Introduction Due to the progressive aging of the population, there is increasing concern and interest on age-related disorders, with the aim of promoting as much autonomy and quality of life as possible in the elderly. The concept of activities of daily living (ADL) as an expression of the functional state was introduced by Katz (1) and developed by Lawton, who proposed dividing ADL in basic activities (BADL), such as eating, taking care of the hygiene, using the bathroom or getting dressed; and instrumental activities (IADL), more demanding in terms of cognitive function, such as shopping, handling money, cooking, housekeeping and using the telephone (2). These abilities of daily living define how independently people live. They rely on cognitive functions like memory and attention, but also on automatic procedures (procedural memory), strengthened by habits and routines that often guarantee some level of independence, despite eventual progressive cognitive impairments (3). More recently, the concept of complex activities of daily living (CADL) was developed, which involves superior cognitive functions, translated in activities like the ability to maintain a job, travel and plan travelling, participate in groups or community movements, drive, plan events or play games (4). Functional evaluation is sensitive to slight changes in cognition, namely memory, attention and executive functions that may not be easily identified through routine neuropsychological testing (5) but play an important role in the early difficulties that patients experience in their real life context. Thus, even slight changes in cognitive function may be sufficient to produce gradual loss of CADL and subsequently IADL (3, 6, 7). The concept of Mild Cognitive Impairment (MCI) has evolved in the last decade to characterize a transitional state between normal cognitive aging and dementia. Patients with MCI have cognitive complaints and objective impairment in memory and/or other cognitive domains, without major repercussions in daily life, and are not demented (8). MCI is a condition that often progresses to dementia; in particular, amnestic MCI is frequently an incipient stage of Alzheimer’s disease (AD) (9). Thus, diagnosis of MCI may lead to an adequate early intervention allowing patients and families to do a more appropriate long term planning of their lives (10). One of the requisites in the original MCI diagnosis criteria is maintenance of normal activities of daily living (8). According to a recent revision of these criteria, patients should have no difficulties with BADL, but can have slight impairments in IADL and CADL (11). It is presently recognized that keeping the absence of impairment in all activities of daily living as a diagnostic criteria would probably be too restrictive, resulting in an underestimation of the MCI prevalence (3, 12) and hindering the ability to predict dementia (5). Several studies have shown a significantly higher frequency of functional impairment in patients with MCI when compared to the normal FUNCTIONAL EVALUATION DISTINGUISHES MCI PATIENTS FROM HEALTHY ELDERLY PEOPLE - THE ADCS/MCI/ADL SCALE H. PEDROSA 1 , A. DE SA 2 , M. GUERREIRO 1,3 , J. MAROCO 4 , M.R. SIMOES 5 , D. GALASKO 6 , A. DE MENDONCA 1,7 1. Dementia Clinics, Institute of Molecular Medicine and Faculty of Medicine of Lisbon, Lisbon, Portugal; 2. Neurology Clinics, Hospital of Santo André, Leiria, Portugal; 3. Laboratory of Language, Institute of Molecular Medicine and Faculty of Medicine of Lisbon, Lisbon, Portugal; 4. Superior Institute of Applied Psychology, Lisbon, Portugal; 5. Psychological Assessment Service, Faculty of Psychology and Educational Sciences of the University of Coimbra, Coimbra, Portugal; 6. Department of Neurosciences, University of California, San Diego, US; 7. Laboratory of Neurosciences, Institute of Molecular Medicine and Faculty of Medicine of Lisbon, Lisbon, Portugal. Corresponding author and reprint requests: Alexandre de Mendonça, Laboratory of Neurosciences, Institute of Molecular Medicine, Av Prof Egas Moniz, 1649-028 Lisbon, Portugal, Telephone 351217985183, Telefax, 351217999454, mendonca@fm.ul.pt Abstract: Patients with MCI may present minor impairments in activities of daily living (ADL). The main objective of this work was to evaluate the ability of two versions of the Alzheimer's Disease Cooperative Study / Activities of Daily Living scale adapted for MCI patients (ADCS/MCI/ADL18 and ADCS/MCI/ADL24) to distinguish patients with MCI from healthy control subjects. Participants were 60 years or older and community dwelling: 31 control subjects, 30 aMCI patients and 33 AD patients. A protocol of neuropsychological tests, global evaluation scales, functional scales, and depressive symptoms assessment was used. Activities of balancing the cheque book, using a telephone, going shopping, taking medication regularly, finding objects, talking about current events, watching television, initiating complex activities, keeping appointments or meetings, reading, getting around outside the home and driving a car were impaired in aMCI patients. The ADCS/MCI/ADL24 scale was better than the ADCS/MCI/ADL18 scale in distinguishing aMCI patients from healthy controls (sensitivity=0.87, specificity=0.87, ROC c=0.887, cut-off point=52/53). The detection of initial functional changes with appropriate scales may contribute to the early diagnosis of MCI and the development of targeted interventions to improve everyday function or prolong independence. Key words: Mild Cognitive Impairment, functional evaluation, activities of daily living, ADCS/MCI/ADL, Alzheimer’s disease. 703 The Journal of Nutrition, Health & Aging© Volume 14, Number 8, 2010 JNHA: CLINICAL TRIALS AND AGING Received August 19, 2009 Accepted for publication December 7, 2009 704 The Journal of Nutrition, Health & Aging© Volume 14, Number 8, 2010 FUNCTIONAL EVALUATION IN MCI population (3, 5, 6, 13, 14). In the PAQUID project (5), those patients with MCI who presented impairment in IADL had greater probability to progress to dementia, and less chances of going back to normality after 2 years, when compared to patients with MCI but without functional impairment. Despite the value of complementing neuropsychological evaluation with functional measures in MCI patients, there are still no recommended instruments, reference values or objective orientations regarding the degree of ADL impairment in this population (3, 5, 12). In fact, most available instruments were usually designed to evaluate people with dementia, and are not sensitive enough to detect changes in patients in the initial phases of cognitive decline, like MCI patients (10, 11, 14-16). The development and generalization of new instruments designed to evaluate daily function in subjects with MCI would allow a detailed characterization of the ADL changes in these patients and possibly, when added to the neuropsychological evaluation, lead to a more accurate diagnosis of the condition. The Alzheimer's Disease Cooperative Study / Activities of Daily Living scale for MCI patients (ADCS/MCI/ADL) is a functional evaluation scale for MCI patients, based on the information provided by an informant/carer, that describes the performance of patients in several activities of daily living. It was adapted by Douglas Galasko and co-workers from the original ADCS/ADL scale, which was constructed to evaluate patients with dementia in the Alzheimer’s Disease Cooperative Study, as a measure of the AD patients’ performance in ADL (17). The ADCS/MCI/ADL has been used in several studies and clinical trials to monitor the evolution of patients with MCI (6, 7, 18, 19). After the development of the ADCS/MCI/ADL 18 items scale, the authors decided to add 6 experimental items, considered more appropriate to the MCI population – this version with 24 items will be henceforth referred to as the ADCS/MCI/ADL24 (and the 18 items version will be further referred to as the ADCS/MCI/ADL18). Presently, to our knowledge, only one study determined the sensitivity and specificity values for the diagnosis of MCI versus controls, using the shorter version of the scale (7). The main objective of this work is to compare the ability of both versions of the scale (ADCS/MCI/ADL18 and ADCS/MCI/ADL24) in distinguishing patients with MCI from healthy controls. Other objectives are to evaluate the ability of the scale to distinguish patients with MCI from patients with AD, and to characterize the main functional features that differentiate healthy controls, patients with MCI, and patients with AD. Methods Participants Participants were patients with MCI and patients with AD attending two Memory Clinics and a hospital neurology outpatient clinic. For reasons of sample homogeneity, only patients with the amnestic type of MCI (aMCI) were recruited. Control subjects were volunteers, usually spouses or friends of patients who were requested to participate in the study. The ADL reports from all groups were collected from an informant/caregiver who lived with the subject or regularly spent time with the subject (mostly spouses or sons/daughters). The study was approved by the local ethics committee. Before any procedure, the participants gave their informed consent. To be eligible for the study, all participants had to be 60 years or older and community dwelling. Specific inclusion criteria for the groups were: Control group (1) No evidence for cognitive deterioration or cognitive complaints; (2) Mini Mental State Examination (MMSE) above cut-off (see below); (3) Immediate free recall of story A from the Logical Memory (LM) subtest of the Wechsler Memory Scales above cut-off (see below); (4) Maintained activities of daily living as evaluated by normal Lawton Instrumental Activities of Daily Living (LIADL) scale, that is to say, no item from this scale suffered any change. aMCI Inclusion criteria for aMCI were adapted from the criteria proposed by the Working Group in MCI of the European Alzheimer’s Disease Consortium (12, 13): (1) Cognitive complaints and cognitive decline during the last year, reported by the patient and/or family; (2) MMSE above cut-off; (3) Immediate free recall of story A from the Logical Memory subtest of the Wechsler Memory Scales at least 1 standard deviation (SD) below the norm for age and education; (4) Maintained activities of daily living or slight impairment in instrumental activities of daily living, in other words, no more than one item from the LIADL scale suffered any changes (20); (5) Absence of dementia, according to the DSM IV – TR criteria (21). AD Diagnosis of the AD patients was based on the DSM IV – TR criteria (21). Exclusion criteria for all groups: (1) Presence of other neurological and/or psychiatric pathologies that could cause cognitive impairment; (2) History of alcohol or drug abuse; (3) Symptoms of severe depression, that is, Geriatric Depression Scale (GDS) > 20. Of the 108 participants initially evaluated, 14 were excluded from the study for the following reasons: severe depression symptoms at time of evaluation (GDS>20), which could be a confounding variable in the MCI diagnosis (n=2); history of 705 The Journal of Nutrition, Health & Aging© Volume 14, Number 8, 2010 JNHA: CLINICAL TRIALS AND AGING stroke (n=7); psychiatric illness (n=1); lack of collaboration from the caregiver, being in a hurry (n=2); controls with low performance in neuropsychological tests (n=2). Procedures All aMCI and AD cases were subjected to clinical history, neurological examination, laboratorial evaluation and brain imaging (CT scan or NMR scan) (22). All participants had the same evaluation protocol which comprised: (1) Mini Mental State Examination (MMSE) (23). The MMSE is widely used for brief evaluation of the mental state and screening of dementia; the normative cut-off values for the Portuguese population adjusted to education were used (24). Subjects had to score above 22 if they had ≤11 years of education, or above 27 if they had >11 years of education. These cut-off values adjusted to the education levels were similar to those found in other studies (25, 26). (2) Logical Memory subtest from the Wechsler Memory Scale (WMS) (27), which is included in the Battery of Lisbon for the Evaluation of Dementia (BLAD) (28). Memory was considered impaired when the subjects scored on immediate free recall of story A of the test at least 1 standard deviation (SD) below the normal for age and education. Although in other studies performance was considered abnormal when scores are 1.5 SD below the mean for age and education matched control subjects, there is no standard cut-off to implement the memory impairment criteria (11, 29). A cut-off value of 1 SD was adopted considering that it allows the identification of subjects with slight cognitive changes but already fulfilling MCI criteria and at a high risk of developing dementia; also, the use of the cut-off value of 1.5 SD could exclude subjects that from a clinical point of view suffered from MCI (30). (3) Geriatric Depression Scale (GDS) (31, 32). The GDS is a self-report assessment used specifically to evaluate depression in the elderly. The complete version (30 items) was used for this study. (4) Clinical Dementia Rating Scale (CDR) (32, 33). The CDR is a structured-interview protocol that assesses the cognitive and functional performance in six areas: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care, in order to quantify the severity of dementia symptoms. (5) Blessed Dementia Rating Scale (BDRS) (32, 34). The BDRS is a brief behavioural scale based on an interview to a close informant, assessing functional ability for activities of daily living and changes in personality. (6) Lawton Instrumental Activities of Daily Living Scale (LIADL) (2, 32). The LIADL score reflects the number of impaired activities and ranges from 0 (no impairment) to 8 (changes in all items). Items were classified as not applicable if the activity had never been done before or if the subject stopped doing it for reasons other than cognitive difficulty (35). Activities of daily living were considered preserved if no item from the LIADL scale suffered any change, or mildly affected if only one item from the LIADL scale was altered (20). (7) The Alzheimer's Disease Cooperative Study / Activities of Daily Living scale for MCI patients (ADCS/MCI/ADL) is a functional scale based on the information provided by an informant/caregiver that describes the performance of patients in several activities of daily living (17). The original version of ADCS/MCI/ADL comprises 18 items (ADCS/MCI/ADL18, score of 0 to 53). The version with 24 items (ADCS/MCI/ADL24, score of 0 to 69) has 6 further items and is considered more adapted to the MCI population. Statistical Analysis Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS 15.0, SPSS Inc: Chicago, IL). A significance level = 0.05 was used in all analyses. The outliers analysis was done taking into account the primary variable in the study – ADCS/MCI/ADL. No outliers (defined as values 1.5 times lower than the 1st quartile or 1.5 times higher than the 3rd quartile) (36) were found in all the groups. We checked the homogenous distributions of the demographical variables, namely age and education with ANOVA one-way and sex with the Chi-square test. In what regards the functional description of the groups, we analysed participation frequencies in the tasks/activities defined in the items of the scale and searched for significant differences among the groups in each item, using Kruskal-Wallis non- parametric ANOVA followed by LSD on ranks (36) (the Chi- square test was used for item 24). This procedure was also used to search for significant differences in the neuropsychological evaluation among groups, since the assumption of normal distribution and homogeneity of variances was not fulfilled in neuropsychological evaluation tests. We defined cut-off points for both versions of the scale and studied the scale sensitivity and specificity values for each cut- off point. After defining the cut-off point with the best sensitivity and specificity values, we determined the discriminant performance of the scale, observing the Receiver Operating Characteristic curve (ROC) (36) and compared the Areas Under the Curve (AUC) with the Z test (37) to check for significant differences between both versions of the scale. Results Ninety-four participants (55 women and 39 men) were included in the study, divided in 3 groups: control (n=31); aMCI (n=30) and AD (n=33). There were no statistical differences among the groups regarding the demographical variables (Table 1). The three groups scored differently in the neuropsychological tests, MMSE and Logical Memory, as well as in global scales, CDR and Blessed Dementia Scale, and in functional scales, Lawton and ADCS/MCI/ADL (Table 1). Regarding evaluation of depressive symptoms, there were significant differences in the GDS scores between the aMCI and AD, and control and AD groups, but not between the control and the aMCI groups (Table 1). FUNCTIONAL EVALUATION IN MCI The Journal of Nutrition, Health & Aging© Volume 14, Number 8, 2010 706 Table 1 Demographical variables and results in neuropsychological tests, global evaluation scales, functional scales, and depressive symptoms in control subjects, patients with aMCI and patients with AD. MMSE, Mini Mental State Examination; LM, Logical Memory subtest from the Wechsler Memory Scale; CDR, Clinical Dementia Rating Scale; GDS, Geriatric Depression Scale; BDRS, Blessed Dementia Rating Scale; LIADL, Lawton Instrumental Activities of Daily Living Scale; ADCS/MCI/ADL, Alzheimer's Disease Cooperative Study / Activities of Daily Living scale adapted for aMCI patients. Significant differences among the groups were assessed with one-way ANOVA for age and education, the Chi-square for sex, and Kruskal-Wallis non- parametric ANOVA followed by LSD on ranks for all the other measures. NS = not statistically significant. Control aMCI AD Statistics p-value Statistical significance N 31 30 33 Age (years) Mean (SD) 72.2 (8.0) 75.7 (6.4) 76.1 (7.5) Min 60 60 62 F= 2.826 (2) 0.064 NS Max 90 91 91 Sex Men 18 10 11 X 2 = 5.23 (2) 0.073 NS Women 13 20 22 Education (years) 3.3 (1.9) 4.9 (3.1) 3.5 (2.9) F=2.942 (2) 0.058 NS MMSE 27.7 (3.0) 24.4 (3.3) 16.5 (5.2) X 2 KW (2) = 53.13 < 0.001 C > MCI > AD LM 9.3 (2.9) 5.6 (2.5) 1.5 (2.2) X 2 KW (2) = 56.56 < 0.001 C > MCI > AD CDR 0.0 (0.0) 0.5 (0.0) 1.6 (0.7) X 2 KW (2) = 89.41 < 0.001 C < MCI < AD GDS 6.9 (3.8) 8.6 (4.5) 11.3 (4.7) X 2 KW (2) = 13.70 < 0.001 C, MCI < AD BDRS 1.1 (1.4) 3.6 (1.6) 8.8 (4.8) X 2 KW (2) = 66.32 < 0.001 C < MCI < AD LIADL 8.0 (0.0) 7.3 (0.5) 2.8 (2.1) X 2 KW (2) = 45.15 < 0.001 C > MCI > AD ADCS MCI ADL18 47.0 (4.2) 39.6 (6.3) 17.8 (11.8) X 2 KW (2) = 66.86 < 0.001 C > MCI > AD ADCS MCI ADL24 59.3 (6.7) 46.7 (8.3) 20.7 (13.2) X 2 KW (2) = 69.49 < 0.001 C > MCI > AD Table 2 Performances in the distinct items of ADCS/MCI/ADL scale in controls, aMCI patients, and AD patients. The mean (SD) scores are shown. Statistical significance was tested using Kruskal-Wallis non-parametric ANOVA followed by LSD on ranks except for item 24, where the Chi-square test was used – item 24: percentage of subjects who experienced an extraordinary circumstance that could influence performance in ADL. NS = not statistically significant Item Control aMCI AD Statistical significance 1 – finding personal belongings 3.0 (0.2) 2.6 (0.5) 1.5 (0.8) C>MCI>AD 2 – selecting one’s clothes 2.6 (0.9) 2.5 (1.0) 1.4 (1.4) C, MCI > AD 3 – getting dressed 4.0 (0.0) 4.0 (0.2) 2.7 (1.6) C, MCI > AD 4 – cleaning a room 1.2 (0.9) 1.3 (0.9) 0.5 (0.7) C, MCI > AD 5 – balancing the cheque book 1.3 (0.9) 0.9 (0.9) 0.0 (0.2) C>MCI>AD 6 – writing notes 1.0 (0.9) 0.8 (0.8) 0.0 (0.0) C, MCI > AD 7 – doing the laundry 1.1 (1.0) 1.3 (0.9) 0.5 (0.8) C, MCI > AD 8 – keeping appointments 2.8 (0.5) 1.8 (1.0) 0.8 (0.8) C>MCI>AD 9 – using a telephone 3.6 (0.9) 2.7 (2.4) 1.0 (1.1) C>MCI>AD 10 – making a meal or snack 2.7 (0.6) 2.4 (0.9) 0.9 (1.2) C, MCI > AD 11 – travelling out of home 2.8 (0.8) 2.5 (0.9) 0.9 (1.1) C>MCI>AD 12 – talking about current events 3.8 (0.4) 2.7 (1.1) 1.6 (1.5) C>MCI>AD 13 – reading for over 5 minutes 2.4 (1.2) 1.5 (1.2) 0.4 (0.8) C>MCI>AD 14 - watching television 3.0 (0.0) 2.2 (1.0) 1.2 (1.0) C>MCI>AD 15 – shopping 1.8 (0.5) 1.4 (0.7) 0.3 (0.6) C>MCI>AD 16 – being left on one’s own 3.0 (0.2) 2.9 (0.4) 2.1 (1.1) C, MCI > AD 17 – using household appliances 3.9 (0.2) 3.7 (0.8) 1.6 (1.8) C, MCI > AD 18 – practicing hobbies 2.8 (0.8) 2.4 (1.2) 0.8 (1.2) C, MCI > AD 19 – driving a car 1.8 (1.4) 0.6 (1.1) 0.2 (0.7) C > MCI, AD 20 – taking medications 3.8 (0.5) 3.1 (1.1) 1.3 (0.9) C>MCI>AD 21 – carrying through complex activities 2.3 (1.3) 0.9 (1.4) 0.2 (0.8) C > MCI, AD 22 – initiating complex activities 1.7 (1.4) 0.5 (1.1) 0.0 (0.2) C > MCI, AD 23 – time taken to perform complex tasks 2.5 (0.9) 2.2 (0.6) 1.1 (1.0) C>MCI>AD 24 – extraordinary circumstances 23% 13% 3% NS JNHA: CLINICAL TRIALS AND AGING The Journal of Nutrition, Health & Aging© Volume 14, Number 8, 2010 707 Table 3 Capability of the ADCS/MCI/ADL scale (18-item and 24-item versions) to distinguish among controls, aMCI patients and AD patients. AUC, Area Under the Curve, Receiver Operating Characteristic curve Version of the scale Groups Mean (SD) Cut-off point Sensitivity Specificity AUC False False Negatives Positives ADCS MCI ADL 18 Control 46.6 (5.3) 44/ 45 73% 74% 0.842 26.6% 25.8% aMCI 39.5 (6.5) aMCI 39.5 (6.5) 33/ 34 88% 83% 0.956 12.9% 16.6% AD 17.8 (11.8) ADCS MCI ADL 24 Control 58.9 (7.7) 52/ 53 87% 87% 0.887 13.3% 12.9% aMCI 46.7 (8.3) aMCI 46.7 (8.3) 37/ 38 85% 87% 0.955 15.2% 13.3% AD 20.7 (13.2) Figure 1 Frequencies of the participation of controls, aMCI patients and AD patients in the tasks (1 to 22) evaluated by the ADCS/MCI/ADL scale. See Table 2 for characterization of the specific items of the scale. Item 23 is not shown because it relates to the speed on performance of complex activities. Item 24 is also not shown because it inquires about exceptional circumstances that could interfere with the performance of ADL Figure 2 Receiver Operating Characteristic (ROC) curves for the discrimination between controls and MCI (A) using the ADCS/MCI/ADL18 (ROC c=0.842) and the ADCS/MCI/ADL24 (ROC c=0.887) were significantly different (z=1.97; p=0.049) - ADCS/MCI/ADL24 is superior in distinguishing MCI patients from healthy controls. ROC curves for the discrimination between MCI and AD patients (B) using the ADCS/MCI/ADL18 (ROC c=0.956) and ADCS/MCI/ADL24 (ROC c=0.955) were not significantly different (z=0.043; p=0.965) The frequencies in which the three groups participated in the tasks evaluated by the ADCS/MCI/ADL are shown in Figure 1. Comparison of the scores in the distinct items of the ADCS/MCI/ADL scale for the three groups of subjects is shown in Table 2. Patients with aMCI were impaired relatively to healthy controls in demanding tasks, whereas they performed well in more basic tasks, where only AD patients had difficulties (Table 2). The capability of the ADCS/MCI/ADL to distinguish among controls, aMCI patients and AD patients was analysed. The cut- off points that best discriminate between controls and aMCI patients, and between aMCI patients and AD patients, for both ADCS/MCI/ADL18 and ADCS/MCI/ADL24, are shown in Table 3. Although AUC analysis revealed good discriminant capacity for both versions of the scale, ADCS/MCI/ADL24 presented higher values for the discrimination between aMCI patients and healthy controls, with good sensitivity (0.87) and specificity (0.87) values, and a high discriminant performance (ROC c=0.887; 95% Confidence Interval ]0.802-0.972[; cut-off point of 52/53) (Figure 2 and Table 3). The shorter ADCS/MCI/ADL18 scale version had only moderate sensitivity (0.73) and specificity (0.74) values, and a lower discriminant performance (ROC c=0.842; 95% Confidence Interval ]0.747-0.938[; cut-off point of 45/46), in distinguishing aMCI patients from healthy controls. The comparison of the AUC with the Z test (38) revealed the ROC curves for Control vs. aMCI were significantly different (z=1.97; p=0.049) but not for the aMCI vs. AD patients (z=0.043; p=0.965). Thus, ADCS/MCI/ADL24 was superior to ADCS/MCI/ADL18 in distinguishing aMCI patients from healthy controls, but not aMCI from AD patients. Discussion The detection of subjects in the initial phases of cognitive decline, as in MCI, may be difficult. Research criteria require the use of sensitive memory and learning tests, which are not always available in routine clinical practice. Inquiry about IADL performance to obtain a total score and to assess the types of IADL that are impaired could offer a way to complement mental state testing. The detection of mild functional disturbances, predominantly involving complex activities, could allow a better distinction of MCI patients from healthy elderly people (11). The present study showed that the ADCS/MCI/ADL24 scale had a high accuracy and was superior to ADCS/MCI/ADL18 scale in distinguishing aMCI patients from healthy controls. A previous study presented sensitivity and specificity values for the ADCS/MCI/ADL18 scale, however, a different scoring system was used, from 0 to 57 (7), instead of 0 to 53, precluding direct comparison with the present results. The increase in diagnostic efficiency of ADCS/MCI/ADL24 towards ADCS/MCI/ADL18 can be explained by the nature of the items introduced in the last part of the scale, which refer to complex abilities, like driving a car or organizing the medication, where subtle difficulties may be revealed in MCI patients. Thus, the ADCS/MCI/ADL24 is a sensitive and specific instrument to aid in accurately discriminating aMCI patients from healthy elderly people. In contrast, regarding the distinction between aMCI and AD patients, both versions of the scale, ADCS/MCI/ADL24 and ADCS/MCI/ADL18, performed similarly, since the complex items introduced in the final part of ADCS/MCI/ADL24 should be difficult for both aMCI patients and AD patients. Main functional features differentiate healthy controls, patients with aMCI, and patients with AD. In general, MCI subjects have an intermediate performance, between the control group and the AD group (38). We found a functional decline from the control group to the aMCI group and from this to the AD group, both in the total ADCS/MCI/ADL score and in the number of activities in which all patients participated. This corroborates previous studies that showed significantly lower scores in the MCI patients when compared to healthy controls (7) and in AD patients when compared to MCI patients (19). Because functional impairment is part of the diagnosis of AD, and patients with moderate AD (mean MMSE of 16), were enrolled, we found that the AD group was impaired across a wide range of IADL activities. There was a clear gradient of progressive functional decline from controls to aMCI and then to AD. It is interesting that decline in daily activities follows a specific pattern, so that higher order functional abilities tend to decline first, and basic activities of daily living are affected last. Among the ADCS/MCI/ADL questions, those that are highly dependent on memory, planning and sustained attention also appeared to be the earliest and most severely affected in aMCI in our study. Recent studies in a Canadian cohort, with participants over 65 years old, showed this relationship between loss of specific ADLs and the cognitive status at the beginning of the functional loss (39), although there might be overlapping in some activities. Furthermore, the instrumental activities performed away from home tend to get affected earlier than do those usually performed at home (3, 39). The activities that we found to decline in aMCI patients as compared to healthy controls were controlling the cheque book, using a telephone, going shopping, taking medications regularly, finding objects, talking about current events, watching television, initiating complex activities, keeping appointments or meetings, reading and carrying through complex activities. Interestingly, this decline was also found in previous studies, even when using different scales (10, 40). The present study also identified the tasks of getting around outside the home and driving a car as affected in aMCI patients as compared to controls. The activities in which the MCI patients begin to show impairment seem to depend on large cognitive resources, namely memory, psychomotor speed, attention and executive functions (38), although these patients can still perform basic activities of daily living just as well as healthy controls. As the disease progresses, and AD is diagnosed, FUNCTIONAL EVALUATION IN MCI The Journal of Nutrition, Health & Aging© Volume 14, Number 8, 2010 708 patients show significant limitations in most items, and initiate obvious difficulties in basic ADL, that are not shared either by controls or by MCI patients. Several limitations must be recognized in the present study. The MCI patients that were recruited were of the amnestic type, and no information was obtained regarding other MCI types. On the other hand, the characteristics of patients being seen in a clinical setting may differ from individuals in the community that fulfil criteria for MCI but did not actively seek clinical evaluation, and thus the present results may not generalize to community-based MCI samples. The detection of initial functional changes with appropriate scales may contribute to the early diagnosis of MCI, and may also identify those patients who are at greater risk for further decline (41). The present study showed that the ADCS/MCI/ADL24 scale has a high accuracy in distinguishing aMCI patients from healthy controls. The early detection of these patients and the recognition of specific difficulties should allow timely and targeted interventions to improve everyday function or prolong independence. 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JNHA: CLINICAL TRIALS AND AGING The Journal of Nutrition, Health & Aging© Volume 14, Number 8, 2010 709 . functional impairment in patients with MCI when compared to the normal FUNCTIONAL EVALUATION DISTINGUISHES MCI PATIENTS FROM HEALTHY ELDERLY PEOPLE - THE ADCS /MCI/ ADL SCALE H outside the home and driving a car were impaired in aMCI patients. The ADCS /MCI/ ADL24 scale was better than the ADCS /MCI/ ADL18 scale in distinguishing aMCI patients