Mild cognitive impairment: Historical development and summary of research

Dialogues in Clinical Neuroscience

Volumn 6, Issue 4, 2004, Pages 351-367

  Golomb, James ^a   Kluger, Alan ^a,b   Ferris, Steven H ^a  

^a NEW YORK UNIVERSITY MEDICAL CENTER   (United States)

^b CITY UNIVERSITY OF NEW YORK   (United States)

Author keywords

Diagnostic criteria; Mild cognitive impairment; Neuroimaging; Pathology; Prediction; Prevalence; Treatment

Indexed keywords

ALPHA TOCOPHEROL; AMYLOID BETA PROTEIN[1-42]; BIOLOGICAL MARKER; DONEPEZIL; GALANTAMINE; MEMANTINE; RIVASTIGMINE; ROFECOXIB;

ALZHEIMER DISEASE; AUTOPSY; CEREBROSPINAL FLUID; CLINICAL TRIAL; COGNITION; COGNITIVE DEFECT; FUNCTIONAL MAGNETIC RESONANCE IMAGING; HUMAN; METHODOLOGY; MOLECULAR GENETICS; NEUROIMAGING; NEUROPATHOLOGY; NEUROPSYCHOLOGY; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PHOTON EMISSION TOMOGRAPHY; POSITRON EMISSION TOMOGRAPHY; PREVALENCE; REVIEW; TASK PERFORMANCE;

EID: 11144232697     PISSN: 12948322     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (157)

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994.
2. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. 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. 1984;34:939-944.
3. Kral VA. Senescent forgetfulness: benign and malignant. Can Med Assoc J. 1962;86:257-260.
4. Crook T, Bartus RT, Ferris SH, Whitehouse P, Cohen GD, Gershon S. Age-associated memory impairment: proposed diagnostic criteria and measures of clinical change - Report of a NIMH Work Group. Dev Neuropsychol. 1986;2:261-276.
5. Blackford RC, La Rue A. Criteria for diagnosing age-associated memory impairment: proposed improvement from the field. Dev Neuropsychol. 1989;5:295-306.
6. Levy R. Aging-associated cognitive decline. Int Psychogeriatr. 1994;6:63-68.
7. Reisberg B, Ferris SH, de Leon MJ, Crook T. The global deterioration scale for assessment of primary degenerative dementia. Am J Psychiatry. 1982;139:1136-1139.
8. Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL. A new clinical scale for the staging of dementia. Br J Psychiatry. 1982;140:566-572.
9. Roth M, Tym E, Mountjoy CQ, et al. CAMDEX: a standard instrument for the diagnosis of mental disorder in the elderly with special reference to the early detection of dementia. Br J Psychiatry. 1986;149:698-709.
10. Gurland BJ, Dean LL, Copeland J, Gurland R, Golden R. Criteria for the diagnosis of dementia in the community elderly. Gerontologist. 1982;22:180-186.
11. Bowen J, Teri L, Kukull W, McCormick W, McCurry SM, Larson EB. Progression to dementia in patients with isolated memory loss. Lancet. 1997;349:763-765.
12. World Health Organization. The ICD-10 Classification of Mental and Behavioral Disorders. Clinical descriptions and diagnostic guidelines. Geneva, Switzerland: World Health Organization; 1992.
13. Ebly EM, Hogan DB, Parhad IM. Cognitive impairment in the nondemented elderly. Arch Neurol. 1995;52:612-619.
14. Tierney MC, Szalai JP, Snow WG, et al. A prospective study of the clinical utility of ApoE genotype in the prediction of outcome in patients with memory impairment. Neurology. 1996;46:149-154.
15. Graham JE, Rockwood K, Beattie EL, et al. Prevalence and severity of cognitive impairment with and without dementia in an elderly population. Lancet. 1997;349:1793-1796.
16. Reisberg B, Ferris SH, de Leon MJ, et al. Stage-specific behavioral, cognitive, and in vivo changes in community residing subjects with age-associated memory impairment (AAMI) and primary degenerative dementia of the Alzheimer type. Drug Dev Res. 1988;15:101-114.
17. Flicker C, Ferris SH, Reisberg B. Mild cognitive impairment in the elderly: predictors of dementia. Neurology. 1991;41:1006-1009.
18. Petersen RC, Smith GE, Ivnik RJ, et al. Apolipoprotein E status as a predictor of the development of Alzheimer's disease in memory-impaired individuals. JAMA. 1995;273:1274-1278.
19. Rivas-Vazquez RA, Mendez C, Rey GJ, Carrazana EJ. Mild cognitive impairment: new neuropsychological and pharmacological target. Arch Clin Neuropsychol. 2004;19:11-27.
20. Dubois B. "Prodromal Alzheimer's disease": a more useful concept than mild cognitive impairment? Curr Opin Neurol. 2000;13:367-369.
21. Morris JC, Storandt M, Miller JP, et al. Mild cognitive impairment represents early-stage Alzheimer disease. Arch Neurol. 2001;58:397-405.
22. Petersen RC, Doody R, Kurz A, et al. Current concepts in mild cognitive impairment. Arch Neurol. 2001;58:1985-1992.
23. de Mendonca A, Ribeiro F, Guerreiro M, Garcia C. Frontotemporal mild cognitive impairment. J Alzheimer's Dis. 2004;6:1-9.
24. Golomb J, Kluger A, Garrard P, Ferris S. Clinician's Manual on Mild Cognitive Impairment. London, UK: Science Press; 2001.
25. Kluger A, Gianutsos JG, Golomb J, et al. Patterns of motor impairment in normal aging, mild cognitive decline, and early Alzheimer's disease. J Gerontol Psychol Sci. 1997;52B:P28-P39.
26. Guarch J, Marcos T, Salamero M, Blesa R. Neuropsychological markers of dementia in patients with memory complaints. Int J Geriatr Psychiatry. 2004;19:352-358.
27. Jacobs DM, Sano M, Dooneief G, Marder K, Bell KL, Stern Y. Neuropsychological detection and characterization of preclinical Alzheimer's disease. Neurology. 1995;45:957-962.
28. Masur DM, Sliwinski M, Lipton RB, Blau AD, Crystal HA. Neuropsychological prediction of dementia and the absence of dementia in healthy elderly persons. Neurology. 1994;44:1427-1432.
29. Elias MF, Beiser A, Wolf PA, Au R, White RF, D'Agostino RB. The preclinical phase of Alzheimer disease. Arch Neurol. 2000;57:808-813.
30. Gauthier S, Touchon J. Subclassification of mild cognitive impairment in research and in clinical practice. In: Gauthier S, Scheltens P, Cummings J, eds. Alzheimer's Disease and Related Disorders. London, UK: Martin Dunitz; 2004:61-69.
31. Ritchie K, Artero S, Touchon J. Classification criteria for mild cognitive impairment: a population-based validation study. Neurology. 2001;56:37-42.
32. Vogel A, Stokholm J, Gade A, Andersen BB, Hejl AM, Waldemar G. Awareness of deficits in mild cognitive impairment and Alzheimer's disease: do MCI patients have impaired insight? Dement Geriatr Cogn Disord. 2004;17:181-187.
33. Ritchie K. Mild cognitive impairment: an epidemiological perspective. Dialogues Clin Neurosci. 2004;6:401-408.
34. Bischkopf J, Busse A, Angermeyer MC. Mild cognitive impairment - a review of prevalence, incidence and outcome according to current approaches. Acta Psychiatr Scand. 2002;106:403-414.
35. Yesavage JA, O'Hara R, Kraemer H, et al. Modeling the prevalence and incidence of Alzheimer's disease and mild cognitive impairment. J Psychiatr Res. 2002;36:281-286.
36. Bruscoli M, Lovestone S. Is MCI really just early dementia? A systematic review of conversion studies. Int Psychogeriatr. 2004;16:129-140.
37. Bozoki A, Giordani B, Heidebrink JL, Berent S, Foster NL. Mild cognitive impairments predict dementia in nondemented elderly patients with memory loss. Arch Neurol. 2001;58:411-416.
38. Devanand DP, Folz M, Gorlyn M, Moeller JR, Stern Y. Questionable dementia: clinical course and predictors of outcome. J Am Geriatr Soc. 1997;45:321-328.
39. Huang C, Wahlund L, Dierks T, Julin P, Winblad B, Jelic V. Discrimination of Alzheimer's disease and mild cognitive impairment by equivalent EEG sources: a cross-sectional and longitudinal study. Clin Neurophysiol. 2000;111:1961-1967.
40. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999;56:303-308.
41. Tierney MC, Szalai JP, Snow WG, et al. Prediction of probable Alzheiemer's disease in memory-impaired patients: a prospective longitudinal study. Neurology. 1996;46:661-665.
42. Wolf H, Ecke GM, Bettin S, Dietrich J, Gertz HJ. Do white matter changes contribute to the subsequent development of dementia in patients with mild cognitive impairment? A longitudinal study. Int J Geriatr Psychiatry. 2000;15:803-812.
43. Daly E, Zaitchik D, Copeland M, Schmahmann J, Gunther J, Albert M. Predicting conversion to Alzheimer disease using standardized clinical information. Arch Neurol. 2000;57:675-680.
44. Grober E, Lipton RB, Hall C, Crystal H. Memory impairment on free and cued selective reminding predicts dementia. Neurology. 2000;54:827-832.
45. Hogan DB, Ebly EM. Predicting who will develop dementia in a cohort of Canadian seniors. Can J Neurol Sci. 2000;27:18-24.
46. Jack CRJ, Petersen RC, Xu YC, et al. Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment. Neurology. 1999;52:1397-1403.
47. Johansson B, Zarit SH. Early cognitive markers of the incidence of dementia and mortality: a longitudinal population-based study of the oldest old. Int J Geriatr Psychiatry. 1997;12:53-59.
48. Kluger A, Ferris SH, Golomb J, Mittelman MS, Reisberg B. Neuropsychological prediction of decline to dementia in nondemented elderly. J Geriatr Psychiatry Neurol. 1999;12:168-179.
49. Li YS, Meyer JS, Thornby J. Longitudinal follow-up of depressive symptoms among normal versus cognitively impaired elderly. Int J Geriatr Psychiatry. 2001;16:718-727.
50. Paykel ES, Huppert FA, Brayne C. Incidence of dementia and cognitive decline in over-75s in Cambridge: overview of cohort study. Soc Psychiatry Psychiatr Epidemiol. 1998;33:387-392.
51. Visser PJ, Scheltens P, Verby FRJ, et al. Medial temporal lobe atrophy and memory dysfunction as predictors for dementia in subjects with mild cognitive impairment. J Neurol. 1999;246:477-485.
52. Petersen RC, Stevens JC, Ganguli M, Tangalos EG, Cummings JL, DeKosky ST. Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001;56:1133-1142.
53. Bachman DL, Wolf PA, Linn RT, et al. Incidence of dementia and probable Alzheimer's disease in a general population: the Framingham Study. Neurology. 1993;43(3 Pt 1):515-519.
54. Hahn-Barma V, Chamayou C, Rogan C, Sarazin M, Dubois B. Neuropsychological methods in mild cognitive impairment. Dialogues Clin Neurosci. 2004;6:396-399.
55. Storandt M, Hill RD. Very mild senile dementia of the Alzheimer type. II. Psychometric test performance. Arch Neurol. 1989;46:383-386.
56. Mitrushina M, Satz P, Van Gorp W. Some putative cognitive precursors in subjects hypothesized to be at-risk for dementia. Arch Clin Neuropsychol. 1989;4:323-333.
57. Morris JC, McKeel DW, Storandt M, et al. Very mild Alzheimer's disease: informant-based clinical, psychometric, and pathological distinction from normal aging. Neurology. 1991;41:469-478.
58. Grundman M, Petersen RC, Ferris SH, et al. Mild cognitive impairment can be distinguished from Alzheimer disease and normal aging for clinical trials. Arch Neurol. 2004;61:59-66.
59. Kluger A, Golomb J, Ferris SH. Mild Cognitive Impairment. In: Nawab Qizilbash, ed. Evidence-Based Dementia Practice. Oxford, UK: Blackwell Science; 2002:341-354.
60. Rubin EH, Morris JC, Grant EA, Vendegna T. Very mild senile dementia of the Alzheimer type. I. Clinical assessment. Arch Neurol. 1989;46:379-382.
61. Fuld PA, David MM, Blau AD, Crystal H, Aronson MK. Object-memory evaluation for prospective detection of dementia in normal functioning elderly: predictive and normative data. J Clin Exp Neuropsychol. 1990;12:520-528.
62. Dal Forno G, Corrada M, Resnick S, Kawas C. Prediction of the risk of dementia in clinically normal subjects. Neurology. 1995;45(suppl 4):A171.
63. Neuropathology Group. Medical Research Council Cognitive Function and Aging Study. Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). Lancet. 2001;357:169-175.
64. Braak H, Braak E. Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiol Aging. 1997;18:351-357.
65. Haroutunian V, Purohit DP, Perl DP, et al. Neurofibrillary tangles in non-demented elderly subjects and mild Alzheimer disease. Arch Neurol. 1999;56:713-718.
66. Price JL, Morris JC. Tangles and plaques in nondemented aging and "preclinical" Alzheimer's disease. Ann Neurol. 1999;45:358-368.
67. Hulette CM, Welsh-Bohmer KA, Murray MG, Saunders AM, Mash DC, McIntyre LM. Neuropathological and neuropsychological changes in "normal" aging: evidence for preclinical Alzheimer disease in cognitively normal individuals. J Neuropathol Exp Neurol. 1998;57:1168-1174.
68. Price JL, Ko AI, Wade MJ, Tsou SK, McKeel DW, Morris JC. Neuron number in the entorhinal cortex and CA1 in preclinical Alzheimer disease. Arch Neurol. 2001;58:1395-1402.
69. Kordower JH, Chu Y, Stebbins GT, et al. Loss and atrophy of layer II entorhinal cortex neurons in elderly people with mild cognitive impairment. Ann Neurol. 2001;49:202-213.
70. Scheff SW, Price DA. Synaptic pathology in Alzheimer's disease: a review of ultrastructural studies. Neurobiol Aging. 2003;24:1029-1046.
71. Mesulam M, Shaw P, Mash D, Weintraub S. Cholinergic nucleus basalis tauopathy emerges early in the aging-MCI-AD continuum. Ann Neurol. 2004;55:815-828.
72. DeKosky ST, Ikonomovic MD, Styren SD, et al. Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment. Ann Neurol. 2002;51:145-155.
73. Bobinski M, Wegiel J, Wisniewski HM, et al. Neurofibrillary pathology - correlation with hippocampal formation atrophy in Alzheimer disease. Neurobiol Aging. 1996;17:909-919.
74. West MJ, Coleman PD, Flood DG, Troncoso JC. Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease. Lancet. 1994;344:769-772.
75. Galton CJ, Gomez-Anson B, Antoun N, et al. Temporal lobe rating scale: application to Alzheimer's disease and frontotemporal dementia. J Neurol Neurosurg Psychiatry. 2001;70:165-173.
76. Camicioli R, Moore MM, Kinney A, Corbridge E, Glassberg K, Kaye JA. Parkinson's disease is associated with hippocampal atrophy. Mov Disord. 2003;18:784-790.
77. Theodore WH, Gaillard WD. Neuroimaging and the progression of epilepsy. Prog Brain Res. 2002;135:305-313.
78. Gosche KM, Mortimer JA, Smith CD, Markesbery WR, Snowdon DA. Hippocampal volume as an index of Alzheimer neuropathology: findings from the Nun Study. Neurology. 2002;58:1476-1482.
79. Jack CR, Jr, Dickson DW, Parisi JE, et al. Antemortem MRI findings correlate with hippocampal neuropathology in typical aging and dementia. Neurology. 2002;58:750-757.
80. Convit A, de Leon MJ, Golomb J, et al. Hippocampal atrophy in early Alzheimer's disease: anatomic specificity and validation. Psychiatr Q. 1993;64:371-387.
81. Jack CRJ, Petersen RC, Xu YC, et al. Medial temporal atrophy on MRI in normal aging and very mild Alzheimer's disease. Neurology. 1997;49:786-794.
82. Krasuski JS, Alexander GE, Horwitz B, et al. Volumes of medial temporal lobe structures in patients with Alzheimer's disease and mild cognitive impairment (and in healthy controls). Biol Psychiatry. 1998;43:60-68.
83. Wolf H, Grunwald M, Kruggel F, et al. Hippocampal volume discriminates between normal cognition; questionable and mild dementia in the elderly. Neurobiol Aging. 2001;22:177-186.
84. de Leon MJ, Golomb J, George AE, et al. The radiologic prediction of Alzheimer's disease: the atrophic hippocampal formation. Am J Neuroradiol. 1993;14:897-906.
85. Killiany RJ, Gomez-Isla T, Moss M, et al. Use of structural magnetic resonance imaging to predict who will get Alzheimer's disease. Ann Neurol. 2000;47:430-439.
86. Fox NC, Warrington EK, Freeborough PA, et al. Presymptomatic hippocampal atrophy in Alzheimer's disease. A longitudinal MRI study. Brain. 1996;119(Pt 6):2001-2007.
87. Golomb J, de Leon MJ, Kluger A, George AE, Tarshish C, Ferris SH. Hippocampal atrophy in normal aging: an association with recent memory impairment. Arch Neurol. 1993;50:967-973.
88. Golomb J, Kluger A, de Leon MJ, et al. Hippocampal formation size in normal human aging: a correlate of delayed secondary memory performance. Learn Mem. 1994;1:45-54.
89. Killiany RJ, Hyman BT, Gomez-Isla T, et al. MRI measures of entorhinal cortex vs hippocampus in preclinical AD. Neurology. 2002;58:1188-1196.
90. Xu Y, Jack CR, Jr, O'Brien PC, et al. Usefulness of MRI measures of entorhinal cortex versus hippocampus in AD. Neurology. 2000;54:1760-1767.
91. Bobinski M, de Leon MJ, Convit A, et al. MRI of entorhinal cortex in mild Alzheimer's disease. Lancet. 1999;353:38-40.
92. Dickerson BC, Goncharova I, Sullivan MP, et al. MRI-derived entorhinal and hippocampal atrophy in incipient and very mild Alzheimer's disease. Neurobiol Aging. 2001;22:747-754.
93. Pennanen C, Kivipelto M, Tuomainen S, et al. Hippocampus and entorhinal cortex in mild cognitive impairment and early AD. Neurobiol Aging. 2004;25:303-310.
94. Golomb J, Kluger A, de Leon MJ, et al. Hippocampal formation size predicts declining memory performance in normal aging. Neurology. 1996;47:810-813.
95. Mungas D, Reed BR, Jagust WJ, et al. Volumetric MRI predicts rate of cognitive decline related to AD and cerebrovascular disease. Neurology. 2002;59:867-873.
96. Rusinek H, De Santi S, Frid D, et al. Regional brain atrophy rate predicts future cognitive decline: 6-year longitudinal MR imaging study of normal aging. Radiology. 2003;229:691-696.
97. Rodrigue KM, Raz N. Shrinkage of the entorhinal cortex over 5 years predicts memory performance in healthy adults. J Neurosci. 2004;24:956-963.
98. Jack CR, Shiung MM, Gunter JL, et al. Comparison of different MRI brain atrophy rate measures with clinical disease progression in AD. Neurology. 2004;62:591-600.
99. Ferris SH, de Leon MJ, Wolf AP, et al. Positron emission tomography in the study of aging and senile dementia. Neurobiol Aging. 1980;1:127-131.
100. 18F]fluorodeoxyglucose. J Comp Assisted Tomogr. 1983;7:590-598.
101. Smith GS, de Leon MJ, George AE, et al. Topography of cross-sectional and longitudinal glucose metabolic deficits in Alzheimer's disease. Pathophysiologic implications. Arch Neurol. 1992;49:1142-1150.
102. Pietrini P, Azari NP, Grady CL, et al. Pattern of cerebral metabolic interactions in a subject with isolated amnesia at risk for Alzheimer's disease: a longitudinal evaluation. Dementia. 1993;4:94-101.
103. Minoshima S, Giordani B, Berent S, Frey KA, Foster NL, Kuhl DE. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease. Ann Neurol. 1997;42:85-94.
104. Mielke R, Kessler J, Szelies B, Herholz K, Wienhard K, Heiss WD. Normal and pathological aging - findings of positron-emission-tomography. J Neural Transm (Budapest). 1998;105:821-837.
105. Berent S, Giordani B, Foster N, et al. Neuropsychological function and cerebral glucose utilization in isolated memory impairment and Alzheimer's disease. J Psychiatr Res. 1999;33:7-16.
106. Nestor PJ, Fryer TD, Ikeda M, Hodges JR. Retrosplenial cortex (BA 29/30) hypometabolism in mild cognitive impairment (prodromal Alzheimer's disease). Eur J Neurosci. 2003;18:2663-2667.
107. Reiman EM, Uecker A, Caselli RJ, et al. Hippocampal volumes in cognitively normal persons at genetic risk for Alzheimer's disease. Ann Neurol. 1998;44:288-291.
108. Ishii K, Sasaki M, Yamaji S, Sakamoto S, Kitagaki H, Mori E. Relatively preserved hippocampal glucose metabolism in mild Alzheimer's disease. Dement Geriatr Cogn Disord. 1998;9:317-322.
109. Nestor PJ, Fryer TD, Smielewski P, Hodges JR. Limbic hypometabolism in Alzheimer's disease and mild cognitive impairment. Ann Neurol. 2003;54:343-351.
110. De Santi S, de Leon MJ, Rusinek H, et al. Hippocampal formation glucose metabolism and volume losses in MCI and AD. Neurobiol Aging. 2001;22:529-539.
111. 18F]fluoro-2-deoxy-D-glucose/poitron- emission tomography (FDG/PET). Proc Natl Acad Sci U S A 2001;98:10966-10971.
112. Johnson KA, Jones K, Holman BL, et al. Preclinical prediction of Alzheimer's disease using SPECT. Neurology. 1998;50:1563-1571.
113. Huang C, Wahlund LO, Svensson L, Winblad B, Julin P. Cingulate cortex hypoperfusion predicts Alzheimer's disease in mild cognitive impairment. BMC Neurol. 2002;2:9.
114. Machulda MM, Ward HA, Borowski B, et al. Comparison of memory fMRI response among normal, MCI, and Alzheimer's patients. Neurology. 2003;61:500-506.
115. Small SA, Perera GM, DeLaPaz R, Mayeux R, Stern Y. Differential regional dysfunction of the hippocampal formation among elderly with memory decline and Alzheimer's disease. Ann Neurol. 1999;45:466-472.
116. Dickerson RC, Salat DH, Bates JF, et al. Medial temporal lobe function and structure in mild cognitive impairment. Ann Neurol. 2004;56:27-35.
117. Bookheimer SY, Strojwas MH, Cohen MS, et al. Patterns of brain activation in people at risk for Alzheimer's disease. N Engl J Med. 2000;343:450-456.
118. Valenzuela MJ, Sachdev P. Magnetic resonance spectroscopy in AD. Neurology. 2001;56:592-598.
119. 1H-MR spectroscopy differentiates mild cognitive impairment from normal brain aging. Neuroreport. 2001;12:2315-2317.
120. 1H MRS study. Neurology. 2000;55:210-217.
121. 1H MRS study. Am J Psychiatry. 1999;156:1879-1886.
122. 1H magnetic resonance spectroscopic metabolic pattern in the medial temporal lobes of patients with mild cognitive impairment and Alzheimer disease. Brain Res. 2004;1003:26-35.
123. 1H magnetic resonance spectroscopy, cognitive function, and apolipoprotein E genotype in normal aging, mild cognitive impairment and Alzheimer's disease. J Int Neuropsychol Soc. 2002;8:934-942.
124. Klunk WE, Engler H, Nordberg A, et al. Imaging brain amyloid in Alzheimer's disease with Pittsburgh compound-B. Ann Neurol. 2004;55:306-319.
125. Shoghi-Jadid K, Small GW, Agdeppa ED, et al. Localization of neurofibrillary tangles and β-amyloid plaques in the brains of living patients with Alzheimer disease. Am J Geriatr Psychiatry. 2002;10:24-35.
126. Vigo-Pelfrey C, Seubert P, Barbour R, et al. Elevation of microtubule-associated protein tau in the cerebrospinal fluid of patients with Alzheimer's disease. Neurology. 1995;45:788-793.
127. Iqbal K, Grundke-Iqbal I. Elevated levels of tau and ubiquitin in brain and cerebrospinal fluid in Alzheimer's disease. Int Psychogeriatr. 1997;9(suppl 1):289-296.
128. Motter R, Vigo-Pelfrey C, Kholodenko D, et al. Reduction of β-amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer's disease. Ann Neurol. 1995;38:643-648.
129. Hampel H, Blennow K. CSF tau and β-amyloid as biomarkers for mild cognitive impairment. Dialogues Clin Neurosci. 2004;6:379-390.
130. Blennow K, Hampel H. CSF markers for incipient Alzheimer's disease. Lancet Neurol. 2003;2:605-613.
131. Itoh N, Arai H, Urakami K, et al. Large-scale, multicenter study of cerebrospinal fluid tau protein phosphorylated at serine 199 for the antemortem diagnosis of Alzheimer's disease. Ann Neurol. 2001;50:150-156.
132. Ishiguro K, Ohno H, Arai H, et al. Phosphorylated tau in human cerebrospinal fluid is a diagnostic marker for Alzheimer's disease. Neurosci Lett. 1999;270:91-94.
133. Andreasen N, Vanmechelen E, Vanderstichele H, Davidsson P, Blennow K. Cerebrospinal fluid levels of total-tau, phospho-tau and Aβ42 predicts development of Alzheimer's disease in patients with mild cognitive impairment. Acta Neurol Scand. 2003;(suppl 179):47-51.
134. Arai H, Ishiguro K, Ohno H, et al. CSF phosphorylated tau protein and mild cognitive impairment: a prospective study. Exp Neurol. 2000;166:201-203.
135. Riemenschneider M, Lautenschlager N, Wagenpfeil S, Diehl J, Drzezga A, Kurz A. Cerebrospinal fluid tau and beta-amyloid 42 proteins identify Alzheimer disease in subjects with mild cognitive impairment. Arch Neurol. 2002;59:1729-1734.
136. Andreasen N, Minthon L, Vanmechelen E, et al. Cerebrospinal fluid tau and Aβ42 as predictors of development of Alzheimer's disease in patients with mild cognitive impairment. Neurosci Lett. 1999;273:5-8.
137. Maruyama M, Matsui T, Tanji H, et al. Cerebrospinal fluid tau protein and periventricular white matter lesions in patients with mild cognitive impairment: implications for 2 major pathways. Arch Neurol. 2004;61:716-720.
138. Hampel H, Teipel SJ, Fuchsberger T, et al. Value of CSF β-amyloid 1-42 and tau as predictors of Alzheimer's disease in patients with mild cognitive impairment. Mol Psychiatry. 2004;9:705-710.
139. Saunders AM, Strittmatter WJ, Schmechel D, et al. Association of apolipoprotein E allele ε4 with late-onset familial and sporadic Alzheimer's disease. Neurology. 1999;43:1467-1472.
140. Poirier J, Davignon J, Bouthillier D, Kogan S, Bertrand P, Gauthier S. Apolipoprotein E polymorphism and Alzheimer's disease. Lancet. 1993;342:697-699.
141. Blesa R, Adroer R, Santacruz P, Ascaso C, Tolosa E, Oliva R. High apolipoprotein E ε4 Allele frequency in age-related memory decline. Ann Neurol. 1996;39:548-551.
142. Traykov L, Rigaud AS, Baudic S, Smagghe A, Boller F, Forette F. Apolipoprotein E epsilon 4 allele frequency in demented and cognitively impaired patients with and without cerebrovascular disease. J Neurol Sci. 2002;203-204:177-181.
143. Lopez OL, Jagust WJ, Dulberg C, et al. Risk factors for mild cognitive impairment in the Cardiovascular Health Study Cognition Study. Part 2. Arch Neurol. 2003;60:1394-1399.
144. Tervo S, Kivipelto M, Hanninen T, et al. Incidence and risk factors for mild cognitive impairment: a population-based 3-year follow-up study of cognitively healthy elderly subjects. Dement Geriatr Cogn Disord. 2004;17:196-203.
145. Small BJ, Graves AB, McEvoy CL, Crawford FC, Mullan M, Mortimer JA. Is APOE-epsilon4 a risk factor for cognitive impairment in normal aging? Neurology. 2000;54:2082-2088.
146. Haan MN, Shemanski L, Jagust WJ, Manolio TA, Kuller L. The role of APOE epsilon4 in modulating effects of other risk factors for cognitive decline in elderly persons. JAMA. 1999;282:40-46.
147. Helkala EL, Koivisto K, Hanninen T, et al. Memory functions in human subjects with different apolipoprotein E phenotypes during a 3-year population-based follow-up study. Neurosci Lett. 1996;204:177-180.
148. Feskens EJ, Havekes LM, Kalmijn S, de Knijff P, Launer LJ, Kromhout D. Apolipoprotein e4 allele and cognitive decline in elderly men. BMJ. 1994;309:1202-1206.
149. Small GW, Chen ST, Komo S, et al. Memory self-appraisal in middle-aged and older adults with the apolipoprotein E-4 allele. Am J Psychiatry. 1999;156:1035-1038.
150. Caselli RJ, Graff-Radford NR, Reiman EM, et al. Preclinical memory decline in cognitively normal apolipoprotein E-epsilon4 homozygotes. Neurology. 1999;53:201-207.
151. Caselli RJ, Osborne D, Reiman EM, et al. Preclinical cognitive decline in late middle-aged asymptomatic apolipoprotein E-e4/4 homozygotes: a replication study. J Neurol Sci. 2001;189:93-98.
152. Baxter LC, Caselli RJ, Johnson SC, Reiman E, Osborne D. Apolipoprotein E epsilon 4 affects new learning in cognitively normal individuals at risk for Alzheimer's disease. Neurobiol Aging. 2003;24:947-952.
153. Gauthier S. Pharmacotherapy of mild cognitive impairment. Dialogues Clin Neurosci. 2004;6:391-395.
154. Salloway S, Ferris S, Kluger A, et al. Efficacy of donepezil in mild cognitive impairment: a randomized placebo-controlled trial. Neurology. 2004;63:651-657.
155. Peterson R, Thomas R, Thal L. Donepezil and vitamin E as treatments for mild cognitive impairment. Paper presented at: 9th International Conference on Alzheimer's Disease and Related Disorders; July 17-22, 2004; Philadelphia, PA.
156. Gold M, Nye JS, Goldstein HR, Truyen L. Initial evaluation of galantamine for mild cognitive impairment: results from two double-blind, randomized, placebo-controlled studies. Paper presented at: 9th International Conference on Alzheimer's Disease and Related Disorders; July 17-22, 2004; Philadelphia, PA.
157. Visser H, Thal L, Ferris S, et al. A randomized, double-blind, placebo-controlled study of rofecoxib in patiens with mild cognitive impairment. Poster presented at: 42nd Annual Meeting of the American College of Neuropsychopharmacology; December 7-11, 2003; San Juan, Puerto Rico.