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Neuropsychological and neuroimaging changes in preclinical Alzheimer's disease

  • ELIZABETH W. TWAMLEY (a1), SUSAN A. LEGENDRE ROPACKI (a2) and MARK W. BONDI (a1) (a3)
Abstract

Alzheimer's disease (AD) is a common, devastating form of dementia. With the advent of promising symptomatic treatment, the importance of recognizing AD at its very earliest stages has increased. We review the extant neuropsychological and neuroimaging literature on preclinical AD, focusing on longitudinal studies of initially nondemented individuals and cross-sectional investigations comparing at-risk with normal individuals. We systematically reviewed 91 studies of neuropsychological functioning, structural neuroimaging, or functional neuroimaging in preclinical AD. The neuropsychological studies indicated that preclinical AD might be characterized by subtle deficits in a broad range of neuropsychological domains, particularly in attention, learning and memory, executive functioning, processing speed, and language. Recent findings from neuroimaging research suggest that volume loss and cerebral blood flow or metabolic changes, particularly in the temporal lobe, may be detected before the onset of dementia. There exist several markers of a preclinical period of AD, in which specific cognitive and biochemical changes precede the clinical manifestations. The preclinical indicators of AD reflect early compromise of generalized brain integrity and temporal lobe functioning in particular. (JINS, 2006, 12, 707–735.)

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Corresponding author
Correspondence and reprint requests to: Elizabeth W. Twamley, Ph.D., University of California, San Diego, Department of Psychiatry, 9500 Gilman Drive (0851), La Jolla, CA 92093. E-mail: etwamley@ucsd.edu
References
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Albert, M.S. (1996). Cognitive and neurobiologic markers of early Alzheimer's disease. Proceedings of the National Academy of Sciences, 93, 13,54713,551.

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.

Albert, S.M., Gurland, B., Maestre, G., Jacobs, D.M., Stern, Y., & Mayeux, R. (1995). APOE genotype influences functional status among elderly without dementia. American Journal of Medical Genetics, 60, 583587.

Arnold, S.E., Hyman, B.T., Flory, J., Damasio, A.R., & van Hoesen G.W. (1991). The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer's disease. Cerebral Cortex, 1, 103116.

Azari, N.P., Pettigrew, K.D., Schapiro, M.R., Haxby, J.V., Grady, C.L., Pietrini, P., Salerno, J.A., Heston, L.L., Rapoport, S.I., & Horwitz, B. (1993). Early detection of Alzheimer disease: A statistical approach using positron emission tomographic data. Journal of Cerebral Blood Flow and Metabolism, 13, 438447.

Bäckman, L., Jones, S., Berger, A., Laukka, E.J., & Small, B.J. (2005). Cognitive impairment in preclinical Alzheimer's disease: A meta-analysis. Neuropsychology, 19, 520531.

Bäckman, 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 of Aging, 13, 267276.

Bäckman, L., Small, B.J., & Fratiglioni, L. (2001). Stability of the preclinical episodic memory deficit in Alzheimer's disease. Brain, 124, 96102.

Baxter, L.C., Caselli, R.J., Johnson, S.C., Reiman, E., & Osborne, D. (2003). Apolipoprotein E ε4 affects new learning in cognitively normal individuals at risk for Alzheimer's disease. Neurobiology of Aging, 24, 947952.

Becker, J.T., Mintum, M.A., Aleva, K., Wiseman, M.B., Nichols, T., & DeKosky, S.T. (1996). Compensatory reallocation of brain resources supporting verbal episodic memory in Alzheimer's disease. Neurology, 46, 692700.

Bennett, D.A., Schneider, J.A., Wilson, R.S., Bienias, J.L., Berry-Kravis, E., & Arnold, S.E. (2005). Amyloid mediates the association of apolipoprotein E ε4 allele to cognitive function in older people. Journal of Neurology, Neurosurgery, and Psychiatry, 76, 11941199.

Berr, C., Dufouil, C., Brousseau, T., Richard, F., Amouyel, P., Marceteau, E., & Alperovitch, A. (1996). Early effect of ApoE-ε4 allele on cognitive results in a group of highly performing subjects: The EVA study. Neuroscience Letters, 218, 912.

Bobinski, M., de Leon, M.J., Convit, A., De Saniti, S., Wegiel, J., Tarschish, C.Y., Saint Louis, L.A., & Wisniewski, H.M. (1999). MRI of entorhinal cortex in mild Alzheimer's disease. Lancet, 353, 3840.

Bondareff, W., Mountjoy, C.Q., & Roth, M. (1982). Loss of neurons of origin of the adrenergic projection to cerebral cortex (nucleus locus ceruleus) in senile dementia. Neurology, 32, 164168.

Bondi, M.W., Houston, W.S., Eyler, L.T., & Brown, G.G. (2005). FMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer's disease. Neurology, 64, 501508.

Bondi, M.W., Monsch, A.U., Galasko, D., Butters, N., Salmon, D.P., & Delis, D.C. (1994). Preclinical cognitive markers of dementia of the Alzheimer type. Neuropsychology, 8, 374384.

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.

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-ε4 allele in non-demented older adults. Neurology, 45, 22032206.

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

Braak, H. & Braak, E. (1995). Staging of Alzheimer's disease-related neurofibrillary changes. Neurobiology of Aging, 16, 271284.

Braak, H., Braak, E., Bohl, J., & Bratzke, H. (1998). Evolution of Alzheimer's disease related cortical lesions. Journal of Neural Transmission, 54, 97106.

Bretsky, P., Guralnik, J.M., Launer, L., Albert, M., & Seeman, T.E. (2003). The role of APOE-ε4 in longitudinal cognitive decline: MacArthur studies of successful aging. Neurology, 60, 10771081.

Brookmeyer, R., Gray, S., & Kawas, C. (1998). Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset. American Journal of Public Health, 88, 13371342.

Bunce, D., Fratiglioni, L., Small, B.J., Winblad, B., & Bäckman, L. (2004). APOE and cognitive decline in preclinical Alzheimer disease and non-demented aging. Neurology, 63, 816821.

Burggren, A.C., Small, G.W., Sabb, F.W., & Bookheimer, S.Y. (2002). Specificity of brain activation patterns in people at genetic risk for Alzheimer's disease. American Journal of Geriatric Psychiatry, 10, 4451.

Caselli, R.J., Graff-Radford, N.R., Reiman, E.M., Weaver, A., Osborn, D., Lucas, J., Uecker, A., & Thiobodeau, S.N. (1999). Preclinical memory decline in cognitively normal apolipoprotein E-epsilon4 homozygotes. Neurology, 53, 201213.

Caselli, R.J., Osbourne, 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-ε4/4 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. (2000). Cognitive tests that best discriminate between presymptomatic AD and those who remain nondemented. Neurology, 55, 18471853.

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

Cohen, R.M., Small, C., Lalonde, F., Friz, J., & Sunderland, T. (2001). Effect of apolipoprotein E genotype on hippocampal volume loss in aging healthy women. Neurology, 57, 22232228.

Collie, A. & Maruff, P. (2000). The neuropsychology of preclinical Alzheimer's disease and mild cognitive impairment. Neuroscience and Biobehavioral Reviews, 24, 365374.

Corder, E.H., Saunders, A.M., Strittmatter, W.J., Schmechel, D.E., Gaskell, P.C., Small, G.W., Roses, A.D., Haines, H.L., & Pericak-Vance, M.A. (1993). Gene dose of apolipoprotein E ε4 allele and the risk of Alzheimer's disease in late onset families. Science, 261, 921923.

Dartigues, J.F., Commenges, D., Letenneur, L., Barberger-Gateau, P., Gilleron, V., Fabrigoule, C., Mazaux, J.M., Orgogozo, J.M., & Salamon, R. (1997). Cognitive predictors of dementia in elderly community residents. Neuroepidemiology, 16, 2939.

Deary, I.J., Whiteman, M.C., Pattie, A., Starr, J.M., Hayward, C., Wright, A.F., Visscher, P.M., Tynan, M.C., & Whalley, L.J. (2004). Apolipoprotein E gene variability and cognitive functions at age 79: A follow-up of the Scottish Mental Survey of 1932. Psychology and Aging, 19, 367371.

DeKosky, S.T., Ikonomovic, M.D., Styren, S.D., Beckett, L., Wisniewski, S., Bennett, D.A., Cochran, E.J., Kordower, J.H., & Mufson, E.J. (2002). Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment. Annals of Neurology, 51, 145155.

DeKosky, S.T. & Orgogozo, J.M. (2001). Alzheimer disease: Diagnosis, costs, and dimensions of treatment. Alzheimer's Disease and Associated Disorders, 15, S3S7.

de Leon, M.J., George, A.E., Golomb, J., Tarshish, C.Y., McRae, T., De Santi, S., McRae, T., Ferris, S.H., Reisberg, B., Ince, C., Rusinek, H., Bobinski, M., Quinn, B., Miller, D.C., & Wisiniewski, H.M. (1997). Frequency of hippocampal formation atrophy in normal aging and Alzheimer's disease. Neurobiology of Aging, 18, 111.

den Heijer, T., Oudkerk, M., Launer, L.J., van Dujin, C.M., Hofman, A., & Breteler, M.M.B. (2002). Hippocampal, amygdalar, and global brain atrophy in different apolipoprotein E genotypes. Neurology, 59, 746748.

D'Esposito, M., Zarahn, E., Aguirre, G.K., & Rypma, B. (1999). The effect of normal aging on the coupling of neural activity to the BOLD hemodynamic response. Neuroimage, 10, 614.

Dik, M.G., Jonker, C., Bouter, L.M., Geerlings, M.I., van Kamp, G.J., & Deeg, D.J. (2000). APOE-epsilon4 is associated with memory decline in cognitively impaired elderly. Neurology, 54, 14921497.

Durany, N., Michel, T., Kurt, J., Cruz-Sanchez, F.F., Crevos-Navarro, J., & Riederer, P. (2000). Brain-derived neurotrophic factor and neurotrophin-3 levels in Alzheimer's disease brains. International Journal of Developmental Neuroscience, 18, 807813.

Egan, M.F., Kojima, M., Callicott, J.H., Goldberg, T.E., Kolachana, B.S., Bertolino, E.Z., Gold, B., Goldman, D., Dean, M., Lu, B., & Weinberger, D.R. (2003). The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell, 112, 257269.

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

Ercoli, L.M., Siddarth, P., Dunkin, J.J., Bramen, J., & Small, G.W. (2003). MMSE items predict cognitive decline in persons with genetic risk for Alzheimer's disease. Journal of Geriatric Psychiatry and Neurology, 16, 6773.

Fabrigoule, C., Rouch, I., Taberly, A., Letenneur, L., Commenges, D., Mazaux, J.M., Orgogozo, J.M., & Dartigues, J.F. (1998). Cognitive process in preclinical phase of dementia. Brain, 121, 135141.

Fillenbaum, G.G., Landerman, L.R., Blazer, D.G., Saunders, A.M., Harris, T.B., & Launer, L.J. (2001). The relationship of APOE genotype to cognitive functioning in older African-American and Caucasian community residents. Journal of the American Geriatrics Society, 49, 11481155.

Flory, J.D., Manuck, S.B., Ferrell, R.E., Ryan, C.M., & Muldoon, M.F. (2000). Memory performance and the apolipoprotein E polymorphism in a community sample of middle-aged adults. American Journal of Medical Genetics (Neuropsychiatric Genetics), 96, 707711.

Fox, N.C., Crum, W.R., Scahill, R.I., Stevens, J.M., Janssen, J.C., & Rossor, M.N. (2001). Imaging of onset and progression of Alzheimer's disease with voxel-compression mapping of serial magnetic resonance images. Lancet, 358, 201205.

Fox, N.C., Warrington, E.K., Freeborough, P.A., Hartikainen, P., Kennedy, A.M., Stevens, J.M., & Rossor, M.N. (1996). Presymptomatic hippocampal atrophy in Alzheimer's disease: A longitudinal MRI study. Brain, 119, 20012007.

Fox, N.C., Warrington, E.K., Seiffer, A.K., Agnew, S.K., & Rossor, M.N. (1998). Presymptomatic cognitive deficits in individuals at risk of familial Alzheimer's disease: A longitudinal prospective study. Brain, 121, 16311639.

Goldman, W.P., Price, J.L., Storandt, M., Grant, E.A., McKeel, D.W., Rubin, E.H., & Morris, J.C. (2001). Absence of cognitive impairment or decline in preclinical Alzheimer's disease. Neurology, 56, 361367.

Greenwood, P.M., Sunderland, T., Putnam, K., Levy, J., & Parasuraman, R. (2005a). Scaling of visuospatial attention undergoes differential longitudinal change as a function of APOE genotype prior to old age: Results from the NIMH BIOCARD study. Neuropsychology, 19, 830842.

Greenwood, P.M., Lambert, C., Sunderland, T., & Parasuraman, R. (2005b). Effects of the apolipoprotein E genotype on spatial attention, working memory, and their interaction in healthy, middle-aged adults: Results from the National Institute of Mental Health's BIOCARD study. Neuropsychology, 19, 199211.

Greenwood, P.M., Sunderland, T., Friz, J.L., & Parasuraman, R. (2000). Genetics and visual attention: Selective deficits in healthy adult carriers of the ε4 allele of the apolipoprotein E gene. Proceedings of the National Academy of Sciences, 97, 11,66111,666.

Grober, E. & Kawas, C. (1997). Learning and retention in preclinical and early Alzheimer's disease. Psychology and Aging, 12, 183188.

Gunter, J.L., Shiung, M.M., Manduca, A., & Jack, C.R. (2003). Methodological considerations for measuring rates of brain atrophy. Journal of Magnetic Resonance Imaging, 18, 1624.

Hall, C.B., Lipton, R.B., Sliwinski, M., & Stewart, W.F. (2000). Statistics in Medicine, 19, 15551566.

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.

Haxby, J.V., Grady, C.L., Duara, R., Schlageter, N., Berg, G., & Rapoport, S.I. (1986). Neocortical metabolic abnormalities precede nonmemory cognitive defects in early Alzheimer's-type dementia. Archives of Neurology, 43, 882885.

Helkala, E.L., Koivisto, K., Hänninen, T., Vanhanen, M., Kervinen, K., Kuusisto, J., Mykkänen, L., Kesäniemi, Y.A., Laakso, M., & Riekkinen, P. (1996). Memory functions in human subjects with different apolipoprotein E phenotypes during a 3-year population-based follow-up study. Neuroscience Letters, 204, 177180.

Hofer, S.M., Christensen, H., Mackinnon, A.J., Korten, A.E., Jorm, A.F., Henderson, A.S., & Easteal, S. (2002). Change in cognitive functioning associated with ApoE genotype in a community sample of older adults. Psychology and Aging, 17, 194208.

Hom, J., Turner, M.B., Risser, R., Bonte, F.J., & Tintner, R. (1994). Cognitive deficits in asymptomatic first-degree relatives of Alzheimer's disease patients. Experimental Neuropsychology, 16, 568576.

Houston, W.S., Delis, D.C., Lansing, A., Cobell, C., Jacobson, M., Salmon, D.P., & Bondi, M.W. (2005). Executive function asymmetry in older adults genetically at risk for Alzheimer's disease: Verbal versus design fluency. Journal of the International Neuropsychological Society, 11, 863870.

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.

Hulette, C.M., Welsh-Bohmer, K.A., Murray, M.G., Saunders, A.M., Mash, D.C., & McIntyre, L.M. (1998). Neuropathological and neuropsychological changes in “normal” aging: Evidence for preclinical Alzheimer disease in cognitively normal individuals. Journal of Neuropathology and Experimental Neurology, 57, 11681174.

Hyman, B.T., Van Hoesen, G.W., Damasio, A.R., & Barnes, C.L. (1984). Alzheimer's disease: Cell-specific pathology isolates the hippocampal formation. Science, 225, 11681170.

Jack, C.R., Petersen, R.C., Xu, Y., O'Brien, P., Waring, S., Tangalos, E., Smith, G., Ivnik, R., Thibodeau, S., & Kokmen, E. (1998). Hippocampal atrophy and ApoE genotype are independently associated with Alzheimer's disease. Annals of Neurology, 43, 303310.

Jack, C.R., Shiung, M.M., Weigand, S.D., O'Brien, P.C., Gunter, J.L., Boeve, B.F., Knopman, D.S., Smith, G.E., Ivnik, R.J., Tangalos, E.G., & Petersen, R.C. (2005). Brain atrophy rates predict subsequent clinical conversion in normal elderly and amnestic MCI. Neurology, 65, 12271231.

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.

Jacobson, M., Delis, D.C., Bondi, M.W., & Salmon, D.P. (2005a). Asymmetry in auditory and spatial attention span in normal elderly genetically at risk for Alzheimer's disease. Journal of Clinical and Experimental Neuropsychology, 27, 240253.

Jacobson, M.W., Delis, D.C., Lansing, A., Houston, W.S., Olsen, R., Wetter, S., Bondi, M.W., & Salmon, D.P. (2005b). Asymmetries in global-local processing abilities in elderly with the Apolipoprotein-E ε4 allele. Neuropsychology, 19, 822829.

Jacobson, M., Delis, D.C., Bondi, M.W., & Salmon, D.P. (2002). Do neuropsychological tests detect preclinical Alzheimer's disease: Individual-test versus cognitive-discrepancy score analysis. Neuropsychology, 16, 132139.

Jernigan, T.J., Archibald, S.L., Fennema-Notestine, C., Gamst, A.C., Stout, J.C., Bonner, J., & Hesselink, J.R. (2001). Effects of age on tissues and regions of the cerebrum and cerebellum. Neurobiology of Aging, 22, 581594.

Johnson, S.C., Baxter, L.C., Susskind-Wilder, L., Connor, D.J., Sabbagh, M.N., & Caselli, R.J. (2004). Hippocampal adaptation to face repetition in healthy elderly and mild cognitive impairment. Neuropsychologia, 42, 980989.

Jonker, C., Schmand, B., Lindeboom, J., Havekes, L.M., & Launer, L.J. (1998). Association between apolipoprotein E ε4 and the rate of cognitive decline in community-dwelling elderly individuals with and without dementia. Archives of Neurology, 55, 10651069.

Katzman, R., Aronson, M., Fuld, P., Kawas, C., Brown, T., Morgenstern, H., Frishman, W., Gidez, L., Eder, H., & Ooi, W.L. (1989). Development of dementing illness in an 80-year-old volunteer cohort. Annals of Neurology, 25, 317324.

Kaye, J.A., Swihart, T., Howieson, D., Dame, A., Moore, M.M., Karnos, T., Camicioli, R., Ball, M., Oken, B., & Sexton, G. (1997). Volume loss of the hippocampus and temporal lobe in healthy elderly persons destined to develop dementia. Neurology, 48, 12971304.

Kennedy, A.M., Frackowiak, R.S., Newman, S.K., Bloomfield, P.M., Seaward, J., Roques, P., Lewington, G., Cunningham, V.J., & Rossor, M.N. (1995). Deficits in cerebral glucose metabolism demonstrated by positron emission tomography in individuals at risk of familial Alzheimer's disease. Neuroscience Letters, 186, 1720.

Kim, K.W., Youn, J.C., Jhoo, J.H., Lee, D.Y., Lee, K.U., Lee, J.H., & Woo, J.I. (2002). Apolipoprotein E ε4 allele is not associated with the cognitive impairment in community-dwelling normal elderly individuals. International Journal of Geriatric Psychiatry, 17, 635640.

Klages, J.D., Fisk, J.D., & Rockwood, K. (2003). APOE genotype, memory test performance, and the risk of Alzheimer's disease in the Canadian Study of Health and Aging. Dementia and Geriatric Cognitive Disorders, 15, 15.

Knopman, D.S., DeKosky, S.T., Cummings, J.L., Chui, H., Corey-Bloom, J., Relkin, N., Small, G.W., Miller, B., & Stevens, J.C. (2001). Practice parameter: Diagnosis of dementia (an evidence-based review). Neurology, 56, 11431153.

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

Laukka, E.J., Jones, S., Small, B.J., Fratiglioni, L., & Bäckman, L. (2004). Similar patterns of cognitive deficits in the preclinical phases of vascular dementia and Alzheimer's disease. Journal of the International Neuropsychological Society, 10, 382391.

Levy, J.A., Bergeson, J., Putnam, K., Rosen, V., Cohen, R., Lalonde, F., Mirza, N., Linker, G., & Sunderland, T. (2004). Context-specific memory and apolipoprotein E (ApoE) ε4: Cognitive evidence from the NIMH prospective study of risk for Alzheimer's disease. Journal of the International Neuropsychological Society, 10, 362370.

Lindeboom, J., Schmand, B., Tulner, L., Walstra, G., & Jonker, C. (2002). Visual association test to detect early dementia of the Alzheimer type. Journal of Neurology, Neurosurgery, and Psychiatry, 73, 126133.

Lindsay, J., Laurin, D., Verreault, R., Hébert, R., Helliwell, B., Hill, G.B., & McDowell, I. (2002). Risk factors for Alzheimer's disease: A prospective analysis from the Canadian Study of Health and Aging. American Journal of Epidemiology, 156, 445453.

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.

Martins, C.A.R., Oulhaj, A., de Jager, C.A., & Williams, J.H. (2005). APOE alleles predict the rate of cognitive decline in Alzheimer disease: A nonlinear model. Neurology, 65, 18881893.

Masur, D.M., Sliwinski, M., Lipton, R.B., Blau, A.D., & Crystal, H.A. (1994). Neuropsychological prediction of dementia and the absence of dementia in healthy elderly persons. Neurology, 44, 14271432.

Mayeux, R., Saunders, A.M., Shea, S., Mirra, S., Evans, D., Roses, A.D., Hyman, B.T., Crain, B., Tang, M.-X., & Phelps, C.H. (1998). Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer's disease. The New England Journal of Medicine, 338, 506511.

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.

Medina, D., Detoledo-Morrell, L., Urresta, F., Gabrieli, J.D., Moseley, M., Fleischman, D., Bennett, D.A., Leurgans, S., Turner, D.A., & Stebbins, G.T. (2006). White matter changes in mild cognitive impairment and AD: A diffusion tensor imaging study. Neurobiology of Aging, 27, 663672.

Morris, J.C., Storandt, M., McKeel, D.W., Rubin, E.H., Price, J.L., Grant, E.A., & Berg, L. (1996). Cerebral amyloid deposition and diffuse plaques in “normal” aging: Evidence for presymptomatic and very mild Alzheimer's disease. Neurology, 46, 707719.

Murphy, C., Bacon, A.W., Bondi, M.W., & Salmon, D.P. (1998). Apolipoprotein E status is associated with odor identification deficits in nondemented older persons. Annals of the New York Academy of Science, 855, 744750.

Nielsen, H., Lolk, A., Andersen, K., Andersen, J., & Kragh-Sørenson, P. (1999). Characteristics of elderly who develop Alzheimer's disease during the next two years: A neuropsychological study using CAMCOG. The Odense study. International Journal of Geriatric Psychiatry, 14, 957963.

Pendleton, N., Payton, A., van den Boogerd, E.H., Holland, F., Diggle, P., Rabbitt, P.M.A., Horan, M.A., Worthington, J., Ollier, W.E.R. (2002). Apolipoprotein E genotype does not predict decline in intelligence in healthy older adults. Neuroscience Letters, 324, 7476.

Pericak-Vance, M.A., Grubber, J., Bailey, L.R., Hedges, D., West, S., Santoro, L., Kenmerer, B., Hall, J.L., Saunders, A.M., Roses, A.D., Small, G.W., Scott, W.K., Conneally, P.M., Vance, J.M., & Haines, J.L. (2000). Identification of novel genes in late-onset Alzheimer's disease. Experimental Gerontology, 35, 13431352.

Petersen, R.D., Stevens, J.C., Ganguli, M., Tangalos, E.G., Cummings, J.L., & DeKosky, S.T. (2001). Practice parameter. Early detection of dementia: Mild cognitive impairment (an evidence-based review). Neurology, 56, 11331142.

Plassman, B.L., Welsh-Bohmer, K.A., Bigler, E.D., Johnson, S.C., Anderson, C.V., Helms, M.J., Saunders, A.M., & Breitner, J.C. (1997). Apolipoprotein E ε4 allele and hippocampal volume in twin with normal cognition. Neurology, 48, 985989.

Price, J.L. & Morris, J.C. (1999). Tangles and plaques in non-demented aging and “preclinical” Alzheimer's disease. Annals of Neurology, 45, 358368.

Rapp, M.A. & Reischies, F.M. (2005). Attention and executive control predict Alzheimer disease in late life. American Journal of Geriatric Psychiatry, 13, 134141.

Reed, T., Carmelli, D., Swan, G.E., Breitner, J.C., Welsh, K.A., Jarvik, G.P., Deeb, S., & Auwerx, J. (1994). Lower cognitive performance in normal older adult male twins carrying the apolipoprotein E ε4 allele. Archives of Neurology, 51, 11891192.

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.

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 person's homozygous for the ε4 allele for apolipoprotein E. New England Journal of Medicine, 334, 752758.

Reiman, E.M., Chen, K., Alexander, G.E., Caselli, R., Brandy, D., Osborne, D., Saunders, A.M., & Hardy, J. (2004). Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia. Proceedings of the National Academy of the Sciences, 101, 284289.

Reiman, E.M., Uecker, A., Caselli, R., Lewis, S., Brandy, D., de Leon, M., De Santi, S., Convit, A., Osborne, D., Weaver, A., & Thibodeau, S.N. (1998). Hippocampal volumes in cognitively normal persons at genetic risk for Alzheimer's disease. Annals of Neurology, 44, 288291.

Rocca, W.A., Cha, R.H., Waring, S.C., & Kokmen, E. (1998). Incidence of dementia and Alzheimer's disease: A reanalysis of data from Rochester, Minnesota, 1975–1984. American Journal of Epidemiology, 148, 5162.

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

Rubin, E.H., Storandt, M., Miller, 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.

Salo, A., Ylikoski, R., Verkkoniemi, A., Polvikoski, T., Juva, K., Rastas, S., Kontula, K., Kainulainen, K., Niinistö, L., Notkola, I.-L., & Sulkava, R. (2001). Does apolipoprotein E influence learning and memory in the nondemented oldest old?International Psychogeriatrics, 13, 451459.

Saxton, J., Lopez, O.L., Ratcliff, G., Dulberg, C., Fried, L.P., Carlson, M.C., Newman, A.B., & Kuller, L. (2004). Preclinical Alzheimer disease: Neuropsychological test performance 1.5 to 8 years prior to onset. Neurology, 63, 23412347.

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 ε4 allele in the normal elderly: Neuropsychological and brain MRI correlates. Clinical Genetics, 50, 293299.

Schmitt, F.A., Davis, D.G., Wekstein, D.R., Smith, C.D., Ashford, J.W., & Markesbery, W.R. (2000). “Preclinical” AD revisited: Neuropathology of cognitively normal older adults. Neurology, 55, 370376.

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.

Small, B.J., Fratiglioni, L., Viitanen, M., Winblad, B., & Backman, L. (2000). The course of cognitive impairment in preclinical Alzheimer disease: Three- and 6-year follow-up of a population-based sample. Archives of Neurology, 57, 839844.

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

Small, B.J., Herlitz, A., Fratiglioni, L., Almkvist, O., & Bäckman, L. (1997). Cognitive predictors of incident Alzheimer's disease: A prospective longitudinal study. Neuropsychology, 11, 413420.

Small, B.J., Rosnick, C.B., Fratiglioni, L., & Bäckman, L. (2004). Apolipoprotein E and cognitive performance: A meta-analysis. Psychology and Aging, 19, 592600.

Small, G.W., Komo, S., La Rue, A., Saxena, S., Phelps, M.E., Massiotta, J.C., Saunders, A.M., Haines, J.L., Pericak-Vance, M.A., & Roses, A.D. (1996). Early detection of Alzheimer's disease by combining apolipoprotein E and neuroimaging. Annals of the New York Academy of Sciences, 802, 7078.

Small, G.W., Mazziotta, J.C., Collins, M.T., Baxter, L.R., Phelps, M.E., Mandelkern, M.A., Kaplan, A., La Rue, A., Adamson, C.F., Chang, L., Guza, 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.

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.

Snowdon, D.A., Kemper, S.J., Mortimer, J.A., Greiner, L.H., Wekstein, D.R., & Markesbery, W.R. (1996). Linguistic ability in early life and cognitive function and Alzheimer's disease in late life. Findings from the nun study. Journal of the American Medical Association, 275, 528532.

Staehelin, H.B., Perrig-Chiello, P., Mitrache, C., Miserez, A.R., & Perrig, W.J. (1999). Apolipoprotein E genotypes and cognitive functions in healthy elderly persons. Acta Neurologica Scandinavica, 100, 5360.

Terry, R.D., Masliah, E., Salmon, D.P., Butters, N., DeTeresa, R., Hill, R., Hansen, L.A., & Katzman, R. (1991). Physical basis of cognitive alterations in Alzheimer's disease: Synapse loss in the major correlate of cognitive impairment. Annals of Neurology, 30, 572580.

Tohgi, H., Takahashi, S., Kato, E., Homma, A., Niina, R., Sasaki, K., Yonezawa, H., & Sasaki, M. (1997). Reduced size of right hippocampus in 39- to 80-year-old normal subjects carrying the apolipoprotein E e4 allele. Neuroscience Letters, 236, 2124.

Whalley, L.J., Starr, J.M., Athawes, R., Hunter, D., Pattie, A., & Deary, I.J. (2000). Childhood mental ability and dementia. Neurology, 55, 14281429.

Wilson, R.S., Schneider, J.A., Barnes, L.L., Beckett, L.A., Aggarwal, N.T., Cochran, E.J., Berry-Kravis, E., Bach, J., Fox, J.H., Evans, D.A., & Bennett, D.A. (2002). The apolipoprotein E ε4 allele and decline in different cognitive systems during a 6-year period. Archives of Neurology, 59, 11541160.

Winnock, M., Letenneur, L., Jacqmin-Gadda, H., Dallongeville, J., Amouyel, P., & Dartigues, J.F. (2002). Longitudinal analysis of the effect of the apolipoprotein E ε4 and education on cognitive performance in elderly subjects: The PAQUID study. Journal of Neurology, Neurosurgery, and Psychiatry, 72, 794797.

Wolf, H., Jelic, V., Gertz, H-J., Nordberg, A., Julin, P., & Wahlund, L-O. (2003). A critical discussion of the role of neuroimaging in mild cognitive impairment. Acta Neurologica Scandinavica, 107, 5276.

Wu, C., Pike, V.W., & Wang, Y. (2005). Amyloid imaging: From benchtop to bedside. Current Topics in Developmental Biology, 70, 171213.

Xu, Y., Jack, C.R., O'Brien, P.C., Kokmen, E., Smith, G.E., Ivnik, R.J., Boeve, B.F., Tangalos, R.G., & Petersen, R.C. (2000). Usefulness of MRI measures of entorhinal cortex versus hippocampus in AD. Neurology, 54, 1767.

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.

Yoshitake, T., Kiyohara, Y., Kato, I., Ohmura, T., Iwamoto, H., Nakayama, K., Ohmori, S., Nomiyama, K., Kawaon, H., Ueda, K., Sueishi, K., Tsuneyosh, M., & Fujishima, M. (1995). Incidence and risk factors of vascular dementia and Alzheimer's disease in a defined elderly Japanese population: The Hisayama study. Neurology, 45, 11611168.

Zonderman, A.B., Giambra, L.M., Arenberg, D., Resnick, S.M., Costa, P.T., & Kawas, C.H. (1995). Changes in immediate visual memory predict cognitive impairment. Archives of Clinical Neuropsychology, 10, 111123.

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Journal of the International Neuropsychological Society
  • ISSN: 1355-6177
  • EISSN: 1469-7661
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