Mild cognitive impairment: Epidemiology, pathology, and clinical assessment

INTRODUCTION

Mild cognitive impairment (MCI) is an intermediate state between normal cognition and dementia. While specific changes in cognition are frequently observed in normal aging, there is increasing evidence that some forms of cognitive impairment are recognizable as an early manifestation of dementia [1]. As the following topic review will highlight, MCI is a heterogeneous state and there remains controversy over aspects of the construct. However, the utility of this paradigm centers around the recognition that dementia is not a dichotomous state; thus refining our understanding of the layers of transition will improve the understanding of cognitive decline and ultimately benefit patients.

This topic will review the definition of MCI and related terms, as well as the epidemiology, pathology, and clinical assessment of MCI. The prognosis and treatment of MCI and topics related to dementia, including diagnosis, treatment, risk factors, and prevention of dementia, are discussed separately. (See "Mild cognitive impairment: Prognosis and treatment" and "Treatment of dementia" and "Risk factors for dementia" and "Prevention of dementia" and "Clinical manifestations and diagnosis of Alzheimer disease".)

DEFINITIONS

Mild cognitive impairment (MCI) refers to cognitive impairment that does not meet the criteria for dementia. Several criteria for, and subtypes of, MCI have been proposed [1-3]. These criteria and subtypes differ somewhat, although there is considerable overlap. In general, these criteria include a measurable deficit in cognition in at least one domain, in the absence of dementia or impairment in activities of daily living.

As originally constructed, the concept of MCI emphasized memory impairment and its status as a precursor state for Alzheimer disease (AD). Subsequently, it was recognized that MCI can be heterogeneous in terms of clinical presentation, etiology, prognosis, and prevalence [3-5], and the construct was expanded to broaden the scope of MCI to other cognitive domains, thereby extending the early detection of other dementias in their prodromal stages [6-8]. Although these criteria were developed as a concept relating early changes in specific cognitive domains to those areas most commonly affected in the disorders (eg, memory problems and AD), pathological and long-term clinical follow-up data to support this paradigm are limited [8,9].

These criteria are imprecise. Considerable judgment is required in making the distinction between impairments that are normal for the elderly population and, on the other extreme, that do not represent dementia. What constitutes impairment in daily living is different for each individual. Such distinctions draw upon clinical expertise and do not rely on psychometric testing alone. These appraisals can differ between assessors and this may account for some of the conflicting results in studies of this disorder. Some clinicians and investigators have challenged specific aspects of the criteria including the requirements for subjective cognitive complaints and intact activities of daily living [10-12].

                 

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Mar 2014. | This topic last updated: Oct 14, 2013.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2014 UpToDate, Inc.
References
Top
  1. Petersen RC, Smith GE, Waring SC, et al. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 1999; 56:303.
  2. 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.
  3. Voisin T, Touchon J, Vellas B. Mild cognitive impairment: a nosological entity? Curr Opin Neurol 2003; 16 Suppl 2:S43.
  4. Ganguli M, Dodge HH, Shen C, DeKosky ST. Mild cognitive impairment, amnestic type: an epidemiologic study. Neurology 2004; 63:115.
  5. Petersen, RC. Conceptual overview. In: Mild Cognitive Impairment: Aging to Alzheimer's Disease, Petersen, RC (Ed), Oxford University Press, New York 2003. p.1.
  6. Petersen RC, Stevens JC, Ganguli M, et al. 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.
  7. Salmon D, Hodges JR. Introduction: mild cognitive impairment--cognitive, behavioral, and biological factors. Neurocase 2005; 11:1.
  8. Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med 2004; 256:183.
  9. Busse A, Hensel A, Gühne U, et al. Mild cognitive impairment: long-term course of four clinical subtypes. Neurology 2006; 67:2176.
  10. Ritchie K, Artero S, Touchon J. Classification criteria for mild cognitive impairment: a population-based validation study. Neurology 2001; 56:37.
  11. Fisk JD, Merry HR, Rockwood K. Variations in case definition affect prevalence but not outcomes of mild cognitive impairment. Neurology 2003; 61:1179.
  12. Mitchell AJ. Is it time to separate subjective cognitive complaints from the diagnosis of mild cognitive impairment? Age Ageing 2008; 37:497.
  13. Morris JC, Storandt M, Miller JP, et al. Mild cognitive impairment represents early-stage Alzheimer disease. Arch Neurol 2001; 58:397.
  14. Petersen RC, Roberts RO, Knopman DS, et al. Mild cognitive impairment: ten years later. Arch Neurol 2009; 66:1447.
  15. Roberts RO, Geda YE, Knopman DS, et al. The Mayo Clinic Study of Aging: design and sampling, participation, baseline measures and sample characteristics. Neuroepidemiology 2008; 30:58.
  16. Bozoki A, Giordani B, Heidebrink JL, et al. Mild cognitive impairments predict dementia in nondemented elderly patients with memory loss. Arch Neurol 2001; 58:411.
  17. DeCarli C. Mild cognitive impairment: prevalence, prognosis, aetiology, and treatment. Lancet Neurol 2003; 2:15.
  18. Nordlund A, Rolstad S, Hellström P, et al. The Goteborg MCI study: mild cognitive impairment is a heterogeneous condition. J Neurol Neurosurg Psychiatry 2005; 76:1485.
  19. Rasquin SM, Lodder J, Visser PJ, et al. Predictive accuracy of MCI subtypes for Alzheimer's disease and vascular dementia in subjects with mild cognitive impairment: a 2-year follow-up study. Dement Geriatr Cogn Disord 2005; 19:113.
  20. Alexopoulos P, Grimmer T, Perneczky R, et al. Progression to dementia in clinical subtypes of mild cognitive impairment. Dement Geriatr Cogn Disord 2006; 22:27.
  21. Matthews FE, Stephan BC, McKeith IG, et al. Two-year progression from mild cognitive impairment to dementia: to what extent do different definitions agree? J Am Geriatr Soc 2008; 56:1424.
  22. Taragano FE, Allegri RF, Krupitzki H, et al. Mild behavioral impairment and risk of dementia: a prospective cohort study of 358 patients. J Clin Psychiatry 2009; 70:584.
  23. Kwong LK, Neumann M, Sampathu DM, et al. TDP-43 proteinopathy: the neuropathology underlying major forms of sporadic and familial frontotemporal lobar degeneration and motor neuron disease. Acta Neuropathol 2007; 114:63.
  24. Molano J, Boeve B, Ferman T, et al. Mild cognitive impairment associated with limbic and neocortical Lewy body disease: a clinicopathological study. Brain 2010; 133:540.
  25. Zanetti M, Ballabio C, Abbate C, et al. Mild cognitive impairment subtypes and vascular dementia in community-dwelling elderly people: a 3-year follow-up study. J Am Geriatr Soc 2006; 54:580.
  26. Stokholm J, Jakobsen O, Czarna JM, et al. Years of severe and isolated amnesia can precede the development of dementia in early-onset Alzheimer's disease. Neurocase 2005; 11:48.
  27. Nestor PJ, Scheltens P, Hodges JR. Advances in the early detection of Alzheimer's disease. Nat Med 2004; 10 Suppl:S34.
  28. Ritchie K, Touchon J. Mild cognitive impairment: conceptual basis and current nosological status. Lancet 2000; 355:225.
  29. Graham JE, Rockwood K, Beattie BL, et al. Prevalence and severity of cognitive impairment with and without dementia in an elderly population. Lancet 1997; 349:1793.
  30. Crook, TH, Bartus, RT, Ferris, SH, et al. Age-associated memory impairment: proposed diagnostic creiteria measures clinical change - report of a National Institute of Mental Health Work Group. Dev Neuropsychol 1986; 2:261.
  31. Levy R. Aging-associated cognitive decline. Working Party of the International Psychogeriatric Association in collaboration with the World Health Organization. Int Psychogeriatr 1994; 6:63.
  32. Richards M, Touchon J, Ledesert B, Richie K. Cognitive decline in ageing: are AAMI and AACD distinct entities? Int J Geriatr Psychiatry 1999; 14:534.
  33. Small BJ, Mobly JL, Laukka EJ, et al. Cognitive deficits in preclinical Alzheimer's disease. Acta Neurol Scand Suppl 2003; 179:29.
  34. Larrieu S, Letenneur L, Orgogozo JM, et al. Incidence and outcome of mild cognitive impairment in a population-based prospective cohort. Neurology 2002; 59:1594.
  35. Tschanz JT, Welsh-Bohmer KA, Lyketsos CG, et al. Conversion to dementia from mild cognitive disorder: the Cache County Study. Neurology 2006; 67:229.
  36. Busse A, Bischkopf J, Riedel-Heller SG, et al. Mild cognitive impairment: prevalence and predictive validity according to current approaches. Acta Neurol Scand 2003; 108:71.
  37. Luck T, Riedel-Heller SG, Kaduszkiewicz H, et al. Mild cognitive impairment in general practice: age-specific prevalence and correlate results from the German study on ageing, cognition and dementia in primary care patients (AgeCoDe). Dement Geriatr Cogn Disord 2007; 24:307.
  38. Lopez OL, Jagust WJ, DeKosky ST, et al. Prevalence and classification of mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 1. Arch Neurol 2003; 60:1385.
  39. Plassman BL, Langa KM, Fisher GG, et al. Prevalence of cognitive impairment without dementia in the United States. Ann Intern Med 2008; 148:427.
  40. Petersen RC, Roberts RO, Knopman DS, et al. Prevalence of mild cognitive impairment is higher in men. The Mayo Clinic Study of Aging. Neurology 2010; 75:889.
  41. Manly JJ, Tang MX, Schupf N, et al. Frequency and course of mild cognitive impairment in a multiethnic community. Ann Neurol 2008; 63:494.
  42. Caracciolo B, Palmer K, Monastero R, et al. Occurrence of cognitive impairment and dementia in the community: a 9-year-long prospective study. Neurology 2008; 70:1778.
  43. Luck T, Luppa M, Briel S, et al. Mild cognitive impairment: incidence and risk factors: results of the leipzig longitudinal study of the aged. J Am Geriatr Soc 2010; 58:1903.
  44. Luck T, Luppa M, Briel S, Riedel-Heller SG. Incidence of mild cognitive impairment: a systematic review. Dement Geriatr Cogn Disord 2010; 29:164.
  45. Plassman BL, Langa KM, McCammon RJ, et al. Incidence of dementia and cognitive impairment, not dementia in the United States. Ann Neurol 2011; 70:418.
  46. Roberts RO, Geda YE, Knopman DS, et al. The incidence of MCI differs by subtype and is higher in men: the Mayo Clinic Study of Aging. Neurology 2012; 78:342.
  47. Lopez OL, Becker JT, Chang YF, et al. Incidence of mild cognitive impairment in the Pittsburgh Cardiovascular Health Study-Cognition Study. Neurology 2012; 79:1599.
  48. Ganguli M, Fu B, Snitz BE, et al. Mild cognitive impairment: incidence and vascular risk factors in a population-based cohort. Neurology 2013; 80:2112.
  49. Manly JJ, Bell-McGinty S, Tang MX, et al. Implementing diagnostic criteria and estimating frequency of mild cognitive impairment in an urban community. Arch Neurol 2005; 62:1739.
  50. Kryscio RJ, Schmitt FA, Salazar JC, et al. Risk factors for transitions from normal to mild cognitive impairment and dementia. Neurology 2006; 66:828.
  51. Das SK, Bose P, Biswas A, et al. An epidemiologic study of mild cognitive impairment in Kolkata, India. Neurology 2007; 68:2019.
  52. Tyas SL, Salazar JC, Snowdon DA, et al. Transitions to mild cognitive impairments, dementia, and death: findings from the Nun Study. Am J Epidemiol 2007; 165:1231.
  53. DeCarli C, Miller BL, Swan GE, et al. Cerebrovascular and brain morphologic correlates of mild cognitive impairment in the National Heart, Lung, and Blood Institute Twin Study. Arch Neurol 2001; 58:643.
  54. Luchsinger JA, Reitz C, Patel B, et al. Relation of diabetes to mild cognitive impairment. Arch Neurol 2007; 64:570.
  55. Reitz C, Tang MX, Manly J, et al. Hypertension and the risk of mild cognitive impairment. Arch Neurol 2007; 64:1734.
  56. Roberts RO, Geda YE, Knopman DS, et al. Association of duration and severity of diabetes mellitus with mild cognitive impairment. Arch Neurol 2008; 65:1066.
  57. Roberts RO, Geda YE, Knopman DS, et al. Cardiac disease associated with increased risk of nonamnestic cognitive impairment: stronger effect on women. JAMA Neurol 2013; 70:374.
  58. Schultz MR, Lyons MJ, Franz CE, et al. Apolipoprotein E genotype and memory in the sixth decade of life. Neurology 2008; 70:1771.
  59. Farlow MR, He Y, Tekin S, et al. Impact of APOE in mild cognitive impairment. Neurology 2004; 63:1898.
  60. Boyle PA, Buchman AS, Wilson RS, et al. The APOE epsilon4 allele is associated with incident mild cognitive impairment among community-dwelling older persons. Neuroepidemiology 2010; 34:43.
  61. Bennett DA, Schneider JA, Bienias JL, et al. Mild cognitive impairment is related to Alzheimer disease pathology and cerebral infarctions. Neurology 2005; 64:834.
  62. Petersen RC, Parisi JE, Dickson DW, et al. Neuropathologic features of amnestic mild cognitive impairment. Arch Neurol 2006; 63:665.
  63. Sabbagh MN, Shah F, Reid RT, et al. Pathologic and nicotinic receptor binding differences between mild cognitive impairment, Alzheimer disease, and normal aging. Arch Neurol 2006; 63:1771.
  64. Davis KL, Mohs RC, Marin D, et al. Cholinergic markers in elderly patients with early signs of Alzheimer disease. JAMA 1999; 281:1401.
  65. 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.
  66. Markesbery WR, Schmitt FA, Kryscio RJ, et al. Neuropathologic substrate of mild cognitive impairment. Arch Neurol 2006; 63:38.
  67. Guillozet AL, Weintraub S, Mash DC, Mesulam MM. Neurofibrillary tangles, amyloid, and memory in aging and mild cognitive impairment. Arch Neurol 2003; 60:729.
  68. Jicha GA, Parisi JE, Dickson DW, et al. Neuropathologic outcome of mild cognitive impairment following progression to clinical dementia. Arch Neurol 2006; 63:674.
  69. Schneider JA, Arvanitakis Z, Leurgans SE, Bennett DA. The neuropathology of probable Alzheimer disease and mild cognitive impairment. Ann Neurol 2009; 66:200.
  70. Wilson RS, Leurgans SE, Boyle PA, et al. Neurodegenerative basis of age-related cognitive decline. Neurology 2010; 75:1070.
  71. Tobiansky R, Blizard R, Livingston G, Mann A. The Gospel Oak Study stage IV: the clinical relevance of subjective memory impairment in older people. Psychol Med 1995; 25:779.
  72. Geerlings MI, Jonker C, Bouter LM, et al. Association between memory complaints and incident Alzheimer's disease in elderly people with normal baseline cognition. Am J Psychiatry 1999; 156:531.
  73. van Norden AG, Fick WF, de Laat KF, et al. Subjective cognitive failures and hippocampal volume in elderly with white matter lesions. Neurology 2008; 71:1152.
  74. Scheef L, Spottke A, Daerr M, et al. Glucose metabolism, gray matter structure, and memory decline in subjective memory impairment. Neurology 2012; 79:1332.
  75. Riedel-Heller SG, Matschinger H, Schork A, Angermeyer MC. Do memory complaints indicate the presence of cognitive impairment? Results of a field study. Eur Arch Psychiatry Clin Neurosci 1999; 249:197.
  76. Petersen RC, Doody R, Kurz A, et al. Current concepts in mild cognitive impairment. Arch Neurol 2001; 58:1985.
  77. Stewart R, Dufouil C, Godin O, et al. Neuroimaging correlates of subjective memory deficits in a community population. Neurology 2008; 70:1601.
  78. Tabert MH, Albert SM, Borukhova-Milov L, et al. Functional deficits in patients with mild cognitive impairment: prediction of AD. Neurology 2002; 58:758.
  79. Palmer K, Berger AK, Monastero R, et al. Predictors of progression from mild cognitive impairment to Alzheimer disease. Neurology 2007; 68:1596.
  80. Feldman H, Scheltens P, Scarpini E, et al. Behavioral symptoms in mild cognitive impairment. Neurology 2004; 62:1199.
  81. Geda YE, Roberts RO, Knopman DS, et al. Prevalence of neuropsychiatric symptoms in mild cognitive impairment and normal cognitive aging: population-based study. Arch Gen Psychiatry 2008; 65:1193.
  82. Okura T, Plassman BL, Steffens DC, et al. Prevalence of neuropsychiatric symptoms and their association with functional limitations in older adults in the United States: the aging, demographics, and memory study. J Am Geriatr Soc 2010; 58:330.
  83. Gabryelewicz T, Styczynska M, Pfeffer A, et al. Prevalence of major and minor depression in elderly persons with mild cognitive impairment--MADRS factor analysis. Int J Geriatr Psychiatry 2004; 19:1168.
  84. Kumar R, Jorm AF, Parslow RA, Sachdev PS. Depression in mild cognitive impairment in a community sample of individuals 60-64 years old. Int Psychogeriatr 2006; 18:471.
  85. Lopez OL, Becker JT, Sweet RA. Non-cognitive symptoms in mild cognitive impairment subjects. Neurocase 2005; 11:65.
  86. Lyketsos CG, Lopez O, Jones B, et al. Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study. JAMA 2002; 288:1475.
  87. Vinkers DJ, Gussekloo J, Stek ML, et al. Temporal relation between depression and cognitive impairment in old age: prospective population based study. BMJ 2004; 329:881.
  88. Wilson RS, Schneider JA, Boyle PA, et al. Chronic distress and incidence of mild cognitive impairment. Neurology 2007; 68:2085.
  89. Geda YE, Knopman DS, Mrazek DA, et al. Depression, apolipoprotein E genotype, and the incidence of mild cognitive impairment: a prospective cohort study. Arch Neurol 2006; 63:435.
  90. Goveas JS, Espeland MA, Woods NF, et al. Depressive symptoms and incidence of mild cognitive impairment and probable dementia in elderly women: the Women's Health Initiative Memory Study. J Am Geriatr Soc 2011; 59:57.
  91. Caracciolo B, Bäckman L, Monastero R, et al. The symptom of low mood in the prodromal stage of mild cognitive impairment and dementia: a cohort study of a community dwelling elderly population. J Neurol Neurosurg Psychiatry 2011; 82:788.
  92. Visser PJ, Scheltens P, Verhey FR. Do MCI criteria in drug trials accurately identify subjects with predementia Alzheimer's disease? J Neurol Neurosurg Psychiatry 2005; 76:1348.
  93. Wilson RS, Arnold SE, Beck TL, et al. Change in depressive symptoms during the prodromal phase of Alzheimer disease. Arch Gen Psychiatry 2008; 65:439.
  94. Wilson RS, Hoganson GM, Rajan KB, et al. Temporal course of depressive symptoms during the development of Alzheimer disease. Neurology 2010; 75:21.
  95. Triebel KL, Martin R, Griffith HR, et al. Declining financial capacity in mild cognitive impairment: A 1-year longitudinal study. Neurology 2009; 73:928.
  96. Chang YL, Bondi MW, McEvoy LK, et al. Global clinical dementia rating of 0.5 in MCI masks variability related to level of function. Neurology 2011; 76:652.
  97. Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12:189.
  98. Kokmen E, Smith GE, Petersen RC, et al. The short test of mental status. Correlations with standardized psychometric testing. Arch Neurol 1991; 48:725.
  99. Nasreddine ZS, Phillips NA, Bédirian V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 2005; 53:695.
  100. Petersen RC, Thomas RG, Grundman M, et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med 2005; 352:2379.
  101. Saxton J, Snitz BE, Lopez OL, et al. Functional and cognitive criteria produce different rates of mild cognitive impairment and conversion to dementia. J Neurol Neurosurg Psychiatry 2009; 80:737.
  102. Isella V, Villa L, Russo A, et al. Discriminative and predictive power of an informant report in mild cognitive impairment. J Neurol Neurosurg Psychiatry 2006; 77:166.
  103. Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011; 7:270.
  104. Boustani M, Hall KS, Lane KA, et al. The association between cognition and histamine-2 receptor antagonists in African Americans. J Am Geriatr Soc 2007; 55:1248.
  105. Carrière I, Fourrier-Reglat A, Dartigues JF, et al. Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: the 3-city study. Arch Intern Med 2009; 169:1317.