Reduced hippocampal metabolism in MCI and AD: automated FDG-PET image analysis
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.
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- "An additional fourth ROI with both hippocampi was included. This latter measurement was performed through HIPMASK , a technique specifically developed to measure hippocampal metabolism sampling that overcomes errors in spatial alignment of small structures such as the hippocampus and with an anatomically variable position; it is an automated technique based on the optimization of positive likelihood ratio that enables rapid PET sampling of brain subregions. Mean glucose metabolism intensity data were extracted for both left and right hippocampus normalized to pons as the reference region. "
ABSTRACT: The neural and cognitive substrates of measures of orientation as used in clinical trials and examinations have not been comprehensively examined.
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- "Numerous epidemiologic studies have shown that diabetes and insulin resistance are strong risk factors for cognitive decline and AD      , and we and others have shown that impaired glucose metabolism is associated with increased progression from mild cognitive impairment to AD  . Moreover, clinical studies using FDG-PET have demonstrated that decreased glucose metabolism occurs very early in AD brain and is predictive of disease diagnosis  . "
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 · 4.66 Impact Factor
- "Semantic dementia (Neary et al., 1998), also referred to as the semantic variant of primary progressive aphasia (Gorno-Tempini et al., 2011) or temporal variant of frontotemporal lobar degeneration (Seeley et al., 2005), is characterized by a gradual and modality-independent loss of semantic knowledge, resulting in specific language disturbances with impaired naming and word comprehension but a fluent and grammatically correct speech. Neuroimaging studies showed that, in both diseases, the medial temporal lobe undergoes atrophy (Chan et al., 2001; Galton et al., 2001; Nestor et al., 2006; Schroeter and Neumann, 2011; Duval et al., 2012; La Joie et al., 2012) and hypometabolism (Desgranges et al., 2007; Rabinovici et al., 2008; Mosconi et al., 2005; Nestor et al., 2006; Duval et al., 2012; La Joie et al., 2012). This has been highlighted as a paradox given the widely documented relationship between hippocampal impairment and early episodic memory deficits in AD (Deweer et al., 1995; Kö hler et al., 1998; Laakso et al., 2000; Scheltens et al., 1992; Ché telat et al., 2003) faced to the relative preservation of dayto-day episodic memory in SD (Chan et al., 2001; Galton et al., 2001; Nestor et al., 2006; Pleizier et al., 2012). "