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

University of Florence, Florens, Tuscany, Italy
Neurology (Impact Factor: 8.29). 07/2005; 64(11):1860-7. DOI: 10.1212/01.WNL.0000163856.13524.08
Source: PubMed


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
32 Reads
  • Source
    • "campus through the perforant pathway ( Van Hoesen and Pandya , 1975 ) . CA3 neurons project Schaffer collaterals to CA1 pyramidal neurons , which finally project to the subiculum and deep EC layers IV , V and VI ( EC - IV - VI ; Figure 1 ) . The MTL undergoes atrophy and hypometabolism not only in AD but also in MCI stages ( Press et al . , 1989 ; Mosconi et al . , 2005 ; La Joie et al . , 2013 ) , an effect observed at least 4 years in advance to cognitive symptoms ( Tondelli et al . , 2012 ) . Indeed , disruption of the hippocampus , a critical component of this memory circuit , is sufficient to produce anterograde amnesia ( Zola - Morgan et al . , 1986 ) . The EC is severely affected by pathological"
    [Show abstract] [Hide abstract]
    ABSTRACT: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by abnormal accumulation of β-amyloid and tau and synapse dysfunction in memory-related neural circuits. Pathological and functional changes in the medial temporal lobe, a region essential for explicit memory encoding, contribute to cognitive decline in AD. Surprisingly, functional imaging studies show increased activity of the hippocampus and associated cortical regions during memory tasks in presymptomatic and early AD stages, whereas brain activity declines as the disease progresses. These findings suggest an emerging scenario where early pathogenic events might increase neuronal excitability leading to enhanced brain activity before clinical manifestations of the disease, a stage that is followed by decreased brain activity as neurodegeneration progresses. The mechanisms linking pathology with synaptic excitability and plasticity changes leading to memory loss in AD remain largely unclear. Recent studies suggest that increased brain activity parallels enhanced expression of genes involved in synaptic transmission and plasticity in preclinical stages, whereas expression of synaptic and activity-dependent genes are reduced by the onset of pathological and cognitive symptoms. Here, we review recent evidences indicating a relationship between transcriptional deregulation of synaptic genes and neuronal activity and memory loss in AD and mouse models. These findings provide the basis for potential clinical applications of memory-related transcriptional programs and their regulatory mechanisms as novel biomarkers and therapeutic targets to restore brain function in AD and other cognitive disorders.
    Frontiers in Cellular Neuroscience 08/2015; 9. DOI:10.3389/fncel.2015.00318 · 4.29 Impact Factor
  • 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 · 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). "

Show more