Reduced hippocampal metabolism in MCI and AD: automated FDG-PET image analysis

University of Florence, Florens, Tuscany, Italy
Neurology (Impact Factor: 8.3). 07/2005; 64(11):1860-7. DOI: 10.1212/01.WNL.0000163856.13524.08
Source: PubMed

ABSTRACT To facilitate image analysis, most recent 2-[18F]fluoro-2-deoxy-d-glucose PET (FDG-PET) studies of glucose metabolism (MRglc) have used automated voxel-based analysis (VBA) procedures but paradoxically none reports hippocampus MRglc reductions in mild cognitive impairment (MCI) or Alzheimer disease (AD). Only a few studies, those using regions of interest (ROIs), report hippocampal reductions. The authors created an automated and anatomically valid mask technique to sample the hippocampus on PET (HipMask).
Hippocampal ROIs drawn on the MRI of 48 subjects (20 healthy elderly [NL], 16 MCI, and 12 AD) were used to develop the HipMask. The HipMask technique was applied in an FDG-PET study of NL (n = 11), MCI (n = 13), and AD (n = 12), and compared to both MRI-guided ROIs and VBA methods.
HipMask and ROI hippocampal sampling produced significant and equivalent MRglc reductions for contrasts between MCI and AD relative to NL. The VBA showed typical cortical effects but failed to show hippocampal MRglc reductions in either clinical group. Hippocampal MRglc was the only discriminator of NL vs MCI (78% accuracy) and added to the cortical MRglc in classifying NL vs AD and MCI vs AD.
The new HipMask technique provides accurate and rapid assessment of the hippocampus on PET without the use of regions of interest. Hippocampal glucose metabolism reductions are found in both mild cognitive impairment and Alzheimer disease and contribute to their diagnostic classification. These results suggest re-examination of prior voxel-based analysis 2-[18F]fluoro-2-deoxy-d-glucose PET studies that failed to report hippocampal effects.

1 Follower
  • Source
    • "Numerous epidemiologic studies have shown that diabetes and insulin resistance are strong risk factors for cognitive decline and AD [55] [56] [57] [58] [59] [60], and we and others have shown that impaired glucose metabolism is associated with increased progression from mild cognitive impairment to AD [61] [62]. Moreover, clinical studies using FDG-PET have demonstrated that decreased glucose metabolism occurs very early in AD brain and is predictive of disease diagnosis [63] [64]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Although Alzheimer's Disease (AD) is the most common neurodegenerative disease, the etiology of AD is not well understood. In some cases, genetic factors explain AD risk, but a high percentage of late-onset AD is unexplained. The fact that AD is associated with a number of physical and systemic manifestations suggests that AD is a multifactorial disease that affects both the CNS and periphery. Interestingly, a common feature of many systemic processes linked to AD is involvement in energy metabolism. The goals of this review are to 1) explore the evidence that peripheral processes contribute to AD risk, 2) explore ways that AD modulates whole-body changes, and 3) discuss the role of genetics, mitochondria, and vascular mechanisms as underlying factors that could mediate both central and peripheral manifestations of AD. Despite efforts to strictly define AD as a homogeneous CNS disease, there may be no single etiologic pathway leading to the syndrome of AD dementia. Rather, the neurodegenerative process may involve some degree of baseline genetic risk that is modified by external risk factors. Continued research into the diverse but related processes linked to AD risk is necessary for successful development of disease -modifying therapies.
    Biochimica et Biophysica Acta 04/2014; 1842(9). DOI:10.1016/j.bbadis.2014.04.012
  • Source
    • "Alzheimer's disease is the most common cause of dementia, and is associated with accumulation of amyloid-b, tau, and progressive brain atrophy (Blennow et al., 2006). Early in the development of Alzheimer's disease, brain function in specific regions is reduced, as reflected by regionally reduced glucose metabolism (Friedland et al., 1983, 1989; Reiman et al., 1996; Silverman et al., 2001; Ché telat et al., 2003; Mosconi et al., 2005, 2008) and cerebral blood flow (CBF) (Johnson et al., 1987; Ishii et al., 1997) measured by PET. Moreover, brain accumulation of amyloid-b is associated with both brain atrophy and CBF changes, as detected by 15 O-H 2 O PET in cognitively healthy controls (Sojkova et al., 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Patients with Alzheimer's disease have reduced cerebral blood flow measured by arterial spin labelling magnetic resonance imaging, but it is unclear how this is related to amyloid-β pathology. Using 182 subjects from the Alzheimer's Disease Neuroimaging Initiative we tested associations of amyloid-β with regional cerebral blood flow in healthy controls (n = 51), early (n = 66) and late (n = 41) mild cognitive impairment, and Alzheimer's disease with dementia (n = 24). Based on the theory that Alzheimer's disease starts with amyloid-β accumulation and progresses with symptoms and secondary pathologies in different trajectories, we tested if cerebral blood flow differed between amyloid-β-negative controls and -positive subjects in different diagnostic groups, and if amyloid-β had different associations with cerebral blood flow and grey matter volume. Global amyloid-β load was measured by florbetapir positron emission tomography, and regional blood flow and volume were measured in eight a priori defined regions of interest. Cerebral blood flow was reduced in patients with dementia in most brain regions. Higher amyloid-β load was related to lower cerebral blood flow in several regions, independent of diagnostic group. When comparing amyloid-β-positive subjects with -negative controls, we found reductions of cerebral blood flow in several diagnostic groups, including in precuneus, entorhinal cortex and hippocampus (dementia), inferior parietal cortex (late mild cognitive impairment and dementia), and inferior temporal cortex (early and late mild cognitive impairment and dementia). The associations of amyloid-β with cerebral blood flow and volume differed across the disease spectrum, with high amyloid-β being associated with greater cerebral blood flow reduction in controls and greater volume reduction in late mild cognitive impairment and dementia. In addition to disease stage, amyloid-β pathology affects cerebral blood flow across the span from controls to dementia patients. Amyloid-β pathology has different associations with cerebral blood flow and volume, and may cause more loss of blood flow in early stages, whereas volume loss dominates in late disease stages.
    Brain 03/2014; 137(5). DOI:10.1093/brain/awu043
  • Source
    • "n ¼ 14 HC n ¼ 13 AD n ¼ 9 VD No 28% Y in gray matter 23% Y in white matter for AD and VD Benson et al. (1983) [194] n ¼ 16 HC n ¼ 8 AD No Y 49% for AD Cutler et al. (1985) [195] n ¼ 25 HC n ¼ 5 mild to moderate AD n ¼ 2 severe AD No 25-50% Y for severe AD in frontal, parietal, temporal, occipital lobes compared to mild-mod AD and HC Rapoport et al. (1986) [196] n ¼ 10 HC n ¼ 47 mild to moderate AD No 18-31% Y for AD Chawluk et al. (1987) [197] n ¼ 17 HC n ¼ 24 AD Yes 8% Y for AD Alavi et al. (1993) [198] n ¼ 17 HC n ¼ 20 AD Yes 11% Y for AD Mielke et al. (1994) [199] n ¼ 13 HC n ¼ 20 AD No Y for AD in temporoparietal and occipital cortex Metzler et al. (1996) [49] n ¼ 10 HC n ¼ 8 AD Yes Y for AD in frontal, temporal, and posterior parietal lobes Hock et al. (1997) [52] n ¼ 17 HC n ¼ 19 AD No Y for AD in parietal lobe Ibanez et al. (1998) [48] n ¼ 19 HC n ¼ 5 mild AD n ¼ 6 moderate AD n ¼ 4 severe AD Yes Y for AD in precuneaus and posterior cingulate cortex Mosconi et al. (2005) [50] n ¼ 11 HC n ¼ 13 MCI n ¼ 12 AD Yes 18% Y for MCI 27% Y for AD in hippocampus compared with HC Minoshima et al. (2007) [200] n ¼ 22 HC n ¼ 8 AD Yes 20-21% Y for AD in posterior cingulate and cinguloparietal transitional area Li et al. (2008) [37] "
    [Show abstract] [Hide abstract]
    ABSTRACT: Lower brain glucose metabolism is present before the onset of clinically measurable cognitive decline in two groups of people at risk of Alzheimer's disease--carriers of apolipoprotein E4, and in those with a maternal family history of AD. Supported by emerging evidence from in vitro and animal studies, these reports suggest that brain hypometabolism may precede and therefore contribute to the neuropathologic cascade leading to cognitive decline in AD. The reason brain hypometabolism develops is unclear but may include defects in brain glucose transport, disrupted glycolysis, and/or impaired mitochondrial function. Methodologic issues presently preclude knowing with certainty whether or not aging in the absence of cognitive impairment is necessarily associated with lower brain glucose metabolism. Nevertheless, aging appears to increase the risk of deteriorating systemic control of glucose utilization, which, in turn, may increase the risk of declining brain glucose uptake, at least in some brain regions. A contributing role of deteriorating glucose availability to or metabolism by the brain in AD does not exclude the opposite effect, i.e., that neurodegenerative processes in AD further decrease brain glucose metabolism because of reduced synaptic functionality and hence reduced energy needs, thereby completing a vicious cycle. Strategies to reduce the risk of AD by breaking this cycle should aim to (1) improve insulin sensitivity by improving systemic glucose utilization, or (2) bypass deteriorating brain glucose metabolism using approaches that safely induce mild, sustainable ketonemia.
    Nutrition 10/2010; 27(1):3-20. DOI:10.1016/j.nut.2010.07.021
Show more