Functional Network Endophenotypes Unravel the Effects of Apolipoprotein E Epsilon 4 in Middle-Aged Adults

Goveas, Joseph S.; Xie, Chunming; Chen, Gang; Li, Wenjun; Ward, B. Douglas; Franczak, Malgorzata B.; Jones, Jennifer L.; Antuono, Piero G.; Li, Shi-Jiang
February 2013
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
Academic Journal
Apolipoprotein E-ε4 (APOE-ε4) accentuates memory decline, structural volume loss and cerebral amyloid deposition in cognitively healthy adults. We investigated whether APOE-ε4 carriers will show disruptions in the intrinsic cognitive networks, including the default mode (DMN), executive control (ECN) and salience (SN) networks, relative to noncarriers in middle-aged healthy adults; and the extent to which episodic-memory performance is related to the altered functional connectivity (Fc) in these networks. Resting-state functional connectivity MRI (R-fMRI) was used to measure the differences in the DMN, ECN and SN Fc between 20 APOE-ε4 carriers and 26 noncarriers. Multiple linear regression analyses were performed to determine the relationship between episodic-memory performance and Fc differences in the three resting-state networks across all subjects. There were no significant differences in the demographic and neuropsychological characteristics and the gray-matter volumes in the carriers and noncarriers. While mostly diminished DMN and ECN functional connectivities were seen, enhanced connections to the DMN structures were found in the SN in ε4 carriers. Altered DMN and ECN were associated with episodic memory performance. Significant Fc differences in the brain networks implicated in cognition were seen in middle-aged individuals with a genetic risk for AD, in the absence of cognitive decline and gray-matter atrophy. Prospective studies are essential to elucidate the potential of R-fMRI technique as a biomarker for predicting conversion from normal to early AD in healthy APOE-ε4 carriers.


Related Articles

  • Mediterranean food for thought? Scarmeas, Nikolaos // Journal of Neurology, Neurosurgery & Psychiatry;Dec2013, Vol. 84 Issue 12, p1297 

    The author reflects on a research on the possible effects of the Mediterranean diet (MedDiet) on neurological diseases, especially, cognitive decline. He states that in the research, evaluation was performed not on the basis of neurophysiological factors and hence cannot be relied upon. He...

  • Insights from neuropsychology: pinpointing the role of the posterior parietal cortex in episodic and working memory. Berryhill, Marian E. // Frontiers in Integrative Neuroscience;Jun2012, Vol. 6, p1 

    The role of posterior parietal cortex (PPC) in various forms of memory is a current topic of interest in the broader field of cognitive neuroscience. This large cortical region has been linked with a wide range of mnemonic functions affecting each stage of memory processing: encoding,...

  • A bidirectional relationship between physical activity and executive function in older adults. Daly, Michael; McMinn, David; Allan, Julia L. // Frontiers in Human Neuroscience;Jan2015, Vol. 8, p1 

    Physically active lifestyles contribute to better executive function. However, it is unclear whether high levels of executive function lead people to be more active. This study uses a large sample and multi-wave data to identify whether a reciprocal association exists between physical activity...

  • In Brief.  // Nature Reviews Genetics;May2008, Vol. 9 Issue 5, p323 

    The article offers brief information on various researches in genetics. A study on the genetic interactions in genetic disorder indicates that unlike gene functions, genetic interactions in human can be predicted from those of lower organisms. A new method for increasing the power of genome-wide...

  • Frontotemporal lobar degeneration: recent progress in antemortem diagnosis. Bian, Hong; Grossman, Murray // Acta Neuropathologica;Jul2007, Vol. 114 Issue 1, p23 

    Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disorder characterized by changes in behaviour and language dysfunction. Two broad pathological subdivisions of FTLD are recognized in a recent classification scheme based on biochemical features: tau-positive pathology due to the...

  • Early biomarkers for post-stroke cognitive impairment. Qian, Lai; Ding, Lidong; Cheng, Liqun; Zhu, Xiaolei; Zhao, Hui; Jin, Jiali; Guan, Dening; Zhang, Bing; Chen, Xuemei; Xu, Yun // Journal of Neurology;Oct2012, Vol. 259 Issue 10, p2111 

    The aim of this study was to investigate whether some biomarkers could predict cognitive impairment after stroke. One hundred fifty-two first-ever stroke patients were recruited within 6-72 h after the onset of symptoms. Blood was drawn within 1 h after admission for determining biomarkers....

  • Lack of reliable evidence for a distinctive ϵ4−related cognitive phenotype that is independent from clinical diagnostic status: findings from the Australian Imaging, Biomarkers and Lifestyle Study. Foster, Jonathan K.; Albrecht, Matthew A.; Savage, Greg; Lautenschlager, Nicola T.; Ellis, Kathryn A.; Maruff, Paul; Szoeke, Cassandra; Taddei, Kevin; Martins, Ralph; Masters, Colin L.; Ames, David // Brain: A Journal of Neurology;Jul2013, Vol. 136 Issue 7, p2201 

    Individuals who carry the apolipoprotein E ϵ4 polymorphism have an increased risk of late-onset Alzheimer’s disease. However, because possession of the ϵ4 allele confers an increased risk for the diagnosis of dementia, it has proven problematic in older individuals...

  • Neurocognition in Bipolar Disorder and Juvenile Bipolar Disorder. Cahill, Catherine M.; Walter, Garry; Malhi, Gin S. // Journal of the Canadian Academy of Child & Adolescent Psychiatry;2009, Vol. 18 Issue 3, p221 

    Introduction: In the ongoing quest for improved diagnostic markers of bipolar illness, the focus of research has gradually shifted to examining the onset of mood difficulties early in life and investigating the potential corollaries of such early onset such as cognitive impairment, disruption of...

  • Plasma Based Markers of [11C] PiB-PET Brain Amyloid Burden. Kiddle, Steven John; Thambisetty, Madhav; Simmons, Andrew; Riddoch-Contreras, Joanna; Hye, Abdul; Westman, Eric; Pike, Ian; Ward, Malcolm; Johnston, Caroline; Lupton, Michelle Katharine; Lunnon, Katie; Soininen, Hilkka; Kłoszewska, Iwona; Tsolaki, Magda; Vellas, Bruno; Mecocci, Patrizia; Lovestone, Simon; Newhouse, Stephen; Dobson, Richard; Bush, Ashley I. // PLoS ONE;Sep2012, Vol. 7 Issue 9, Special section p1 

    Changes in brain amyloid burden have been shown to relate to Alzheimer's disease pathology, and are believed to precede the development of cognitive decline. There is thus a need for inexpensive and non-invasive screening methods that are able to accurately estimate brain amyloid burden as a...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics