Hostname: page-component-7c8c6479df-27gpq Total loading time: 0 Render date: 2024-03-19T08:56:43.957Z Has data issue: false hasContentIssue false

Alterations in dorsal and ventral posterior cingulate connectivity in APOE ε4 carriers at risk of Alzheimer's disease

Published online by Cambridge University Press:  02 January 2018

Rebecca Kerestes*
Affiliation:
Department of Radiology, The Royal Melbourne Hospital, University of Melbourne, Parkville, Australia and Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
Pramit M. Phal
Affiliation:
Department of Radiology, The Royal Melbourne Hospital, University of Melbourne, Parkville, Australia
Chris Steward
Affiliation:
Department of Radiology, The Royal Melbourne Hospital, University of Melbourne, Parkville, Australia
Bradford A. Moffat
Affiliation:
Department of Radiology, The Royal Melbourne Hospital, University of Melbourne, Parkville, Australia
Simon Salinas
Affiliation:
Department of Radiology, The Royal Melbourne Hospital, University of Melbourne, Parkville, Australia
Kay L. Cox
Affiliation:
School of Medicine and Pharmacology, University of Western Australia, Perth, Australia
Kathryn A. Ellis
Affiliation:
Academic Unit for Psychiatry of Old Age, St. Vincent's Health, Department of Psychiatry, University of Melbourne, Melbourne, Australia
Elizabeth V. Cyarto
Affiliation:
National Ageing Research Institute, University of Melbourne, Parkville, Australia
David Ames
Affiliation:
Academic Unit for Psychiatry of Old Age, St Vincent's Health, Department of Psychiatry, University of Melbourne, Melbourne, Australia and National Ageing Research Institute, University of Melbourne, Parkville, Australia
Ralph N. Martins
Affiliation:
School of Medical Sciences, Edith Cowan University, Perth, Australia
Colin L. Masters
Affiliation:
The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia
Christopher C. Rowe
Affiliation:
Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Australia
Matthew J. Sharman
Affiliation:
School of Health Sciences, University of Tasmania, Hobart, Australia
Olivier Salvado
Affiliation:
Commonwealth Scientific Industrial Research Organization Preventative Health National Research Flagship, Australian e-Health Research Centre, Brisbane, Australia
Cassandra Szoeke
Affiliation:
National Ageing Research Institute, University of Melbourne, Parkville, Australia
Michelle Lai
Affiliation:
National Ageing Research Institute, University of Melbourne, Parkville, Australia
Nicola T. Lautenschlager
Affiliation:
Academic Unit for Psychiatry of Old Age, St. Vincent's Health, Department of Psychiatry, University of Melbourne, Melbourne, Australia and North Western Mental Health, Melbourne Health, Melbourne, Australia
Patricia M. Desmond
Affiliation:
Department of Radiology, The Royal Melbourne Hospital, University of Melbourne, Parkville, Australia
*
R. Kerestes, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. Email: kerestesrv@upmc.edu
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
Background

Recent evidence suggests that exercise plays a role in cognition and that the posterior cingulate cortex (PCC) can be divided into dorsal and ventral subregions based on distinct connectivity patterns.

Aims

To examine the effect of physical activity and division of the PCC on brain functional connectivity measures in subjective memory complainers (SMC) carrying the epsilon 4 allele of apolipoprotein E (APOE 4) allele.

Method

Participants were 22 SMC carrying the APOE ɛ4 allele (ɛ4+; mean age 72.18 years) and 58 SMC non-carriers (ɛ4–; mean age 72.79 years). Connectivity of four dorsal and ventral seeds was examined. Relationships between PCC connectivity and physical activity measures were explored.

Results

ɛ4+ individuals showed increased connectivity between the dorsal PCC and dorsolateral prefrontal cortex, and the ventral PCC and supplementary motor area (SMA). Greater levels of physical activity correlated with the magnitude of ventral PCC–SMA connectivity.

Conclusions

The results provide the first evidence that ɛ4+ individuals at increased risk of cognitive decline show distinct alterations in dorsal and ventral PCC functional connectivity.

Type
Research Article
Creative Commons
Creative Common License - CCCreative Common License - BYCreative Common License - NCCreative Common License - ND
This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Copyright
Copyright © The Royal College of Psychiatrists 2015

Footnotes

*

These authors contributed equally to this work.

Declaration of interest

D.A. has served on scientific advisory boards for Novartis, Eli Lilly, Janssen, Prana and Pfizer, and as Editor-in-Chief for International Psychogeriatrics; received speaker honoraria from Pfizer and Lundbeck, and research support from Eli Lilly, GlaxoSmithKline, Forest Laboratories, Novartis, and CSIRO. C.L.M. has received consulting fees from Eli Lilly and Prana Biotechnology, and has stock ownership in Prana Biotechnology. C.C.R. has received consultancy payments from Roche and Piramal, and research support from Avid Radiopharmaceuticals, Eli Lilly, GE Healthcare, Piramal and Navidea for amyloid imaging. C.S. has provided clinical consultancy and been on scientific advisory committees for the Australian CSIRO, Alzheimer's Australia, University of Melbourne and other relationships, which are subject to confidentiality clauses; she has been a named Chief Investigator on investigator-driven collaborative research projects in partnership with Pfizer, Merck, Piramal, Bayer and GE Healthcare. Her research programme has received support from the National Health and Medical Research Council Alzheimer's Association, Collier Trust, Scobie and Claire McKinnon Foundation, JO and JR Wicking Trust, Shepherd Foundation, Brain Foundation, Mason Foundation, Ramaciotti Foundation, Alzheimer's Australia and the Royal Australian College of Physicians.

References

1 Bertram, L, McQueen, MB, Mullin, K, Blacker, D, Tanzi, RE. Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nat Genet 2007; 39: 1723.CrossRefGoogle ScholarPubMed
2 Fleisher, AS, Sherzai, A, Taylor, C, Langbaum, JB, Chen, K, Buxton, RB. Resting-state BOLD networks versus task-associated functional MRI for distinguishing Alzheimer's disease risk groups. Neuroimage 2009; 47: 1678–90.CrossRefGoogle ScholarPubMed
3 Filippini, N, MacIntosh, BJ, Hough, MG, Goodwin, GM, Frisoni, GB, Smith, SM, et al. Distinct patterns of brain activity in young carriers of the APOE-epsilon4 allele. Proc Natl Acad Sci USA 2009; 106: 7209–14.CrossRefGoogle ScholarPubMed
4 Machulda, MM, Jones, DT, Vemuri, P, McDade, E, Avula, R, Przybelski, S, et al. Effect of APOE ε4 status on intrinsic network connectivity in cognitively normal elderly subjects. Arch Neurol 2011; 68: 1131–6.CrossRefGoogle ScholarPubMed
5 Fornito, A, Bullmore, ET. What can spontaneous fluctuations of the blood oxygenation-level-dependent signal tell us about psychiatric disorders? Curr Opin Psychiatry 2010; 23: 239–49.CrossRefGoogle ScholarPubMed
6 Raichle, ME, MacLeod, AM, Snyder, AZ, Powers, WJ, Gusnard, DA, Shulman, GL. A default mode of brain function. Proc Natl Acad Sci U S A 2001; 98: 676–82.CrossRefGoogle ScholarPubMed
7 Buckner, RL, Andrews-Hanna, JR, Schacter, DL. The brain's default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci 2008; 1124: 138.CrossRefGoogle ScholarPubMed
8 Sorg, C, Riedl, V, Muhlau, M, Calhoun, VD, Eichele, T, Laer, L, et al. Selective changes of resting-state networks in individuals at risk for Alzheimer's disease. Proc Natl Acad Sci USA 2007; 104: 18760–5.CrossRefGoogle ScholarPubMed
9 Petrella, JR, Sheldon, FC, Prince, SE, Calhoun, VD, Doraiswamy, PM. Default mode network connectivity in stable vs progressive mild cognitive impairment. Neurology 2011; 76: 511–7.CrossRefGoogle ScholarPubMed
10 Hafkemeijer, A, Altmann-Schneider, I, Oleksik, AM, van de Wiel, L, Middelkoop, HA, van Buchem, MA, et al. Increased functional connectivity and brain atrophy in elderly with subjective memory complaints. Brain Connect 2013; 3: 353–62.CrossRefGoogle ScholarPubMed
11 Sheline, YI, Morris, JC, Snyder, AZ, Price, JL, Yan, Z, D'Angelo, G, et al. APOE4 allele disrupts resting state fMRI connectivity in the absence of amyloid plaques or decreased CSF Aβ42. J Neurosci 2010; 30: 1703–40.CrossRefGoogle ScholarPubMed
12 Minoshima, S, Giordani, B, Berent, S, Frey, KA, Foster, NL, Kuhl, DE. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease. Ann Neurol 1997; 42: 8594.CrossRefGoogle ScholarPubMed
13 Greicius, MD, Srivastava, G, Reiss, AL, Menon, V. Default-mode network activity distinguishes Alzheimer's disease from healthy aging: evidence from functional MRI. Proc Natl Acad Sci USA 2004; 101: 4637–42.CrossRefGoogle ScholarPubMed
14 Buckner, RL, Snyder, AZ, Shannon, BJ, LaRossa, G, Sachs, R, Fotenos, AF, et al. Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory. J Neurosci 2005; 25: 7709–17.CrossRefGoogle ScholarPubMed
15 Leech, R, Sharp, DJ. The role of the posterior cingulate cortex in cognition and disease. Brain 2014; 137: 1232.CrossRefGoogle ScholarPubMed
16 Margulies, DS, Vincent, JL, Kelly, C, Lohmann, G, Uddin, LQ, Biswal, BB, et al. Precuneus shares intrinsic functional architecture in humans and monkeys. Proc Natl Acad Sci U S A 2009; 106: 20069–74.CrossRefGoogle ScholarPubMed
17 Leech, R, Braga, R, Sharp, DJ. Echoes of the brain within the posterior cingulate cortex. J Neurosci 2012; 32: 215–22.CrossRefGoogle ScholarPubMed
18 Cyarto, EV, Lautenschlager, NT, Desmond, PM, Ames, D, Szoeke, C, Salvado, O, et al. Protocol for a randomized controlled trial evaluating the effect of physical activity on delaying the progression of white matter changes on MRI in older adults with memory complaints and mild cognitive impairment: the AIBL Active trial. BMC Psychiatry 2012; 12: 167.CrossRefGoogle ScholarPubMed
19 Voss, MW, Prakash, RS, Erickson, KI, Basak, C, Chaddock, L, Kim, JS, et al. Plasticity of brain networks in a randomized intervention trial of exercise training in older adults. Front Aging Neurosci 2010a; 2: e32.Google Scholar
20 Voss, MW, Erickson, KI, Prakash, RS, Chaddock, L, Malkowski, E, Alves, H, et al. Functional connectivity: a source of variance in the association between cardiorespiratory fitness and cognition? Neuropsychologia 2010; 48: 1394–406.CrossRefGoogle ScholarPubMed
21 Welsh, KA, Butters, N, Mohs, RC, Beekly, D, Edland, S, Fillenbaum, G, et al. The consortium to establish a registry for Alzheimer's disease (CERAD). Part V. A normative study of the neuropsychological battery. Neurology 1994; 44: 609–14.CrossRefGoogle Scholar
22 Hixson, JE, Vernier, DT. Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with Hhal. J Lipid Res 1990; 31: 545–8.CrossRefGoogle Scholar
23 Avants, BB, Tustison, NJ, Song, G, Cook, PA, Klein, A, Gee, JC. A reproducible evaluation of ANTs similarity metric performance in brain image registration. Neuroimage 2011; 54: 2033–44.CrossRefGoogle ScholarPubMed
24 Kerestes, R, Harrison, BJ, Dandash, O, Stephanou, K, Whittle, S, Pujol, J, et al. Specific functional connectivity alterations of the dorsal striatum in young people with depression. Neuroimage Clin 2014; 7: 266–72.Google ScholarPubMed
25 Van Dijk, KR, Hedden, T, Venkataraman, A, Evans, KC, Lazar, SW, Buckner, RL. Intrinsic functional connectivity as a tool for human connectomics: theory, properties, and optimization. J Neurophysiol 2010; 103: 297321.CrossRefGoogle ScholarPubMed
26 Song, XW, Dong, ZY, Long, XY, Li, SF, Zuo, XN, Zhu, CZ, et al. REST: a toolkit for resting-state functional magnetic resonance imaging data processing. PLoS One 2011; 6: e25031.CrossRefGoogle Scholar
27 Marcus, BH, Banspach, SW, Lefebvre, RC, Rossi, JS, Carleton, RA, Abrams, DB. Using the stages of change model to increase the adoption of physical activity among community participants. Am J Health Promot 1992; 6: 424–9.CrossRefGoogle ScholarPubMed
28 Rickli, RE, Jones, CJ. The reliability and validity of a 6-minute walk test as a measure of physical endurance in older adults. JAPA 1998; 6: 363–75.Google Scholar
29 Yang, AC, Huang, CC, Liu, ME, Liou, YJ, Hong, CJ, Lo, MT, et al. The APOE ε4 allele affects complexity and functional connectivity of resting brain activity in healthy adults. Hum Brain Mapp 2014; 35: 3238–48.CrossRefGoogle Scholar
30 Hagmann, P, Cammoun, L, Gigandet, X, Meuli, R, Honey, CJ, Wedeen, VJ, et al. Mapping the structural core of human cerebral cortex. PLoS Biol 2008; 6: e159.CrossRefGoogle ScholarPubMed
31 Kobayashi, Y, Amaral, DG. Macaque monkey retrosplenial cortex: III. Cortical efferents. J Comp Neurol 2007; 502: 810–33.CrossRefGoogle ScholarPubMed
32 Gili, T, Cercignani, M, Serra, L, Perri, R, Giove, F, Maraviglia, B, et al. Regional brain atrophy and functional disconnection across Alzheimer's disease evolution. J Neurol Neurosurg Psychiatry 2011; 82:5866.CrossRefGoogle ScholarPubMed
33 Zhang, HY, Wang, SJ, Xing, J, Liu, B, Ma, ZL, Yang, M, et al. Detection of PCC functional connectivity characteristics in resting-state fMRI in mild Alzheimer's disease. Behav Brain Res 2009; 197: 103–8.CrossRefGoogle ScholarPubMed
34 Vincent, JL, Kahn, I, Snyder, AZ, Raichle, ME, Buckner, RL. Evidence for a frontoparietal control system revealed by intrinsic functional connectivity. J Neurophysiol 2008; 100: 3328–42.CrossRefGoogle ScholarPubMed
35 Middleton, LE, Barnes, DE, Lui, LY, Yaffe, K. Physical activity over the life course and its association with cognitive performance and impairment in old age. J Am Geriatr Soc 2010; 58: 1322–6.CrossRefGoogle ScholarPubMed
36 Scarmeas, N, Luchsinger, JA, Schupf, N, Brickman, AM, Cosentino, S, Tang, MX, et al. Physical activity, diet, and risk of Alzheimer disease. JAMA 2009; 302: 627–37.Google ScholarPubMed
37 Lautenschlager, NT, Cox, KL, Flicker, L, Foster, JK, van Bockxmeer, FM, Xiao, J, et al. Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial. JAMA 2008; 300: 1027–37.CrossRefGoogle ScholarPubMed
38 Baker, LD, Frank, LL, Foster-Schubert, K, Green, PS, Wilkinson, CW, McTiernan, A, et al. Effects of aerobic exercise on mild cognitive impairment: a controlled trial. Arch Neurol 2010; 67: 71–9.CrossRefGoogle ScholarPubMed
39 Wu, T, Hallett, M. The influence of normal human ageing on automatic movements. J Physiol 2005; 562: 605–15.CrossRefGoogle ScholarPubMed
Supplementary material: PDF

Kerestes et al. supplementary material

Supplementary Material

Download Kerestes et al. supplementary material(PDF)
PDF 247.7 KB
Submit a response

eLetters

No eLetters have been published for this article.