The Alzheimer’s Disease-Related Glucose Metabolic Brain Pattern

Teune, Laura K.; Strijkert, Fijanne; Renken, Remco; Izaks, Gerbrand J.; Vries, Jeroen J de; Segbers, Marcel; Roerdink, Jos B. T. M.; Dierckx, Rudi; Leenders, Klaus L.

doi:10.2174/156720501108140910114230

Cited by 44 publications

(60 citation statements)

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“…We and others have used 18 F-fluorodeoxyglucose (FDG)-PET and fMRI to identify diseasespecific networks in PD, AD, Huntington disease, and other conditions. [7][8][9][10][11][12][13] We have shown that akinesia-rigidity in PD correlates with the expression of a PD motor-related pattern (PDRP) 10,11 such that more severe symptoms are reflected in higher PDRP scores; tremor is mediated by a distinct cerebello-thalamocortical network 14 ; and the expression of a distinct PD cognition-related pattern (PDCP), characterized by diminished metabolism in the medial frontal and parietal regions, rises as cognitive function deteriorates. [15][16][17][18] Similarly, in AD, neuropsychological test performance correlates with the expression of an AD-related pattern (ADRP) characterized by covarying reductions in hippocampal, superior temporal, and parieto-occipital resting-state activity.…”

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confidence: 99%

Distinct brain networks underlie cognitive dysfunction in Parkinson and Alzheimer diseases

et al. 2016

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Objective: To determine whether cognitive impairment in Parkinson disease (PD) and Alzheimer disease (AD) derives from the same network pathology.Methods: We analyzed 18 F-fluorodeoxyglucose PET scans from 40 patients with AD and 40 agematched healthy controls from the Alzheimer's Disease Neuroimaging Initiative and scanned an additional 10 patients with AD and 10 healthy controls at The Feinstein Institute for Medical Research to derive an AD-related metabolic pattern (ADRP) analogous to our previously established PD cognition-related pattern (PDCP) and PD motor-related pattern (PDRP). We computed individual subject expression values for ADRP and PDCP in 89 patients with PD and correlated summary scores for cognitive functioning with network expression. We also evaluated changes in ADRP and PDCP expression in a separate group of 15 patients with PD scanned serially over a 4-year period.Results: Analysis revealed a significant AD-related metabolic topography characterized by covarying metabolic reductions in the hippocampus, parahippocampal gyrus, and parietal and temporal association regions. Expression of ADRP, but not PDCP, was elevated in both AD groups and correlated with worse cognitive summary scores. Patients with PD showed slight ADRP expression, due to topographic overlap with the network underlying PD motor-related pattern degeneration, but only their PDCP expression values increased as cognitive function and executive performance declined. Longitudinal data in PD disclosed an analogous dissociation of network expression. Conclusions:Cognitive dysfunction in PD is associated with a specific brain network that is largely spatially and functionally distinct from that seen in relation to AD. Cognitive impairment is commonly observed in patients with Parkinson disease (PD), even early in the clinical course, 1,2 but its cause remains unclear. The postmortem observation of amyloid-b plaques and tau neurofibrilliary tangles, pathologic hallmarks of Alzheimer disease (AD), in individuals with PD and dementia has led to the hypothesis that the cognitive changes in PD are caused by comorbid AD.3-5 Many patients with PD have substantial cognitive loss without forming plaques and tangles, however, and the severity of neuropsychological deficits in patients with PD with coexisting cortical Lewy body and AD-like pathology correlates only with From the Center for Neurosciences (P.J.M., M.N., W

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confidence: 99%

Distinct brain networks underlie cognitive dysfunction in Parkinson and Alzheimer diseases

et al. 2016

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“…The so-called metabolic networks of the brain are acquired in a similar manner to fMRI-derived networks, namely by analyzing temporal [ 155 ]. Such metabolic networks were recently constructed for PD [ 156 ] and AD [ 157 ]. Structural brain networks represent physical connections between brain regions by white matter fi ber tracts.…”

Section: Disease-specifi C Brain Networkmentioning

confidence: 99%

Neurological Diseases from a Systems Medicine Point of View

Ostaszewski

Skupin

Balling

2016

Methods in Molecular Biology

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The diffi culty to understand, diagnose, and treat neurological disorders stems from the great complexity of the central nervous system on different levels of physiological granularity. The individual components, their interactions, and dynamics involved in brain development and function can be represented as molecular, cellular, or functional networks, where diseases are perturbations of networks. These networks can become a useful research tool in investigating neurological disorders if they are properly tailored to refl ect corresponding mechanisms. Here, we review approaches to construct networks specifi c for neurological disorders describing disease-related pathology on different scales: the molecular, cellular, and brain level. We also briefl y discuss cross-scale network analysis as a necessary integrator of these scales.

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“…AD is characterized pathologically by accumulation of amyloid -peptiderich senile plaques, neurofibrillary tangles [composed of aggregated hyperphosphorylated tau], and loss of synapses. A major clinical sign of AD is decreased glucose utilization in temporoparietal and other brain regions (Teune et al, 2014). Type 2 diabetes mellitus (T2DM) is a major risk factor for development of AD, and brains from subjects with AD and T2DM have elevated indices of oxidative and nitrosative stress (Hoyer, 2002;Craft et al, 2005;de Felice, 2013;de la Monte, 2009;Calvo-Ochoa et al, 2015;Butterfield et al, 2014b).…”

Section: Accepted Manuscriptmentioning

confidence: 99%