Hostname: page-component-7c8c6479df-27gpq Total loading time: 0 Render date: 2024-03-27T02:58:43.042Z Has data issue: false hasContentIssue false

Executive function asymmetry in older adults genetically at-risk for Alzheimer's disease: Verbal versus design fluency

Published online by Cambridge University Press:  16 December 2005

WES S. HOUSTON
Affiliation:
University of Iowa, Department of Neurology, Division of Cognitive Neuroscience, Iowa City, Iowa
DEAN C. DELIS
Affiliation:
VA San Diego Healthcare System, San Diego, California University of California, San Diego, School of Medicine, Department of Psychiatry, San Diego, California
AMY LANSING
Affiliation:
University of California, San Diego, School of Medicine, Department of Psychiatry, San Diego, California
MARK W. JACOBSON
Affiliation:
VA San Diego Healthcare System, San Diego, California University of California, San Diego, School of Medicine, Department of Psychiatry, San Diego, California
KRYSTAL R. COBELL
Affiliation:
VA San Diego Healthcare System, San Diego, California
DAVID P. SALMON
Affiliation:
University of California, San Diego, School of Medicine, Department of Neurosciences, San Diego, California
MARK W. BONDI
Affiliation:
VA San Diego Healthcare System, San Diego, California University of California, San Diego, School of Medicine, Department of Psychiatry, San Diego, California

Abstract

Recent studies have reported cognitive asymmetries in patients with Alzheimer's disease (AD) and in individuals with apolipoprotein E ε4 (APOE ε4) genotype who are in the preclinical phase of AD. This increased frequency of cognitive asymmetry, typically defined as a significant discrepancy (in either direction) between verbal and spatial abilities, often occurs despite an absence of differences on traditional measures of central tendency (i.e., mean test scores). We prospectively studied the relationship between APOE genotype and two modality-specific executive-function tasks: The Verbal Fluency and Design Fluency tests of the Delis-Kaplan Executive Function System (D-KEFS) in 52 normal functioning older adult participants who were grouped according to the presence (n = 24) or absence (n = 28) of the APOE ε4 allele. Nondemented older adults with the APOE ε4 allele demonstrated a greater frequency of cognitive asymmetric profile on the new switching conditions of the Verbal and Design Fluency measures than the APOE non-ε4 individuals. This study further supports the utility of assessing cognitive asymmetry for the detection of subtle cognitive differences in individuals at-risk for AD, and suggests that dual-task executive function tests (i.e., fluency plus switching) may serve as a useful preclinical marker of AD. (JINS, 2005, 11, 863–870.)

Type
Research Article
Copyright
© 2005 The International Neuropsychological Society

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

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.Google Scholar
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.Google Scholar
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-ε allele in nondemented older adults. Neurology, 45, 22032206.Google Scholar
Bookheimer, S.Y., Strojwas, M.H., Cohen, M.S., Saunders, A.M., Pericak-Vance, M.A., & Mazziotta, J.C. (2000). Patterns of brain activation in people at risk for Alzheimer's disease. New England Journal of Medicine, 343, 450456.Google Scholar
Caselli, R.J., Osborne, D., Reiman, E.M., Hentz, J.G., Barbieri, C.J., Saunders, A.M., Hardy, J., Graff-Radford, G., 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.Google Scholar
Chey, J., Kim, J.W., & Cho, H.Y. (2000). Effects of apolipoprotein E phenotypes on the neuropsychological functions of community-dwelling elderly individuals without dementia. Neuroscience Letters, 289, 230234.Google Scholar
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.Google Scholar
Craft, S., Teri, L., Edland, S.D., Kukull, W.A., Schellenberg, G., McCormick, W.C., Bowen, J.D., & Larsen, E.B. (1998). Accelerated decline in apolipoprotein E-ε4 homozygotes with Alzheimer's disease. Neurology, 51, 149151.CrossRefGoogle Scholar
Delis, D.C., Kaplan, E., & Kramer, J.H. (2001a). The Delis-Kaplan executive function system–examiner's manual. New York: The Psychological Corporation.
Delis, D.C., Kaplan, E., & Kramer, J.H. (2001b). The Delis-Kaplan executive function system–technical manual. New York: The Psychological Corporation.
Delis, D.C., Massman, P.J., Butters, N., Salmon, D.P., Shear, P.K., Demadura, T., & Filoteo, J.V. (1992). Spatial cognition in Alzheimer's disease: Subtypes of global-local impairment. Journal of Clinical and Experimental Neuropsychology, 14, 46377.Google Scholar
Demadura, T., Delis, D.C., Jacobson, M., & Salmon, D. (2001). Do subgroups of patients with Alzheimer's disease exhibit asymmetric deficits on memory tests? Journal of Clinical and Experimental Neuropsychology, 23, 164171.Google Scholar
Elias, M.F., Beiser, A., Wolf, P.A., Au, R., White, R.F., & D'Agostino, R.B. (2000). The preclinical phase of Alzheimer disease. Archives of Neurology, 57, 808813.Google Scholar
Evans, D.A., Beckett, L.A., Field, T.S., Feng, L., Albert, M.S., Bennett, D.A., Tycko, B., & Mayeux, R. (1997). Apolipoprotein E epsilon4 and incidence of Alzheimer disease in a community population of older persons. Journal of the American Medical Association, 277, 822824.Google Scholar
Finton, M.J., Lucas, J.A., Rippeth, J.D., Bohac, D.L., Smith, G.E., Ivnik, R.J., Petersen, R.C., & Graff-Radford, N.R. (2003). Cognitive asymmetries associated with apolipoprotein E genotype in patients with Alzheimer's disease. Journal of the International Neuropsychological Society, 9, 751759.Google Scholar
Fisher, N.J., Rourke, B.P., & Bieliauskas, L.A. (1999). Neuropsychological subgroups of patients with Alzheimer's disease: An examination of the first 10 years of CERAD data. Journal of Clinical and Experimental Neuropsychology, 21, 488518.Google Scholar
Galasko, D., Kwo-on-Yuen, P.F., Klauber, M.R., & Thal, L.J. (1990). Neurological findings in Alzheimer's disease and normal aging. Archives of Neurology, 47, 625627.Google Scholar
Giacobini, E. (2000). Cholinesterase inhibitors stabilize Alzheimer disease. Neurochemical Research, 25, 11851190.Google Scholar
Haxby, J.V., Duara, R., Grady, C.L., Cutler, N.R., & Rapoport, S.I. (1985). Relations between neuropsychological and cerebral metabolic asymmetries in early Alzheimer's disease. Journal of Cerebral Blood Flow and Metabolism, 5, 193200.Google Scholar
Henderson, A.S., Easteal, S., Jorm, A.F., Mackinnon, A.J., Korten, A.E., Christensen, H., Croft, L., & Jacomb, P.A. (1995). Apolipoprotein E allele epsilon 4, dementia, and cognitive decline in a population sample. Lancet, 347, 542.Google Scholar
Hogh, P., Knudsen, G.M., Kjaer, K.H., Jorgensen, O.S., Paulson, O.B., & Waldemar, G. (2001). Single photon emission computed tomography and apolipoprotein E in Alzheimer's disease: impact of the epsilon4 allele on regional cerebral blood flow. Journal of Geriatric Psychiatry and Neurology, 14, 4251.Google Scholar
Jacobs, D.M., Sano, M., Dooneief, G., Marder, K., Bell, K.L., & Stern, Y. (1995). Neuropsychological detection and characterization of preclinical Alzheimer's disease. Neurology, 45, 957962.Google Scholar
Jacobson, M.W., Delis, D.C., Bondi, M.W., & Salmon, D.P. (2002). Do neuropsychological tests detect preclinical Alzheimer's disease: Individual-test versus cognitive-discrepancy score analyses. Neuropsychology, 16, 132139.Google Scholar
Kaplan, E., Goodglass, H., & Weintraub, S. (1983). The Boston Naming Test (2nd ed.). Philadelphia: Lea & Febiger.
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.Google Scholar
Linn, R.T., Wolf, P.A., Bachman, D.L., Knoefel, J.E., Cobb, J.L., & Belanger, A.J. (1995). The “preclinical phase” of probable Alzheimer's disease: A 13-year prospective study of the Framingham cohort. Archives of Neurology, 52, 485490.Google Scholar
Martin, A. (1990). Neuropsychology of Alzheimer's disease: The case for subgroups. In M.F. Schwartz (Ed.). Modular deficits in Alzheimer-type dementia (pp. 143175). Cambridge, MA: The MIT Press.
Matarazzo, J.D. & Herman, D.O. (1985). Clinical uses of the WAIS-R: Base rates of differences between VIQ and PIQ in the WAIS-R standardization sample. In B.B. Wolman (Ed.), Handbook of intelligence: Theories, measurements, and applications (pp. 899932). New York: John Wiley.
Mattis, S. (1973). Dementia Rating Scale. Odessa, FL: Psychological Assessment Resources.
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.Google Scholar
Monsch, A.U., Bondi, M.W., Salmon, D.P., Butters, N., Thal, L.J., Hansen, L.A., Wiederholt, W.C., Cahn, D.A., & Klauber, M.R. (1995). Clinical validity of the Mattis dementia rating scale in detecting dementia of the Alzheimer type. A double cross-validation and application to a community-dwelling sample. Archives of Neurology, 52, 899904.Google Scholar
Myers, R.H., Schaefer, E.J., Wilson, P.W.F., D'Agostino, R., Ordovas, J.M., Espino, A., Au, R., White, R.F., Knoefel, J.E., Cobb, J.L., McNulty, K.A., Beiser, A., & Wolf, P.A. (1996). Apoliprotein E element 4 association with dementia in a population-based study: The Framingham study. Neurology, 46, 673677.Google Scholar
Reiman, E.M., Caselli, R.J., Chen, K., Alexander, G.E., Bandy, D., & Frost, J. (2001). Declining brain activity in cognitively normal apolipoprotein E 4 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.Google Scholar
Reiman, E.M., Caselli, R.J., Yun, L.S., Chen, K., Bandy, D., Minoshima, S., Tibodeau, S.N., & Osborne, D. (1996). Preclinical evidence of Alzheimer's disease in persons homozygous for the ε4 allele for Apolipoprotein E. The New England Journal of Medicine, 334, 752758.Google Scholar
Roses, A.D. (1997). A model for susceptibility polymorphisms for complex diseases: Apolipoprotein E and Alzheimer disease. Neurogenetics, 1, 311.Google Scholar
Salmon, D.P. & Butters, N.M. (1992). Neuropsychological assessment of dementia in the elderly. In R. Katzman & J.W. Row (Eds.), Principals of geriatric neurology (pp. 144163). New York: F.A. Davis.
Saunders, A.M., Strittmatter, W.J., Schmechel, D., St. George-Hyslop, P.H., Perick-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 ε4 with late-onset familial and sporadic Alzheimer's disease. Neurology, 43, 14671472.Google Scholar
Schenk, D., Barbour, R., Dunn, W., Gordon, G., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K., Kholodenko, D., Lee, M., Liao, Z., Lieberburg, I., Motter, R., Mutter, L., Soriano, F., Shopp, G., Vasquez, N., Vandevert, C., Walker, S., Wogulis, M., Yednock, T., Games, D., & Seubert, P. (1999, July 8). Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature, 400, 173177.Google Scholar
Small, B.J., Basun, H., & Bäckman, 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.Google Scholar
Small, G.W., Mazziotta, M.D., Collins, M.T., Baxter, L.R., Phelps, M.E., Mandelkern, M.A., Kaplan, A., La Rue, A., Adamson, C.F., Chang, L., Guze, B.H., Corder, E.H., Saunders, A.M., Haines, J.L., Pericak-Vance, M.A., & Roses, A.D. (1995). Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease. Journal of the American Medical Association, 273, 942947.Google Scholar
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.Google Scholar
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 β-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proceedings of the National Academy of Sciences (USA), 90, 19771981.Google Scholar
Warzok, R.W., Kessler, C., Apel, G., Schwarz, A., Egensperger, R., Schreiber, D., Herbst, E.W., Wolf, E., Walther, R., & Walker, L.C. (1998). Apolipoprotein E4 promotes incipient Alzheimer pathology in the elderly. Alzheimer Disease and Associated Disorders, 121, 3339.Google Scholar
Wechsler, D. (1974). Wechsler Intelligence Scale for Children–Revised. San Antonio, TX: The Psychological Corporation.