Vol. 3 nº 1 - Jan/Feb/Mar de 2009
Original Article Pages 41 to 48
 

Comparison of performance in neuropsychological tests in amnestic Mild Cognitive Impairment and Alzheimer's disease patients
Comparação do desempenho em testes neuropsicológicos em pacientes com comprometimento cognitivo leve amnéstico e com doença de Alzheimer

Authors: Patrícia Helena Figueirêdo do Vale1, Lívia Spíndola1, Maira Okada de Oliveira1, Cristiane Garcia da Costa Armentano1, Claudia Sellitto Porto2, Sonia Maria Dozzi Brucki3

PDF

Descriptors: Mild Cognitive Impairment, Amnestic Mild Cognitive Impairment, Alzheimer's disease, neuropsychological tests, memory.
Descritores:
Comprometimento Cognitivo Leve, Comprometimento Cognitivo Leve Amnéstico, doença de Alzheimer, testes neuropsicológicos, memória.

ABSTRACT:
Mild Cognitive Impairment (MCI) can be an intermediate state between normality and dementia in some patients. An early diagnosis, through neuropsychological assessment, could identify individuals at risk of developing dementia. Objective: To verify differences in performance on neuropsychological tests among controls, amnestic MCI (aMCI) and Alzheimer's disease (AD) patients. Methods: Sixty-eight AD patients (mean age 73.77±7.24; mean schooling 9.04±4.83; 40 women and 28 men), 34 aMCI patients (mean age 74.44±7.05; mean schooling 12.35±4.01; 20 women) and 60 controls (mean age 68.90±7.48; mean schooling 10.72±4.74; 42 women) were submitted to a neuropsychological assessment composed of tasks assessing executive functions, language, constructive abilities, reasoning and memory. Results: There were statistically significant differences in performance across all tests among control, aMCI and AD groups, and also between only controls and AD patients. On comparing control and aMCI groups, we found statistically significant differences in memory tasks, except for immediate recall of Visual Reproduction. There were also statistically significant differences between aMCI and AD groups on tasks of constructive and visuoperceptual abilities, attention, language and memory, except for delayed recall of Visual Reproduction. Conclusions: Neuropsychological assessment was able to discriminate aMCI from AD patients in almost all tests except for delayed recall of Visual Reproduction, visual organization (Hooper) and executive functions (WCST); and discriminate controls from AD patients in all tests, and controls from aMCI patients in all memory tests except for immediate recall of Visual Reproduction.

RESUMO:
Comprometimento Cognitivo Leve (CCL) pode ser um estágio entre normalidade e demência em alguns pacientes. Um diagnóstico precoce, com avaliação neuropsicológica, pode identificar indivíduos com risco para desenvolvimento de demência. Objetivo: Verificar diferenças no desempenho em testes neuropsicológicos entre controles, pacientes com CCL amnéstico (CCLa) e com doença de Alzheimer (DA). Métodos: Sessenta e oito pacientes com DA (média de idade 73,77±7,24; média de escolaridade 9,04±4,83; 40 mulheres), 34 pacientes com CCLa (média de idade 74,44±7,05; média de escolaridade 12,35±4,01; 20 mulheres) e 60 controles (média de idade 68,90±7,48; média de escolaridade 10,72±4,74; 42 mulheres) foram submetidos à ampla avaliação neuropsicológica. Resultados: Houve diferenças estatisticamente significativas em todos os testes entre os grupos controle, CCLa e DA, e entre controles e o grupo DA. Na comparação entre controles e pacientes com CCLa foram encontradas diferenças estatisticamente significativas nos testes de memória, exceto na evocação imediata do teste de Reprodução Visual. Foram também encontradas diferenças estatisticamente significativas entre pacientes com CCLa e DA, nas tarefas de habilidades construtivas e visuoperceptuais, atenção, linguagem e memória, com exceção da evocação tardia do teste Reprodução Visual. Conclusões: A avaliação neuropsicológica foi capaz de discriminar pacientes com CCLa de pacientes com DA em quase todos os testes exceto na evocação tardia do teste Reprodução Visual, organização visual (Hooper) e funções executivas (WCST); controles de pacientes com DA em todos os testes, e controles de pacientes com CCLa nos testes de memória, exceto na evocação imediata do teste Reprodução Visual.

Mild Cognitive Impairment (MCI) is a term proposed by Petersen et al.1 to report a clinical syndrome presented by individuals with measurable cognitive deficits who do not fulfill criteria for diagnosis of dementia but who are at high risk of developing it, mainly in the form of Alzheimer's disease (AD).2

The diagnosis of MCI is established based on evidence of cognitive disorder in non-demented individuals who present complaints (preferably corroborated by an informant) in conjunction with objectively measured cognitive deficits, preserved activities of daily living, and intact or minimally impaired complex instrumental functions.2,3

The clinical presentations of MCI can be classified accordingly to three subtypes: amnestic MCI (aMCI), multiple domains (mdMCI) and nonmemory single domain (naMCI single domain) MCI. In aMCI, memory is impaired, but the other cognitive functions can be preserved. On the other hand, mdMCI is characterized by cognitive impairments in other domains such as language, attention, executive functions or visuospatial skills. In these cases, if memory is significantly impaired then this confers aMCI multiple domains, and if not naMCI multiple domains. In the naMCI single domain only one function beyond memory is impaired (e.g. language or visuospatial).2,3

Subjects with MCI can progress to AD or other dementia, remain stable or even recover, although when a person with aMCI has a suspected degenerative disorder this is most likely a case of prodromal AD.2-4

Data on the prevalence of MCI and the conversion rate to dementia vary widely, depending on the different defining criteria applied5. In a cohort study, Fisher et al.6 compared the conversion rate of the subtypes of MCI to AD in elderly subjects, followed for 30 months. The conversion rates were 48.7% for subjects with aMCI and 28.6% for those with non-amnestic MCI. The rate of conversion to AD among healthy subjects was 12.6%. Visser et al.7 conducted a 10-year follow up study involving subjects with cognitive impairment aged 40 to 85 years to investigate the risk of dementia, and reported rates of conversion of 27% in subjects with cognitive complaints, 28% in subjects with aging-associated cognitive decline, 44% in subjects with mild functional impairment, and 48% in subjects with amnestic MCI.

Controversy exists as to how MCI can be best assessed, as there is insufficient evidence to recommend specific tests2. Petersen et al.1 compared MCI patients, mild AD and controls on a neuropsychological battery and observed that subjects with MCI performed worse than controls, but better than AD patients on memory tasks, and proved more similar to control subjects than to AD patients on measures of general cognition and other nonmemory indexes. In longitudinal studies, delayed recall tests were found to be good predictors of progression to AD8,9, while poor performance in delayed recall and executive function tests indicate a high risk of progression to dementia. Arnaiz and Almkvist4 believe that beyond memory tests, tasks evaluating other cognitive functions such as verbal abilities and learning, visuospatial function, attention and executive functions are important for screening and diagnosis of MCI and early AD.

The aim of this study was to verify differences in performance on neuropsychological tests by controls, aMCI and AD patients.


Methods

In this retrospective study we reviewed 102 medical files of subjects which were divided into three groups: controls (n=60), Alzheimer's disease patients (n=68), and aMCI patients (n=34) (Table 1).




All patients were evaluated by members of the Behavioral and Cognitive Neurology Unit of the Department of Neurology at the University of Sao Paulo School of Medicine and from the Center of Cognitive Disorders (CEREDIC) and had been submitted to a general clinical and neurological evaluation and to screening tests comprising the Mini-Mental State Examination (MMSE)10, Brief Cognitive Screening Battery (BCSB),11,12 and Functional Activities Questionnaire.13,14

The patients were classified with mild dementia according to the American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, Third Edition, revised (DSM-III-R)15 criteria and probable AD according to National Institute of Neurological Disorders and Communicative Disorders and Stroke Alzheimer Disease and Related Disorders Association (NINCDS-ADRDA) criteria16. Amnestic MCI patients were diagnosed based on the criteria proposed by Petersen et al.3,17

All patients were also submitted to a comprehensive neuropsychological battery of tests including: executive functions (Trail Making Test versions A and B, Wisconsin Card Sorting Test - WCST);18 visual perception (Hooper Visual Organization Test,19 Raven's Progressive Matrices20); language (Boston Naming Test,21,22 semantic verbal fluency18); constructive abilities (Block Design, Wechsler Adult Intelligence Scale - WAIS23, Rey Complex Figure Copy18,24); visual and verbal memory tests (Visual Reproduction of the Wechsler Memory Scale - Revised - WMS-R,25 Rey Complex Figure - delayed recall18,24, WMS-R Logical Memory,25 Rey Auditory Verbal Learning Test - RAVLT26).

Cases of moderate or severe AD, and those presenting other disorders that could affect cognitive functions and non-corrected visual or auditory disorders were excluded.

The control group was composed of 60 volunteers (42 women and 18 men) with no memory or functional disturbances. To be included they had to score above the median values for their educational level on the MMSE,10 below 22 in the Memory Complaint Questionnaire (MAQ-Q)27 and below 3.84 on the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE).28 Subjects with neurological disease, history of alcoholism, depression, or any other psychiatric disorder, non-corrected visual or auditory disorders, motor disorders, or users of psychotropic drugs that could affect cognitive functions were excluded. Chronic diseases such as hypertension, diabetes mellitus and cardiac disorders, if adequately controlled, were not criteria for exclusion.

All patients and control individuals who agreed to participate in the study signed a written informed consent term. This study was approved by the Ethics Committee of the Hospital das Clínicas of the University of São Paulo School of Medicine.


Statistical analysis

We used the Chi-square test to evaluate associations between the categorical variables and the results. When the variables were continuous, the comparisons were performed by Mann-Whitney for two samples, and by the Kruskall-Wallis test for more than two samples. The value of significance accepted was 0.01.

All statistical analysis was carried out using the program Statistical Package for the Social Sciences (SPSS), for Windows, version 10.0.


Results

No differences related to gender (p=0.364) were found among the control group, aMCI and AD patients, but statistically significant differences related to age (p<0.001) and schooling (p=0.03) were observed (Table 1).

Comparison among controls, aMCI and AD patients on neuropsychological assessments yielded statistically significant differences in all tests applied (Table 2).




When control group and AD patients were compared, statistically significant differences were found in all tests (Table 3).




Comparison between the control group and aMCI patients revealed statistically significant differences in memory tasks (visual and verbal) for immediate and delayed recall, except for the immediate recall of Visual Reproduction test (Table 4).




Statistically significant differences were observed between aMCI and AD patients on tasks of constructive and visuoperceptual abilities; attention; language and memory (except for delayed recall of Visual Reproduction test). No statistically significant differences in visual organization (measured by Hooper) and executive functions were noted (measured by WCST) (Table 5).




Discussion

Comparison of control group, aMCI and AD patients revealed a statistically significant difference in all tests applied. Our finding of differences among the groups for all cognitive functions evaluated is in line with results of several other studies. Boeve et al.29 demonstrated that MCI patients showed intermediate scores on memory tasks which lay between normal subjects and dementia patients. As expected, comparisons between control group and AD patients yielded statistically significant differences in all tests applied, where this result corroborates with characteristics of AD in that beyond memory impairments, other functions including attention, language, reasoning and visuospatial abilities are also damaged.30

Neuropsychological assessment was able to discriminate controls from aMCI patients through memory tasks, except for the immediate recall of Visual Reproduction. These findings may be explained since memory begins to decline early in the disease process while the most important evidence for aMCI is poor performance on memory tests3,4,31-34. Petersen et al.1 compared controls, MCI and mild AD patients by a neuropsychological assessment comprising the MMSE, WAIS-R, WMS-R, Dementia Rating Scale, Free and Cued Selective Reminding Test (FCSRT) and Rey Auditory Verbal Learning Test (RAVLT). The results showed similar performance on measures of general cognition between controls and MCI, but subjects with MCI were more significantly impaired on memory tasks. Perri et al.35 investigated different aspects of episodic long-term, short-term and implicit long-term memory in aMCI patients. Results showed normal short-term memory abilities, while the episodic long-term memory showed poorer results in aMCI than in controls. The authors affirmed that although some episodic memory functions were relatively well preserved, others appeared to have deteriorated to a level comparable to that of mild AD patients.

Statistically significant differences were observed between AD and aMCI patients in tasks of constructive and visuoperceptual abilities, attention, language, immediate and delayed recall verbal memory and immediate visual memory. The differences observed in other tasks beyond memory tests can be explained by the fact that AD patients present more severe disorders in many other cognitive domains such as attention, visuospatial abilities, language and complex motor tasks.1,4,36 Kramer et al.37 compared aMCI subjects, with presumably isolated memory impairment, with controls and very mild AD patients using a battery of neuropsychological tests. As expected, deficits in episodic memory were observed, but the aMCI group performed less well than controls yet better than the AD group on design fluency, category fluency, a set shifting task and the Stroop interference condition. Economou et al.38 compared patients with aMCI, mild AD and controls on nonepisodic memory measures. Working memory, processing speed, semantic fluency and complex motor tasks were significantly worse in the mild AD than the aMCI group. Rozzini et al.39 investigated the risk factors associated with conversion of aMCI to dementia of Alzheimer type. Subjects who converted to AD over time were classified as demented and subjects that remained unchanged, or became cognitively normal during follow-up were defined as Stable. After a one-year period, demented individuals presented worse performance on phonemic verbal fluency, Raven's colored matrices, Trail Making test A and B, and in Instrumental Activities of Daily Living than Stable subjects.

No statistically significant difference was observed between AD and aMCI patients in the delayed recall stage of the Visual Reproduction. Alescio-Lautier et al.40 found that both MCI and AD patients' had impairments on visual tasks. Griffith et al.41 showed that on the DRS, Initiation/Perseveration scores below 37 and Visual Reproduction Percent Retention scores below 26% correctly identified AD converters with 76.9% sensitivity and 91.7% specificity.

Many studies4,29,33 have shown that MCI subjects have a neuropsychological performance which lies between normal older individuals and demented patients. However, neuropsychological features for MCI classification are not yet well established. Studies42-44 have suggested that there is probably a continuum between aMCI and AD at early stages, which hampers discrimination among these groups, where the results of our study confirmed these difficulties. According to Nelson and O'Connor45 there is no consensus regarding an optimal test battery useful in the detection of MCI. Nonetheless, a well-constructed neuropsychological battery which comprises tests investigating specific aspects of memory complaints can detect subtle cognitive deficits that can easily be overlooked, particularly in patients with a high intellectual baseline. Winblad et al.2 suggested that individual slopes of decline in both functional and cognitive performance may be the best measures for diagnosing MCI. According to Celone et al.46 a longitudinal follow-up is necessary, however, to determine whether MCI subjects are indeed in the early phases of AD.

The present study confirmed that a well-constructed neuropsychological battery is important to reach differential diagnosis among controls, aMCI and AD patients, but in order to achieve diagnostic accuracy the scales must be used in conjunction with clinical features, functional activities investigation, biomarkers and neuroimaging measures.

In our sample, differences in age and schooling among the groups reached statistical significance. The limitation of this study was the absence of investigation of possible interference of these variables on performance in the neuropsychological tests.


References

1. Petersen RC, Smith GE, Waring SC, et al. Mild Cognitive Impairment: clinical characterization and outcome. Arch Neurol 1999;56:303-308.

2. Winblad B, Palmer K, Kivipelto M, et al. Mild cognitive impairment - beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Int Med 2004;256:240-246.

3. Petersen RC, Doody R, Kurz A, et al. Current concepts in Mild Cognitive Impairment. Arch Neurol 2001;58:1985-1992.

4. Arnáiz E, Almkvist O. Neuropsychological features of mild cognitive impairment and preclinical Alzheimer's disease. Acta Neurol Scand 2003;107(Suppl. 179):34-41.

5. Dawe B, Procter A. Concepts of mild memory impairment in the elderly and their relationship to dementia - a review. Int J Geriatr Psychiatry 1998;7:473- 479.

6. Fischer P, Jungwirth S, Zehetmayer S, et al. Conversion from subtypes of mild cognitive impairment to Alzheimer dementia. Neurology 2007;68:288-291.

7. Visser PJ, Kester A, Jolles J, et al. Ten-year risk of dementia in subjects with mild cognitive impairment. Neurology 2006;7:1201-1207.

8. Flicker C, Ferris SH, Reisberg B. Mild cognitive impairment in the elderly: predictors of dementia. Neurology 1991;41:1006-09.

9. Bäckman L, Small BJ, Fratiglioni L. Stability of the preclinical episodic memory deficit in Alzheimer's disease. Brain 2001;124:96-102.

10. Brucki SMD, Nitrini R, Caramelli P, Bertolucci PHF, Okamoto I H. Suggestions of utilization of the Mini-mental state examination in Brazil. Arq Neuropsiquiatr 2003;61:777-781.

11. Nitrini R, Lefèvre BH, Mathias SC, et al. Neuropsychological tests of simple application for diagnosing dementia. Arq Neuropsiquiatr 1994;52:457-465.

12. Nitrini R, Carameli P, Porto CS, et al. Avaliação Cognitiva Breve no diagnóstico de doença de Alzheimer leve. Arq Neuropsiquiatr 2005;63;27.

13. Pfeffer RI, Kusosaki TT, Harrah Jr CH, Chance JM, Filos S. Measurement of functional Activities in Older Adults in the Community. J Gerontol 1982;37:323-329.

14. Nitrini R, Caramelli P, Bottino CMC, Damasceno BP, Brucki SMD, Anghinah R. Diagnóstico de doença de Alzheimer no Brasil: avaliação cognitiva e funcional. Recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia. Arq Neuropsiquiatr 2005;63:720-727.

15. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 3 ed. Ver Washington, DC: American Psychiatric Association;1987.

16. McKann G, Drachman D, Folstein M, Katzman R, Prince D, Staklan EM. Clinical diagnosis of Alzheimer's Disease: report of the NINCDS-ADRDA work group under the auspices of department of health and human services force on Alzheimer's Disease. Neurology 1984;34:939-944.

17. 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;56:1133-1142.

18. Spreen O, Strauss E. A Compendium of Neuropsychological Tests. Administration, Norms, and Commentary. Second Edition. Oxford University Press;1998.

19. Hooper Visual Organization Test (VOT) Manual. Los Angeles, CA: Western Psychological Services;1983.

20. Raven JC, Raven J, Courth JH. Manual Matrizes Progressivas Coloridas. São Paulo: Casa do Psicólogo;1988.

21. Goodglass H, Kaplan E. The assessment of aphasia and related disorders. 2nd ed. Philadelphia: Lea & Febiger;1987.

22. Radanovic M, Mansur LL, Scaff M. Normative data for the Brazilian population in the Boston Diagnostic Aphasia Examination: influence of schooling. Braz J Med Biol Res 2004;37:1731-1738.

23. Wechsler D. Teste de Inteligencia para adultos (WAIS). Manual. 2a Edição. Buenos Aires, Argentina. Editorial Paidos;1993.

24. Rey A. Figuras Complexas de Rey. Casa do Psicólogo;1998.

25. Wechsler D. Wechsler Memory Scale. Manual The Psychological Corporation Harcourt Brace Jovanovich;1987.

26. Diniz LFM, Cruz MF, Torres VM, Consenza, RM. Teste de aprendizagem auditivo verbal de Rey: normas para uma população brasileira. Rev Bras Neurol 2000;36:79-83.

27. Mattos P, Lino V, Rizo L, Alfano A, et al. Memory complaints and test performance in health elderly persons. Arq Neuropsiquiatr 2003;61: 920-924.

28. Jorm, AF. A short form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE): development and cross-validation. Psychol Med 1994;24:145-153.

29. Boeve B, McCormick J, Smith G, et al. Mild Cognitive impairment in the oldest old. Neurology 2008;60:477-480.

30. Mesulam MM. Principles of Behavior and Cognitive Neurology. Second Edition. New York: Oxford;2000:1-540.

31. 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.

32. Chen P, Ratcliff G, Phil D, et al. Cognitive tests that best discriminate between presymptomatic AD and those who remain nondemented. Neurology 2000, 55:1847-1853.

33. Grundeman M, Petersen RC, Ferris SH, et al. Mild Cognitive Impairment can be distinguished from Alzheimer and normal aging for clinical trials. Arch Neurol 2004;61:59-66.

34. Blacker D, Lee H, Muzikansky A, et al. Neuropsychological measures in normal individuals that predict subsequent cognitive decline. Arch Neurol 2007;64:862-871.

35. Perri R, Serra L, Carlesimo GA, Caltagirone C. Preclinical dementia: an Italian multicentre study on amnestic mild cognitive impairment. Dement Geriatr Cogn Disord 2007;23:289-300.

36. Feldman HH, Jacova C. Mild Cognitive Impairment. Am J Geriatr Psychiatry 2005;13:645-655.

37. Kramer JH, Nelson A, Johnson JK, et al. Multiple cognitive deficits in amnestic mild cognitive impairment. Dement Geriatr Cogn Disord 2006;22:306-311.

38. Economou A, Papageorgiou SG, Karageorgiou C, Vassilopoulos D. Nonepisodic memory deficits in amnestic MCI. Cogn Behav Neurol 2007;20:99-106.

39. Rozzini L, Chilovi BV, Conti M, et al. Conversion of amnestic Mild Cognitive Impairment to dementia of Alzheimer type is independent to memory deterioration. Int J Geriatr Psychiatry 2007;22:1217-1222.

40. Alescio-Lautier B, Michael BF, Herrera C, et al. Visual and visuospatial short-term memory in mild cognitive impairment and Alzheimer disease: Role of attention. Neuropsychologia 2007;45:1948-1960.

41. Griffith HR, Netson KL, Harrel LE, Zamrini EY, Brockington JC, Marson DC. Amnestic mild cognitive impairment: diagnostic outcomes and clinical prediction over a two-year time period. J Int Neuropsychol Soc 2006;12:166-175.

42. Tabert MH, Manly JJ, Liu X, et al. Neuropsychological prediction of conversion to Alzheimer disease in patients with mild cognitive impairment. Arch Gen Psychiatry 2006;63: 916-924.

43. Clemént F, Belleville S, Gauthier S. Cognitive complaint in mild cognitive impairment and Alzheimer's disease. J Int Neuropsychol Soc, 2008, 14:222-232.

44. Morris JC, Storandt M, Miller JP, et al. Mild cognitive impairment represents early-stage Alzheimer disease. Arch Neurol 2001;58:397-405.

45. Nelson AP, O'Connor MG. Mild Cognitive Impairment: A neuropsychological perspective. CNS Spectr 2008;13: 56-64.

46. Celone KA, Calhoun VD, Dickerson BC, et al. Alterations in memory networks in mild cognitive impairment and Alzheimer's disease: An independent component analysis. J Neurosci 2006;26:10222-10231.








1 Psychologist, Behavioral and Cognitive Neurology Unit, Department of Neurology of the University of São Paulo School of Medicine and Cognitive Disorders Reference Center (CEREDIC), Hospital das Clínicas of the University of São Paulo School of Medicine, São Paulo, SP, Brazil.
2 PhD, Behavioral and Cognitive Neurology Unit, Department of Neurology of the University of São Paulo School of Medicine and Cognitive Disorders Reference Center (CEREDIC), Hospital das Clínicas of the University of São Paulo School of Medicine, São Paulo, SP, Brazil.
3 MD, PhD, Behavioral and Cognitive Neurology Unit, Department of Neurology of the University of São Paulo School of Medicine and Cognitive Disorders Reference Center (CEREDIC), Hospital das Clínicas of the University of São Paulo School of Medicine, São Paulo, SP, Brazil.

Patrícia Helena Figueirêdo do Vale-Rua Teodoro Sampaio, 408/83 - 05406-000 São Paulo SP - Brazil. E-mail: patriciafigvale@terra.com.br

Disclosure: The authors reports no conflicts of interest. Sources of aid: None.
Received October 20, 2008. Accepted in final form December 29, 2008

 

Home Contact