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Dissociation of remote and anterograde memory impairment and neural correlates in alcoholic Korsakoff syndrome



Alcoholic Korsakoff's syndrome (KS) is marked by remote memory impairment together with characteristic profound anterograde memory deficits. Despite previous studies of memory processes in KS, questions remain regarding the nature and severity of these impairments and identification of brain systems that underlie these different memory impairments. This study examined remote and anterograde memory function in 5 KS patients in comparison with 8 patients with Alzheimer's disease (AD) and 24 normal control subjects (NC). In addition, relationships between memory performance and regional brain volumes were examined in the KS group. Overall, the KS group showed severe impairment on both remote and anterograde memory measures, performing at the level of the AD group on most measures. Differences were observed on the pattern of temporal gradient for verbal recognition, with KS exhibiting a more steeply graded rate of decline over the most recent period examined. Severity of the remote memory deficit in KS was not associated with severity of anterograde memory deficit. Examination of brain structure–function relationships in the KS subjects revealed that photo naming of remote historical information was related to posterior cortical white matter volumes but not hippocampal volumes; sequencing was related to prefrontal but not hippocampal volumes. By contrast, a measure of anterograde memory for nonverbal visual material showed a relationship to hippocampal but not regional cortical white matter volumes. This set of dissociations, which parallels that observed in our earlier study of AD, is now documented in KS and provides further evidence that these separate cortical and limbic brain systems are principal neural substrates of the remote and anterograde memory and sequencing deficits in KS. (JINS, 2004, 10, 427–441.)


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Reprint requests to: Edith V. Sullivan, Ph.D., Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine (MC5723), 401 Quarry Road, Stanford, CA 94305-5723. E-mail:


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Agartz, I., Momenan, R., Rawlings, R.R., Kerich, M.J., & Hommer, D.W. (1999). Hippocampal volume in patients with alcohol dependence. Archives of General Psychiatry, 56, 356363.
Aggleton, J.P. & Brown, M.W. (1999). Episodic memory, amnesia, and the hippocampal–anterior thalamic axis. Behavioral Brain Science, 22, 425444.
Aggleton, J.P. & Saunders, R.C. (1997). The relationships between temporal lobe and diencephalic structures implicated in anterograde amnesia. Memory, 5, 4971.
Albert, M.S., Butters, N., & Brandt, J. (1981). Patterns of remote memory in amnesic and demented patients. Archives of Neurology, 38, 495500.
Albert, M.S., Butters, N., & Levin, J. (1979). Temporal gradients in the retrograde amnesia of patients with alcoholic Korsakoff's disease. Archives of Neurology, 36, 211216.
American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders. Washington, DC.
Beatty, W.W., Salmon, D.P., Butters, N., Heindel, W.C., & Granholm, E.L. (1988). Retrograde amnesia in patients with Alzheimer's disease or Huntington's disease. Neurobiology of Aging, 9, 181186.
Butters, N. & Albert, M.S. (1982). Processes underlying failures to recall remote events. In L.S. Cermak (Ed.), Human memory and amnesia (pp. 257274). Hillsdale, NJ: Erlbaum.
Butters, N. & Cermak, L.S. (1980). Alcoholic Korsakoff's syndrome. New York: Academic Press, Inc.
Butters, N. & Stuss, D.T. (1989). Diencephalic amnesia. In F. Boller & J. Grafman (Eds.), Handbook of neuropsychology, Vol. 3 (pp. 107148). Amsterdam: Elsevier.
Cermak, L.S., Butters, N., & Goodglass, H. (1971). The extent of memory loss in Korsakoff patients. Neuropsychologia, 9, 307315.
Clark, R.E., Broadbent, N.J., Zola, S.M., & Squire, L.R. (2002). Anterograde amnesia and temporally graded retrograde amnesia for a nonspatial memory task after lesions of hippocampus and subiculum. Journal of Neuroscience, 22, 46634669.
Corkin, S. (1982). Some relationships between global amnesias and the memory impairment of Alzheimer's disease. In S. Corkin, K. Davis, J.H. Growdon, E. Usdin, & R.J. Wurtman (Eds.), Alzheimer's disease: A report of progress in research (pp. 149164). New York: Raven Press.
Corkin, S., Cohen, N.J., Sullivan, E.V., Clegg, R.A., Rosen, T.J., & Ackerman, R.H. (1985). Analyses of global memory impairment of different etiologies. Annals of the New York Academy of Sciences, 44, 1040.
Damasio, A.R. & Damasio, H. (1993). Cortical systems underlying knowledge retrieval: Evidence from human lesion studies. In T.A. Poggio & D.A. Glaser (Eds.), Exploring brain functions: Models in neuroscience (pp. 233248). New York: Wiley & Sons.
Davila, M.D., Shear, P.K., Lane, B., Sullivan, E.V., & Pfefferbaum, A. (1994). Mammillary body and cerebellar shrinkage in chronic alcoholics: An MRI and neuropsychological study. Neuropsychology, 8, 433444.
Deweer, B., Lehericy, S., Pillon, B., Baulac, M., Chiras, J., Marsault, C., Agid, Y., & Dubois, B. (1995). Memory disorders in probable Alzheimer's disease: The role of hippocampal atrophy as shown with MRI. Journal of Neurology, Neurosurgery and Psychiatry, 58, 590597.
Downes, J.J., Mayes, A.R., MacDonald, C., & Hunkin, N.M. (2002). Temporal order memory in patients with Korsakoff's syndrome and medial temporal amnesia. Neuropsychologia, 40, 853861.
Fama, R., Shear, P.K., Marsh, L., Yesavage, J., Tinklenberg, J.R., Lim, K.O., Pfefferbaum, A., & Sullivan, E.V. (2001). Remote memory for public figures in Alzheimer's disease: Relationships to regional cortical and limbic brain volumes. Journal of the International Neuropsychological Society, 7, 384390.
Fama, R., Sullivan, E.V., Shear, P.K., Marsh, L., Yesavage, J.A., Tinklenberg, J.R., Lim, K.O., & Pfefferbaum, A. (1997). Selective cortical and hippocampal volume correlates of Mattis Dementia Rating Scale in Alzheimer's disease. Archives of Neurology, 54, 719728.
Fama, R., Sullivan, E.V., Shear, P.K., Stein, M., Yesavage, J.A., Tinklenberg, J.R., & Pfefferbaum, A. (2000). Extent, pattern, and correlates of remote memory impairment in Alzheimer's disease and Parkinson's disease. Neuropsychology, 14, 265276.
Folstein, M.F., Folstein, S.E., & McHugh, P.R. (1975). Mini-mental state: A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189198.
Haist, F., Gore, J.B., & Mao, H. (2001). Consolidation of human memory over decades revealed by functional magnetic resonance imaging. Nature Neuroscience, 4, 11391145.
Hamsher, K. & Roberts, R.J. (1985). Memory for recent U.S. presidents in patients with cerebral disease. Journal of Clinical and Experimental Neuropsychology, 7, 113.
Harding, A., Halliday, G., Caine, D., & Kril, J. (2000). Degeneration of anterior thalamic nuclei differentiates alcoholics with amnesia. Brain, 123, 141154.
Harper, C.G. & Kril, J.J. (1993). Neuropathological changes in alcoholics. In W.A. Hunt & S.J. Nixon (Eds.), Alcohol induced brain damage: NIAAA Research Monograph No. 22 (pp. 3969). Rockville, MD: National Institute of Health.
Heaton, R.K. (1981). Wisconsin Card Sorting Test manual. Odessa, FL: Psychological Assessment Resources, Inc.
Hodges, J.R. (1995). Retrograde amnesia. In A.D. Baddeley, B.A. Wilson, & F.N. Watts (Eds.), Handbook of memory disorders (pp. 81107). New York: John Wiley & Sons.
Hodges, J.R., Salmon, D.P., & Butters, N. (1992). Semantic memory impairment in Alzheimer's disease: Failure of access or degraded knowledge? Neuropsychologia, 30, 301314.
Hodges, J.R., Salmon, D.P., & Butters, N. (1993). Recognition and naming of famous faces in Alzheimer's disease: A cognitive analysis. Neuropsychologia, 31, 775788.
Huff, F.J., Collins, C., Corkin, S., & Rosen, T.J. (1986). Equivalent forms of the Boston Naming Test. Journal of Clinical and Experimental Neuropsychology, 8, 556562.
Hunkin, N.M., Parkin, A.J., Bradley, V.A., Burrows, E.H., Aldrich, F.K., Jansari, A., & Burdon-Cooper, C. (1995). Focal retrograde amnesia following closed head injury: A case study and theoretical account. Neuropsychologia, 33, 509523.
Jack, C., Petersen, R., Xu, Y., O'Brien, P., Smith, G., Ivnik, R., Tangalos, E., & Kokmen, E. (1998). Rate of medial temporal-lobe atrophy in typical aging and Alzheimer's disease. Neurology, 51, 993999.
Jernigan, T.L., Schafer, K., Butters, N., & Cermak, L.S. (1991). Magnetic resonance imaging of alcoholic Korsakoff patients. Neuropsychopharmacology, 4, 175186.
Kaplan, E., Goodglass, H., & Weintraub, S. (1976). Boston Naming Test, Experimental Edition. Boston University.
Kapur, N., Ellison, D., Parkin, A.J., Hunkin, N.M., Burrows, E., Sampson, S.A., & Morrison, E.A. (1994). Bilateral temporal lobe pathology with sparing of medial temporal lobe structures: Lesion profile and pattern of memory disorder. Neuropsychologia, 32, 23.
Kensinger, E.A., Ullman, M.T., & Corkin, S. (2001). Bilateral medial temporal lobe damage does not affect lexical or grammatical processing: Evidence from amnesic patient H.M. Hippocampus, 11, 347360.
Khachaturian, Z.S. (1985). Diagnosis of Alzheimer's disease. Archives of Neurology, 42, 10971105.
Killiany, R.J., Gomez-Isla, T., Moss, M., Kikinis, R., Sandor, T., Jolesz, F., Tanzi, R., Jones, K., Hyman, B.T., & Albert, M.S. (2000). Use of structural magnetic resonance imaging to predict who will get Alzheimer's disease. Annals of Neurology, 47, 430439.
Killiany, R.J., Moss, M.B., Albert, M.S., Sandor, T., Tieman, J., & Jolesz, F. (1993). Temporal lobe regions on magnetic resonance imaging identify patients with early Alzheimer's disease. Archives of Neurology, 50, 949954.
Kopelman, M.D. (1989). Remote and autobiographical memory, temporal context memory and frontal atrophy in Korsakoff and Alzheimer patients. Neuropsychologia, 27, 437460.
Kopelman, M.D. (1995). The Korsakoff syndrome. British Journal of Psychiatry, 166, 154173.
Kopelman, M.D. & Stanhope, N. (2002). Anterograde and retrograde amnesia following frontal lobe, temporal lobe and diencephalic lesions. In L.R. Squire & D.L. Schacter (Eds.), Neuropsychology of memory (3rd ed., pp. 4760). New York: Guilford Press.
Kopelman, M.D., Stanhope, N., & Kingsley, D. (1999). Retrograde amnesia in patients with diencephalic, temporal lobe or frontal lesions. Neuropsychologia, 37, 939958.
Laakso, M.P., Soininen, H., Partanen, K., Helkala, E.-L., Hartikainen, P., Vainio, P., Hallikainen, M., Hanninen, T., & Riekkinen, P.J. (1995). Volumes of hippocampus, amygdala and frontal lobes in the MRI-based diagnosis of early Alzheimer's disease: Correlation with memory functions. Journal of Neural Transmission, 9, 7386.
Maguire, E.A., Henson, R.N., Mummery, C.J., & Frith, C.D. (2001). Activity in prefrontal cortex, not hippocampus, varies parametrically with the increasing remoteness of memories. Neuroreport, 12, 441444.
McFie, J. & Thompson, J.A. (1972). Picture Arrangement: A measure of frontal lobe function? British Journal of Psychiatry, 121, 547552.
McKhann, G., Drachman, D., Folstein, M., & Katzman, R. (1984). Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's disease. Neurology, 37, 939944.
Milner, B. (1958). Psychological deficits produced by temporal-lobe excision. Research Publication of the Association for Research of Nervous and Mental Diseases, 36, 244257.
Milner, B. (1963). Effects of different brain lesions on card sorting. Archives of Neurology, 9, 90100.
Nadel, L., Samsonovich, A., Ryan, L., & Moscovitch, M. (2000). Multiple trace theory of human memory: Computational, neuroimaging, and neuropsychological results. Hippocampus, 10, 352368.
Nelson, H.E. (1982). The National Adult Reading Test (NART). Windsor, Ontario, Canada: Nelson Publishing Company.
Parkin, A.J., Montaldi, D., Leng, N.R., & Hunkin, N.M. (1990). Contextual cueing effects in the remote memory of alcoholic Korsakoff patients and normal subjects. Quarterly Journal of Experimental Psychology A, 42, 585596.
Pfefferbaum, A., Mathalon, D.H., Sullivan, E.V., Rawles, J.M., Zipursky, R.B., & Lim, K.O. (1994). A quantitative magnetic resonance imaging study of changes in brain morphology from infancy to late adulthood. Archives of Neurology, 51, 874887.
Pfefferbaum, A. & Sullivan, E.V. (2002). Microstructural but not macrostructural disruption of white matter in women with chronic alcoholism. Neuroimage, 15, 708718.
Pfefferbaum, A., Sullivan, E.V., Hedehus, M., Adalsteinsson, E., Lim, K.O., & Moseley, M. (2000). In vivo detection and functional correlates of white matter microstructural disruption in chronic alcoholism. Alcoholism: Clinical and Experimental Research, 24, 12141221.
Ryan, L., Nadel, L., Keil, K., Putnam, K., Schnyer, D., Trouard, T., & Moscovitch, M. (2001). Hippocampal complex and retrieval of recent and very remote autobiographical memories: Evidence from functional magnetic resonance imaging in neurologically intact people. Hippocampus, 11, 707714.
Sagar, H.J., Cohen, N.J., Sullivan, E.V., Corkin, S., & Growdon, J.H. (1988). Remote memory function in Alzheimer's disease and Parkinson's disease. Brain, 111, 201222.
Sanders, H.I. & Warrington, E.K. (1971). Memory for remote events in amnesic patients. Brain, 94, 661668.
Shear, P.K., Sullivan, E.V., Lane, B., & Pfefferbaum, A. (1996). Mammillary body and cerebellar shrinkage in chronic alcoholics with and without amnesia. Alcoholism: Clinical and Experimental Research, 20, 14891495.
Shimamura, A.P. (1989). Disorders of memory: The cognitive science perspective. In F. Boller & J. Grafman (Eds.), Handbook of neuropsychology, Vol. 3 (pp. 3573). New York: Elsevier.
Siegel, S. & Castellan, N.J. (1988). Nonparametric statistics for the behavioral sciences (2nd ed.). New York: McGraw-Hill.
Squire, L.R. (1982). Comparisons between forms of amnesia: Some deficits are unique to Korsakoff's syndrome. Journal of Experimental Psychology: Learning, Memory and Cognition, 8, 560571.
Squire, L.R. & Alvarez, P. (1995). Retrograde amnesia and memory consolidation: A neurobiological perspective. Current Opinion in Neurobiology, 5, 169177.
Squire, L.R., Amaral, D.G., & Press, G.A. (1990). Magnetic resonance imaging of the hippocampal formation and mammillary nuclei distinguish medial temporal lobe and diencephalic amnesia. Journal of Neuroscience, 10, 31063117.
Squire, L.R., Haist, F., & Shimamura, A.P. (1989). The neurology of memory: Quantitative assessment of retrograde amnesia in two groups of amnesic patients. Journal of Neuroscience, 9, 828839.
Squire, L.R., Knowlton, B., & Musen, G. (1993). The structure and organization of memory. Annual Review of Psychology, 44, 453495.
Sullivan, E.V., Lane, B., Rosenbloom, M.J., Deshmukh, A., Desmond, J., Lim, K.O., & Pfefferbaum, A. (1999). In vivo mammillary body volume deficits in amnesic and nonamnesic alcoholics. Alcoholism: Clinical and Experimental Research, 23, 16291536.
Sullivan, E.V. & Marsh, L. (2003). Hippocampal volume deficits contribute to the amnesia of alcoholic Korsakoff's syndrome. Neurology, 61, 17161719.
Sullivan, E.V., Marsh, L., Lim, K.O., & Pfefferbaum, A. (2001). Equivalent hippocampal volume deficits in Korsakoff's syndrome and Alzheimer's disease [Abstract]. Journal of the International Neuropsychological Society, 7, 232.
Sullivan, E.V., Marsh, L., Mathalon, D.H., Lim, K.O., & Pfefferbaum, A. (1995a). Age-related decline in MRI volumes of temporal lobe gray matter but not hippocampus. Neurobiology of Aging, 16, 591606.
Sullivan, E.V., Marsh, L., Mathalon, D.H., Lim, K.O., & Pfefferbaum, A. (1995b). Anterior hippocampal volume deficits in nonamnesic, aging chronic alcoholics. Alcoholism: Clinical and Experimental Research, 19, 110122.
Sullivan, E.V., Mathalon, D.H., Zipursky, R.B., Kersteen-Tucker, Z., Knight, R.T., & Pfefferbaum, A. (1993). Factors of the Wisconsin Card Sorting Test as a test of dorsolateral prefrontal cortical function in schizophrenia and alcoholism. Psychiatry Research, 46, 175199.
Sullivan, E.V., Rosenbloom, M.J., & Pfefferbaum, A. (2000). Pattern of motor and cognitive deficits in detoxified alcoholic men. Alcoholism: Clinical and Experimental Research, 24, 611621.
Sullivan, E.V., Sagar, H.J., Gabrieli, J.D.E., Corkin, S., & Growdon, J.H. (1989). Different cognitive profiles on standard behavioral tests in Parkinson's disease and Alzheimer's disease. Journal of Clinical and Experimental Neuropsychology, 11, 799820.
Ungerleider, L.G. (1995). Functional brain imaging studies of cortical mechanisms for memory. Science, 270, 769775.
Victor, M., Adams, R.D., & Collins, G.H. (1989). The Wernicke-Korsakoff syndrome and related neurologic disorders due to alcoholism and malnutrition (2nd ed.). Philadelphia: F.A. Davis Co.
Warrington, E. (1984). Recognition Memory Test manual. Windsor, UK: Nelson Publishing Company.
Wechsler, D. (1981). Wechsler Adult Intelligence Scale–Revised. San Antonio, TX: The Psychological Corporation.
Wechsler, D. (1987). Wechsler Memory Scale–Revised. San Antonio, TX: The Psychological Corporation.
Wilson, R.S., Kaszniak, A.W., & Fox, J.H. (1981). Remote memory in senile dementia. Cortex, 17, 4148.


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Dissociation of remote and anterograde memory impairment and neural correlates in alcoholic Korsakoff syndrome



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