mean [SD] age, 71.1 [8.6] years), 98 (42.2%) had positive results detected on PET scan. By 36 months, the rates of progression to probable AD were 36.2% overall (81 of 224 patients), 53.6% (52 of 97) for patients with positive results detected on PET scan, and 22.8% (29 of 127) for patients with negative results detected on PET scan. Hazard ratios for association with progression were 2.51 (95% CI, 1.57-3.99; P < .001) for a positive β-amyloid scan alone (primary outcome measure), 5.60 (95% CI, 3.14-9.98; P < .001) with additional low hippocampal volume, and 8.45 (95% CI, 4.40-16.24; P < .001) when poorer cognitive status was added to the model.Conclusions and relevanceA combination of positive results of flutemetamol F 18-labeled PET, low hippocampal volume, and cognitive status corresponded with a high probability of risk of progression from aMCI to probable AD within 36 months.

Project description:Background and Purpose- The clinical utility of positron emission tomography (PET) imaging in evaluating carotid artery plaque vulnerability remains unclear. Two tracers of recent interest for carotid plaque imaging are 18F-fluorodeoxyglucose (18F-FDG) and 18F-sodium fluoride (18F-NaF). We performed a systematic review and meta-analysis evaluating the association between carotid artery 18F-FDG or 18F-NaF uptake and recent or future cerebral ischemic events. Methods- A systematic review of Ovid MEDLINE, Ovid EMBASE, and the Cochrane library was conducted from inception to December 2017 for articles evaluating PET tracer uptake in recently symptomatic versus asymptomatic carotid arteries, and articles evaluating carotid uptake in relation to future ischemic events. Cerebral ischemic events were defined as ipsilateral strokes, transient ischemic attacks, or amaurosis fugax. We quantitatively pooled studies by a random-effects model when 3 or more studies were amenable for analysis. We assessed the standardized mean difference between tracer uptake in the symptomatic versus asymptomatic carotid artery using Cohen's d metric. Results- After screening 4144 unique articles, 13 prospective cohort studies assessing carotid artery 18F-FDG uptake in patients with recent cerebral ischemia were eligible for review. Eleven cohorts of 290 subjects scanned with 18F-FDG were eligible for meta-analysis. We found that carotid arteries ipsilateral to recent ischemic events had significantly higher 18F-FDG uptake than asymptomatic arteries (Cohen's d =0.492; CI=0.130-0.855; P=0.008) as well as significant heterogeneity (Cochran's Q =31.5; P=0.0005; I2=68.3%). Meta-regression was not performed due to the limited number of studies in the analysis. Only 2 studies investigating 18F-NaF PET imaging, and another 2 articles investigating ischemic event recurrence were found. Conclusions- Recent ipsilateral cerebral ischemia may be associated with increased carotid 18F-FDG uptake on PET imaging regardless of degree of carotid stenosis, although significant heterogeneity was found, and these results should be interpreted with caution. Emerging evidence suggests a similar association may be present with 18F-NaF plaque uptake. More studies are warranted to provide definitive conclusions on the utility of 18F-FDG or 18F-NaF in carotid plaque evaluation before investigating carotid PET as a diagnostic tool for cerebral ischemic events.

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Dataset Information

Differential impact of body mass index and leptin on baseline and longitudinal positron emission tomography measurements of the cerebral metabolic rate for glucose in amnestic mild cognitive impairment.

Introduction

Materials and methods

Results

Discussion

Publications

Differential impact of body mass index and leptin on baseline and longitudinal positron emission tomography measurements of the cerebral metabolic rate for glucose in amnestic mild cognitive impairment.

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