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Motor and functional changes in different stages of Alzheimer's disease

Abstracts

BACKGROUND: Alzheimer's disease (AD) is the most prevalent dementia, being associated with cognitive, behavioral, and functional alterations. However, clarifying the influence of the disease worsening in the decline of these functions is of major relevance. OBJECTIVE: Compare specific cognitive functions, motor functions and activities of daily living (ADL) of AD patients in different stages of the disease. METHODS: Cognitive and motor functions, as well as ADL of 74 AD patients (35 patients CDR1; 20 patients CDR2; 19 patients CDR3) were evaluated. RESULTS: Motor function and independency in the ADL have presented a non-linear decline. While motor function shows a greater decline from the mild to the moderate phase, ADL present a greater decline in the severe stage of the disease. DISCUSSION: Motor function decline is more evident in both moderate and severe stages of AD, associated with losses in physical capacity and increases in risk of falls. The patients' loss of independency to perform instrumental ADL occurs in a non-linear pattern and it is much greater than both physical and cognitive declines when these parameters are objectively evaluated in the three phases of the disease.

Functional capacity; dementia; mobility; cognition


CONTEXTO: A doença de Alzheimer (DA) é a demência de maior prevalência e está associada a alterações cognitivas, comportamentais e funcionais. Entretanto, faz-se necessário esclarecer a influência do agravamento da doença no declínio dessas funções. OBJETIVO: Comparar funções cognitivas específicas, funções motoras e atividades de vida diária (AVD) de pacientes com DA em diferentes estágios da doença. MÉTODOS: Foram avaliadas as funções cognitivas, as funções motoras e as AVD de 74 pacientes com doença de Alzheimer (35 pacientes CDR1; 20 pacientes CDR2; 19 pacientes CDR3). RESULTADOS: A função motora e a independência das AVD apresentam declínio não linear. Enquanto a função motora apresenta maior declínio na fase leve para moderada, as AVD básicas sofrem maior declínio na fase grave da doença. CONCLUSÃO: O declínio motor é mais importante nas fases moderada e grave, associado a valores de perda de capacidade física e risco de quedas. Verifica-se que a perda de independência para realização das AVD instrumentais dos pacientes é muito maior do que o declínio físico e cognitivo avaliado objetivamente nas três fases da doença.

Capacidade funcional; demência; mobilidade; cognição


ORIGINAL ARTICLE

IInstitute of Federal University of Rio de Janeiro (IPUB/UFRJ), Brazil, Laboratory of Geriatric Neuropsychiatry and Laboratory of Neuroscience of Exercise, Gama Filho University (UGF), Brazil

IICenter for Alzheimer's Disease and related disorders, IPUB/UFRJ; Medical Science Faculty of State University of Rio de Janeiro (FCM/UERJ); National Research Council (CNPq), Brazil

IIINational School of Public Health, Oswaldo Cruz Foundation (Fiocruz), Post-graduation Program in Physical Education at UGF; Laboratory of Neuroscience of Exercise (LaNEx/UGF)

Address correspondence to

ABSTRACT

BACKGROUND: Alzheimer's disease (AD) is the most prevalent dementia, being associated with cognitive, behavioral, and functional alterations. However, clarifying the influence of the disease worsening in the decline of these functions is of major relevance.

OBJECTIVE: Compare specific cognitive functions, motor functions and activities of daily living (ADL) of AD patients in different stages of the disease.

METHODS: Cognitive and motor functions, as well as ADL of 74 AD patients (35 patients CDR1; 20 patients CDR2; 19 patients CDR3) were evaluated.

RESULTS: Motor function and independency in the ADL have presented a non-linear decline. While motor function shows a greater decline from the mild to the moderate phase, ADL present a greater decline in the severe stage of the disease.

DISCUSSION: Motor function decline is more evident in both moderate and severe stages of AD, associated with losses in physical capacity and increases in risk of falls. The patients' loss of independency to perform instrumental ADL occurs in a non-linear pattern and it is much greater than both physical and cognitive declines when these parameters are objectively evaluated in the three phases of the disease.

Keywords: Functional capacity, dementia, mobility, cognition.

Introduction

The prevalence of dementia increases as longevity rises, reaching 20% in Latin America1 and specifically 38.9% in Brazilian elderly with more than 85 years of age2. Currently, the global cost involved in the treatment of dementia represents 315 million dollars per year, with the annual cost reaching US$ 17,964.00 per patient. The progressive loss of autonomy, as well as the progressive dependence and necessity of specific care contribute for the high risk of institutionalization3. For these reasons, cognitive decline and mental diseases in ageing persons have become a major public health problem3.

Functional capacity may be defined as the ability to perform basic (BADL) and instrumental (IADL)4 activities of daily living. The IADL (most complex activities) require a better cognitive status (they are associated with self-management tasks), whereas BADL are related to self-care. Both motor function (strength, flexibility, aerobic capacity, and balance), and cognitive function (executive function, attention, and memory) influence the autonomy to perform activities of daily living (ADL). The ADL are progressively impaired in the AD patient, which increases the demand for care of family members and/or caregivers. AD patients only present impairments in BADL in the severe stage of the disease, although IADL may be impaired at all phases5.

In the earlier stages of the disease, we often find loss of episodic memory and difficulty in the acquisition of new tasks. These damages gradually evolve to other cognitive impairments, such as judgment capacity, calculus, abstract reasoning, and visuo-spatial abilities. Fluent aphasia may occur in the intermediate phases, presenting as difficulty in naming objects or choosing the right words to express an idea, as well as apraxia. In the terminal stages of the disease, some remarkable changes may be observed, such as alterations in sleep-wake cycle, behavioral changes (irritability and aggressiveness), psychotic symptoms, and inability to walk, speak and perform self-care5. The progressive deficits in explicit memory (since explicit memory is needed for the functioning of the procedural memory) theoretically explains the functional decline pattern from IADL to BADL6. The global cognitive impairment is related to the functional decline, but the executive dysfunction may explain only 17% of the variations in the IADL and 9% of the variations in the BADL in AD patients6.

Despite the linear cognitive decline in AD, loss of autonomy in the ADL does not follow the same pattern, becoming necessary to understand the features which influence the alterations caused by the worsening of the disease.

In addition to cognitive changes and impairments in ADL, motor abnormalities may also be observed in AD patients. Gait disturbances (diminished gait velocity, reduced step length, and reduced step width), decreased limb strength7, and changes in postural control may be present in the initial phases of dementia or even in the pre-clinical stage of AD. Elderly with mild cognitive impairment already present reduced balance and coordination and declined levels of physical activity, leading to increased risk of lesions, falls, and fractures8. Accordingly, 60% of elderly patients with cognitive decline suffer falls, twice more than those without impairment8. All of these changes are associated with the loss of independency and quality of life.

The aim of the present study was to compare specific cognitive functions (memory, attention, executive function, and speed processing), motor functions (dynamic balance, gait, physical fitness, and flexibility), and ADL of AD patients in different stages of the disease. Although there might be a constant decline of all evaluated functions, we expect that the impact of these detrimental changes in ADL will not occur in a linear manner.

Methods

Subjects

The sample of this cross-sectional study was composed by patients with ages ranging from 60 to 85 years, diagnosed with AD according to the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) in the three stages of the disease (mild, moderate, severe), based on the results obtained after the application of the Clinical Dementia Rating Scale (CDR). All patients have been treated in the Center for Alzheimer's disease and were taken acetylcholinesterase inhibitors (Rivastigmine and Donepezil) (Table 1).

Furthermore, the recruitment of healthy elderly subjects has been conducted through a convenience sample in order to obtain normative data to their corresponding ages. Subjects with sequel of cerebrovascular accident, comorbidities with other neurodegenerative diseases, mood disorders, use of psychoactive medication, patients unable to perform the physical tests and illiterate were excluded from the study, since these clinical conditions may be confounding factors in both motor and cognitive deficits of AD. This study was approved by the Ethics Committee of the Institute of Psychiatry of the Federal University of Rio de Janeiro, and all participants signed informed consent forms before the procedures.

Instruments

Physical evaluations, cognitive tests, and ADL assessments have been applied in the subjects of the study. All the assessments have been done on the same day and have lasted for approximately two hours, with the cognitive tests being assessed before any other evaluation. Then the functional tests and ADL assessments have been performed. The specifications of the evaluations are described below:

1. Cognitive assessment

(a) Trails A9 (ability to maintain mental engagement, visual tracking, motor skills, and operational memory), (b) digit span10 (verbal attention and operational memory), (c) Rey's test of auditory-verbal learning11 (recent memory, learning, susceptibility to interference, retention after other activities, and recognition memory), (d) CAMCOG12 (fixation memory, evocation and recognizing, language, praxis, executive function, besides the global cognitive evaluation by the Mini-Mental State Examination - MMSE), (e) clock test12 (executive function, visual, spatial, and constructive abilities, (f) verbal fluency test12 (executive function, semantic memory, and language), and (g) MMSE12.

2. Motor function assessment

(a) POMA-BR13 (balance and gait), (b) Berg14 (functional evaluation of balance performance), (c) functional reach test14 (ability in controlling the dislocation of the center of gravity on a fixed base of support), (d) timed up and go test15 - TUG (basic functional mobility), (e) modified timed up and go test - mTUG (balance and verbal fluency), and (f) sit and stand test15 (dexterity in the performance of sit and stand test, and lower limb strength).

3. ADL assessment

(a) Lawton16 (patient's ability to perform IADL), (b) Pfeffer's questionnaire17 (functionality), and (c) Katz Index18 (patient's ability to perform BADL).

These tests demonstrated high validity and interrater reliability9-18.

Statistical analysis

For the comparison among the three groups (CDR1-mild, CDR2-moderate, and CDR3-severe) an ANOVA One-way has been applied to the parametric variables and the Kruskall-Wallis test has been applied to the non-parametric data. The software SPSS® (version 15.0) was used in the statistical analysis. The significance level accepted in this study was p < 0.05. To evaluate the effect size (ES) of all groups (CDR1, CDR2 e CDR3) the Cohen's ES has been performed by the following formula: ES = M1-M2/Pooled SD; where M1 = average of a reference group of healthy elderly (age = 63 ± 3 years; education = 11 ± 5 years; MMSE = 28 ± 3 points). According to Cohen, the ES has been classified as trivial (< 0.5), moderate (0.5-0.8), or strong (> 0.8).

Results

Descriptive analysis of the sample has shown that the three groups (CDR1, CDR2 and CDR3) did not present significant differences regarding to age, duration of disease, sex, and marital status. Education has shown significant difference from CDR1 group in relation to CDR3 group (CDR1 > CDR3). As expected, MMSE results presented significant differences among the groups, where CDR1 > CDR2 > CDR3.

CDR1 group has presented better performance than CDR2 group in all cognitive tests. A significant difference in performance between CDR2 and CDR3 has also been observed (CDR1 > CDR2 > CDR3). Results of direct order digit span, reverse order digit span, and total score digit span have presented significant differences in verbal attention, speed processing, operational memory, and executive function in CDR1 group when compared to both CDR2 and CDR3 groups, showing that CDR1 patients have better performance than the other two groups. There were no significant differences in Trails A test. These data are represented in table 2.

The results of physical capacity assessments pointed out to an important performance decrease in the CDR2 group (Table 3). Significant differences were found in Berg Scale, modified time up and go test, sit-and-stand test, total POMA, POMA gait and POMA (balance and functional reach) when CDR1 group was compared to both CDR2 and CDR3 groups.

With the worsening of symptoms, autonomy in BADL and IADL has been significantly inferior. Katz scale has showed significant difference in independence levels in both CDR1 and CDR2 groups compared to CDR3, because of the better performance of these first two groups. Table 3 shows the results of ADL.

There has been a large effect size (ES > 0.8) in the decline of basic and instrumental activities of daily living at all stages of AD. This behavior was increasing and linear according to the worsening of the disease (CDR1 < CDR2 < CDR3). However, the ES was much more expressive in the evaluation of independency in IADL of AD patients, showing ES values greater than 7.0 to these activities. ES values of cognitive function, motor function and ADL are represented in the figures 1, 2, and 3 .



Discussion

This study sought to investigate the alterations in motor and cognitive function, and ADL in AD patients in the three stages of the disease. The most relevant finding of the present investigation was the fact that the greatest motor decline occurred in the moderate and severe phases compared to the mild stage of AD. Despite the fact that decline in motor, cognitive, and functional capacities may be observed since the beginning of AD, this decline does not occur uniformly in the different stages of the disease. The loss of independence of the patients to manage ADL is not consistent with the physical and cognitive decline observed by the physical and neuropsychological tests.

As expected, cognitive function has showed a continuous decline with the evolution of the disease. However, the same behavior could not be seen in motor function. In the present study, the greater impairment has been observed between the mild and moderate phases in this domain. CDR1 patients have presented motor function similar to that expected to healthy elderly. This finding is in accordance with the literature, once studies have been showing that the risk of fall is similar in AD patients and healthy elderly in the mild stage of the disease. However, motor processes regulated by complex cortical mechanisms (such as sitting and rising from a chair) may be affected in both mild and moderate AD stages, predisposing patients to the risk of falls19. In the present investigation, moderate and severe AD patients have been at risk for functional loss and falls, much greater than expected to healthy elderly, in the Senior Fitness Test, and in Berg and POMA scales. Changes in motor function in AD may occur because of use of psychotropic drugs, extrapyramidal signs, myoclonus, and frontal gait, raising the risk of falls, institutionalization, and death in this population20.

In the present study, ADL impairment has occurred in a different manner when compared to cognitive decline and motor function. Despite IADL have declined since the initial phases, BADL have declined only in the severe stage of the disease. This finding is in accordance with the literature, since studies have been demonstrating that patients present decline in IADL performance in the mild stage of AD, and impairment in BADL only becomes posteriorly21. In the initial stage of AD, patients were able to perform BADL22, presen­ting impaired capacity in such activities in more severe stages of the disease23 This decline in BADL is not evident until moderate and severe stages7. Moreover, deficits in BADL may develop for more than one decade24.

In the severe phase, patients may completely lose the ability to perform IADL, although functional decline may be observed since the initial stages of AD23. Declines in IADL and BADL may overlap during moderate and severe stages of the disease4 AD patients suffer a progressive loss in the abilities to live independently because of cognitive impairment and poor memory functioning25. While both BADL and IADL are affected in AD, IADL are the first ones to decline. Basically, functional impairment is the distinction point between AD and mild cognitive impairment22.

A follow up study including 107 AD patients who have been evaluated at baseline, 6 months, and 12 months later showed that patients did not present deficits in BADL even in the presence of severe cognitive impairment, whereas IADL were affected in the initial phase of the disease26. Another study with a sample of 34 AD patients who were evaluated at baseline, 18 months, and 24 months later has found a strong relationship between cognition and IADL in the initial stages of AD. Such association becomes weaker as the disease progresses, increasing the association with psychiatric symptoms27.

There seems to be a stronger relationship between IADL results and cognitive performance than between BADL and cognitive function22. As IADL require a more complex neuropsychological organization, such activities are much more vulnerable in the early stages of cognitive decline4. Theoretically, the progression of the deficit from explicit memory to procedure memory explains the earlier declines in IADL and, later, in BADL. The decline in IADL takes place when the episodic memory deficit becomes apparent, since this type of memory is of major importance in the performance of such activities. The procedure memory keeps its normal until the later stages of AD, making the BADL preserved until the later stages of the disease28.

On the other hand, a novel finding in this study was the large size effect observed between CDR2 and CDR3 for ADL (ES > 0,8). Although all functions are impaired in the physical and cognitive assessments in the three stages of the disease, the independence in IADL is not altered the same way. We have observed a greater decline in ADL than in motor and cognitive functions. This may be associated with the fact that the caregiver might underestimate or overestimate the patient's capacity in realizing ADL. Another possibility could be the lack of sensibility of the physical and neuropsychological tests to determine the real limitations of the patients for the necessities presented in daily living, in both basic and instrumental activities.

The findings of the present study are of major relevance, since they allow the identification of cognitive decline, motor impairment, and functional prejudice in each stage of AD, helping to develop strategies for prevention and treatment of disease.

Exercise may be used as a preventive strategy, since studies shown that its regular practice is of great importance in maintaining balance, strength, and cognition in AD patients29,30. Furthermore, exercise is associated with lower prevalence and incidence of dementia (32%), as well as cognitive decline30. Studies demonstrate that general

exercise programs (endurance, mobility, and coordination) may slow down the deterioration in ADL performance, significantly increase global functional capacity, and raise the ability to perform ADL independently29.

Some limitations must be considered in the present investigation. Because it is a cross-sectional study, one may not establish a cause-effect relationship among the disease staging and cognitive impairment, functional decline, and motor changes. In addition, the sample size may have influenced the results.

In summary, this study showed a linear decline in all global cognitive functions and increased motor decline occurring bet­ween mild and moderate stages of AD. Regarding ADL, a non-linear decline could be observed, being more evident in the moderate and severe phases of the disease. We found that the loss of independence in carrying out IADL of patients is much larger than the physical and cognitive decline as objectively assessed in moderate and severe stages of the disease.

References

  • 1. Nitrini R. Dementia in the developing world. Dement Neuropsychol. 2009;3:1.
  • 2. Herrera E, Caramelli P, Silveira ASB, Nitrini R. Epidemiologic survey of dementia in a community-dwelling Brazilian population. Alzheimer Dis Assoc Disord. 2002;16:103-8.
  • 3. Gorzoni ML, Pires SL. Aspectos clínicos da demência senil em instituições asilares. Rev Psiq Clín. 2006;33(1):18-23.
  • 4. Niegovan V, Hing MM, Mitchell SL, Molnar FJ. The hierarchy of functional loss associated with cognitive decline in older persons. J Gerontol A Biol Sci Med Sci. 2001;56:638-43.
  • 5. Neto JG, Tamelini MG, Forlenza OV. Diagnóstico diferencial das demências. Rev Psiq Clín. 2005;32(3):119-30.
  • 6. Boyle PA, Malloy PF, Salloway S, Cahn-Weiner DA, Cohen R, Cummings JL. Executive dysfunction and apathy predict functional impairment in Alzheimer disease. Am J Geriatr Psychiatry. 2003;11:214-21.
  • 7. Scherder E, Eggermont L, Swaab D, Heuvelenet MV, Kamsma Y, Greef M, et al. Gait in ageing and associated dementias; its relationship with cognition. Neurosci Biobehav Rev. 2006;31:485-97.
  • 8. Davis JC, Hsiung GYR, Ambrose TL. Challenges moving forward with economic evaluations of exercise intervention strategies aimed at combating cognitive impairment and dementia. Br J Sports Med. 2011;45:470-2.
  • 9. Ashendorf L, Jefferson AL, O'Cannor MK, Chaisson C, Green RC, Stern RA.Trail making test errors in normal aging, mild cognitive impairment, and dementia. Arch Clin Neuropsychol. 2008;23:129-37.
  • 10. Lezak MD. Neuropsychological assessment. New York: Oxford University Press; 1995.
  • 11. Paula JJ, Melo LPC, Nicolato R, Moraes EN, Bicalho MA, Hamdan AC, et al. Fidedignidade e validade de constructo do Teste de Aprendizagem Auditivo-Verbal de Rey em idosos brasileiros. Rev Psiq Clín. 2012;39(1):19-23.
  • 12. Bottino CM, Almeida OP, Tamai S, Forlenza OV, Scalco MZ, Carvalho IAM, et al. Entrevista estruturada para o diagnóstico de transtornos mentais em idosos - CAMDEX - The Cambridge examination for mental disorders of the elderly. Brazilian version (translated and adapted on behalf of the editors). Cambridge University Press; 1999.
  • 13. Gomes GC. Tradução, adaptação transcultural e exame das propriedades de medida da escala "Performance Oriented Mobility Assessment" (POMA) para uma amostragem de idosos brasileiros institucionalizados [dissertação]. Universidade Estadual de Campinas; 2003.
  • 14. Miyamoto ST, Junior IL, Berg KO, Ramos LR, Natour J. Brazilian version of the Berg balance scale. Braz J Med Biol Res. 2004;37:1411-21.
  • 15. Rikli RE, Jones CJ. Senior fitness manual. Champaign: Human Kinetics; 2001.
  • 16. Lawton MP, Brody EM. Assessment of older people: self maintaining and instrumental activities of daily living. Gerontologist. 1969;9:179-86.
  • 17. Pfeffer RI, Kurosaki TT, Harrah CH, Chance JM, Filos S. Measurement of functional activities in older adults in the community. J Gerontol. 1982;37:323-9.
  • 18. Katz S, Downs TD, Cash HR, Grotz RC. Progress in the development of the index of ADL. Gerontologist. 1970;1:20-30.
  • 19. Kato EM, Radonovic M, Caramelli P, Brucki SM, Nitrini R. Evaluation of the balance control in Alzheimer disease. Arq Neuropsiquiatr. 2005;63:110.
  • 20. Camicioli R, Bouchard T, Licis L. Dual tasks and walking fast: relationship to extra-pyramidal sings in advanced Alzheimer's disease. J Neurol Sci. 2006;248:205-9.
  • 21. Holtzer R, Wegesin DJ, Albert SM, Marder K, Bell K, Albert M, et al. The rate of cognitive decline and risk of reaching clinical milestones in Alzheimer disease. Arch Neurol. 2003;60:1137-42.
  • 22. Hall JR, Vo HT, Johnson LA, Barber RC, O'Bryant SE. The link between cognitive measures and ADLs and IADL functioning in mild Alzheimer's: what has gender got to do with it? Int J Alzheimer's Dis. 2011;2011:1-6.
  • 23. Geen CR, Mohs RC, Schmeidler J, Aryan M, Davis KL. Functional decline in Alzheimer's disease: a longitudinal study. J Am Geriatr Soc. 1993;41:654-61.
  • 24. Stern Y, Liu X, Albert M, Brandt J, Jacob DM, Del Castillo-Castaneda C, et al. Application of a growth curve approach to modeling the progression of Alzheimer's disease. J Gerontol A Biolog Sci Med Sci. 1996;51:179-84.
  • 25. Tekin S, Fairbanks A, Connor SO, Rosenberg S, Cummings JL. Activities of daily living in Alzheimer's disease: neuropsychiatric, cognitive and medical illness influences. Am J Geriatr Psychiatry. 2001;9:81-6.
  • 26. Suh GH, Ju YS, Yeon BK, Shah A. A longitudinal study of Alzheimer's disease: rates of cognitive and functional decline. Int J Geriatr Psychiatry. 2004;19:817-24.
  • 27. Monaci L, Morris RG. Neuropsychological screening performance and the association with activities of daily living and instrumental activities of daily living in dementia: baseline and 18-to 24-month follow-up. Int J Geriatr Psychiatry. 2011;27:197-204.
  • 28. Zantte O, Binetti G, Magni E, Rozzini L, Biachetti A, Trabucchi M. Procedural memory stimulation in Alzheimer's disease: impact of the training programme. Acta Neurol Scand. 1997;95:152-7.
  • 29. Arcoverde C, Andrea D, Araújo N, Laks J. Ejercicio físico y demencia mixta: un caso clínico. Psicogeriatria. 2011;3:93-6.
  • 30. Larson EB, Wang L, Bowen JD. Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Ann Intern Med. 2006;144:73-81.
  • Motor and functional changes in different stages of Alzheimer's disease

    Melissa ZidanI; Cynthia ArcoverdeI; Narahana Bom de AraújoI; Paulo VasquesI; Alexandre RiosI; Jerson LaksII; Andrea DeslandesIII
  • Publication Dates

    • Publication in this collection
      14 Nov 2012
    • Date of issue
      2012

    History

    • Received
      30 Jan 2012
    • Accepted
      12 Sept 2012
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