The influence of age and mild cognitive impairment on associative memory performance and underlying brain networks
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Associative memory is essential to everyday activities, such as the binding of faces and corresponding names to form single bits of information. However, this ability often becomes impaired with increasing age. The most important neural substrate of associative memory is the hippocampus, a structure crucially implicated in the pathogenesis of Alzheimer’s disease (AD). The main aim of this study was to compare neural correlates of associative memory in healthy aging and mild cognitive impairment (MCI), an at-risk state for AD. We used fMRI to investigate differences in brain activation and connectivity between young controls (n = 20), elderly controls (n = 32) and MCI patients (n = 21) during associative memory retrieval. We observed lower hippocampal activation in MCI patients than control groups during a face-name recognition task, and the magnitude of this decrement was correlated with lower associative memory performance. Further, increased activation in precentral regions in all older adults indicated a stronger involvement of the task positive network (TPN) with age. Finally, functional connectivity analysis revealed a stronger link of hippocampal and striatal components in older adults in comparison to young controls, regardless of memory impairment. In elderly controls, this went hand-in-hand with a stronger activation of striatal areas. Increased TPN activation may be linked to greater reliance on cognitive control in both older groups, while increased functional connectivity between the hippocampus and the striatum may suggest dedifferentiation, especially in elderly controls.
KeywordsAging Mild cognitive impairment (MCI) Hippocampus Task positive network (TPN) Functional connectivity
We thank the volunteers for their time and their interest in research, and the core unit Brainimaging for their support. The study was funded by an intramural grant from the University Clinic Giessen and Marburg (Project Number 31/2009 MR).
Conflict of interest
Christiane S. H. Oedekoven, Andreas Jansen, James L. Keidel, Tilo Kircher, and Dirk Leube declare that they have no conflicts of interest with respect to the research, authorship, and/or publication of this article.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.
- Albert, M. S., DeKosky, S. T., Dickson, D., Dubois, B., Feldman, H. H., Fox, N. C., & Phelps, C. H. (2011). The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia, 7(3), 270–279. doi: 10.1016/j.jalz.2011.03.008.CrossRefGoogle Scholar
- Bartrés-Faz, D., Serra-Grabulosa, J. M., Sun, F. T., Solé-Padullés, C., Rami, L., Molinuevo, J. L., & D’Esposito, M. (2008). Functional connectivity of the hippocampus in elderly with mild memory dysfunction carrying the APOE epsilon4 allele. Neurobiology of Aging, 29(11), 1644–1653. doi: 10.1016/j.neurobiolaging.2007.04.021.CrossRefPubMedGoogle Scholar
- Bernard, F. A., Bullmore, E. T., Graham, K. S., Thompson, S. A., Hodges, J. R., & Fletcher, P. C. (2004). The hippocampal region is involved in successful recognition of both remote and recent famous faces. NeuroImage, 22(4), 1704–1714. doi: 10.1016/j.neuroimage.2004.03.036.CrossRefPubMedGoogle Scholar
- Cabeza, R. E., & Dennis, N. A. (2012). “Frontal lobes and aging: deterioration and compensation,” in Principles of frontal lobe function, eds. Stuss, D. T. and Knight, R.885 T. (New York: Oxford University Press)Google Scholar
- Celone, K. A., Calhoun, V. D., Dickerson, B. C., Atri, A., Chua, E. F., Miller, S. L., & Sperling, R. A. (2006). Alterations in memory networks in mild cognitive impairment and Alzheimer’s disease: an independent component analysis. The Journal of Neuroscience, 26(40), 10222–10231. doi: 10.1523/JNEUROSCI. 2250-06.2006.CrossRefPubMedGoogle Scholar
- Dennis, N. A., & Cabeza, R. E. (2008). Neuroimaging of healthy cognitive aging. In F. I. M. Craik & T. A. Salthouse (Eds.), Handbook of aging and cognition (pp. 1–54).Google Scholar
- Dickerson, B. C., Salat, D. H., Greve, D. N., Chua, E. F., Rand-Giovannetti, E., Rentz, D. M., & Sperling, R. A. (2005). Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD. Neurology, 65(3), 404–411. doi: 10.1212/01.wnl.0000171450.97464.49.PubMedCentralCrossRefPubMedGoogle Scholar
- Dickerson, B. C., & Sperling, R. A. (2008). Functional abnormalities of the medial temporal lobe memory system in mild cognitive impairment and Alzheimer’s disease: insights from functional MRI studies. Neuropsychologia, 46(6), 1624–1635. doi: 10.1016/j.neuropsychologia.2007.11.030.PubMedCentralCrossRefPubMedGoogle Scholar
- Doeller, C. F., King, J. A., & Burgess, N. (2008). Parallel striatal and hippocampal systems for landmarks and boundaries in spatial memory. Proceedings of the National Academy of Sciences of the United States of America, 105, 5915–5920. doi: 10.1073/pnas.0801489105.PubMedCentralCrossRefPubMedGoogle Scholar
- Fox, M. D., Snyder, A. Z., Vincent, J. L., Corbetta, M., Van Essen, D. C., & Raichle, M. E. (2005). The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proceedings of the National Academy of Sciences of the United States of America, 102(27), 9673–9678. doi: 10.1073/pnas.0504136102.PubMedCentralCrossRefPubMedGoogle Scholar
- Grady, C. L., Protzner, A. B., Kovacevic, N., Strother, S. C., Afshin-Pour, B., Wojtowicz, M., & McIntosh, A. R. (2010). A multivariate analysis of age-related differences in default mode and task-positive networks across multiple cognitive domains. Cerebral Cortex, 20(6), 1432–1447. doi: 10.1093/cercor/bhp207.PubMedCentralCrossRefPubMedGoogle Scholar
- Johnson, S. C., Schmitz, T. W., Moritz, C. H., Meyerand, M. E., Rowley, H. A., Alexander, A. L., & Alexander, G. E. (2006). Activation of brain regions vulnerable to Alzheimer’s disease: the effect of mild cognitive impairment. Neurobiology of Aging, 27(11), 1604–1612. doi: 10.1016/j.neurobiolaging.2005.09.017.PubMedCentralCrossRefPubMedGoogle Scholar
- Kircher, T., Weis, S., Leube, D., Freymann, K., Erb, M., Jessen, F., & Krach, S. (2008). Anterior hippocampus orchestrates successful encoding and retrieval of non-relational memory: an event-related fMRI study. European Archives of Psychiatry and Clinical Neuroscience, 258(6), 363–372. doi: 10.1007/s00406-008-0805-z.CrossRefPubMedGoogle Scholar
- Langenecker, S. A., Briceno, E. M., Hamid, N. M., & Nielson, K. A. (2007). An evaluation of distinct volumetric and functional MRI contributions toward understanding age and task performance: a study in the basal ganglia. Brain Research, 1135(1), 58–68. doi: 10.1016/j.brainres.2006.11.068.PubMedCentralCrossRefPubMedGoogle Scholar
- Lustig, C., Snyder, A. Z., Bhakta, M., O’Brien, K. C., McAvoy, M., Raichle, M. E., & Buckner, R. L. (2003). Functional deactivations: change with age and dementia of the Alzheimer type. Proceedings of the National Academy of Sciences of the United States of America, 100(24), 14504–14509. doi: 10.1073/pnas.2235925100.PubMedCentralCrossRefPubMedGoogle Scholar
- McCormick, C., Moscovitch, M., Protzner, A. B., Huber, C. G., & McAndrews, M. P. (2010). Hippocampal-neocortical networks differ during encoding and retrieval of relational memory: functional and effective connectivity analyses. Neuropsychologia, 48(11), 3272–3281. doi: 10.1016/j.neuropsychologia.2010.07.010.CrossRefPubMedGoogle Scholar
- O’Brien, J. L., O’Keefe, K. M., LaViolette, P. S., DeLuca, A. N., Blacker, D., Dickerson, B. C., & Sperling, R. A. (2010). Longitudinal fMRI in elderly reveals loss of hippocampal activation with clinical decline. Neurology, 74(24), 1969–1976. doi: 10.1212/WNL.0b013e3181e3966e.PubMedCentralCrossRefPubMedGoogle Scholar
- Pike, K. E., Kinsella, G. J., Ong, B., Mullaly, E., Rand, E., Storey, E., & Parsons, S. (2012). Names and numberplates: quasi-everyday associative memory tasks for distinguishing amnestic mild cognitive impairment from healthy aging. Journal of Clinical and Experimental Neuropsychology, 34(3), 269–278. doi: 10.1080/13803395.2011.633498.CrossRefPubMedGoogle Scholar
- Spreng, R. N., Wojtowicz, M., & Grady, C. L. (2010). Reliable differences in brain activity between young and old adults: a quantitative meta-analysis across multiple cognitive domains. Neuroscience and Biobehavioral Reviews, 34(8), 1178–1194. doi: 10.1016/j.neubiorev.2010.01.009.CrossRefPubMedGoogle Scholar
- Troyer, A. K., D’Souza, N. A., Vandermorris, S., & Murphy, K. J. (2011). Age-related differences in associative memory depend on the types of associations that are formed. Neuropsychology, Development, and Cognition. Section B, Aging, Neuropsychology and Cognition, 18(3), 340–352. doi: 10.1080/13825585.2011.553273.CrossRefPubMedGoogle Scholar
- Tsukiura, T., Sekiguchi, A., Yomogida, Y., Nakagawa, S., Shigemune, Y., Kambara, T., & Kawashima, R. (2011). Effects of aging on hippocampal and anterior temporal activations during successful retrieval of memory for face-name associations. Journal of Cognitive Neuroscience, 23(1), 200–213. doi: 10.1162/jocn.2010.21476.CrossRefPubMedGoogle Scholar