Hypometabolism exceeds atrophy in presymptomatic early-onset familial Alzheimer's disease.

Department of Psychiatry, New York University School of Medicine, New York, New York, USA.
Journal of Nuclear Medicine (Impact Factor: 5.56). 11/2006; 47(11):1778-86.
Source: PubMed

ABSTRACT The aim of the present study is to compare brain atrophy with hypometabolism as preclinical markers of Alzheimer's disease (AD) by studying presymptomatic individuals from families with known early-onset autosomal dominant AD (FAD) carrying mutations in the Presenilin 1 gene.
Seven asymptomatic at-risk FAD individuals (age, 35-49 y; 4 women; education >/= 12 y) and 7 matched healthy control subjects received complete clinical, neuropsychologic, MRI, and (18)F-FDG PET examinations. Regions of interest (ROIs: whole brain [WB], hippocampus [Hip], entorhinal cortex [EC], posterior cingulate cortex [PCC], inferior parietal lobule [IPL], and superior temporal gyrus (STG]) were drawn on the MRI scans of all subjects and used to measure volumes on MRI and glucose metabolism (MRglc) from the MRI-coregistered, atrophy-corrected PET scans.
Compared with controls and after correcting for head size, MRI volume reductions in FAD subjects were restricted to the IPL (18%, P < 0.02). After atrophy correction and adjusting for pons MRglc, PET MRglc reductions were found in all FAD subjects compared with controls in the WB (13%), bilaterally in the IPL (17%) and in the STG (12%), and in the left EC (21%), PCC (20%), and Hip (12%) (P values < 0.05). PET MRglc measurements were consistently less variable than MRI measures, yielding significantly larger effect sizes in separating FAD from controls.
Presymptomatic FAD individuals show widespread MRglc reductions consistent with the typical AD PET pattern in the relative absence of structural brain atrophy. These data further suggest that PET MRglc measures may serve as biomarkers for the preclinical diagnosis of AD.

Download full-text


Available from: Benedetta Nacmias, Jun 30, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Functional brain imaging is a common tool in monitoring the progression of neurodegenerative and neurological disorders. Identifying functional brain imaging derived features that can accurately detect neurological disease is of primary importance to the medical community. Research in computer vision techniques to identify objects in photographs have reported high accuracies in that domain, but their direct applicability to identifying disease in functional imaging is still under investigation in the medical community. In particular, Serre et al. ([2005]: In: IEEE Conference on Computer Vision and Pattern Recognition (CVPR-05). pp 994-1000) introduced a biophysically inspired filtering method emulating visual processing in striate cortex which they applied to perform object recognition in photographs. In this work, the model described by Serre et al. [2005] is extended to three-dimensional volumetric images to perform signal detection in functional brain imaging (PET, SPECT). The filter outputs are used to train both neural network and logistic regression classifiers and tested on two distinct datasets: ADNI Alzheimer's disease 2-deoxy-D-glucose (FDG) PET and National Football League players Tc99m HMPAO SPECT. The filtering pipeline is analyzed to identify which steps are most important for classification accuracy. Our results compare favorably with other published classification results and outperform those of a blinded expert human rater, suggesting the utility of this approach. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
    Human Brain Mapping 01/2014; 35(1). DOI:10.1002/hbm.22149 · 6.92 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Rare autosomal dominant mutations result in familial Alzheimer's disease (FAD) with a relatively consistent age of onset within families. This provides an estimate of years until disease onset (relative age) in mutation carriers. Increased AD risk has been associated with differences in functional magnetic resonance imaging (fMRI) activity during memory tasks, but most of these studies have focused on possession of apolipoprotein E allele 4 (APOE4), a risk factor, but not causative variant, of late-onset AD. Evaluation of fMRI activity in presymptomatic FAD mutation carriers versus noncarriers provides insight into preclinical changes in those who will certainly develop AD in a prescribed period of time. Adults from FAD mutation-carrying families (nine mutation carriers, eight noncarriers) underwent fMRI scanning while performing a memory task. We examined fMRI signal differences between carriers and noncarriers, and how signal related to fMRI task performance within mutation status group, controlling for relative age and education. Mutation noncarriers had greater retrieval period activity than carriers in several AD-relevant regions, including the left hippocampus. Better performing noncarriers showed greater encoding period activity including in the parahippocampal gyrus. Poorer performing carriers showed greater retrieval period signal, including in the frontal and temporal lobes, suggesting underlying pathological processes. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
    Human Brain Mapping 12/2013; 34(12). DOI:10.1002/hbm.22141 · 6.92 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite decades of study, it is still unclear whether regional brain glucose uptake is lower in the cognitively healthy elderly. Whether regional brain uptake of ketones (β-hydroxybutyrate and acetoacetate [AcAc]), the main alternative brain fuel to glucose, changes with age is unknown. We used a sequential, dual tracer positron emission tomography (PET) protocol to quantify brain (18)F-fluorodeoxyglucose ((18)F-FDG) and (11)C-AcAc uptake in two studies with healthy, male Sprague-Dawley rats: (i) Aged (21 months; 21M) versus young (4 months; 4M) rats, and (ii) The effect of a 14 day high-fat ketogenic diet (KD) on brain (18)F-FDG and (11)C-AcAc uptake in 24 month old rats (24M). Similar whole brain volumes assessed by magnetic resonance imaging, were observed in aged 21M versus 4M rats, but the lateral ventricles were 30% larger in the 21M rats (p=0.001). Whole brain cerebral metabolic rates of AcAc (CMR(AcAc)) and glucose (CMR(glc)) did not differ between 21M and 4M rats, but were 28% and 44% higher, respectively, in 24M-KD compared to 24M rats. The region-to-whole brain ratio of CMR(glc) was 37-41% lower in the cortex and 40-45% lower in the cerebellum compared to CMR(AcAc) in 4M and 21M rats. We conclude that a quantitative measure of uptake of the brain's two principal exogenous fuels was generally similar in healthy aged and young rats, that the % of distribution across brain regions differed between ketones and glucose, and that brain uptake of both fuels was stimulated by mild, experimental ketonemia.
    Brain research 10/2012; 1488. DOI:10.1016/j.brainres.2012.10.008 · 2.83 Impact Factor