Skip to main content
×
Home
    • Aa
    • Aa

Context-specific memory and apolipoprotein E (ApoE) ε4: Cognitive evidence from the NIMH prospective study of risk for Alzheimer's disease

  • JAMES A. LEVY (a1), JUDY BERGESON (a1), KAREN PUTNAM (a1), VIRGINIA ROSEN (a1), ROBERT COHEN (a1), FRANCOIS LALONDE (a1), NADEEM MIRZA (a1), GARY LINKER (a1) and TREY SUNDERLAND (a1)...
Abstract

The aim of the study was to determine whether the ε4 allele of the apolipoprotein E (ApoE) gene was associated primarily with context-specific memory among individuals at genetic risk for developing Alzheimer's disease. The effect of ApoE status on comprehensive neuropsychological results was examined in 176 healthy adults during baseline cognitive testing in the NIMH Prospective Study of Biomarkers for Older Controls at Risk for Alzheimer's Disease (NIMH Prospective BIOCARD Study). The presence of the ε4 allele was associated with significantly lower total scores on the Logical Memory II subtest of the Wechsler Memory Scale–Revised and percent of information retained after delay. Further analysis indicated the prose recall and retention effect was partially explained by a small subgroup of ε4 homozygotes, suggesting a gradually progressive process that may be presaged with specific cognitive measures. The current results may represent an ε4-associated breakdown between gist-related information and context-bound veridical recall. This relative disconnection may be understood in light of putative ε4-related preclinical accumulation of Alzheimer pathology (tangles and plaques) in the entorhinal cortex (EC) and among frontal networks, as well as the possibility of less-efficient compensatory strategies. (JINS, 2004, 10, 362–370.)

Copyright
Corresponding author
Address correspondence and reprint requests to: James A. Levy, National Institute of Mental Health, Geriatric Psychiatry Branch, 9000 Rockville Pike, Building 10-3N228, MSC 1275, Bethesda, MD 20892. E-mail: jameslevy@mail.nih.gov
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

Albert, M.S., Moss, M.B., Tanzi, R., & Jones, K. (2001). Preclinical prediction of AD using neuropsychological tests. Journal of the International Neuropsychological Society, 7, 631639.

Arnaiz, E., Jelic, V., Almkvist, O., Wahlund, L.-O., Winblad, B., Valind, S., & Nordberg, A. (2001). Impaired cerebral glucose metabolism and cognitive functioning predict deterioration in mild cognitive impairment. NeuroReport, 12, 851855.

Backman, L. & Small, B.J. (1998). Influences of cognitive support on episodic remembering: Tracing the process of loss from normal aging to Alzheimer's disease. Psychology and Aging, 13, 267276.

Balota, D.A., Watson, J.M., Duchek, J.M., & Ferraro, F.R. (1999). Cross-modal semantic and homograph priming in healthy young, healthy old, and in Alzheimer's disease individuals. Journal of the International Neuropsychological Society, 5, 626640.

Batting, W.F. & Montague, W.E. (1969). Category norms for verbal items in 56 categories: A replication and extension of the Connecticut category norms. Journal of Experimental Psychology Monograph, 80, 146.

Berr, C., Dufouil, C., Brousseau, T., Richard, F., Amouyel, P., Marceteau, E., & Alperovitch, A. (1996). Early effect of ApoE-E4 allele on cognitive results in a group of highly performing subjects: The EVA study. Neuroscience Letters, 218, 912.

Blacker, D., Haines, J.L., Rodes, L., Terwedow, H., Go, R.C.P., Harrell, L.E., Perry, R.T., Bassett, S.S., Chase, G., Meyers, D., Albert, M.S., & Tanzi, R. (1997). ApoE–4 and age of onset of Alzheimer's disease: The NIMH genetics initiative. Neurology, 48, 139147.

Blair, J.R. & Spreen, O. (1989). Predicting premorbid IQ: A revision of the National Adult Reading Test. Clinical Neuropsychologist, 3, 129136.

Bondi, M.W., Salmon, D.P., Monsch, A.U., Galasko, D., Butters, N., Klauber, M.R., Thal, L.J., & Saitoh, T. (1995). Episodic memory changes are associated with the APOE-E4 allele in nondemented older adults. Neurology, 45, 22032206.

Bondi, M.W., Salmon, D.P., Galasko, D., Thomas, R.G., & Thal, L.J. (1999). Neuropsychological function and apolipoprotein E genotype in the preclinical detection of Alzheimer's disease. Psychology and Aging, 14, 295303.

Bookheimer, S.Y., Strojwas, M.H., Cohen, M.S., Saunders, A.M., Pericak-Vance, M.A., Mazziotta, J., & Small, G.W. (2000). Patterns of brain activation in people at risk for Alzheimer's disease. New England Journal of Medicine, 343, 450456.

Bozoki, A., Giordani, B., Heidebrink, J.L., Berent, S., & Foster, N.L. (2001). Mild cognitive impairments predict dementia in nondemented elderly patients with memory loss. Archives of Neurology, 58, 411416.

Braak, H. & Braak, E. (1991). Neuropathological stageing of Alzheimer-related changes. Acta Neuropathologica, 82, 239259.

Brainerd, C.J. & Reyna, V.F. (1990). Gist is the grist: Fuzzy-trace theory and the intuitionism. Developmental Review, 10, 347.

Budson, A.E., Daffner, K.R., Desikan, R., & Schacter, D.L. (2000). When false recognition is unopposed by true recognition: Gist-based memory distortion in Alzheimer's disease. Neuropsychology, 14, 277287.

Buschke, H. (1973). Selective reminding for analysis of memory and learning. Journal of Verbal Learning and Verbal Behavior, 12, 4350.

Caselli, R.J., Graff-Radford, N.R., Reiman, E.M., Weaver, A., Osborne, D., Lucas, J., Uecker, A., & Thibodeau, S.N. (1999). Preclinical memory decline in cognitively normal apolipoprotein E-E4 homozygotes. Neurology, 53, 201207.

Caselli, R.J., Osborne, D., Reiman, E.M., Hentz, J.G., Barbieri, C.J., Saunders, A.M., Hardy, J., Graff-Radford, N.R., Hall, G.R., & Alexander, G.E. (2001). Preclinical cognitive decline in late middle-aged asymptomatic apolipoprotein E-e4/4 homozygotes: A replication study. Journal of the Neurological Sciences, 189, 9398.

Chen, J.G., Edwards, C.L., Vidyarthi, S., Pitchumoni, S., Tabrizi, S., Barboriak, D., Charles, H.C., & Doraiswamy, P.M. (2002). Learning and recall in subjects at genetic risk for Alzheimer's disease. Journal of Neuropsychiatry and Clinical Neurosciences, 14, 5863.

Chen, P., Ratcliff, G., Belle, S.H., Cauley, J.A., DeKosky, S.T., & Ganguli, M. (2001). Patterns of cognitive decline in presymptomatic Alzheimer disease. Archives of General Psychiatry, 58, 853858.

Corder, E.H., Saunders, A.M., Strittmatter, W.J., Schmechel, D.E., Gaskell, P.C., Small, G.W., Roses, A.D., Haines, J.L., & Pericak-Vance, M.A. (1993). Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science, 261, 921923.

de Leon, M.J., Convit, A., Wolf, O.T., Tarshish, C.Y., DeSanti, S., Rusinek, H., Tsai, W., Kandil, E., Scherer, A.J., Roche, A., Imossi, A., Thorn, E., Bobinski, M., Caraos, C., Lesbre, P., Schlyer, D., Poirier, J., Reisberg, B., & Fowler, J. (2001). Prediction of cognitive decline in normal elderly subjects with 2-[18F]fluoro-2-deoxy-D-glucose/positron-emission tomography (FDG/PET). Proceedings of the National Academy of Sciences, 98, 1096610971.

De Santi, S., de Leon, M.J., Rusinek, H., Convit, A., Tarshish, C.Y., Roche, A., Tsai, W.H., Kandil, E., Boppana, M., Daisley, K., Wang, G.J., Schlyer, R., & Fowler, J. (2001). Hippocampal formation glucose metabolism and volume losses in MCI and AD. Neurobiology of Aging, 22, 529539.

Dik, M.G., Jonker, C., Bouter, L.M., Geerlings, M.I., van Kamp, G.J., & Deeg, D.J.H. (2000). APOE-E4 is associated with memory decline in cognitively impaired elderly. Neurology, 54, 14921497.

Elias, M.F., Beiser, A., Wolf, P.A., Au., R., White, R.F., & D'Agostino, R.B. (2000). The preclinical phase of Alzheimer disease: A 22-year prospective of the Framingham cohort. Archives of Neurology, 57, 808813.

Farrer, L.A., Cupples, A., Haines, J.L., Hyman, B., Kukull, W.A., Mayeux, R., Myers, R.H., Pericak-Vance, M.A., Risch, N., & van Duijn, C.M. (1997). Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. Journal of the American Medical Association, 278, 13491356.

Fernandez, G., Brewer, J.B., Zhao, Z., Glover, G.H., & Gabrieli, J.D.E. (1999). Level of sustained entorhinal activity at study correlates with subsequent cued-recall performance: A functional magnetic resonance imaging study with high acquisition rate. Hippocampus, 9, 3544.

Frank, L.M., Brown, E.N., & Wilson, M. (2000). Trajectory encoding in the hippocampus and entorhinal cortex. Neuron, 27, 169178.

Ghebremedhin, E., Schultz, C., Braak, E., & Braak, H. (1998). High frequency of apolipoprotein E E4 allele in young individuals with very mild Alzheimer's disease-related neurofibrillary changes. Experimental Neurology, 153, 152155.

Greenwood, P.M., Sunderland, T., Friz, J.L., & Parasuraman, R. (2000). Genetics and visual attention: Selective deficits in healthy adult carriers of the E4 allele of the apolipoprotein E gene. Proceedings of the National Academy of Sciences, 97, 1166111666.

Haist, F., Gore, J.B., & Mao, H. (2001). Consolidation of human memory over decades revealed by functional magnetic resonance imaging. Nature Neuroscience, 4, 11391145.

Helkala, E.-L., Kovisto, K., Hanninen, T., Vanhanen, M., Kervinen, K., Kuusisto, J., Mykkanen, L., Kesaniemi, Y.A., Laakso, M., & Riekkinen, P., Sr. (1995). The association of apolipoprotein E polymorphism with memory: A population based study. Neuroscience Letters, 191, 141144.

Helkala, E.-L., Kovisto, K., Hanninen, T., Vanhanen, M., Kervinen, K., Kuusisto, J., Mykkanen, L., Kesaniemi, Y.A., Laakso, M., & Riekkinan, P., Sr. (1996). Memory functions in human subjects with different apolipoprotein E phenotypes during a 3-year population-based follow-up study. Neuroscience Letters, 204, 177180.

Howieson, D.B., Dame, A., Camicioli, R., Sexton, G., Payami, H., & Kaye, J.A. (1997). Cognitive markers preceding Alzheimer's dementia in the healthy oldest old. Journal of the American Geriatric Society, 45, 584589.

Hyman, B.T., Van Hoesen, G.W., Kromer, L.J., & Damasio, A.R. (1986). Preforant pathway changes and the memory impairment of Alzheimer's disease. Annals of Neurology, 20, 472481.

Janowsky, J.S., Shimamura, A.P., & Squire, L.R. (1989). Source memory impairment in patients with frontal lobe lesions. Neuropsychologia, 27, 10431056

Johnson, D.K., Storandt, M., & Balota, D.A. (2003). A discourse analysis of logical memory recall in normal aging and dementia of the Alzheimer type. Neuropsychology, 17, 8292.

Juottonen, K., Lehtovirta, M., Helisalmi, S., Riekkinen, P.J., & Soininen, H. (1998). Major decrease in the volume of the entorhinal cortex in patients with Alzheimer's disease carrying the apolipoprotein E E4 allele. Journal of Neurology, Neurosurgery, and Psychiatry, 65, 322327.

Kantarci, K., Smith, G.E., Ivnik, R.J., Petersen, R.C., Boeve, B.F., Knopman, D.S., Tangalos, E.G., & Jack, C.R., Jr. (2002). 1H magnetic resonance spectroscopy, cognitive function, and apolipoprotein E genotype in normal aging, mild cognitive impairment and Alzheimer's disease. Journal of the International Neuropsychological Society, 8, 934942.

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., Hyman, B.T., Gomez-Isla, T., Moss, M.B., Kikinis, R., Jolesz, F., Tanzi, R., Jones, K., & Albert, M.S. (2002). MRI measures of entorhinal cortex vs. hippocampus in preclinical AD. Neurology, 58, 11881196.

Kordower, J.H., Chu, Y., Stebbins, G.T., DeKoksy, S.T., Cochran, E.J., Bennett, D., & Mufson, E.J. (2001). Loss and atrophy of layer II entorhinal cortex neurons in elderly people with mild cognitive impairment. Annals of Neurology, 49, 202213.

Lange, K.L., Bondi, M.W., Salmon, D.P., Galasko, D., Delis, D.C., Thomas, R.G., & Thal, L.J. (2002). Decline in verbal memory during preclinical Alzheimer's disease: Examination of the effect of APOE genotype. Journal of the International Neuropsychological Society, 8, 943955.

Linn, R.T., Wolf, P.A., Bachman, D.L., Knoefel, J.E., Cobb, J.L., Belanger, A.J., Kaplan, E.F., & D'Agostino, R.B. (1995). The ‘preclinical phase’ of probable Alzheimer's disease: A 13-year prospective study of the Framingham cohort. Archives of Neurology, 52, 485490.

Marquis, S., Moore, M.M., Howieson, D.B., Sexton, G., Payami, H., Kaye, J.A., & Camicioli, R. (2002). Independent predictors of cognitive decline in healthy elderly persons. Archives of Neurology, 59, 601606.

Mayeux, R., Small, S.A., Tang, M.-X., Tycko, B., & Stern, Y. (2001). Memory performance in healthy elderly without Alzheimer's disease: Effects of time and apolipoprotein-E. Neurobiology of Aging, 22, 683689.

O'Hara, R., Yesavage, J.A., Kraemer, H.C., Mauricio, M., Friedman, L.F., & Murphy, G.M. (1998). The APOE E4 allele is associated with decline on delayed recall performance in community-dwelling older adults. Journal of the American Geriatric Society, 46, 14931498.

Parasuraman, R., Greenwood, P.M., & Sunderland, T. (2002). The Apolipoprotein E gene, attention, and brain function. Neuropsychology, 16, 254274.

Reiman, E.M., Caselli, R.J., Yun, L.S., Chen, K., Bandy, D., Minoshima, S., Thibodeau, S.N., & Osborne, D. (1996). Preclinical evidence of Alzheimer's disease in persons homozygous for the ε4 allele for apolipoprotein E. New England Journal of Medicine, 334, 752758.

Reiman, E.M., Caselli, R.J., Chen, K., Alexander, G.E., Bandy, D., & Frost, J. (2001). Declining brain activity in cognitively normal apolipoprotein E ε4 heterozygotes: A foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer's disease. Proceedings of the National Academy of Sciences, 98, 33343339.

Rosen, V.M., Bergeson, J.L., Putnam, K., Harwell, A., & Sunderland, T. (2002). Working memory and apolipoprotein E: What's the connection?Neuropsychologia, 40, 22262233.

Rubin, E.H., Storandt, M., Miller, J.P., Kinscherf, D.A., Grant, E.A., Morris, J.C., & Berg, L. (1998). A prospective study of cognitive function and onset of dementia in cognitively healthy elders. Archives of Neurology, 55, 395401.

Saunders, A.M., Strittmatter, W.J., Schmechel, D., St. George-Hyslop, P.H., Pericak-Vance, M.A., Joo, S.H., Rosi, B.L., Gusella, J.F., Crapper-MacLachlan, D.R., Alberts, M.J., Hulette, C., Crain, B., Goldgaber, D., & Roses, A.D. (1993). Association of apolipoprotein E allele E4 with late-onset familial and sporadic Alzheimer's disease. Neurology, 43, 14671472.

Schiffman, S.S., Graham, B.G., Sattely-Miller, E.A., Zervakis, J., & Welsh-Bohmer, K. (2002). Taste, smell and neuropsychological performance of individuals at familial risk for Alzheimer's disease. Neurobiology of Aging, 23, 397404.

Schmidt, H., Schmidt, R., Fazekas, F., Semmler, J., Kapeller, P., Reinhart, B., & Kostner, G.M. (1996). Apolipoprotein E E4 allele in the normal elderly: Neuropsychologic and brain MRI correlates. Clinical Genetics, 50, 293299.

Simon, E., Leach, L., Winocur, G., & Moscovitch, M. (1994). Intact primary memory in mild to moderate Alzheimer disease: Indices from the California Verbal Learning Test. Journal of Clinical and Experimental Neuropsychology, 16, 414422.

Small, B.J., Basun, H., & Backman, L. (1998). Three-year changes in cognitive performance as a function of apolipoprotein E genotype: Evidence from very old adults without dementia. Psychology and Aging, 13, 8087.

Small, B.J., Dixon, R.A., Hultsch, D.F., & Hertzog, C. (1999). Longitudinal changes in quantitative and qualitative indicators of word and story recall in young-old and old-old adults. Journal of Gerontology: Psychological Sciences, 54B, P107P115.

Small, B.J., Graves, A.B., McEvoy, C.L., Crawford, F.C., Mullan, M., & Mortimer, J.A. (2000). Is APOE-ε4 a risk factor for cognitive impairment in normal aging?Neurology, 54, 20822088.

Small, G.W., Ercoli, L.M., Silverman, D.H.S., Huang, S.-C., Komo, S., Bookheimer, S.Y., Lavrotsky, H., Miller, K., Siddarth, P., Rasgon, N.L., Mazziotta, J.C., Saxena, S., Wu, H.M., Mega, M.S., Cummings, J.L., Saunders, A.M., Pericak-Vance, M.A., Roses, A.D., Barrio, J.R., & Phelps, M.E. (2000). Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease. Proceedings of the National Academy of Sciences, 97, 60376042.

Smith, C.D., Anderson, A.H., Kryscio, R.J., Schmitt, F.A., Kindy, M.S., Blonder, L.X., & Avison, M.J. (1999). Altered brain activation in cognitively intact individuals at high risk for Alzheimer's disease. Neurology, 53, 13911396.

Smith, G.E., Bohac, D.L., Waring, S.C., Kokmen, E., Tangalos, E.G., Ivnik, R.J., & Petersen, R.C. (1998). Apolipoprotein E genotype influences cognitive ‘phenotype’ in patients with Alzheimer's disease but not in healthy control subjects. Neurology, 50, 355362.

Smith, J.A. & Knight, R.G. (2002). Memory processing in Alzheimer's disease. Neuropsychologia, 40, 666682.

Spencer, W.D. & Raz, N. (1995). Differential effects of aging on memory for content and context: A meta-analysis. Psychology and Aging, 10, 527539.

Storandt, M. & Hill, R.D. (1989). Very mild senile dementia of the Alzheimer type: II. Psychometric test performance. Archives of Neurology, 46, 383386.

Storandt, M., Botwinick, J., Danzinger, W.L., Berg, L., & Hughes, C.P. (1984). Psychometric differentiation of mild senile dementia of the Alzheimer type. Archives of Neurology, 41, 477499.

Strittmatter, W.J., Saunders, A.M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G.S., & Roses, A.D. (1993). Apolipoprotein E: High-avidity binding to B-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proceedings of the National Academy of Sciences, 90, 19771981.

Tierney, M.C., Szalai, J.P., Snow, W.G., Fisher, R.H., Tsuda, T., Chi, H., MacLachlan, D.R., & St. George-Hyslop, P.H. (1996). A prospective study of the clinical utility of ApoE genotype in the prediction of outcome in patients with memory impairment. Neurology, 46, 149154.

Tun, P.A., Wingfield, A., Rosen, M.J., & Blanchard, C. (1998). Response latencies for false memories: Gist-based processes in normal aging. Psychology and Aging, 13, 230241.

Van Petten, C., Senkfor, A.J., & Newberg, W.M. (2000). Memory for drawings in locations: Spatial source memory and event-related potentials. Psychophysiology, 37, 551564.

Wilson, R.S., Schneider, J.A., Barnes, L.L., Beckett, L.A., Aggarwal, N.T., Cochran, E.J., Beiry-Kravis, E., Bach, J., Fox, J.H., Evans, D.A., & Bennett, D.A. (2002). The apolipoprotein E E4 allele and decline in different cognitive systems during a 6-year period. Archives of Neurology, 59, 11541160.

Wu, Y.-Y., Delgado, R., Costello, R., Sunderland, T., Dukoff, R., & Csako, G. (2000). Quantitative assessment of apolipoprotein E genotypes by image analysis of PCR-RFLP fragments. Clinica Chimica Acta, 293, 213221.

Yaffe, K., Cauley, J., Sands, L., & Browner, W. (1997). Apolipoprotein E phenotype and cognitive decline in a prospective study of elderly community women. Archives of Neurology, 54, 11101114.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Journal of the International Neuropsychological Society
  • ISSN: 1355-6177
  • EISSN: 1469-7661
  • URL: /core/journals/journal-of-the-international-neuropsychological-society
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords: