Abstract
This paper reviews the growing amount of evidence supporting the hypothesis that Alzheimer's disease includes a disconnection syndrome. This evidence came mainly from neuropathological, electrophysiological, and neuroimaging studies. Moreover, a few recent neuropsychological studies have also explored the effects of a disconnection between cerebral areas on cognitive functioning. Finally, and more generally, the contribution of this interpretation to the understanding of Alzheimer's disease cognitive deficits is considered.
Similar content being viewed by others
REFERENCES
Arendt, T. (2001). Alzheimer's disease as a disorder of mechanisms underlying structural brain self-organization. Neuroscience 102: 723-765.
Arriagada, P. V., Growdon, J. H., Hedley-Whyte, E. T., and Hyman, B. T. (1992). Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease. Neurology 42: 631-639.
Azari, N. P., Rapoport, S. I., Grady, C. L., Schapiro, M. B., Salerno, J. A., Gonzales-Aviles, A., et al. (1992). Patterns of interregional correlations of cerebral glucose metabolic rates in patients with dementia of the Alzheimer type. Neurodegeneration 1: 101-111.
Baddeley, A. D. (1986). Working Memory, Oxford University Press, Oxford.
Baddeley, A. D., Baddeley, H. A., Bucks, R. S., and Wilcock, G. K. (2001). Attentional control in Alzheimer's disease. Brain 124: 1492-1508.
Baddeley, A. D., Logie, R., Bressi, S., Della Sala, S., and Spinnler, H. (1986). Dementia and working memory. Q. J. Exp. Psychol. 38: 603-618.
Baddeley, A., Della Sala, S., Papagno, C., and Spinnler, H. (1997). Dual-task performance in dysexecutive and nondysexecutive patients with a frontal lesion. Neuropsychology 11: 187-194.
Baddeley, A. D., Bressi, S., Della Sala, S., Logie, R., and Spinnler, H. (1991). The decline of working memory in Alzheimer's disease: A longitudinal study. Brain 114: 2521-2542.
Belleville, S., Rouleau, N., and Caza, N. (1998). Effects of normal aging on the manipulation of information in working memory. Mem. Cognit. 26: 572-583.
Berendse, H. W., Verbundt, J. P. A., Scheltens, Ph., van Dijk, B. W., and Jonkman, E. J. (2000). Magnetoencephalography analysis of cortical activity in Alzheimer's disease: A pilot study. Clin. Neurophysiol. 11: 604-612.
Besthorn, C., Förstl, H., Geiger-Kabisch, C., Sattel, H., Gasser, T., and Schreitter-Gasser, U. (1994). EEG coherence in Alzheimer disease. Electroencephalogr. Clin. Neurophysiol. 90: 242-245.
Brickenkamp, R. (1966). Le test D2 d'attention concentrée, Editest, Paris.
Buldyrev, S. V., Cruz, L., Gòmez-Isla, T., Gomez-Tortosa, E., Havlin, S., Le, R., et al. (2000). Description of microcolumnar ensembles in association cortex and their disruption in Alzheimer and Lewy body dementias. Proc. Natl. Acad. Sci. USA 97: 5039-5043.
Burgess, P.W., and Shallice, T. (1996). Response suppression, initiation and strategy use following frontal lobe lesions. Neuropsychologia 34: 263-273.
Cabeza, R., McIntosh, A. R., Tulving, E., Nyberg, L., and Grady, C. L. (1997). Age-related differences in effective neural connectivity during encoding and recall. Neuroreport 8: 3479-3483.
Collette, F., Van der Linden, M., Bechet, S., and Salmon, E. (1999a). Phonological loop and central executive functioning in Alzheimer's disease. Neuropsychologia 37: 905-918.
Collette, F., Van der Linden, M., and Salmon, E. (1999b). Executive Dysfunction in Alzheimer's Disease. Cortex 35: 57-72.
Collette, F., Van der Linden, M., Juillerat, A. C., and Meulemans, T. (2003). A cognitive neuropsychological approach to Alzheimer's disease. In: Mulligan, R., Van der Linden, M., and Juillerat, A. C. (eds.), The Clinical Management of Early Alzheimer's Disease, Erlbaum, Mahwah, NJ.
Collette, F., Van der Linden, M., Delrue, G., and Salmon, E. (2002). Frontal hypometabolism does not explain inhibitory dysfunction in Alzheimer's disease. Alzheimer Dis. Assoc. Disordering. 17: 228-238.
Damasio, A. R., Van Hoesen, G. W., and Hyman, B. T. (1990). Reflections on the selectivity of neuropathological changes in Alzheimer's disease. In: Schwartz, M. N. (ed.), Modular Deficits in Alzheimer Type Dementia, MIT Press, Cambridge, pp. 83-100.
Davis, H., Mast, T., Yoshie, N., and Zerlin, S. (1966). The slow response of the human cortex to auditory stimuli: recovery process. Electroencephalogr. Clin. Neurophysiol. 21: 105-113.
Davis, H., Osterhammel, P. A., Wier, C. C., and Gjerdingen, D. B. (1972). Slow vertex potentials: interactions among auditory, tactile, electric and visual stimuli. Electroencephalogr. Clin. Neurophysiol. 33: 537-545.
De Lacoste, M. C., and White, C. L. (1993). The role of cortical connectivity in Alzheimer's disease pathogenesis: A review and model system. Neurobiol. Aging 14: 1-16.
Fabrigoule, C., Rouch, I., Taberly, A., Letenneur, L., Commenges, D., Mazaux, J. M., et al. (1998). Cognitive process in preclinical phase of dementia. Brain 121: 135-141.
Finger, S. (1994). Origins of Neuroscience: A history of explorations into brain function, Oxford University Press, New York.
Friston, K. J. (1999). Schizophrenia and the disconnection hypothesis. Acta Psychiatr. Scand. 99: 68-79.
Frith, C. D., Friston, K. J., Herold, S., Sibersweig, D., Fletcher, P., Cahill, C., et al. (1995). Regional brain activity in chronic schizophrenic patients during the performance of a verbal fluency task. Br. J. Psychiatry 167: 343-349.
Fuster, J. M. (1993). Frontal lobes. Curr. Opin. Neurobiol. 3: 160-165.
Geschwind, N. (1965). Disconnection syndromes in animals and man. Brain 88: 237-294.
Golob, E. J., Miranda, G. G., Johnson, J. K., and Starr, A. (2001). Sensory cortical interactions in aging, mild cognitive impairement, and Alzheimer's disease. Neurobiol. Aging 22: 755-763.
Gòmez-Isla, T., and Hyman, B. T. (1997). Connections and cognitive impairment in Alzheimer's disease. In: Hyman, B. T., Duyckaerts, C., and Christen, Y. (eds.), Connections, Cognition, and Alzheimer's Disease, Springer, Berlin, pp. 149-166.
Gòmez-Isla, T., Price, J. L., McKeel, D.W., Morris, J. C., Growdon, J. H., and Hyman, B. T. (1996). Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer's disease. J. Neurosci. 16: 4491-4500.
Gòmez-Isla, T., Hollister, R., West, H., Mui, S., Growdon, J., Petersen, R. C., et al. (1997). Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease. Ann. Neurol. 41: 17-24.
Grady, C. L., Grimes, A. M., Patronas, N., Sunderland, T., Foster, N. L., and Rapoport, S. I. (1989). Divided attention, as measured by dichotic speech performance, in dementia of the Alzheimer type. Arch. Neurol. 46: 317-320.
Grady, C. L., Furey, M. L., Pietrini, P., Horwitz, B., and Rapoport, S. I. (2001). Altered brain functional connectivity and impaired shortterm memory in Alzheimer's disease. Brain 124: 739-756.
Greene, J. D. W., Hodges, J. R., and Baddeley, A. D. (1995). Autobiographical memory and executive functions in early dementia of Alzheimer type. Neuropsychologia 33: 1647-1670.
Grimes, A. M., Grady, C. L., Foster, N.M., Sunderland, T., and Patronas, N. J. (1985). Central auditory function in Alzheimer's disease. Neurology 35: 352-358.
Grober, E., and Buschke, H. (1987). Genuine memory deficits in dementia. Dev. Neuropsychol. 3: 13-36.
Hampel, H., Teipel, S. J., Alexander, G. E., Horwitz, B., Teichberg, D., Schapiro, M. B., et al. (1998). Corpus callosum atrophy is a possible indicator of region-and cell type-specific neuronal degeneration in Alzheimer Disease. Arch. Neurol. 55: 193-198.
Haxby, J. V., Duara, R., Grady, C. L., Rapoport, S. I., and Cutler, N. R. (1985). Relations between neuropsychological and cerebral metabolic asymmetries in early Alzheimer's disease. J. Cereb. Blood Flow Metab. 5: 193-200.
Horwitz, B., Duara, R., and Rapoport, S. I. (1986). Age differences in intercorrelations between regional cerebral metabolic rates for glucose. Ann. Neurol. 19: 60-67.
Horwitz, B., Grady, C. L., Sclageter, N. L., Duara, R., and Rapoport, S. I. (1987). Intercorrelations of regional glucose metabolic rates in Alzheimer's disease. Brain Res. 407: 294-306.
Jackson, J. H. (1874/1958). On the nature of the duality of the brain. In: Taylor, J. (ed.), Selected Writings of John Hughlings Jackson, Basic Books, New York, pp. 129-145.
Janowski, J. S., Kaye, J. A., and Carper, R. A. (1996). Atrophy of the corpus callosum in Alzheimer's disease versus healthy aging. J. Am. Geriatr. Soc. 44: 798-803.
Laflèche, G., and Albert, M. S. (1995). Executive function deficits in mild Alzheimer's disease. Neuropsychology 9: 313-320.
Lakmache, Y., Lassonde, M., Gauthier, S., Frigon, J. Y., and Lepore, F. (1998). Interhemispheric disconnection syndrome in Alzheimer's disease. Proc. Natl. Acad. Sci. USA 95: 9042-9046.
Lekeu, F., Van der Linden, M., Chicherio, C., Collette, F., Degueldre, C., Franck, G., et al. (2003). Brain correlates of performance in a free/cued recall task with semantic encoding in Alzheimer's disease. Alzheimer Dis. Assoc. Disordering. 17: 35-45.
Le Roc'h, K., Rancurel, G., Poitrenaud, J., Bourgin, P., and Sebban, C. (1993). Fluidité verbale et cohérence EEG dans la maladie d'Alzheimer. Neurophysiol. Clin. 23: 422-433.
Leuchter, A. F., Newton, T. F., Cook, I. A., Walter, D. O., Rosenberg-Thompson, S., and Lachenbruch, P. A. (1992). Changes in brain functional connectivity in alzheimer-type and multi-infarct dementia. Brain 115: 1543-1561.
Lichtheim, L. (1885). On aphasia. Brain 7: 433-484.
Locatelli, T., Cursi, M., Liberati, D., Franceschi, M., and Comi, G. (1998). EEG coherence in Alzheimer's disease. Electroencephalogr. Clin. Neurophysiol. 106: 229-237.
Lyoo, K., Satlin, A., Lee, C. K., and Renshaw, P. F. (1997). Regional atrophy of the corpus callosum in subjects with Alzheimer's disease and multi-infarct dementia. Psychiatry Res.: Neuroimaging 74: 63-72.
Mattis, S. (1973). Dementia rating scale, NFER-Nelson, Winsor.
Mesulam, M. M. (1998). From sensation to cognition. Brain 121: 1013-1052.
Moes, P., Jeeves, M. A., and Cook, K. (1995). Bimanual coordination with aging: Implications for interhemispheric transfer. Dev. Neuropsychol. 11: 23-40.
Mohr, E., Cox, C., Williams, J., Chase, T. N., and Fedio, P. (1990). Impairment of central auditory function in Alzheimer's disease. J. Clin. Exp. Neuropsychol. 12: 235-246.
Morris, R. G. (1994). Working memory in Alzheimer-Type dementia. Neuropsychology 8: 544-554.
Morris, R. G. (1996). Neurobiological correlates of cognitive dysfunction. In: Morris, R. G. (ed.), The Cognitive Neuropsychology of Alzheimer-type Dementia, Oxford University Press, Oxford, pp. 223-254.
Morrison, J., Scherr, S., Lewis, D., Campbell, M., Bloom, F., Rogers, J., et al. (1986). The laminar and regional distribution of neocortical somatostatin and neuritic plaques: Implications for Alzheimer's disease as a global neocortical disconnection syndrome. In: Scheibel, A., Wechsler, A., and Brazier, M. (eds.), The Biological Substrates of Alzheimer's Disease, Academic Press, Orlando, pp. 115-131.
Mottaghy, F. M., Krause, B. J., Kemna, L. J., Töpper, R., Tellmann, L., Beu, M., et al. (2000). Modulation of the neuronal circuitry subserving working memory in healthy human subjects by repetitive transcranial magnetic stimulation. Neurosci. Lett. 280: 167-170.
Nyberg, L., and Cabeza, R. (2000). Brain imaging of memory. In: Tulving, E., and Craik, F. I. M. (eds.), The Oxford Handbook of Memory, Oxford University Press, Oxford, pp. 501-519.
O'sullivan, M., Jones, D. K., Summers, P. E., Morris, R. G., Williams, S. C. R., and Markus, H. S. (2001). Evidence for cortical "disconnection" as a mechanism of age-related cognitive decline. Neurology 57: 632-638.
Pantel, J., Schröder, J., Jauss, M., Essig, M., Minakaran, R., Schönknecht, P., et al. (1999). Topography of callosal atrophy reflects the distribution of regional cerebral volume reduction in Alzheimer's disease. Psychiatry Res. 90: 181-192.
Pascual-Leone, A., Walsh, V., and Rothwell, J. (2000). Transcranial magnetic stimulation in cognitive neuroscience: Virtual lesion, chronometry, and functional connectivity. Curr. Opin. Neurobiol. 10: 232-237.
Pearson, R. C. A., Esiri, M. M., Hiorns, R. W., Wilcock, G. K., and Powell, T. P. S. (1985). Anatomical correlates of the distribution of the pathological changes in the neocortex in Alzheimer's disease. Proc. Natl. Acad. Sci. USA 82: 4531-4534.
Peled, A. (1999). Multiple constraint organization in the brain: A theory for schizophrenia. Brain Res. Bull. 49: 245-250.
Perry, R. J., and Hodges, J. R. (1999). Attention and executive deficits in Alzheimer's disease: A critical review. Brain 122: 383-404.
Petersen, R. C., Smith, G. E., Waring, S. C., Ivnik, R. J., Tangalos, E. G., and Kokmen, E. (1999). Mild cognitive impairment: clinical characterization and outcome. Arch. Neurol. 56: 303-308.
Reuter-Lorentz, P. A., and Stanczak, L. (2000). Differential effects of aging on the functions of the corpus callosum. Dev. Neuropsychol. 18: 113-137.
Rose, S. E., Chen, F., Chalk, J. B., Zelaya, F. O., Strugnell, W. E., Benson, M., et al. (2000). Loss of connectivity in Alzheimer's disease: An evaluation of white matter tract integrity with colour coded MR diffusion tensor imaging. ET J. 69: 528-530.
Schröder, J., Buchsbaum, M. S., Shihabuddin, L., Tang, C., Wie, T. C., Spiegel-Cohen, J., et al. (2001). Patterns of cortical activity and memory performance in Alzheimer's disease. Biol. Psychiatry 49: 426-436.
Shallice, T. (1988). From Neuropsychology to Mental Structures, Cambridge University Press, Cambridge.
Sperry, R. W. (1961). Cerebral organization and behavior. Science 133: 1749-1757.
Stroop, J. R. (1935). Studies of interference in serial verbal reactions. J. Exp. Psychol. 6: 643-661.
Teipel, S. J., Hampel, H., Pietrini, P., Alexander, G. E., Horwitz, B., Daley, E., et al. (1999). Region-specific corpus callosum atrophy correlates with the regional pattern of cortical glucose metabolism in Alzheimer's disease. Arch. Neurol. 56: 467-473.
Tulving, E., and Markowitsch, H. J. (1998). Episodic and declarative memory: role of the hippocampus. Hippocampus 8: 198-204.
Uylings, H. B. M., and de Brabander, J. M. (2002). Neuronal changes in normal human aging and Alzheimer's disease. Brain Cogn. 49: 268-276.
Van der Linden, M., and Coyette, F., and Members of GREMEM (GRECO) (in press). Elaboration d'une version verbale de la procédure de rappel libre/rappel indicé de Grober et Buschke. In: Van der Linden, M., Deweer, B., Adam, S., Coyette, F., and Poitrenaud, J. (eds.), L'évaluation de la mémoire épisodique: Mise au point et étalonnage de quatre épreuves, Solal, Marseille.
Van der Linden, M., Meulemans, Th., Marczewski, Ph., and Collette, F. (2001). The relationships between episodic memory, working memory, and executive functions: The contribution of the prefrontal cortex. Psychol. Belg. 40: 275-297.
Van Hoesen, G.W. (1990). The dissection by Alzheimer's disease of cortical and limbic neural systems relevant to memory. In: McGaugh, J. L., Weinberger, N. M., and Lynch, G. (eds.), Brain Organization and Memory: Cells, Systems and Circuits, Oxford University Press, Oxford, pp. 234-261.
Van Hoesen, G. W. (1997). Ventromedial temporal lobe anatomy, with comments on Alzheimer's disease and temporal injury. J. Neuropsychiatry Clin. Neurosci. 9: 331-341.
Wada, Y., Nanbu, Y., Kikuchi, M., Koshino, Y., Hashimoto, T., and Yamaguchi, N. (1998a). Abnormal functional connectivity in Alzheimer's disease: Intrahemispheric EEG coherence during rest and photic stimulation. Eur. Arch. Psychiatry Clin. Neurosci. 248: 203-208.
Wada, Y., Nanbu, Y., Koshino, Y., Yamaguchi, N., and Hashimoto, T. (1998b). Reduced interhemispheric EEG coherence in Alzheimer's disease: Analysis during rest and photic stimulation. Alzheimer Dis. Assoc. Disord. 12: 175-181.
Weinberger, D. R. (1993). A connectionist approach to the prefrontal cortex. J. Neuropsychiatry Clin. Neurosci. 5: 241-253.
Weis, S., Jellinger, K., and Wegner, E. (1991). Morphometry of the corpus callosum in normal aging and Alzheimer's disease. J. Neural Transm. Suppl. 33: 35-38.
Weissman, D. H., and Banich, M. T. (2000). The cerebral hemispheres cooperate to perform complex but not simple tasks. Neuropsychology 14: 41-59.
Wernicke, C. (1874/1977). Der aphasische symptomencomplex: Eine psychologische studie auf anatomischer basis. In: Eggert, G. H. (ed.), Wernicke's Works on Aphasia: A Sourcebook and Review, Mouton, The Hague, pp. 91-145.
Yamauchi, H., Fukuyama, H., Nagahama, Y., Katsumi, Y., Hayashi, T., Oyanagi, C., et al. (2000). Comparison of the pattern of atrophy of the corpus callosum in frontotemporal dementia, progressive supranuclear palsy and Alzheimer's disease. J. Neurol. Neurosurg. Psychiatry 69: 623-629.
Zimmerman, P., and Fimm, B. (1994) Tests d'évaluation de l'attention (TEA), Psytest, Würselen.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Delbeuck, X., Van der Linden, M. & Collette, F. Alzheimer' Disease as a Disconnection Syndrome?. Neuropsychol Rev 13, 79–92 (2003). https://doi.org/10.1023/A:1023832305702
Issue Date:
DOI: https://doi.org/10.1023/A:1023832305702