Outcome measures for adults with Down Syndrome based on the International Classification of Functioning, Disability, and Health Model: A Systematic Review

Introduction: Adults with Down syndrome (DS) have functional disabilities due to the extra presence of chromosome 21. Objective: To identify the functionality and disability assessment instruments used in research involving adults with DS and associate them with the components of the International Classification of Functioning (ICF). Methods: Two independent researchers analyzed articles from PubMed, Lilacs, Scielo, Science Direct, and Cochrane databases, including cross-sectional and clinical studies whose results involved functionality and disability for individuals with DS (≥18 years), with no publication date limit for the studies. The methodological quality of the studies was analyzed by the Downs & Black Checklist; descriptive analysis was used for the results. This review was registered in PROSPERO (CRD42021234012). Results: 15 articles were analyzed in which 48 instruments were identified for the assessment of adults with DS (36.42±10.62 years); the quality of the articles was considered "good". Of these 48 instruments, 41 were associated with bodily function, 5 instruments were associated with the activity component, one instrument was associated with social participation and one instrument was associated with the environment. Conclusion: Of the 48 instruments identified to assess adults with DS, most were for the Body Function and Structure component; only the 6MWT and CAMDEX-SD have been validated for this population. LIFE-H and MQE were used to assess Social Participation and the Environment, but they cannot be considered dependable, as they have not been confirmed for individuals with DS.


Selection of Articles and Criteria for Inclusion and Exclusion
The abstracts were selected and later read in full, using the following inclusion criteria: 1) articles dealing with DS subjects over 18 years old; 2) articles using assessment instruments or measures related to the ICF biopsychosocial model; 3) articles from crosssectional studies and clinical trials.
After reading them in full, articles were excluded according to the following exclusion criteria: articles that had individuals other than DS adults.Mendeley Desktop software was used to organize selected articles and control bibliographic references.

Data Extraction
The two independent reviewers systematically extracted data from each study and reached a consensus on all items.The information extracted included author and year of publication, sample (number of participants), instruments for measuring Functioning and Disability found in the review, and the frequency with which they appeared (Table 1).The measuring instruments were associated with the ICF's components, following the WHO manual 5 (Table 2).Descriptive analysis was used to tabulate the results.

Quality of article methodology
To assess methodological quality, the Downs & Black Checklist 6 was used (Table 2).This checklist is composed of 27 questions divided into five domains: study quality (ten https://doi.org/10.7322/abcshs.2021292.2015items); external validity (three items); internal validity (seven items); confounding/ selection bias (six items), and sample power (one item).The maximum score achieved in this checklist is 32 points.Item 27 was modified from how it is used in other studies 7,8 , in which the original score would be assigned from 0 to 5 points.This was modified to a score from 0 to 1 point.Thus, a score of 1 was used, if the article had a power calculation or a sample calculation and 0 if the article had none of these calculations.After this modification, the checklist had total scores ranging from 0 to 28 points.Each article received a rating of "excellent" (24-28 points), "good" (19-23), "fair" (14-18) or "poor" (<14 points).

RESULTS
A total of 741 articles were found in the databases, and three more were added that had not been found in the data search (they were found in the references of the selected articles), totaling 744 articles.After reading the title and abstract, 650 were excluded, leaving 91 to be read in full.After reading, 76 articles were excluded, as the research subjects were not exclusively DS adults' diagnoses.Therefore, 15 articles were considered for this review, as shown in the flowchart (Figure 1).Among the components found in the articles, 85% are associated with Body Function, which was the most found component, followed by Activity with 11%; 2% referred to the Participation and Environment components.The mean age of the DS population in the selected articles was 36.42 ± 10.62 years old.
Table 1 shows the 48 assessment instruments for DS individuals associated with the ICF model and the frequency with which they appeared in the study.Tests less frequently associated with Body Function were the Hand Grip Test used to assess upper limb muscle strength, the Sit and Reach Test which assesses the flexibility of upper limbs, Isometric flexion to assess upper limb muscle strength, standing with onefoot support and walking along a straight line on the floor, both to assess balance, and Timed Up and Go (TUG) and 8-Foot Up and Go, both to assess functional mobility associated with the Activities component.Table 2 shows the studies analyzed and their respective assessment instruments for DS adults and their respective links with IFC's components.
Of these 48 instruments, forty-one were related to the Body Function component, five related to activity, one related to participation, and one instrument related to the Environmental component (Figure 2).
Six instruments were used to assess muscle strength, being the Hand Grip Test 43 , Bent Arm Hang 44 , Isometric Flexion 45 , Abdominal 46 , Sit-up Test from a chair 47 , and Lower Limb Explosive Strength 48 .Two instruments aimed to assess flexibility, are the Sit and Reach test for lower limbs 49 and the Reach behind the back for upper limbs 50 , Similarly, both tests may be related to the Activities Component.An instrument was used to evaluate upper limb motor coordination via the Finger-Nose Test 51 another for cardiorespiratory assessment, the Shuttle Test 52 , the 6MWT was used for aerobic and cardiorespiratory Functional Capacity 53 , for Motor coordination, and the Developmental Behavior Checklist -Adult Version (DBC-A) 54 was used for measures emotional and behavioral problems and was developed specifically for use with adults with intellectual and/or developmental disability.https://doi.org/10.7322/abcshs.2021292.2015Three instruments were used to assess Balance, namely standing with single-legged support (10s) 49 walking along a straight line on the floor 49 , and the Flamingo Balance Test 44 .These tests can also be related to the Activities Component.
Of the five instruments that addressed the Activity component, two were used to assess Functional Mobilitythe TUG 44 and 8-Foot Up and Go tests 50 .The Bruininks-Oseretsky Test of Motor Proficiency First Edition 49 was used to assess motor proficiency; the Index of Social Competence (ISC) 52 was used to measure domains of communication, self-care, and community skills; and the Plate Tapping test to evaluate the speed and reaction of the upper limbs 44 .
To assess Social Participation, the Assessment of Life Habits (Life-H) questionnaire 53 was used, and as was the Measure of the Quality of the Environment (MQE) to assess the Environmental component 54

DISCUSSION
The objective of this review was to identify the instruments to assess functionality and disability for DS used in scientific research and report them to the biopsychosocial model of the ICF.
We identified 48 instruments, and variables, to assess the functionality and disability of DS adults, however, we cannot say that these instruments are dependable for this population, since only two instruments, the CAMDEX-DS, and the 6MWT, have been validated for them.

Among the tests associated with Body Function and Structure, the Sit and Stand
Test used in 3 studies 9,16,17 was validated to assess the lower limb muscle strength of elderly people living in the community 51 .It was later validated for older people, showing the difference between genders, with an excellent reliability index (0.84) for men and (0.92) https://doi.org/10.7322/abcshs.2021292.2015for women 45 .In DS adults, it was used by Terblanche and Boer 17 , and reproducibility was evaluated later, achieving an excellent reliability 16 index of 0.99.
Among the tests associated with Body Function and Structure, the Sit and Stand Test used in 3 studies 9,16,17 was validated to assess the lower limb muscle strength of older people living in the community 51 .It was later validated for them, showing the difference between genders, with an excellent reliability index (0.84) for men and (0.92) for women 45 .
In DS adults, it was used by Terblanche and Boer 17 , and reproducibility was evaluated later, achieving an excellent reliability 6 index of 0.99 16 .
The Handgrip Test, used in two studies, was validated to assess upper limb muscle strength for adults with intellectual disabilities 55 , having an excellent reliability index (0.94).It was applied to older people in the community and had an excellent reliability index (0.99) 43 .It was used for DS adults by Terblanche and Boer 17 , to assess physical fitness.Boer and Moss 16 verified its reliability index, which was excellent (0.98).
Isometric Flexion was used in a study to assess upper-body muscle strength and has been validated for healthy adults 44 .It was applied to adolescents with Intellectual Disabilities, with an excellent reliability index (0.98) 55 .In DS adults, the test was used by Terblanche and Boer 17 , and its reproducibility was evaluated, achieving an excellent reliability index (0.99).
The One Foot Support Balance was used in two studies and was validated for older people by Lin et al. 56 .It was applied to adolescents with intellectual disabilities and achieved an excellent reliability index of 0.99 49 .It was also used to assess the physical fitness of DS adults 17 and later had its reproducibility tested 16 , having an excellent reliability index of 0.98 for the lower left limbs and 0.93 for the right lower limb.
The dynamic balance used in the two studies had an excellent reliability index (0.99) for individuals with intellectual disabilities 55 .It was used by Terblanche and Boer 17 https://doi.org/10.7322/abcshs.2021292.2015 in DS adults; reproducibility was evaluated later 16 , achieving an excellent reliability index (0.93).
The ICF defines balance as a component of body function in Chapter 2, "Sensory Functions and Pain", specifically cited by code b235, "Vestibular Function", which includes "Inner ear sensory functions related to position, balance, and movement" 5 .
Chapter 1, Mental Functions of the ICF, broadly encompasses several possibilities for cognitive assessment in a more global manner ranging from orientation, awareness, intellectual, sleep, temperament, and personality to more specific functions such as memory, attention, and emotion 5 .Thus, there are several ways to assess an individual's cognitive function, as seen in this review.Camdex-DS is a version of Camdex that was adapted for DS individuals in the United Kingdom 19 .It was also adapted and validated for the DS Brazilians 18 , being considered the first study to validate an instrument for detecting The WAIS IV 28 was created to assess the intellectual capacity of individuals aged https://doi.org/10.7322/abcshs.2021292.2015brain injury 56,57 and was later validated for adolescents with Down Syndrome 58 .Despite having been used in DS individuals, the test has not been validated for them.
The Neuropsychological Inventory (NPI) 30 is a questionnaire to assess neuropsychiatric symptoms in dementia.It has been validated in Brazilian Portuguese 59 .
Although it was used in the study 12 for DS adults, its validation and reproducibility have not been evaluated for this group.
The Arizona Cognitive Test Battery (ACTB) 35 was initially developed and validated for a neurocognitive assessment of DS in patients aged 7-38 years.It was later validated for older DS people over 45 years of age 15 .ACTB is a battery of tests that include several questionnaires that measure spatial associative memory, set-shifting, inhibitory control and working memory, cerebellar function, motor sequencing, visuomotor tracking, and hand coordination-eye.
The Eurofit Battery was found in only one study and the tests used are found in the Body Function component, being the Flamingo Balance Test, which is in Chapter 2 cited by code b235, "Vestibular Functions" related to balance and movement; Bent Arm test, which belongs to Chapter 7, cited by code b740, "Functions Related to Muscular Endurance"; the Plate Tapping Test belongs to chapter 1, "Mental Functions", code b1470, Psychomotor Control", which controls the motor and psychological response time.These tests were taken from the Eurofit Test Battery created for healthy adults by Oja and Tuxworth 44 and were used in the study 9 to assess DS adults.The Eurofit battery was used to assess the physical fitness of individuals with Intellectual Disabilities and has an excellent reliability 60 index (0.94).
Regarding the activity component, the most evaluated domain refers to mobility (chapter 4 of the activities and participation component).The ICF describes mobility as the movement that occurs when there is a change in the position or location of the body, that https://doi.org/10.7322/abcshs.2021292.2015is, a change from one place to another when walking, running, or going up and down, and when using various forms of transport.Therefore, the ICF determines mobility as a component of Activities 5 .Standing out among the instruments identified for this purpose are the Reach Behind Back Test, TUD, and 8-Foot Up and Go.
The Reaching Behind the Back Test aims to assess flexibility and can be associated with both the Body Structure and Activity components.The test was validated for older people living in the community 51 and for adolescents with intellectual disabilities 55 .In DS adults, the test was applied by Terblanche and Boer 17 , and its reproducibility was later evaluated by Boer and Moss 16 with an excellent reliability index of 0.99 for the left lower limb and 0.93 for the right lower limb.
The TUG and 8-foot Up and Go tests to assess mobility are cited in the ICF book by code D460 "Walking and Moving, Others Specified and Unspecified".The test was validated for frail older adults 50 .In DS adults, the test was applied by Terblanche and Boer 17 , and its reproducibility was evaluated later by Boer and Moss 16 , with an excellent reliability index (0.94).Disabilities 49 , both with an excellent reliability index (0.99).Despite not having been validated for DS, it was used to assess the motor performance of both children with and without DS 62 .

The Bruininks-Oseretsky
The Participation Component is linked to Activities in the ICF book, which is defined as the individual's involvement in a real-life situation 5 .The Assessment of Life https://doi.org/10.7322/abcshs.2021292.2015 Habits (Life-H) was created to be an instrument for measuring social participation 35 .It is a questionnaire that encompasses all the chapters of the ICF's Activity and Participation Component.LIFE-H was used in older people 63 with disabilities with an excellent reliability index (0.98).In SD individuals, it had a high-reliability 20 index (0.89).
The Measure of the Quality of the Environment (MQE) is a questionnaire that measures individuals' perception of their physical and social environment 54 and encompasses the entire Environmental Component of the ICF book 5 .In Stroke, it presented a good reliability 64 index (0.88).In individuals with DS, it presented an excellent reliability index (0.89) 20 .
The study by Foley et al. 20 using the Life-H that assesses social participation and Measure of the Quality of the Environment (MQE) that assesses the Environment, representing the Participation components and Environment, respectively, was analyzed and entered into this review.Despite not meeting the inclusion criteria for presenting a sample of individuals aged 16 years and over, it was considered significant for this analysis as more than 75% of the sample of DS individuals in this study were over 21 years of age.This review found that the most evaluated component was Body Function, specifically Mental Function since Intellectual Disability is one of the most common characteristics in DS 19 .However, this still shows that there is a great lack of assessment methods linked to the Participation and Environmental component, and this gap may be linked to the biomedical model that has only the diagnosis in mind, as it does not consider social factors 5 .
The ICF encompasses more than 1400 categories that are divided into four components 5 , thus making the classification system almost impossible to use in clinical practice.In this sense, there was a need to create Core Sets.These gather information https://doi.org/10.7322/abcshs.2021292.2015beforehand and prioritize serving a specific population, thus making use of the ICF through Core Sets an applicable tool in clinical practice 65 .
Currently, there are Core sets for several health conditions, such as lower back pain 65 , ischemic heart disease 66 , and depression 67 , among others.However, there are still no Core Sets for individuals with DS; nevertheless, there are Core Sets focused on rehabilitation, which include individuals with limitations or restrictions related to health 68 , that can be used for the DS population.
The methodological assessment of the quality of the twelve studies found two studies 14,19 with the lowest score classified as "fair" and one 12 with the highest score being considered a "good" study.The quality criteria with the lowest scores were not describing the sample size or power calculation, not reporting if there were losses, and not reporting adverse events.
The importance of validating instruments for DS adults is highlighted, not only for use in the scientific environment but also for use in clinical practice, since they are extremely important instruments for conducting intervention programs and improving their quality of life.

Limitations of the review
The limitations seen in this review include the lack of homogeneity in the studies.Many were excluded for not evaluating only DS adults.Even though their characteristics persist into adulthood, the separation of this sample into children and adults is necessary since there are other clinical manifestations in the adult phase, different from the pediatric ones.This causes a lack of homogeneity in the studies, few selectable studies, and does not exclude studies with low methodological quality.https://doi.org/10.7322/abcshs.2021292.2015

Conclusion
We found 48 instruments used to assess DS adults, however, only two of these were validated for this population, namely the 6MWT, which assesses functional capacity, and the CAMDEX-SD, which assesses cognition.
The 48 instruments are still used in the biomedical model, since there are many more instruments focused on the assessment of Body Function and Structure, with the main component for cognition.Only one instrument was used to assess the social environment, however, it has not been validated for this population, so we cannot guarantee that it is a reliable instrument for them.https://doi.org/10.7322/abcshs.2021292.2015 https://doi.org/10.7322/abcshs.2021292.2015(Outcomes Assessment)).Lilacs: Down Syndrome AND Adult AND Outcome Measure; Cochrane: (Down Syndrome) AND (Adult) AND (International Classification of Functioning, Disability, and Health); Scielo: Down Syndrome AND Adult AND Outcome Measure and Science Direct: Down Syndrome AND Adult AND Outcome Measure.
Alzheimer's disease and the cognitive decline of DS individuals in Brazil.It is an important instrument as DS patients present aging, premature cognitive decline, and early diagnosis of Alzheimer's Disease 3 .The Cambridge Cognitive Examination adapted for DS individuals (CAMCOG-DS) is a concise group of neuropsychological tests included in the CAMDEX-DS.It was also adapted and validated for the DS Brazilians 18 .DAMES24 is a questionnaire that assesses the cognition and function of Alzheimer's disease.It was used in the study byHanney et al. 11  to assess the cognitive function of DS adults, although it has not been validated for them.RADD is a test battery that was created to assess the cognition of individuals with Intellectual Disabilities27 .It was used to assess cognition and dementia in DS adults living in California and was also used in the study byHanney et al. 11  of DS adults.
Test of Motor Proficiency, Second Edition 61 an assessment of course and fine motor control, found in Chapter 4 of the Activities and Participation component, cited by code d440, "Fine Motor Skills of the Hand".The test battery was initially designed to assess individuals from 4 to 21 years of age, which was revised between 2002-2005.The test was validated for children with Intellectual

Figure 2 :Down
Figure 2: Frequency of instruments associated with ICF components.

Table
1 that the most frequently used tests are associated with Body Function, namely, the 6-minute Walk Test (6MWT) used to assess cardiorespiratory and https://doi.org/10.7322/abcshs.2021292.2015aerobic functional capacity, the Sit and Stand Test which evaluates muscle strength of the lower limbs, the Sit and Reach Test to assess the flexibility of the lower limbs, and the Shuttle Test that assesses cardiorespiratory capacity.
, the Cambridge Examination for Mental

Table 1 :
Measure of the Quality of the Environment (MQE) https://doi.org/10.7322/abcshs.2021292.2015Figure 3: International Classification of Functioning, Disability and Health (ICF) framework.Clinical Global Impression of Change scale (DAMES); Adaptive behavior scale (ABS); The Cambridge Examination for Mental Disorders of Older People with Down's syndrome and Others with Intellectual Disabilities (CAMDEX-DS); The Rapid Assessment for Developmental Disabilities -Second Edition (RADD-2); The Cognitive Drug Research (CDR); The Block Design subtest of the Wechsler Adult Intelligence Scale IV (WAIS-IV); Cambridge Cognitive Examination (CAMCOG); Rivermead Behavioral Memory Test (RBMT); Fuld Object Memory Evaluation (FOME); Cambridge Cognitive Examination for Older Adults with Down Syndrome (CAMCOG-DS) ; modified Cued Recall Test (mCRT); The Vineland Adaptive Behavior Scales, Second Edition (VABS-II); Neuropsychiatric Inventory (NPI); Vineland Adaptive Behavior Scales (VABS); The Dementia Questionnaire for Mentally Retarded Persons (DMR); The Severe Impairment Battery (SIB); Test of Problem Solving (TOPS); Clinical Evaluation of Language Fundamentals Revised (CELF-R); The Arizona Cognitive Test Battery (ACTB);Cambridge Neuropsychological Test Automated Battery (CANTAB);Dementia questionnaire for people with Learning Disabilities (DLD);The Behavior Rating Inventory for Executive Function (BRIEF-Parent Form);NAID Object Memory, NAID Memory for Sentences; Assessment of Life Habits (LIFE-H; Measure of the Quality of the Environment (MQE).https://doi.org/10.7322/abcshs.2021292.2015Outcome of the Instruments that Assess Functioning and Disability in Adults with Syndrome.

Table 2 :
Description of Assessment Measures in Adults with Down Syndrome and Correlation with ICF Components