Skip to main content Accessibility help

Early Identification of Alzheimer's Disease: What Have we Learned from Mild Cognitive Impairment?

  • Howard H. Feldman and Nagaendran Kandiah


Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline, functional disability, and neuropsychiatric symptoms. Initial diagnosis is often delayed to a point when there is significant neurodegenerative pathology and secondary downstream pathogenic sequelae. The disease should be diagnosed during its earliest stage, as this would likely represent an ideal therapeutic window for disease-modifying therapies. Despite recent research that has focused on defining the clinically identifiable at-risk phase that precedes AD, reliable criteria for identifying patients in the prodromal to incipient stages of AD remain elusive.

In addressing the prodrome of AD, it has been clearly recognized that there are age-inappropriate cognitive declines that fall short of meeting the criteria for dementia. Most broadly, patients in this category have been classified as cognitively impaired not demented (CIND). In epidemiological studies, it has been estimated that 19% to 37% of patients ≥65 years of age are CIND. Conditions within the taxonomy of CIND include age-associated memory impairment (AAMI), age-associated cognitive decline (AACD), and mild cognitive impairment (MCI) (Slide 1).

AAMI is defined psychometrically by memory test scores that are ≥1 standard deviation below scores of young healthy control patients. AACD is characterized by scores in any cognitive domain that are ≥1 standard deviation below age- and education-adjusted normal measures. MCI is identified by memory function at a level ≥1.5 standard deviations below age- and education-adjusted means. Of these three conditions, MCI has been investigated most thoroughly and is defined by a clinical phenotype.



Hide All
1.Caselli, RJ, Beach, TG, Yaari, R, Reiman, EM. Alzheimer's disease a century later. J Clin Psychiatry. 2006;67(11):17841800.
2.Terry, AV Jr, Buccafusco, JJ. The cholinergic hypothesis of age and Alzheimer's disease-related cognitive deficits: recent challenges and their implications for novel drug development. J Pharmacol Exp Ther. 2003;306(3):821827.
3.Vellas, B, Andrieu, S, Sampaio, C, Wilcock, G, for the European Task Force group. Disease-modifying trials in Alzheimer's disease: a European task force consensus. Lancet Neurol. 2007;6(1):5662.
4.Hamaguchi, T, Ono, K, Yamada, M. Anti-amyloidogenic therapies: strategies for prevention and treatment of Alzheimer's disease. Cell Mol Life Sci. 2006;63(13):15381552.
5.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(90B8):17931796.
6.Unverzagt, FW, Gao, S, Baiyewu, O, et al.Prevalence of cognitive impairment: data from the Indianapolis Study of Health and Aging. Neurology. 2001;57(9):16551662.
7.Crook, T, Bartus, R, Ferris, SH, et al.Age-associated memory impairment: proposed diagnostic criteria and measures of clinical change: report of a National Institute of Mental Health Work Group. Dev Neuropsychol. 1986;2:261276.
8.Hanninen, T, Koivisto, K, Reinikainen, KJ, et al.Aging-associated cognitive decline. Age Ageing. 1996;25:201205.
9.Petersen, RC, Smith, GE, Waring, SC, Ivnik, RJ, Tangalos, EG, Kokmen, E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999;56(3):303308.
10.Erkinjuntti, T, Laaksonen, R, Sulkava, R, Syrjäläinen, R, Palo, J. Neuropsychological differentiation between normal aging, Alzheimer's disease and vascular dementia. Acta Neurol Scand. 1986;74(5):393403.
11.Anthony, JC, LeResche, L, Niaz, U, von Korff, MR, Folstein, MF. Limits of the ‘Mini-Mental State’ as a screening test for dementia and delirium among hospital patients. Psychol Med. 1982;12(2):397408.
12.Kokmen, E, Naessens, JM, Offord, KP. A short test of mental status: description and preliminary results. Mayo Clin Proc. 1987;62(4):281288.
13.Nasreddine, ZS, Phillips, NA, Bedirian, V, et al.The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53(4):695699.
14.Petersen, RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004;256(3):183194.
15.Stephan, BC, Matthews, FE, McKeith, IG, et al.Early cognitive change in the general population: how do different definitions work? J Am Geriatr Soc. 2007;55(10):15341540.
16.Winblad, B, Gauthier, S, Scinto, L, et al.Safety of galantamine in subjects with mild cognitive impairment. Neurology. 2008. In press.
17.Feldman, HH, Ferris, S, Winblad, B, et al.Effect of rivastigmine on delay to diagnosis of Alzheimer's disease from mild cognitive impairment: the InDDEx study. Lancet Neurol. 2007;6(6):501512.
18.Petersen, RC, Thomas, RG, Grundman, M, et al.Vitamin E and donepezil for the treatment of mild cognitive impairment. N EnglJ Med. 2005;352(23):23792388.
19.Thal, LJ, Ferris, SH, Kirby, L, et al.A randomized, double blind study of rofecoxib in patients with mild cognitive impairment. Neuropsychopharmacology 2005;30(6):12041215.
20.Feldman, H, Scheltens, P, Scarpini, E, Mancione, L, Lane, R. Operational criteria for confirmation of clinical diagnosis of Alzheimer's disease in patients with mild cognitive impairment. Neurobiol Aging. 2004;25(suppl 2):S472.
21.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(10):13481354.
22.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(1):149154.
23.Corder, EH, Huang, R, Cathcart, HM, et al.Membership in genetic groups predicts Alzheimer disease. Rejuvenation Res. 2006;9(1):8993.
24.Potter, GG, Plassman, BL, Helms, MJ, Steffens, DC, Welsh-Bohmer, KA. Age effects of coronary artery bypass graft on cognitive status change among elderly male twins. Neurology. 2004;63(12):22452249.
25.Polidori, MC, Marvardi, M, Cherubini, A, Senin, U, Mecocci, P. Heart disease and vascular risk factors in the cognitively impaired elderly: implications for Alzheimer's dementia. Aging (Milano). 2001;13(3):231239.
26.Morris, JC. Mild cognitive impairment is early-stage Alzheimer disease: time to revise diagnostic criteria. Arch Neurol. 2006;63(1):1516.
27.Dubois, B, Feldman, HH, Jacova, C, et al.Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurol. 2007;6(8):734746.

Early Identification of Alzheimer's Disease: What Have we Learned from Mild Cognitive Impairment?

  • Howard H. Feldman and Nagaendran Kandiah


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed