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Medial temporal lobe atrophy relates to executive dysfunction in Alzheimer's disease

Published online by Cambridge University Press:  25 April 2012

Joukje M. Oosterman ,
Saskia Oosterveld ,
Marcel G. Olde Rikkert ,
Jurgen A. Claassen  and
Roy P. C. Kessels
Joukje M. Oosterman*
Affiliation:
Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands
Saskia Oosterveld
Affiliation:
Radboud University Nijmegen Medical Centre, Department of Geriatric Medicine, Nijmegen, The Netherlands
Marcel G. Olde Rikkert
Affiliation:
Radboud University Nijmegen Medical Centre, Department of Geriatric Medicine, Nijmegen, The Netherlands
Jurgen A. Claassen
Affiliation:
Radboud University Nijmegen Medical Centre, Department of Geriatric Medicine, Nijmegen, The Netherlands
Roy P. C. Kessels
Affiliation:
Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands Radboud University Nijmegen Medical Centre, Department of Geriatric Medicine, Nijmegen, The Netherlands Radboud University Nijmegen Medical Centre, Department of Medical Psychology, Nijmegen, The Netherlands
*
Correspondence should be addressed to: Dr. J.M. Oosterman, Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Montessorilaan 3, 6500 HE Nijmegen, The Netherlands. Phone: +31-24-361-1951. Email: [email protected].
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Abstract

Background: White matter hyperintensities (WMH) have frequently been associated with lower executive function performance. Little is known, however, about the effects of hippocampal atrophy on executive control in Alzheimer's disease (AD). The present study focused on the association of hippocampal atrophy with executive function in AD patients and examined whether a threshold effect is present, indicating that a certain amount of brain damage must be present before cognitive function becomes impaired. Finally, we examined the combined effect of hippocampal atrophy and WMH on cognitive task performance.

Methods: We retrospectively collected neuropsychological and neuroimaging data of 94 AD patients. These patients completed tasks of general cognitive function, executive function, memory, and processing speed. With magnetic resonance imaging (MRI), hippocampal atrophy was rated as medial temporal lobe atrophy (MTA) and cerebrovascular disease was rated as WMH using validated visual rating scales.

Results: Medial temporal lobe atrophy (MTA) was associated with lower executive function, general cognitive function, and episodic memory performance. A threshold effect was present, indicating that severe to very severe, but not moderate, MTA was associated with lower executive function. WMH were significantly associated with a single executive test only, whereas the interaction between WMH and MTA was not significantly related to any of the cognitive tasks.

Conclusions: Our findings suggest that AD neuropathology in itself may be responsible for executive dysfunction. Potential explanations for these findings are discussed, focusing on the role of the hippocampus in executive function tests and reduced frontal-posterior connectivity in this patient sample.

Keywords

hippocampal atrophywhite matter hyperintensitiescognitive controlspeed of processingmemorydementiamild cognitive impairment
Type
Research Article
Information
International Psychogeriatrics , Volume 24 , Issue 9 , September 2012 , pp. 1474 - 1482
Copyright
Copyright © International Psychogeriatric Association 2012

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References

Anderson, K. L., Rajagovindan, R., Ghacibeh, G. A., Meador, K. J. and Ding, M. (2010). Theta oscillations mediate interaction between prefrontal cortex and medial temporal lobe in human memory. Cerebral Cortex, 20, 1604–1612. doi:10.1093/cercor/bhp223.CrossRefGoogle ScholarPubMed
Bastos-Leite, A. J., van der Flier, W. M., van Straaten, E. C., Staekenborg, S. S., Scheltens, P. and Barkhof, F. (2007). The contribution of medial temporal lobe atrophy and vascular pathology to cognitive impairment in vascular dementia. Stroke, 38, 3182–3185. doi:10.1161/STROKEAHA.107.490102.CrossRefGoogle ScholarPubMed
Baudic, S., Barba, G. D., Thibaudet, M. C., Smagghe, A., Remy, P. and Traykov, L. (2006). Executive function deficits in early Alzheimer's disease and their relations with episodic memory. Archives of Clinical Neuropsychology, 21, 15–21. doi:10.1016/j.acn.2005.07.002.CrossRefGoogle ScholarPubMed
Burgmans, S. et al. (2010). Multiple indicators of age-related differences in cerebral white matter and the modifying effects of hypertension. Neuroimage, 49, 2083–2093. doi:10.1016/j.neuroimage.2009.10.035.CrossRefGoogle ScholarPubMed
Burns, J. M. et al. (2005). White matter lesions are prevalent but differentially related with cognition in aging and early Alzheimer disease. Archives of Neurology, 62, 1870–1876. doi:10.1001/archneur.62.12.1870.CrossRefGoogle ScholarPubMed
Collette, F., Van der Linden, M., Delrue, G. and Salmon, E. (2002). Frontal hypometabolism does not explain inhibitory dysfunction in Alzheimer disease. Alzheimer Disease and Associated Disorders, 16, 228–238. doi:10.1097/00002093-200210000-00004.CrossRefGoogle Scholar
Duara, R. et al. (2011). Pre-MCI and MCI: Neuropsychological, clinical, and imaging features and progression rates. American Journal of Geriatric Psychiatry, 19, 951–960. doi:10.1097/JGP.0b013e3182107c69.CrossRefGoogle ScholarPubMed
Erkinjuntti, T. (2002). Diagnosis and management of vascular cognitive impairment and dementia. Journal of Neural Transmission. Supplementum, 63, 91–109.Google Scholar
Fazekas, F., Chawluk, J. B., Alavi, A., Hurtig, H. I. and Zimmerman, R. A. (1987). MR signal abnormalities at 1.5T in Alzheimer's disease and normal ageing. American Journal of Roentgenology, 149, 351–356.CrossRefGoogle Scholar
Gainotti, G., Ferraccioli, M., Vita, M. G. and Marra, C. (2008). Patterns of neuropsychological impairment in MCI patients with small subcortical infarcts or hippocampal atrophy. Journal of the International Neuropsychological Society, 14, 611–619. doi:10.1017/S1355617708080831.CrossRefGoogle ScholarPubMed
Gouw, A. A., et al. (2006). Simple versus complex assessment of white matter hyperintensities in relation to physical performance and cognition: the LADIS study. Journal of Neurology, 253, 1189–1196. doi:10.1007/s00415-006-0193-5.CrossRefGoogle ScholarPubMed
Huang, J., Friedland, R. P. and Auchus, A. P. (2007). Diffusion tensor imaging of normal-appearing white matter in mild cognitive impairment and early Alzheimer disease: preliminary evidence of axonal degeneration in the temporal lobe. American Journal of Neuroradiology, 28, 1943–1948. doi:10.3174/ajnr.A0700.CrossRefGoogle ScholarPubMed
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D. and Stadlan, E. (1984). Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of the Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology, 34, 939–944.CrossRefGoogle ScholarPubMed
Mungas, D. et al. (2005). Longitudinal volumetric MRI change and rate of cognitive decline. Neurology, 65, 565–571. doi:10.1212/01.wnl.0000172913.88973.0d.CrossRefGoogle ScholarPubMed
Nagata, T. et al. (2011). Association between executive dysfunction and hippocampal volume in Alzheimer's disease. International Psychogeriatrics, 23, 764–771. doi:10.1017/S1041610210002164.CrossRefGoogle ScholarPubMed
Oosterman, J. M. et al. (2008a). The role of white matter hyperintensities and medial temporal lobe atrophy in age-related executive dysfunctioning. Brain and Cognition, 68, 128–133. doi:10.1016/j.bandc.2008.03.006.CrossRefGoogle ScholarPubMed
Oosterman, J. M., van Harten, B., Weinstein, H. C., Scheltens, P., Sergeant, J. A. and Scherder, E. J. (2008b). White matter hyperintensities and working memory: an explorative study. Neuropsychology, Development, and Cognition. Section B, Aging Neuropsychology and Cognition, 15, 384–399. doi:10.1080/13825580701879998.CrossRefGoogle ScholarPubMed
Oosterman, J. M. et al. (2010). Assessing mental flexibility: neuroanatomical and neuropsychological correlates of the Trail Making Test in elderly people. The Clinical Neuropsychologist, 24, 203–219. doi:10.1080/13854040903482848.CrossRefGoogle ScholarPubMed
Petersen, R. C. (2004). Mild cognitive impairment as a diagnostic entity. Journal of Internal Medicine, 256, 183–194. doi:10.1111/j.1365-2796.2004.01388.x.CrossRefGoogle ScholarPubMed
Phillips, L. H., Wynn, V., Gilhooly, K. J., Della Sala, S. and Logie, R. H. (1999). The role of memory in the Tower of London task. Memory, 7, 209–231. doi:10.1080/741944066.CrossRefGoogle ScholarPubMed
Scheltens, P. et al. (1992). Atrophy of medial temporal lobes on MRI in “probable” Alzheimer's disease and normal ageing: diagnostic value and neuropsychological correlates. Journal of Neurology, Neurosurgery, and Psychiatry, 55, 967–972. doi:10.1136/jnnp.55.10.967.CrossRefGoogle ScholarPubMed
Skoog, I., Berg, S., Johansson, B., Palmertz, B. and Andreasson, L. A. (1996). The influence of white matter lesions on neuropsychological functioning in demented and non-demented 85-year-olds. Acta Neurologica Scandinavica, 93, 142–148. doi: 10.1111/j.1600-0404.1996.tb00190.x.CrossRefGoogle ScholarPubMed
Takahashi, H. et al. (2007). Memory and frontal lobe functions; possible relations with dopamine D2 receptors in the hippocampus. Neuroimage, 34, 1643–1649. doi:10.1016/j.neuroimage.2006.11.008.CrossRefGoogle ScholarPubMed
Takahashi, H. et al. (2008). Differential contributions of prefrontal and hippocampal dopamine D(1) and D(2) receptors in human cognitive functions. Journal of Neuroscience, 28, 12032–120328. doi: 10.1523/JNEUROSCI.3446-08.2008.CrossRefGoogle Scholar
Tierney, P. L., Dégenètais, E., Thierry, A. M., Glowinski, J. and Gioanni, Y. (2004). Influence of the hippocampus on interneurons of the rat prefrontal cortex. European Journal of Neuroscience, 20, 514–524. doi:10.1111/j.1460-9568.2004.03501.x.CrossRefGoogle ScholarPubMed
Tondelli, M., Wilcock, G. K., Nichelli, P., De Jager, C. A., Jenkinson, M. and Zamboni, G. (2012). Structural MRI changes detectable up to ten years before clinical Alzheimer's disease. Neurobiology of Aging, 33, e25–e36. doi:10.1016/j.neurobiolaging.2011.05.018.CrossRefGoogle ScholarPubMed
van der Flier, W. M. et al. (2005). Medial temporal lobe atrophy and white matter hyperintensities are associated with mild cognitive deficits in non-disabled elderly people: the LADIS study. Journal of Neurology, Neurosurgery, and Psychiatry, 76, 1497–1500. doi: 10.1136/jnnp.2005.064998.CrossRefGoogle ScholarPubMed
Vernooij, M. W. et al. (2007). Incidental findings on brain MRI in the general population. New England Journal of Medicine, 357, 1821–1828. doi:10.1056/NEJMoa070972.CrossRefGoogle ScholarPubMed
Wahlund, L. O., Julin, P., Johansson, S. E., and Scheltens, P. (2000). Visual rating and volumetry of the medial temporal lobe on magnetic resonance imaging in dementia: a comparative study. Journal of Neurology, Neurosurgery and Psychiatry, 69, 630–605. doi:10.1136/jnnp.69.5.630.CrossRefGoogle ScholarPubMed
Westman, E. et al. (2011). Sensitivity and specificity of medial temporal lobe visual ratings and multivariate regional MRI classification in Alzheimer's disease. PLoS One, 6:e22506. doi:10.1371/journal.pone.0022506.CrossRefGoogle ScholarPubMed
Wright, C. B. et al. (2008). White matter hyperintensities and subclinical infarction: associations with psychomotor speed and cognitive flexibility. Stroke, 39, 800–805. doi:10.1161/STROKEAHA.107.484147.CrossRefGoogle ScholarPubMed