Interactive Effect of Apolipoprotein E Genotype and Age on Hippocampal Activation During Memory Processing in Healthy Adults

Nichols, Lisa; Masdeu, Joseph C.; Mattay, Venkata S.; Kohn, Philip D.; Emery, Matthew; Sambataro, Fabio; Kolachana, Bhaskar; Elvevåg, Brita; Kippenhan, Shane; Weinberger, Daniel R.; Berman, Karen F.

doi:10.1001/archgenpsychiatry.2011.1893

Cited by 47 publications

(26 citation statements)

References 74 publications

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“…gray-matter volumes. However, data from another lifespan fMRI study suggested an opposite pattern for hippocampal activation in older adults [27]. In this study there was decreased hippocampal activity during encoding and retrieval of neutral pictures with increasing age, and these decreases were weaker for e4 carriers than for non-carriers.…”

Section: Low Highcontrasting

confidence: 61%

“…In line with this notion, participants were instructed to remember images in the study where older e4 carriers had lower brain activity at encoding [26]. This task is clearly more cognitively challenging than judging the contents of images during study, a task for which greater brain activity in older e4 carriers was observed [27]. Concerning structural brain-imaging markers, longitudinal studies demonstrate more hippocampal atrophy for e4 carriers [29,30] that may contribute to the effects of APOE on functional brain activity.…”

Section: Trends In Cognitive Sciencesmentioning

confidence: 99%

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Aging-related magnification of genetic effects on cognitive and brain integrity

Papenberg

Lindenberger

Bäckman

2015

Trends in Cognitive Sciences

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Section: Low Highcontrasting

confidence: 61%

Section: Trends In Cognitive Sciencesmentioning

confidence: 99%

Aging-related magnification of genetic effects on cognitive and brain integrity

Papenberg

Lindenberger

Bäckman

2015

Trends in Cognitive Sciences

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“…AD targets specific neural networks that have high metabolic demand, and areas within those networks that function as 'connectivity hubs' with other brain regions are particularly at risk, including the posterior cingulate and precuneous, the medial frontal cortex, and the lateral frontal and parietal regions [46,47]. It is intriguing that in functional imaging studies of older adults with normal cognition, these same regions show evidence of initial hyper-metabolism and increased neuronal activity as well as increased Ab deposition [48][49][50][51]. This increased activity is associated with preservation of brain function, suggesting it serves as a compensatory response.…”

Section: Energetics Neural Network and Alzheimer's Diseasementioning

confidence: 99%

Preventing Alzheimer's disease by means of natural selection

Demetrius

Driver

2015

J. R. Soc. Interface.

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The amyloid cascade model for the origin of sporadic forms of Alzheimer's disease (AD) posits that the imbalance in the production and clearance of beta-amyloid is a necessary condition for the disease. A competing theory called the entropic selection hypothesis asserts that the primary cause of sporadic AD is age-induced mitochondrial dysregulation and the following cascade of events: (i) metabolic reprogramming-the upregulation of oxidative phosphorylation in compensation for insufficient energy production in neurons, (ii) natural selection-competition between intact and reprogrammed neurons for energy substrates and (iii) propagation-the spread of the disease due to the selective advantage of neurons with upregulated metabolism. Experimental studies to evaluate the predictions of the amyloid cascade model are being continually retuned to accommodate conflicts of the predictions with empirical data. Clinical trials of treatments for AD based on anti-amyloid therapy have been unsuccessful. We contend that these anomalies and failures stem from a fundamental deficit of the amyloid hypothesis: the model derives from a nuclear-genomic perspective of sporadic AD and discounts the bioenergetic processes that characterize the progression of most age-related disorders. In this article, we review the anomalies of the amyloid model and the theoretical and empirical support for the entropic selection theory. We also discuss the new therapeutic strategies based on natural selection which the model proposes.

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“…AD-related regional brain functional and structural impairments included a decreased volume of the medial temporal lobe (MTL; Geroldi et al, 1999;Hashimoto et al, 2001), lower cerebral metabolic rates (Reiman et al, 1996), greater whole brain atrophy rates (Chen et al, 2007), and disrupted anterior and posterior WM regions (Nierenberg et al, 2005;Persson et al, 2006;Ryan et al, 2011). It was also reported that behavior/performance or cholesterol levels were associated with certain functional (Nichols et al, 2012) and structural (Ryan et al, 2011) brain damage and with glucose hypometabolism in cognitively normal individuals in an APOE e4 status dependent fashion (Reiman et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Disrupted Functional and Structural Networks in Cognitively Normal Elderly Subjects with the APOE ɛ4 Allele

Chen

Zhang

et al. 2014

Neuropsychopharmacol

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As the Apolipoprotein E (APOE) e4 allele is a major genetic risk factor for sporadic Alzheimer's disease (AD), which has been suggested as a disconnection syndrome manifested by the disruption of white matter (WM) integrity and functional connectivity (FC), elucidating the subtle brain structural and functional network changes in cognitively normal e4 carriers is essential for identifying sensitive neuroimaging based biomarkers and understanding the preclinical AD-related abnormality development. We first constructed functional network on the basis of resting-state functional magnetic resonance imaging and a structural network on the basis of diffusion tensor image. Using global, local and nodal efficiencies of these two networks, we then examined (i) the differences of functional and WM structural network between cognitively normal e4 carriers and non-carriers simultaneously, (ii) the sensitivity of these indices as biomarkers, and (iii) their relationship to behavior measurements, as well as to cholesterol level. For e4 carriers, we found reduced global efficiency significantly in WM and marginally in FC, regional FC dysfunctions mainly in medial temporal areas, and more widespread for WM network. Importantly, the right parahippocampal gyrus (PHG.R) was the only region with simultaneous functional and structural damage, and the nodal efficiency of PHG.R in WM network mediates the APOE e4 effect on memory function. Finally, the cholesterol level correlated with WM network differently than with the functional network in e4 carriers. Our results demonstrated e4-specific abnormal structural and functional patterns, which may potentially serve as biomarkers for early detection before the onset of the disease.

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Interactive Effect of Apolipoprotein E Genotype and Age on Hippocampal Activation During Memory Processing in Healthy Adults

Cited by 47 publications

References 74 publications

Aging-related magnification of genetic effects on cognitive and brain integrity

Aging-related magnification of genetic effects on cognitive and brain integrity

Preventing Alzheimer's disease by means of natural selection

Disrupted Functional and Structural Networks in Cognitively Normal Elderly Subjects with the APOE ɛ4 Allele

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