All Title Author
Keywords Abstract

Cognitive and Functional Profiles in Mild-to-Moderate Alzheimer’s Disease and Mild Cognitive Impairment Compared to Healthy Elderly

DOI: 10.4236/aad.2014.34016, PP. 168-186

Keywords: Alzheimer’s Disease, Amnestic Mild Cognitive Impairment, Dementia, Cognition

Full-Text   Cite this paper   Add to My Lib


Background: Amnestic mild cognitive impairment (aMCI) and mild-to-moderate Alzheimer’s disease (AD) are clinically distinct but impact cognitive and functional ability similarly. Comprehensive assessment of cognitive and functional deficits may prove useful in informing differential diagnosis in early stages of dementia and in informing endpoint selection in therapeutic AD trials. Objective: The objective of this study was to characterize patterns of cognitive and functional impairment in aMCI and mild-to-moderate AD subjects compared to cognitively intact healthy elderly (HE). Methods: Thirty-one healthy elderly, 20 aMCI and 19 AD participants were administered a cognitive test battery that included the ADAS-Cog and functional assessments. Z-scores were calculated for all endpoints based on the HE reference group. Results: Cognitive deficits were observed in AD and aMCI participants relative to the referent group. On average, aMCI participants performed 1 - 2 standard deviations below HE on cognitive tests, and AD participants performed 2 - 3 standard deviations below HE. Domain-specific functional deficits among AD participants (z- score -0.4 to -6.4) were consistently greater than those of aMCI participants (z-score 0 to -1.7). Conclusion: This study provides further support for comprehensive assessment and monitoring of cognitive and functional domain scores in the diagnosis and treatment of aMCI and mild AD. Domain-specific cognitive scores may be more useful than composite scores in characterizing impairment and decline. Measuring domains such as attention, processing speed and executive function may increase the sensitivity of detecting disease progression and therapeutic effects, particularly in mild-moderate AD where memory decline may be too slow to detect drug effects during a typical clinical trial.


[1]  Levey, A., Lah, J., Goldstein, F., Steenland, K. and Bliwise, D. (2006) Mild Cognitive Impairment: An Opportunity to Identify Patients at High Risk for Progression to Alzheimer’s Disease. Clinical Therapeutics, 28, 991-1001.
[2]  Petersen, R.C., Doody, R., Kurz, A., Mohs, R.C., Morris, J.C., Rabins, P.V., et al. (2001) Current Concepts in Mild Cognitive Impairment. JAMA Neurology, 58, 1985-1992.
[3]  Artero, S., Petersen, R., Touchon, J. and Ritchie, K. (2006) Revised Criteria for Mild Cognitive Impairment: Validation within a Longitudinal Population Study. Dementia and Geriatric Cognitive Disorders, 22, 465-470.
[4]  Dubois, B., Feldman, H.H., Jacova, C., Dekosky, S.T., Barberger-Gateau, P., Cummings, J., et al. (2007) Research Criteria for the Diagnosis of Alzheimer’s Disease: Revising the NINCDS-ADRDA Criteria. Lancet Neurology, 6, 734- 746.
[5]  Birks, J. (2006) Cholinesterase Inhibitors for Alzheimer’s Disease. The Cochrane Database of Systematic Reviews, Article ID: CD005593.
[6]  Markwick, A., Zamboni, G. and de Jager, C.A. (2012) Profiles of Cognitive Subtest Impairment in the Montreal Cognitive Assessment (MoCA) in a Research Cohort with Normal Mini-Mental State Examination (MMSE) Scores. Journal of Clinical and Experimental Neuropsychology, 34, 750-757.
[7]  Bondi, M.W., Jak, A.J., Delano-Wood, L., Jacobson, M.W., Delis, D.C. and Salmon, D.P. (2008) Neuropsychological Contributions to the Early Identification of Alzheimer’s Disease. Neuropsychology Review, 18, 73-90.
[8]  Karantzoulis, S. and Galvin, J.E. (2011) Distinguishing Alzheimer’s Disease from Other Major Forms of Dementia. Expert Review of Neurotherapeutics, 11, 1579-1591.
[9]  Nordlund, A., Rolstad, S., Hellstrom, P., Sjogren, M., Hansen, S. and Wallin, A. (2005) The Goteborg MCI Study: Mild Cognitive Impairment Is a Heterogeneous Condition. Journal of Neurology, Neurosurgery and Psychiatry, 76, 1485-1490.
[10]  Caine, D. and Hodges, J.R. (2001) Heterogeneity of Semantic and Visuospatial Deficits in Early Alzheimer’s Disease. Neuropsychology, 15, 155-164.
[11]  Carter, S.F., Caine, D., Burns, A., Herholz, K. and Ralph, M.A.L. (2012) Staging of the Cognitive Decline in Alzheimer’s Disease: Insights from a Detailed Neuropsychological Investigation of Mild Cognitive Impairment and Mild Alzheimer’s Disease. International Journal of Geriatric Psychiatry, 27, 423-432.
[12]  Perry, R.J. and Hodges, J.R. (1999) Attention and Executive Deficits in Alzheimer’s Disease: A Critical Review. Brain, 122, 383-404.
[13]  Farias, S.T., Mungas, D., Reed, B.R., Harvey, D., Cahn-Weiner, D. and DeCarli, C. (2006) MCI Is Associated with Deficits in Everyday Functioning. Alzheimer Disease & Associated Disorders, 20, 217-223.
[14]  Perneczky, R., Pohl, C., Sorg, C., Hartmann, J., Tosic, N., Grimmer, T., Heitele, S. and Kurz, A. (2006) Impairment of Activities of Daily Living Requiring Memory or Complex Reasoning as Part of the MCI Syndrome. International Journal of Geriatric Psychiatry, 21, 158-162.
[15]  Reppermund, S., Brodaty, H., Crawford, J.D., Kochan, N.A., Draper, B., Slavin, M.J., et al. (2013) Impairment in Instrumental Activities of Daily Living with High Cognitive Demand Is an Early Marker of Mild Cognitive Impairment: The Sydney Memory and Ageing Study. Psychological Medicine, 43, 2437-2445.
[16]  Goldberg, T.E., Koppel, J., Keehlisen, L., Christen, E., Dreses-Werringloer, U., Conejero-Goldberg, C., Gordon, M.L. and Davies, P. (2010) Performance-Based Measures of Everyday Function in Mild Cognitive Impairment. American Journal of Psychiatry, 167, 845-853.
[17]  Bangen, K.J., Jak, A.J., Schiehser, D.M., Delano-Wood, L., Tuminello, E., Han, S.D., et al. (2010) Complex Activities of Daily Living Vary by Mild Cognitive Impairment Subtype. Journal of the International Neuropsychological Society, 16, 630-639.
[18]  Allaire, J.C., Gamaldo, A., Ayotte, B.J., Sims, R. and Whitfield, K. (2009) Mild Cognitive Impairment and Objective Instrumental Everyday Functioning: The Everyday Cognition Battery Memory Test. Journal of the American Geriatrics Society, 57, 120-125.
[19]  Mioshi, E., Kipps, C.M., Dawson, K., Mitchell, J., Graham, A. and Hodges, J.R. (2007) Activities of Daily Living in Frontotemporal Dementia and Alzheimer Disease. Neurology, 68, 2077-2084.
[20]  Dangour, A.D., Allen, E., Richards, M., Whitehouse, P. and Uauy, R. (2010) Design Considerations in Long-Term Intervention Studies for the Prevention of Cognitive Decline or Dementia. Nutrition Reviews, 68, S16-S21.
[21]  de Jager, C.A., Hogervorst, E., Combrinck, M. and Budge, M.M. (2003) Sensitivity and Specificity of Neuropsychological Tests for Mild Cognitive Impairment, Vascular Cognitive Impairment and Alzheimer’s Disease. Psychological Medicine, 33, 1039-1050.
[22]  de Jager, C.A. and Budge, M.M. (2005) Stability and Predictability of the Classification of Mild Cognitive Impairment as Assessed by Episodic Memory Test Performance over Time. Neurocase, 11, 72-79.
[23]  Hogervorst, E., Combrinck, M., Lapuerta, P., Rue, J., Swales, K. and Budge, M. (2002) The Hopkins Verbal Learning Test and Screening for Dementia. Dementia and Geriatric Cognitive Disorders, 13, 13-20.
[24]  Kramer, J.H., Jurik, J., Sha, S.J., Rankin, K.P., Rosen, H.J., Johnson, J.K. and Miller, B.L. (2003) Distinctive Neuropsychological Patterns in Frontotemporal Dementia, Semantic Dementia, and Alzheimer Disease. Cognitive & Behavioral Neurology, 16, 211-218.
[25]  Libon, D.J., Massimo, L., Moore, P., Coslett, H.B., Chatterjee, A., Aguirre, G.K., et al. (2007) Screening for Frontotemporal Dementias and Alzheimer’s Disease with the Philadelphia Brief Assessment of Cognition: A Preliminary Analysis. Dementia and Geriatric Cognitive Disorders, 24, 441-447.
[26]  Pendlebury, S.T., Markwick, A., de Jager, C.A., Zamboni, G., Wilcock, G.K. and Rothwell, P.M. (2012) Differences in Cognitive Profile between TIA, Stroke and Elderly Memory Research Subjects: A Comparison of the MMSE and MoCA. Cerebrovascular Diseases, 34, 48-54.
[27]  Perry, R.J. and Hodges, J.R. (2000) Differentiating Frontal and Temporal Variant Frontotemporal Dementia from Alzheimer’s Disease. Neurology, 54, 2277-2284.
[28]  de Jager, C.A., Honey, T.E., Birks, J. and Wilcock, G.K. (2010) Retrospective Evaluation of Revised Criteria for the Diagnosis of Alzheimer’s Disease Using a Cohort with Post-Mortem Diagnosis. International Journal of Geriatric Psychiatry, 25, 988-997.
[29]  Huppert, F.A., Brayne, C., Gill, C., Paykel, E.S. and Beardsall, L. (1995) CAMCOG—A Concise Neuropsychological Test to Assist Dementia Diagnosis: Socio-Demographic Determinants in an Elderly Population Sample. British Journal of Clinical Psychology, 34, 529-541.
[30]  Roth, M., Tym, E., Mountjoy, C.Q., Huppert, F.A., Hendrie, H., Verma, S. and Goddard, R. (1986) CAMDEX. A Standardised Instrument for the Diagnosis of Mental Disorder in the Elderly with Special Reference to the Early Detection of Dementia. British Journal of Psychiatry, 149, 698-709.
[31]  Folstein, M.F., Folstein, S.E. and McHugh, P.R. (1975) “Mini-Mental State”. A Practical Method for Grading the Cognitive State of Patients for the Clinician. Journal of Psychiatric Research, 12, 189-198.
[32]  Brandt, J., Spencer, M. and Folstein, M. (1988) The Telephone Interview for Cognitive Status. Neuropsychiatry, Neuropsychology, & Behavioral Neurology, 1, 111-117.
[33]  Morris, J.C. (1997) Clinical Dementia Rating: A Reliable and Valid Diagnostic and Staging Measure for Dementia of the Alzheimer Type. International Psychogeriatrics, 9, 173-176.
[34]  Yesavage, J.A., Brink, T.L., Rose, T.L., Lum, O., Huang, V., Adey, M. and Otto Leirer, V. (1982) Development and Validation of a Geriatric Depression Screening Scale: A Preliminary Report. Journal of Psychiatric Research, 17, 37-49.
[35]  Ferris, S.H., Lucca, U., Mohs, R., Dubois, B., Wesnes, K., Erzigkeit, H., et al. (1997) Objective Psychometric Tests in Clinical Trials of Dementia Drugs. Position Paper from the International Working Group on Harmonization of Dementia Drug Guidelines. Alzheimer Disease and Associated Disorders, 11, 34-38.
[36]  Rosen, W.G., Mohs, R.C. and Davis, K.L. (1984) A New Rating Scale for Alzheimer’s Disease. American Journal of Psychiatry, 141, 1356-1364.
[37]  Cambridge Cognition Ltd. (2013) Cambridge Cognition—The Home of CANTAB. [Internet]. Cambridge Cognition Ltd., Cambridge, c2013.
[38]  Galasko, D., Bennett, D., Sano, M., Ernesto, C., Thomas, R., Grundman, M. and Ferris, S. (1997) An Inventory to Assess Activities of Daily Living for Clinical Trials in Alzheimer’s Disease. Alzheimer Disease & Associated Disorders, 11, S33-S39.
[39]  Sunderland, A., Harris, J. and Baddeley, A. (1983) Do Laboratory Tests Predict Everyday Memory? A Neuropsychological Study. Journal of Verbal Learning and Verbal Behavior, 22, 341-357.
[40]  Graham, D., Cully, J.A., Snow, A.L., Massman, P. and Doody, R. (2004) The Alzheimer’s Disease Assessment Scale- Cognitive Subscale: Normative Data for Older Adults Controls. Alzheimer Disease and Associated Disorders, 18, 236- 240.
[41]  Grundman, M., Petersen, R.C., Ferris, S.H., Thomas, R.G., Aisen, P.S., Bennett, D.A., et al. (2004) Mild Cognitive Impairment Can Be Distinguished from Alzheimer Disease and Normal Aging for Clinical Trials. JAMA Neurology, 61, 59-66.
[42]  Royall, D.R., Cordes, J.A. and Polk, M. (1998) CLOX: An Executive Clock Drawing Task. Journal of Neurology, Neurosurgery & Psychiatry, 64, 588-594.
[43]  Smith, A. (1968) The Symbol-Digit Modalities Test: A Neuropsychologic Test of Learning and Other Cerebral Disorders. In: Learning Disorders, Special Child Publications, Seattle, 83-91.
[44]  Robertson, I.H., Thames Valley Test Company (1994) The Test of Everyday Attention. Thames Valley Test Company.
[45]  Brandt, J., Aretouli, E., Neijstrom, M.S., Samek, J., Manning, K., Albert, M.S., et al. (2009) Selectivity of Executive Function Deficits in Mild Cognitive Impairment. Neuropsychology, 23, 607-618.
[46]  Papp, K.V., Snyder, P.J., Maruff, P., Bartkowiak, J. and Pietrzak, R.H. (2011) Detecting Subtle Changes in Visuospatial Executive Function and Learning in the Amnestic Variant of Mild Cognitive Impairment. PLoS ONE, 6, e21688.
[47]  Voss, S. and Bullock, R. (2004) Executive Function: The Core Feature of Dementia? Dementia and Geriatric Cognitive Disorders, 18, 207-216.
[48]  Brandt, J. (1991) The Hopkins Verbal Learning Test: Development of a New Memory Test with Six Equivalent Forms. Clinical Neuropsychologist, 5, 125-142.
[49]  Cano, S.J., Posner, H.B., Moline, M.L., Hurt, S.W., Swartz, J., Hsu, T. and Hobart, J.C. (2010) The ADAS-Cog in Alzheimer’s Disease Clinical Trials: Psychometric Evaluation of the Sum and Its Parts. Journal of Neurology, Neurosurgery & Psychiatry, 81, 1363-1368.
[50]  Petersen, R.C., Smith, G.E., Waring, S.C., Ivnik, R.J., Tangalos, E.G. and Kokmen, E. (1999) Mild Cognitive Impairment: Clinical Characterization and Outcome. JAMA Neurology, 56, 303-308.
[51]  Winblad, B., Palmer, K., Kivipelto, M., Jelic, V., Fratiglioni, L., Wahlund, L.O., et al. (2004) Mild Cognitive Impairment—Beyond Controversies, towards a Consensus: Report of the International Working Group on Mild Cognitive Impairment. Journal of Internal Medicine, 256, 240-246.
[52]  Marshall, D.A., Rentz, D.M., Frey, M.T., Locascio, J.J., Johnson, K.A. and Sperling, R.A., the Alzheimer’s Disease Neuroimaging Initiative (2011) Executive Function and Instrumental Activities of Daily Living in Mild Cognitive Impairment and Alzheimer’s Disease. Alzheimer’s & Dementia, 7, 300-308.
[53]  Perry, R.J. and Hodges, J.R. (2000) Relationship between Functional and Neuropsychological Performance in Early Alzheimer Disease. Alzheimer Disease & Associated Disorders, 14, 1-10.
[54]  Cornish, I.M. (2000) Factor Structure of the Everyday Memory Questionnaire. British Journal of Psychology, 91, 427- 438.
[55]  Salthouse, T.A. and Babcock, R.L. (1991) Decomposing Adult Age Differences in Working Memory. Developmental Psychology, 27, 763-776.
[56]  Anderson, E., De Jager, C. and Iversen, S. (2006) The Placing Test: Preliminary Investigations of a Quick and Simple Memory Test Designed to Be Sensitive to Pre-Dementia Alzheimer’s Disease but Not to Normal Ageing. Journal of Clinical and Experimental Neuropsychology, 28, 843-858.
[57]  McKenna, P. and Warrington, E.K. (1980) Testing for Nominal Dysphasia. Journal of Neurology, Neurosurgery & Psychiatry, 43, 781-788.


comments powered by Disqus