Effects of the<i>Apolipoprotein E</i>ε4 Allele on Functional MRI during<i>n</i>-Back Working Memory Tasks in Healthy Middle-Aged Adults

Chen, C. J.; Chen, Chih-Chung; Wu, Dean; Chi, N. F.; Chen, P. C.; Liao, Yuan-Mei; Chiu, Hung Wen; Hu, Chaur Jong

doi:10.3174/ajnr.a3369

Cited by 30 publications

(24 citation statements)

References 50 publications

(35 reference statements)

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“…Thus, while supporting Aβ-related hyperactivation previously observed in cognitively normal elderly, the present results provide the novel finding of Aβ-related hyperactivation beyond the MTL-based EM network. These results are consistent with a growing field of research examining the impact of known risk factors in prodromal AD, such as ApoE4 allele, to frontoparietal function and cognitive control (Chen, et al, 2013, Wishart, et al, 2006). …”

Section: Discussionsupporting

confidence: 88%

Aβ-related hyperactivation in frontoparietal control regions in cognitively normal elderly

Steffener

Razlighi

et al. 2015

Neurobiology of Aging

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The accumulation of beta amyloid (Aβ) peptides, a pathological hallmark of Alzheimers disease, has been associated with functional alterations in cognitively normal elderly, most often in the context of episodic memory (EM) with a particular emphasis on the medial temporal lobes. The topography of Aβ deposition, however, highly overlaps with fronto-parietal control (FPC) regions implicated in cognitive control/working memory (WM). To examine Aβ-related functional alternations in the FPC regions during a WM task, we imaged 42 young and 57 cognitively normal elderly using functional magnetic resonance imaging during a letter Sternberg task with varying load. Based on 18F-Florbetaben positron emission tomography (PET) scan, we determined older subjects amyloid positivity (Aβ+) status. Within brain regions commonly recruited by all subject groups during the delay period, age and Aβ deposition were independently associated with load-dependent frontoparietal hyperactivation, while additional compensatory Aβ-related hyperactivity was found beyond the FPC regions. The present results suggest that Aβ-related hyperactivation is not specific to the EM system but occurs in the frontoparietal control regions as well.

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Section: Discussionsupporting

confidence: 88%

Aβ-related hyperactivation in frontoparietal control regions in cognitively normal elderly

Steffener

Razlighi

et al. 2015

Neurobiology of Aging

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“…Although early and significant episodic memory impairment constitutes the clinical core diagnostic criterion of AD (Dubois et al, 2014), there is increasing evidence of early deficits in WM and executive function in patients with MCI and AD (Crawford et al, 2013;Gagnon and Belleville, 2011;Huntley and Howard, 2010;Kessels et al, 2011;Koppel et al, 2014). Moreover, fMRI studies have also suggested a possible subclinical impairment of WM capacity in healthy APOE ε4 carriers (Chen et al, 2013). Here, we investigated the effects of BIN1 rs744373 on the performance of n-back WM tasks in young healthy individuals.…”

Section: Discussionmentioning

confidence: 97%

Bridging Integrator 1 (BIN1) Genotype Effects on Working Memory, Hippocampal Volume, and Functional Connectivity in Young Healthy Individuals

Zhang

et al. 2015

Neuropsychopharmacol

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Alzheimer's disease (AD) is the most common form of dementia and exhibits a considerable level of heritability. The bridging integrator 1 (BIN1) gene has recently been identified in several large genome-wide association studies (GWAS) as the second most important risk locus for AD following apolipoprotein E (APOE). However, how and when the established genetic risk locus BIN1 rs744373 confers risk to late-onset AD has yet to be determined. Here using an imaging genetic strategy in large-sample Chinese subjects, we show that healthy homozygous carriers of the rs744373 risk allele exhibit worse high-load working memory (WM) performance, larger hippocampal volume and lower functional connectivity between the bilateral hippocampus and the right dorsolateral prefrontal cortex (DLPFC), mirroring clinical evidence of disturbed memory and connectivity in patients. Our findings demonstrate that rs744373 itself or a variation in linkage disequilibrium may provide a neurogenetic mechanism for BIN1 while further validating the possibility of combining genetic and neuroimaging strategies to monitor individuals at risk for AD.

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“…In contrast, the T2DM patients had few additional resources available in the highload conditions and, thus, exhibited a significant correlation between the SFG impairments and cognitive processes. We have previously found some evidence from an examination of the effect of APOE4, the strongest genetic risk factor for AD, on brain activation in response to different WM loads (45).…”

Section: Discussionmentioning

confidence: 99%

Altered Brain Activation Patterns Under Different Working Memory Loads in Patients With Type 2 Diabetes

et al. 2014

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OBJECTIVEType 2 diabetes mellitus (T2DM) has important effects on cognition and the risk for Alzheimer disease (AD). Working memory (WM) is a susceptible cognitive domain of mild cognitive impairment and AD. Thus, the identification of brain activation patterns under different WM loads can potentially enhance our understanding of the mechanisms underlying cognitive dysfunction in T2DM. RESEARCH DESIGN AND METHODSThe current study assessed the effects of T2DM on cognitive performance and explored the related neuronal damage through a visual n-back task and functional magnetic resonance imaging. RESULTSWe found that patients with T2DM exhibited worse executive and memory abilities than control subjects. Furthermore, the patterns of brain activation changed under different WM loads in the T2DM patients, who exhibited reduced activation in the left inferior frontal gyrus under low loads and reduced activation in the left middle frontal gyrus and superior frontal gyrus (SFG) under high loads. Thus, more regions of diminished activation were seen in the frontal cortex with increasing task difficulty. Furthermore, we found that lower SFG activation was associated with worse cognitive function. CONCLUSIONSThe findings demonstrate deficient WM in patients with T2DM and the relation between cognitive function and degree of neuronal activity and their relevance to AD risk. Further longitudinal studies are needed to replicate these results and to evaluate the clinical value of brain imaging methods in the prediction of disease progress in these patients.

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Effects of theApolipoprotein Eε4 Allele on Functional MRI duringn-Back Working Memory Tasks in Healthy Middle-Aged Adults

Cited by 30 publications

References 50 publications

Aβ-related hyperactivation in frontoparietal control regions in cognitively normal elderly

Aβ-related hyperactivation in frontoparietal control regions in cognitively normal elderly

Bridging Integrator 1 (BIN1) Genotype Effects on Working Memory, Hippocampal Volume, and Functional Connectivity in Young Healthy Individuals

Altered Brain Activation Patterns Under Different Working Memory Loads in Patients With Type 2 Diabetes

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