Alzheimer's disease

Foster, Norman L.; Chase, Thomas N.; Fedio, Paul; Patronas, Nicholas J.; Brooks, Rodney A.; Chiro, Giovanni Di

doi:10.1212/wnl.33.8.961

Cited by 524 publications

(175 citation statements)

References 7 publications

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“…A variety of PET studies in AD have demonstrated asymmetrically reduced blood flow or metabolic activity in AD patients (Foster et al, 1983;Ishii et al, 2005b;Kawachi et al, 2006;Koss et al, 1985;Martin et al, 1986) and in elderly individuals with cognitive decline (Hunt et al, 2007); however the biological underpinnings of these asymmetries are not quite known. Notably, these asymmetries are often reversed, implying that different individuals might be affected by, or compensate for, AD pathology differently.…”

Section: Discussionmentioning

confidence: 99%

Structural and functional biomarkers of prodromal Alzheimer's disease: A high-dimensional pattern classification study

et al. 2008

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This work builds upon previous studies that reported high sensitivity and specificity in classifying individuals with mild cognitive impairment (MCI), which is often a prodromal phase of Alzheimer's Disease (AD), via pattern classification of MRI scans. The current study integrates MRI and PET 15 O water scans from 30 participants in the Baltimore Longitudinal Study of Aging, and tests the hypothesis that joint evaluation of structure and function can yield higher classification accuracy than either alone. Classification rates of up to 100% accuracy were achieved via leave-one-out cross validation, whereas conservative estimates of generalization performance in new scans, evaluated via bagging cross-validation, yielded an area under the receiver operating characteristic (ROC) curve equal to 0.978 (97.8%), indicating excellent diagnostic accuracy. Spatial maps of regions determined to contribute the most to the classification implicated many temporal, prefrontal, orbitofrontal, and parietal regions. Detecting complex patterns of brain abnormality in early stages of cognitive impairment has pivotal importance for the detection and management of AD. KeywordsAlzheimer's Disease; MCI; high-dimensional Pattern Classification; MRI; PET; voxel-based analysis; diagnosis of AD Amnestic mild cognitive impairment (MCI) is often a prodromal stage to Alzheimer's Disease (AD), as individuals with MCI may convert to AD at an annual rate as high as 15% . Therefore, MCI is frequently considered to be a good target for early AD diagnosis, and for therapeutic interventions. MRI and PET imaging can potentially be used as diagnostic tools that assess brain structure and function in a direct and objective way and have potential utility for diagnosis, prognosis, and evaluation of disease progression and treatment effects.Many imaging studies have found loss of grey matter (GM) and metabolic abnormalities in MCI. Most of the earlier studies were based on volumetric measurements of regions of interest (ROI's) (Chetelat et al., 2002;Convit et al., 2000;Dickerson et al., 2001;Fox et al., 1996a;Kaye et al., 1997;Killiany et al., 2000), such as the hippocampus and the entorhinal cortex, and have confirmed GM atrophy in regions that are known to be affected by AD. However, the pattern of AD pathology is complex and evolves as the disease progresses, starting mainly in the hippocampus and entorhinal cortex, and subsequently spreading throughout temporal and orbitofrontal cortex, posterior cingulate, and association cortex generally (Braak et al., 1998). Therefore, measuring volumes or average PET signals of a few structures cannot capture Voxel-based morphometry (VBM) has been proposed by a number of investigators as a more comprehensive way of measuring the spatial distribution of brain atrophy in MCI and AD, by evaluating images region by region instead of making a priori assumptions about specific ROIs. A variety of VBM-type methods exist (Ashburner and Friston, 2000;Chung et al., 2001;Davatzikos et al., 2001;Davatzikos et al., 1996...

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Section: Discussionmentioning

confidence: 99%

Structural and functional biomarkers of prodromal Alzheimer's disease: A high-dimensional pattern classification study

et al. 2008

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“…Conversely, Di Chiro did not immediately change his perception of Alzheimer's disease. The first studies by the team working with him at the National Institutes of Health indicated the disease to be a focal unilateral brain alteration, clinically related to the main symptoms [12]. When, contrary to the previous observations, Chase et al demonstrated for the first time the typical bilateral posterior hypometabolic pattern, not connected to any of the previously known neurological models and without pathological evidence on CT, Di Chiro declined to be included in the first communication [13]; therefore he did not participate in the primacy of this pivotal observation, which was shared with Friedland and colleagues [14].…”

Section: Baruch Spinozamentioning

confidence: 99%

The new FDG brain revolution: the neurovascular unit and the default network

Sestini¹,

Castagnoli²,

Mansi³

2009

Eur J Nucl Med Mol Imaging

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"Our aim is, more than see new things, to see with new eyes what has already been seen" Baruch SpinozaThe first FDG brain revolutionThe first revolution was explosive. Using 18 F-fluorodeoxyglucose (FDG), it was possible to see and study the living brain in humans! Pioneers were top experts who provided different specialized expertise, but strictly cooperating between themselves [1]. Physicists, engineers and mathematicians were actively involved in producing the best hardware and software. The research on crystals, in identifying the most effective electronics, in defining accurate methods for attenuation and scatter correction and so on, was nevertheless limited by the relatively poor technology, with the main consideration being limited computer power. These developments stimulated a major interest in the brain. Satisfactory sensitivity and resolution, together with reliable solutions to the technical problems, were only achieved with dedicated cerebral PET scanners which had a field of view that permitted exclusive analysis of the brain.Basic scientists had the possibility of realizing a scientific dream: the transfer of data on cerebral glucose metabolism acquired in animals by quantitative autoradiography to humans. Another issue in the original FDG PET research was to consider mandatory absolute quantification. Thus arterial (or arterialized) sampling, to obtain data to be included in mathematical models, was routinely performed. However, because the equations included nonmeasurable parameters, the presence of a lumped constant affected absolute measurement in an individual [2][3][4]. PET teams included (and were directed by) clinical experts including not only nuclear physicians, but also other professionals such as neuroradiologists, neurologists and psychiatrists, who frequently cooperated with psychologists, anatomists and physiologists.Because of the unsatisfactory spatial resolution and the negative influence of the partial volume effect, in presence of glucose uptake in the normal brain, only a low lesion/background ratio was achievable, except for hot spots, i.e. the presence of focal areas of increased uptake determined by physiological and/or pathological causes. Therefore, the use of FDG as a positive indicator was restricted in the first studies and in the search for hot spots, many studies involved physiological stimulation tests (closed/open eyes, auditory system, etc.) in normal subjects [5,6]. Similarly, major interest in pathological analysis was directed to the evaluation of brain tumours, starting from Warburg's hypothesis of higher FDG uptake in malignant lesions with respect to benign ones [7]. With further clinical experience, in the analysis of patients with epilepsy, a higher sensitivity was clearly demonstrated during the ictal phase, the focus being seen as a hot spot, with respect to the interictal period when the lesion was not easily detectable, being an area with a slightly reduced overall FDG uptake [8,9]. Discrepant results in epilepsy clearly demonstrate how, in the absenc...

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“…A study of a small sample of twins concordant for ApoE genotype (mean age = 63 years) found that individuals possessing one ɛ4 allele (n = 6) had smaller hippocampi than those lacking an ɛ4 allele (n = 14), despite similar performance levels on standardized neuropsychological tests (Plassman et al, 1997). In a slightly larger and somewhat younger (50-62 years) sample of ɛ4 homozygotes (n = 11) and non-ɛ4 carriers (n = 22), Reiman et al (1998) found a nonsignificant trend toward smaller hippocampal volume in the ɛ4 group.Positron emission tomography (PET) studies of clinically diagnosed AD patients have shown that there are reductions in cerebral metabolism and blood flow in temporal and parietal cortices Foster, Chase, & Fedio, 1983;Haxby, Duara, Grady, Cutler, & Rapoport, 1985;Ibanez et al, 1998;Rossor, Kennedy, & Frackowiak, 1996). Similar PET metabolic changes are seen in individuals without dementia who have the ApoE-ɛ4 gene (see Rapoport, 2000).…”

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confidence: 97%

The apolipoprotein E gene, attention, and brain function.

Parasuraman¹,

Greenwood²,

Sunderland³

2002

Neuropsychology

108

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The ɛ4 allele of the apolipoprotein E (ApoE) gene is associated with alterations in brain function and is a risk factor for Alzheimer's disease (AD). Changes in components of visuospatial attention with ApoE-ɛ4, aging, and AD are described. Healthy middle-aged adults without dementia who have the ApoE-ɛ4 gene show deficits in spatial attention and working memory that are qualitatively similar to those seen in clinically diagnosed AD patients. The findings support an association between ApoE polymorphism and specific components of visuospatial attention. Molecular mechanisms that may mediate the ApoE-attention link by modulating cholinergic neurotransmission to the posterior parietal cortex are discussed. Studies of attention and brain function in ApoE-ɛ4 carriers without dementia can advance knowledge of the genetics of visual attention, may enhance understanding of the preclinical phase of AD, and may lead to better methods for early AD detection.Apolipoprotein E (ApoE) is an amino acid glycoprotein that is important in lipid storage, transport, and metabolism (Mahley, 1988). Although synthesized mainly in the liver, ApoE is also found in the peripheral and central nervous systems, including the brain. ApoE has long been of interest in medicine, but its importance in neuroscience increased dramatically with the identification of the ɛ4 allele of the ApoE gene on chromosome 19 as a major risk factor for the development of late-onset Alzheimer's disease (AD) in older adults Strittmatter et al., 1993). This discovery led to a growing number of studies examining the role of the ApoE gene in normal brain function and cognition, as well as in disorders such as AD, brain injury, and stroke (Higgins, Large, Rupniak, & Barnes, 1997;Horsburgh, McCarron, White, & Nicol, 2000; J. D. Smith, 2000).Polymorphisms of the ApoE gene are associated with significant alterations in brain morphology (Plassman et al., 1997) and cognitive functioning, including attention (Greenwood, Sunderland, Friz, & Parasuraman, 2000) and memory (Bondi et al., 1995). Studies of ApoE may thus reveal information relevant to the genetics of attention and memory in normal individuals. At the same time, such studies may identify cognitive and neural changes that may be characteristic of preclinical stages of AD. In this article, we review the role of the ApoE gene in normal cognition and in the development of deficits indicative of early AD.Currently, no reliable methods exist for the early detection and treatment of AD. New techniques for preventing, slowing the progression of, and treating AD are being urgently sought. Such efforts would be aided considerably if AD could be detected prior to the clinical diagnosis of AD and before irreversible brain changes occur (Daffner & Scinto, 2000). Postmortem studies show that neuropathological changes occur decades before the onset of NIH Public Access Author ManuscriptNeuropsychology. Author manuscript; available in PMC 2006 January 25. Published in final edited form as:Neuropsychology. 2002 April ; ...

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Alzheimer's disease

Cited by 524 publications

References 7 publications

Structural and functional biomarkers of prodromal Alzheimer's disease: A high-dimensional pattern classification study

Structural and functional biomarkers of prodromal Alzheimer's disease: A high-dimensional pattern classification study

The new FDG brain revolution: the neurovascular unit and the default network

The apolipoprotein E gene, attention, and brain function.

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