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Evaluating Voting Competence in Persons with Alzheimer Disease

Evaluating Voting Competence in Persons with Alzheimer Disease SAGE-Hindawi Access to Research International Journal of Alzheimer’s Disease Volume 2011, Article ID 983895, 6 pages doi:10.4061/2011/983895 Clinical Study 1, 2 1 3 Pietro Tiraboschi, Erica Chito, ` Leonardo Sacco, 1 1 1 Marta Sala, Stefano Stefanini, and Carlo Alberto Defanti Fondazione Europea Ricerca Biomedica (FERB), Centro Alzheimer, Ospedale Briolini, Gazzaniga, Bergamo, Italy Divisione Neurologica, Ospedale Niguarda Ca’ Granda, Milano, Italy Neurocentre of Southern Switzerland, Lugano, Switzerland Correspondence should be addressed to Pietro Tiraboschi, ptiraboschi@yahoo.com Received 14 February 2011; Revised 29 April 2011; Accepted 25 May 2011 Academic Editor: Amos D. Korczyn Copyright © 2011 Pietro Tiraboschi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Voting by persons with dementia raises questions about their decision-making capacity. Methods specifically addressing voting capacity of demented people have been proposed in the US, but never tested elsewhere. We translated and adapted the US Competence Assessment Tool for Voting (CAT-V) to the Italian context, using it before 2006 elections for Prime Minister. Consisting of a brief questionnaire, this tool evaluates the following decision-making abilities: understanding nature and effect of voting, expressing a choice, and reasoning about voting choices. Subjects’ performance was examined in relation to dementia severity. Of 38 subjects with Alzheimer’s disease (AD) enrolled in the study, only three scored the maximum on all CAT-V items. MMSE and CAT-V scores correlated only moderately (r = 0.59; P< 0.0001) with one another, reflecting the variability of subjects’ performance at any disease stage. Most participants (90%), although performing poorly on understanding and reasoning items, scored the maximum on the choice measure. Our results imply that voting capacity in AD is only roughly predicted by MMSE scores and may more accurately be measured by a structured questionnaire, such as the CAT-V. Among the decision-making abilities evaluated by the CAT-V, expressing a choice was by far the least affected by the dementing process. 1. Introduction in at least two cases (2000 US presidential elections and 2006 Italian elections for the Prime Minister designation), a Mental disorders, including dementia, can impair compe- small number of votes had a decisive effect on the results. tence, but a diagnosis of dementia does not imply a complete It is especially in long-term facilities that inappropriate loss of competence [1]. There is a wide consensus on consid- assumptions about the absence of voting capacity may ering competence as the capacity of a person to make a deprive still capable and willing residents of the right to vote specific decision [2]. Voting is a decision of particular interest [4, 5]. since a consensus does not exist on which abilities the patient Recently, a novel test to assess the capacity to vote has with dementia should retain to express a reliable choice been proposed: the Competence Assessment Tool for Voting [3]. Voting is among the fundamental rights of citizens in (CAT-V) [6], which evaluates an individual’s performance on democratic countries. Thus, identifying patients who, despite four decision-making abilities: understanding the nature and the presence of dementia, maintain the capacity to vote effect of voting, appreciating the reality of voting situation, and increasing their chance to take part in a ballot (e.g., making a choice, and reasoning about voting choices. In allowing their caregivers to have a role in facilitating this) this paper, we report the results of a study that applied a would be of crucial importance. Participation in the electoral modified version of the CAT-V to individuals with mild- process by citizens with dementia has become especially moderate AD who were temporarily residents in a long-term important in recent years, both for the growing number of care facility before 2006 Italian elections for designating the individuals suffering from Alzheimer disease (AD) or other Prime minister. Our primary hypothesis was that although progressive cognitive disorders, and in light of the fact that voting capacity would be inversely associated with dementia 2 International Journal of Alzheimer’s Disease severity, the single decision-making abilities evaluated by Table 1: Demographics of the subjects (n = 38). the CAT-V would be affected unequally by the dementing Mean Standard deviation Range process. Age (years) 81.1 5.1 68–93 Gender (M/F) 9/29 — — 2. Methods Education (years) 5.6 2.3 3–13 Disease duration (years) 3.3 1.6 1–8 2.1. Subjects. The subjects included in the present study MMSE score 18.2 4.2 11–27 (n = 38) represent all the patients with mild-moderate dementia (Mini-Mental State Examination [7] (MMSE) ≥ NPI score at baseline 43.0 17.5 11–72 11) and a clinical diagnosis of probable AD (according to NPI score prior to discharge 21.2 11.7 0–50 the National Institute of Neurological and Communicative MMSE, Mini-Mental State Examination, NPI, Neuropsychiatric Inventory. Disorders and Stroke (NINCDS) and the Alzheimer Disease and Related Disorders Association (ADRDA) criteria) [8] Table 2: Subjects’ score distribution on each item of the Compe- who were admitted into the Alzheimer Centre of the tence Assessment Tool for Voting (CAT-V). Ospedale Gazzaniga (Bergamo, Italy) from sixty to thirty days before 2006 Italian general elections. Although, in some CAT-V item and score N % respects, our centre has several characteristics of a long-term Understanding the nature of voting care facility, no patient is a permanent resident. The primary 0 7 18,4 requirement for a patient’s admission into our centre is the 1 10 26,3 presence of behavioural abnormalities or psychopathologic 2 21 55,3 symptoms in the context of a dementing syndrome but, Understanding the effect of voting once these features are significantly relieved, the patient is 0 18 47,4 discharged. 1 6 15,8 2 14 36,8 2.2. Assessment Tool and Scoring. The instrument we used Choice to evaluate the capacity to vote was a modified version of 0 4 10,5 the CAT-V, an instrument that measures a person’s ability to understand the nature and effect of voting, make a choice, 2 34 89,5 appreciate, and reason through a voting decision. These Comparative reasoning criteria were operationalized into five questions preceded by 0 13 34,2 an introduction reminding each person that soon he/she 1 9 23,7 would have the opportunity to take part in a ballot for 2 16 42,1 the election of the Prime Minister. Thus, as opposed to the Generating consequences original US version of the CAT-V, in which subjects are asked 0 21 55,3 to imagine that two candidates are running for Governor and 1 11 28,9 that the day of the interview is the Election Day, the scenario 2 6 15,8 we proposed was real rather than hypothetical. Furthermore, in order to shorten the time of interview, unlike the original, our version of the CAT-V did not include a question evalu- ating subjects’ appreciation of the significance of voting. For interviewed by M. Sala two weeks later, to evaluate the test- each CAT-V item, the scores assigned to each person ranged retest reliability. The scores included in the main data analysis from 2 (correct response reflecting adequate performance) to are those assigned to all participants at baseline by M. Sala 0 (inadequate performance). The instrument and criteria for The Spearman correlation coefficient was used to examine scoring are shown in the appendix. the association of the capacity to vote (as expressed by the score on each of the CAT-V items) with severity of both Every participant was enrolled after an initial contact with his/her principal caregiver. Once informed about the cognitive impairment (as expressed by the MMSE score) and behavioural and psychopathological symptoms (as expressed characteristics of the study and made sure that its results by the Neuropsychiatric Inventory (NPI) [9]score). Each would be used exclusively for research purposes, each par- ticipant (or his/her caregiver) provided a written informed participant was administered the CAT-V, the MMSE, and the NPI during the same session. consent. The study was approved by our local institutional review board. 3. Results 2.3. Data Analyses. All of the 38 participants were inter- viewed and rated by one investigator (M. Sala), who was 3.1. Subjects’ Characteristics. All the subjects who were asked blinded to their MMSE score. Thirty of them were also to participate in the project (n = 38) did complete the interviewed and rated by another investigator (E. Chito). ` interview. Their demographic characteristics are reported in Weighted kappa and Kendall tau-B were used to determine Table 1. There was a clear female preponderance. Severity the interrater reliability. Twenty-nine subjects were again of cognitive impairment was, on average, relatively mild. International Journal of Alzheimer’s Disease 3 Table 3: Cross-tabulation relating scores on understanding and making a choice to scores on reasoning. Score on questions assessing understanding and choice Number of Number of Score on questions subjects subjects Total assessing reasoning scoring 0–5 scoring 6 Number of participants 10 25 9 34 0123456789 10 scoring 0–3 Combined score on all questions of the Number of participants Competence Assessment Tool for Voting scoring 4 Total 26 12 38 Figure 1: Relation of scores on the Mini-Mental Exam to combined scores on all questions of the Competence Assessment Tool for Voting (r = 0.59, P< 0.0001). Table 4: Competence Assessment Tool for Voting (CAT-V) scoring criteria, interrater, and test-retest reliabilities. Cohen Kendall N P value Kappa tau-b Understanding Interrater 30 0.65 0.7 0.0001 and choosing reliability Reasoning 30 0.41 0.65 0.0001 Understanding Test-retest 29 0.42 0.65 0.0001 and choosing reliability 0 123456 Reasoning 29 0.22 0.57 0.0001 Combined score on the three questions Determined in the first 30 of the 38 patients enrolled in the study. assessing understanding and choice Retest was administered only to patients not yet discharged from our center after two weeks (29/38). Figure 2: Relation of scores on the Mini-Mental State Exam to scores on questions assessing understanding and choice (r = 0.61, P< 0.0001). Behavioural and psychopathological symptoms were mod- erately severe at baseline but were significantly relieved prior to discharge. However, a great variability in subjects’ performance was noted at any stage of disease. On questions evaluating 3.2. Performance on CAT-V. Subjects’ performance on CAT- understanding and choice (Figure 2), for example, only 58% V is shown in Table 2. Over a half of the subjects appeared of subjects with mild AD (MMSE ≥ 20) obtained the to fully understand the nature of the vote, but only approx- maximum score but, remarkably, over one-third of those imately a third was entirely able to understand its effect. who scored the maximum was beyond mild-stage disease However, the great majority of participants (∼90%) was (MMSE < 20). deemed to be completely able to make a choice. Conversely, Lower CAT-V scores were also associated with fewer subjects’ ability to reason about voting by comparing the years of education but, as opposed to disease severity, poor choices at disposal and, above all, by evaluating the possible education had an impact exclusively on measures of under- consequences of the preference for a candidate on their life standing and choice (r = 0.32, P = 0.049). was considerably more impaired. In fact, only about 16% of No relationship was found between education and the participants had a completely adequate performance on MMSE scores (r = 0.05, P = 0.76). the latter measure. As shown in Table 3, which relates subjects’ combined 4. Discussion performance on understanding and choice to their perfor- mance on reasoning, only three of the 38 participants (8%) Among persons with mild to moderate AD, global mea- scored the maximum on all items. As emerges from Table 4, sures of cognitive functioning, such as the MMSE, cannot there were better test-retest and interrater reliabilities for adequately substitute for an assessment of voting capacity. scores on understanding and choice than for scores on The present study has examined the capacity to vote in a reasoning. sample of 38 mild-moderate AD patients using a modified version of the CAT-V. Originally designed in the US, this 3.3. Relation of CAT-V Performance to Severity of Dementia. instrument consists of a brief questionnaire, which has There was no relation of CAT-V scores to severity of been translated and adapted to the Italian context and by behavioural and psychopathological symptoms (r =−0.14, which we have explored the following functional abilities: P = 0.41). Conversely, as expected, lower CAT-V scores were understanding the nature and effect of voting, expressing associated with lower MMSE scores (Figures 1, 2,and 3). a choice, reasoning about the choices at disposal, and MMSE scores MMSE Score 4 International Journal of Alzheimer’s Disease with severe AD may also explain the only low-moderate test-retest reliability values of our study (understanding and choice, k = 0.42; reasoning, k = 0.22),aswellasthe less satisfying agreement between our raters than between the raters of the US study (understanding and choice, k = 0.65 versus 0.91; reasoning, k = 0.41 versus 0.74). Subjects with severe AD have in fact a greater likelihood than those with mild-moderate disease to invariably provide completely inadequate performances, so as to be assigned the minimum 01234 score unambiguously and consistently over time. Not requiring a particular expertise, the CAT-V is Combined score on the two questions assessing reasoning easily administrable, since no more than five minutes are Figure 3: Relation of scores on the Mini-Mental State Exam to needed for its administration. This time might further be scores on questions assessing reasoning (r = 0.41, P = 0.01). shortened if one decides to skip the reasoning questions because, at least in our experience, these questions were too demanding even for mildly deteriorated patients and generated performances characterized by insufficient test- reasoning about the consequences of voting. We have also calculated the reliability of the test and its relation to retest and inter-rater reliabilities. Interpreting subjects’ per- dementia severity. formance remains, however, problematic even when analyses are restricted to the questions inherent in the Doe standard On the basis of our results, a full capacity to vote (as expressed by integrity of all above mentioned decision- (understanding and choice). Clearly, performances at the making abilities) appears to be retained by a small minority extremes of the spectrum are not controversial, so that a of AD subjects (3/38), and exclusively at mild-stage disease performance generating the minimum score unequivocally (MMSE ≥ 20). indicates absence of voting capacity and, by contrast, a performance generating the maximum score indicates a full However, when we applied less restrictive criteria for determining voting competence, as those identified in the compliance with the Doe standard. However, intermediate Doe standard (a legal standard based on a 2001 federal scores need a judgement to be made, the basis of which is not obvious and deserves further comments. For example, district court decision in Maine (US), which solely requires an intact ability to understand and make a choice) [10], in both the US and our study, almost all of the participants subjects’ voting capacity was not completely predicted by with intermediate scores appeared to be invariably capable MMSE scores. On understanding and choice measures, in to make a choice, while what varied was their ability to fact, only 58% of our less deteriorated subjects (MMSE ≥ understand the nature and effect of voting. Consequently, if 20) obtained the maximum score but, remarkably, over one- we had applied more liberal criteria than those identified in third of those who scored the maximum were beyond mild- the Doe standard for determining voting competence and, stage disease (MMSE 13–19). As a result, the relation of for example, we had deemed a patient to retain the capacity to vote if he/she was able to express a choice regardless these measures to severity of cognitive impairment was only moderate (r = 0.61). of understanding, the great majority of AD subjects (90% Of note, over two-thirds of our AD patients, although in our study and 88% in the US study) would have been categorized as such. still able to express a choice, did not appear to be entirely able to understand the nature and, especially, the effect of The limitations of this study relate to lack of data from the vote, thereby failing to meet the Doe standard. A similar nondemented persons, whose availability would have been pattern (choice considerably less impaired than understand- extremely helpful in interpreting intermediate scores by the ing) has previously been reported by US investigators [5]. identification of appropriate cutoffs and of more detailed In their study, however, the percentage of AD patients who neuropsychological information than that provided by the failed to fulfil the Doe standard was lower than that seen MMSE. Other issues are the relatively small sample size, the in our study (55% versus 68%), and there was a much relatively narrow range of cognitive impairment, and the more substantial link between declining voting capacity and presence of significant behavioural and psychopathological increasing dementia severity (r = 0.87 versus 0.61). symptoms (although their severity did not appear to influ- There are several possible reasons for the discrepancy ence the performance of our patients on the CAT-V). Since between our results and those previously reported by the this study was restricted to persons with mild-moderate US investigators. For example, compared to these authors, disease, and most of them had significant behavioural we examined a sample characterized by more advanced age disturbances, its results may be not entirely representative (81.1 versus 77.7 years), greater female preponderance (76% of all patients with AD. Despite these flaws, the primary versus 52%), less severe impairment (mean MMSE 18.2 hypothesis of the present study has been tested and verified. versus 16.4), and considerably lower education (5.6 versus 14 There was an inverse relationship between voting capacity years). Furthermore, since we excluded patients with severe and dementia severity but, somewhat unexpectedly, the AD from analyses, the range of cognitive impairment was strength of this association was not substantial. However, more compressed in our sample (MMSE 11–27) than in as predicted, the single decision-making abilities evaluated the US sample (MMSE 2–28). The exclusion of patients by the CAT-V were unequally impaired by the dementing MMSE Score International Journal of Alzheimer’s Disease 5 Table 5 for example watching TV, listening to their campaign issues, ask: What already known on this topic is “Well, that is how you might decide who you like to be People with dementia are underrepresented at the polls. the Prime Minister. But how would actually express your Many of them are denied the opportunity to vote even when choice?”) retaining the mental capacity to do so. Score of 2: Entirely correct response, for example, “I will Methods that address voting capacity of demented people, go to the polls and vote” or “I will cast my vote for one or the such as the Competence Assessment Tool for Voting other”, and so forth. (CAT-V), have been proposed and tested in the US, but never Score of 1: Ambiguous or partially correct response, for elsewhere. example, “That is why we have Election Day”, and so forth. Using the CAT-V in patients with Alzheimer Disease (AD), Score of 0: Incorrect response, for example, ”There is US investigators have shown a robust association between nothing you can do; the TV guys decide”, and so forth. declining voting capacity and increasing dementia severity. What this study adds Understanding the Effect of Voting. “Once the election for Using a modified version of the CAT-V, we found only a Prime Minister is over, how is it going to be decided who moderate association between declining voting capacity and is the winner?” increasing dementia severity in AD. Score of 2: Entirely correct response, for example, “The The capacity to express a choice is largely preserved even in votes will be counted and the candidate with more votes will moderate-stage AD. be the winner.” Many patients with AD, although no longer capable of Score of 1: Ambiguous or partially correct response, for understanding the nature and importance of voting, are still example, “The better between the two candidates will be the able to express a choice. Their right to vote should therefore winner”, and so forth. be respected. Score of 0: Incorrect or irrelevant response. process (reasoning > understanding > choice). On the basis Choice. Hand patient a card with the information in the of these data, the use of a structured interview, such as following paragraph in large print; allow to retain and the CAT-V, may offer advantages over unstructured or consult this card for the remainder of the interview. clinical assessments, especially in light of the fact that global “For the sake of simplicity, the first candidate (of the measures of cognitive functioning, such as the MMSE, do not right party) is willing to lower taxes by decreasing the burden appear to be strong predictors of the capacity to vote. Further of bureaucracy and public administration, in order to make studies are needed to refine the clinicians’ approaches to people spend more as a result of higher income. The second identifying demented people who are still capable to vote candidate (of the left party) is willing to either raise taxes or, from those who are no longer capable. Nevertheless, a tool by fighting tax elusion, keep them unchanged getting every like the CAT-V can adequately assist in this distinction citizen to pay, so that the rights to education and welfare (Table 5). remain protected. Based on either what I have just told you or what you already knew about the candidates, do you think you are able to choose between the two? Mind that I do not Appendix want to know from you which candidate you would vote for, but only if you have made your choice?” Italian Version of the Competency Score of 2: The patient clearly indicates the choice, Assessment Tool for Voting including a reasoned choice not to vote or a manifestation “I will ask you a few questions about next elections. This it is of indetermination (“I still do not know which candidate to going to take five minutes or less. If you do not understand vote for”). something of what I am saying or asking, please let me know Score of 0: No choice is stated because the patient is and I will repeat it. Some of the questions might seem very unable to choose, does not understand what is asked, and so simple to you, but do not worry about that. We only need forth. straightforward answers. Do you have any questions before we start?” Reasoning Understanding. “Next elections will take place within few Comparative Reasoning. If the patient identifies a choice, ask: weeks. Two candidates are running for Prime Minister (make “Why do you think that it is worth voting for either of the the patient name the candidates or, if he/she does not candidates?” or “Why do you think neither of the candidates remember, remind him/her of their names).” deserves to be voted for?” Score of 2: Entirely correct response, for example, Understanding the Nature of Voting. “What will you do to “Because it is right to maintain the welfare state”, “Because pick the Prime Minister on Election Day?” it is right that everybody pays taxes”, “Because the State (if patient gives an indirect answer, describing how he/she should not empty the citizen’s pockets with too high taxes”, or people in general would choose between the candidates, “Because, despite different views, neither of the candidates 6 International Journal of Alzheimer’s Disease will fulfill the promises made before Election Day”, and so Professionals, Oxford University Press, New York, NY, USA, forth. [2] The President’s Commission for the Study of Ethical Problems Score of 1: Ambiguous or partially correct response, for in Medicine and Biomedical and Behavioral Research. Making example, “Healthcare”, “it is better to spend more than spend Health Care Decisions, US Government Printing Office, Wash- less”, and so forth. ington, DC, USA, 1982. Score of 0: The patient fails to mention a comparative [3] J. H. Karlawish, R. J. Bonnie, P. S. Appelbaum et al., attribute of the respective candidates. “Addressing the ethical, legal, and social issues raised by voting by persons with dementia,” Journal of the American Medical Reasoning on Consequences. If the patient is able to make Association, vol. 292, no. 11, pp. 1345–1350, 2004. [4] J. Karlawish, R. J. Bonnie, P. Appelbaum et al., “Identifying his/her choice for either of the candidates or even in the case the barriers and challenges to voting by residents in nursing he/she wants to abstain from voting, ask: “In your opinion, homes and assisted living settings,” Journal of Aging and Social should the first candidate, that one who wants to lower Policy, vol. 20, no. 1, pp. 65–79, 2008. taxes by decreasing the burden of bureaucracy, or second [5] M. Redley, J. C. Hughes, and A. Holland, “Voting and mental candidate, that one who wants to maintain the welfare state capacity,” British Medical Journal, vol. 341, p. c4085, 2010. by fighting against tax elusion, be elected, how could that [6] P. S. Appelbaum, R. J. Bonnie, and J. H. Karlawish, “The affect your life?” capacity to vote of persons with Alzheimer’s disease,” American Score of 2: Entirely correct response, for example, “I Journal of Psychiatry, vol. 162, no. 11, pp. 2094–2100, 2005. will have more money to spend”, “Public Services won’t be [7] M. F. Folstein, S. E. Folstein, and P. R. McHugh, ““Mini mental reduced”, “I cannot predict what will happen, because they state”: a practical method for grading the cognitive state of won’t do what they promised to do”, and so forth. patients for the clinician,” Journal of Psychiatric Research, vol. Score of 1: Ambiguous or partially correct response, for 12, no. 3, pp. 189–198, 1975. [8] G. McKhann, D. Drachman, M. Folstein, R. Katzman, D. example, “Health will improve”, and so forth. Price, and E. M. Stadlan, “Clinical diagnosis of Alzheimer’s Score of 0: The patient does not give a consequence for disease: report of the NINCDS-ADRDA work group under the his/her life or a reason for saying that there are no personally auspices of Department of Health and Human Services Task relevant consequences. Force on Alzheimer’s disease,” Neurology, vol. 34, no. 7, pp. 939–944, 1984. [9] J. L. Cummings, M. Mega, K. Gray, S. Rosenberg-Thompson, Authors’ Contribution D. A. Carusi, and J. Gornbein, “The neuropsychiatric in- All authors contributed to the design of the study. C. A. ventory: comprehensive assessment of psychopathology in dementia,” Neurology, vol. 44, no. 12, pp. 2308–2314, 1994. Defanti and L. Sacco identified the participants. M. Sala [10] Doe v Rowe, 156 F, supplement 2d 35(DMe), 2001. and E. Chito` did the individual interviews. S. Stefanini, L. Sacco, and C. Defanti administered the neuropsychological and neurobehavioural scales. All authors contributed to the analysis and interpretation of data. P. Tiraboschi drafted the article, and all authors revised it critically for important intellectual content. P. Tiraboschi is the guarantor. Conflict of Interests All authors have completed the Unified Competing Interest form (available on request from the corresponding author) and declare that P. Tiraboschi, E. Chito, ` L. Sacco, M. Sala, S. Stefanini, C. A. Defanti, their spouses, partners, and children have not had any supports or relationships with companies that might have an interest in the submitted work. All authors also declare that they have no nonfinancial interest that may be relevant to the submitted work. Ethical Approval The study was approved by our local institutional review board. Each participant (or his/her caregiver) provided a written informed consent. References [1] T.Grisso andP.S.Appelbaum, Assessing Competence to Consent to Treatment: A Guide for Physicians and Other Health MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 International Journal of Journal of Immunology Research Endocrinology Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Submit your manuscripts at http://www.hindawi.com BioMed PPAR Research Research International Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Research and Treatment Cellular Longevity Neurology Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png International Journal of Alzheimer's Disease Hindawi Publishing Corporation

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Abstract

SAGE-Hindawi Access to Research International Journal of Alzheimer’s Disease Volume 2011, Article ID 983895, 6 pages doi:10.4061/2011/983895 Clinical Study 1, 2 1 3 Pietro Tiraboschi, Erica Chito, ` Leonardo Sacco, 1 1 1 Marta Sala, Stefano Stefanini, and Carlo Alberto Defanti Fondazione Europea Ricerca Biomedica (FERB), Centro Alzheimer, Ospedale Briolini, Gazzaniga, Bergamo, Italy Divisione Neurologica, Ospedale Niguarda Ca’ Granda, Milano, Italy Neurocentre of Southern Switzerland, Lugano, Switzerland Correspondence should be addressed to Pietro Tiraboschi, ptiraboschi@yahoo.com Received 14 February 2011; Revised 29 April 2011; Accepted 25 May 2011 Academic Editor: Amos D. Korczyn Copyright © 2011 Pietro Tiraboschi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Voting by persons with dementia raises questions about their decision-making capacity. Methods specifically addressing voting capacity of demented people have been proposed in the US, but never tested elsewhere. We translated and adapted the US Competence Assessment Tool for Voting (CAT-V) to the Italian context, using it before 2006 elections for Prime Minister. Consisting of a brief questionnaire, this tool evaluates the following decision-making abilities: understanding nature and effect of voting, expressing a choice, and reasoning about voting choices. Subjects’ performance was examined in relation to dementia severity. Of 38 subjects with Alzheimer’s disease (AD) enrolled in the study, only three scored the maximum on all CAT-V items. MMSE and CAT-V scores correlated only moderately (r = 0.59; P< 0.0001) with one another, reflecting the variability of subjects’ performance at any disease stage. Most participants (90%), although performing poorly on understanding and reasoning items, scored the maximum on the choice measure. Our results imply that voting capacity in AD is only roughly predicted by MMSE scores and may more accurately be measured by a structured questionnaire, such as the CAT-V. Among the decision-making abilities evaluated by the CAT-V, expressing a choice was by far the least affected by the dementing process. 1. Introduction in at least two cases (2000 US presidential elections and 2006 Italian elections for the Prime Minister designation), a Mental disorders, including dementia, can impair compe- small number of votes had a decisive effect on the results. tence, but a diagnosis of dementia does not imply a complete It is especially in long-term facilities that inappropriate loss of competence [1]. There is a wide consensus on consid- assumptions about the absence of voting capacity may ering competence as the capacity of a person to make a deprive still capable and willing residents of the right to vote specific decision [2]. Voting is a decision of particular interest [4, 5]. since a consensus does not exist on which abilities the patient Recently, a novel test to assess the capacity to vote has with dementia should retain to express a reliable choice been proposed: the Competence Assessment Tool for Voting [3]. Voting is among the fundamental rights of citizens in (CAT-V) [6], which evaluates an individual’s performance on democratic countries. Thus, identifying patients who, despite four decision-making abilities: understanding the nature and the presence of dementia, maintain the capacity to vote effect of voting, appreciating the reality of voting situation, and increasing their chance to take part in a ballot (e.g., making a choice, and reasoning about voting choices. In allowing their caregivers to have a role in facilitating this) this paper, we report the results of a study that applied a would be of crucial importance. Participation in the electoral modified version of the CAT-V to individuals with mild- process by citizens with dementia has become especially moderate AD who were temporarily residents in a long-term important in recent years, both for the growing number of care facility before 2006 Italian elections for designating the individuals suffering from Alzheimer disease (AD) or other Prime minister. Our primary hypothesis was that although progressive cognitive disorders, and in light of the fact that voting capacity would be inversely associated with dementia 2 International Journal of Alzheimer’s Disease severity, the single decision-making abilities evaluated by Table 1: Demographics of the subjects (n = 38). the CAT-V would be affected unequally by the dementing Mean Standard deviation Range process. Age (years) 81.1 5.1 68–93 Gender (M/F) 9/29 — — 2. Methods Education (years) 5.6 2.3 3–13 Disease duration (years) 3.3 1.6 1–8 2.1. Subjects. The subjects included in the present study MMSE score 18.2 4.2 11–27 (n = 38) represent all the patients with mild-moderate dementia (Mini-Mental State Examination [7] (MMSE) ≥ NPI score at baseline 43.0 17.5 11–72 11) and a clinical diagnosis of probable AD (according to NPI score prior to discharge 21.2 11.7 0–50 the National Institute of Neurological and Communicative MMSE, Mini-Mental State Examination, NPI, Neuropsychiatric Inventory. Disorders and Stroke (NINCDS) and the Alzheimer Disease and Related Disorders Association (ADRDA) criteria) [8] Table 2: Subjects’ score distribution on each item of the Compe- who were admitted into the Alzheimer Centre of the tence Assessment Tool for Voting (CAT-V). Ospedale Gazzaniga (Bergamo, Italy) from sixty to thirty days before 2006 Italian general elections. Although, in some CAT-V item and score N % respects, our centre has several characteristics of a long-term Understanding the nature of voting care facility, no patient is a permanent resident. The primary 0 7 18,4 requirement for a patient’s admission into our centre is the 1 10 26,3 presence of behavioural abnormalities or psychopathologic 2 21 55,3 symptoms in the context of a dementing syndrome but, Understanding the effect of voting once these features are significantly relieved, the patient is 0 18 47,4 discharged. 1 6 15,8 2 14 36,8 2.2. Assessment Tool and Scoring. The instrument we used Choice to evaluate the capacity to vote was a modified version of 0 4 10,5 the CAT-V, an instrument that measures a person’s ability to understand the nature and effect of voting, make a choice, 2 34 89,5 appreciate, and reason through a voting decision. These Comparative reasoning criteria were operationalized into five questions preceded by 0 13 34,2 an introduction reminding each person that soon he/she 1 9 23,7 would have the opportunity to take part in a ballot for 2 16 42,1 the election of the Prime Minister. Thus, as opposed to the Generating consequences original US version of the CAT-V, in which subjects are asked 0 21 55,3 to imagine that two candidates are running for Governor and 1 11 28,9 that the day of the interview is the Election Day, the scenario 2 6 15,8 we proposed was real rather than hypothetical. Furthermore, in order to shorten the time of interview, unlike the original, our version of the CAT-V did not include a question evalu- ating subjects’ appreciation of the significance of voting. For interviewed by M. Sala two weeks later, to evaluate the test- each CAT-V item, the scores assigned to each person ranged retest reliability. The scores included in the main data analysis from 2 (correct response reflecting adequate performance) to are those assigned to all participants at baseline by M. Sala 0 (inadequate performance). The instrument and criteria for The Spearman correlation coefficient was used to examine scoring are shown in the appendix. the association of the capacity to vote (as expressed by the score on each of the CAT-V items) with severity of both Every participant was enrolled after an initial contact with his/her principal caregiver. Once informed about the cognitive impairment (as expressed by the MMSE score) and behavioural and psychopathological symptoms (as expressed characteristics of the study and made sure that its results by the Neuropsychiatric Inventory (NPI) [9]score). Each would be used exclusively for research purposes, each par- ticipant (or his/her caregiver) provided a written informed participant was administered the CAT-V, the MMSE, and the NPI during the same session. consent. The study was approved by our local institutional review board. 3. Results 2.3. Data Analyses. All of the 38 participants were inter- viewed and rated by one investigator (M. Sala), who was 3.1. Subjects’ Characteristics. All the subjects who were asked blinded to their MMSE score. Thirty of them were also to participate in the project (n = 38) did complete the interviewed and rated by another investigator (E. Chito). ` interview. Their demographic characteristics are reported in Weighted kappa and Kendall tau-B were used to determine Table 1. There was a clear female preponderance. Severity the interrater reliability. Twenty-nine subjects were again of cognitive impairment was, on average, relatively mild. International Journal of Alzheimer’s Disease 3 Table 3: Cross-tabulation relating scores on understanding and making a choice to scores on reasoning. Score on questions assessing understanding and choice Number of Number of Score on questions subjects subjects Total assessing reasoning scoring 0–5 scoring 6 Number of participants 10 25 9 34 0123456789 10 scoring 0–3 Combined score on all questions of the Number of participants Competence Assessment Tool for Voting scoring 4 Total 26 12 38 Figure 1: Relation of scores on the Mini-Mental Exam to combined scores on all questions of the Competence Assessment Tool for Voting (r = 0.59, P< 0.0001). Table 4: Competence Assessment Tool for Voting (CAT-V) scoring criteria, interrater, and test-retest reliabilities. Cohen Kendall N P value Kappa tau-b Understanding Interrater 30 0.65 0.7 0.0001 and choosing reliability Reasoning 30 0.41 0.65 0.0001 Understanding Test-retest 29 0.42 0.65 0.0001 and choosing reliability 0 123456 Reasoning 29 0.22 0.57 0.0001 Combined score on the three questions Determined in the first 30 of the 38 patients enrolled in the study. assessing understanding and choice Retest was administered only to patients not yet discharged from our center after two weeks (29/38). Figure 2: Relation of scores on the Mini-Mental State Exam to scores on questions assessing understanding and choice (r = 0.61, P< 0.0001). Behavioural and psychopathological symptoms were mod- erately severe at baseline but were significantly relieved prior to discharge. However, a great variability in subjects’ performance was noted at any stage of disease. On questions evaluating 3.2. Performance on CAT-V. Subjects’ performance on CAT- understanding and choice (Figure 2), for example, only 58% V is shown in Table 2. Over a half of the subjects appeared of subjects with mild AD (MMSE ≥ 20) obtained the to fully understand the nature of the vote, but only approx- maximum score but, remarkably, over one-third of those imately a third was entirely able to understand its effect. who scored the maximum was beyond mild-stage disease However, the great majority of participants (∼90%) was (MMSE < 20). deemed to be completely able to make a choice. Conversely, Lower CAT-V scores were also associated with fewer subjects’ ability to reason about voting by comparing the years of education but, as opposed to disease severity, poor choices at disposal and, above all, by evaluating the possible education had an impact exclusively on measures of under- consequences of the preference for a candidate on their life standing and choice (r = 0.32, P = 0.049). was considerably more impaired. In fact, only about 16% of No relationship was found between education and the participants had a completely adequate performance on MMSE scores (r = 0.05, P = 0.76). the latter measure. As shown in Table 3, which relates subjects’ combined 4. Discussion performance on understanding and choice to their perfor- mance on reasoning, only three of the 38 participants (8%) Among persons with mild to moderate AD, global mea- scored the maximum on all items. As emerges from Table 4, sures of cognitive functioning, such as the MMSE, cannot there were better test-retest and interrater reliabilities for adequately substitute for an assessment of voting capacity. scores on understanding and choice than for scores on The present study has examined the capacity to vote in a reasoning. sample of 38 mild-moderate AD patients using a modified version of the CAT-V. Originally designed in the US, this 3.3. Relation of CAT-V Performance to Severity of Dementia. instrument consists of a brief questionnaire, which has There was no relation of CAT-V scores to severity of been translated and adapted to the Italian context and by behavioural and psychopathological symptoms (r =−0.14, which we have explored the following functional abilities: P = 0.41). Conversely, as expected, lower CAT-V scores were understanding the nature and effect of voting, expressing associated with lower MMSE scores (Figures 1, 2,and 3). a choice, reasoning about the choices at disposal, and MMSE scores MMSE Score 4 International Journal of Alzheimer’s Disease with severe AD may also explain the only low-moderate test-retest reliability values of our study (understanding and choice, k = 0.42; reasoning, k = 0.22),aswellasthe less satisfying agreement between our raters than between the raters of the US study (understanding and choice, k = 0.65 versus 0.91; reasoning, k = 0.41 versus 0.74). Subjects with severe AD have in fact a greater likelihood than those with mild-moderate disease to invariably provide completely inadequate performances, so as to be assigned the minimum 01234 score unambiguously and consistently over time. Not requiring a particular expertise, the CAT-V is Combined score on the two questions assessing reasoning easily administrable, since no more than five minutes are Figure 3: Relation of scores on the Mini-Mental State Exam to needed for its administration. This time might further be scores on questions assessing reasoning (r = 0.41, P = 0.01). shortened if one decides to skip the reasoning questions because, at least in our experience, these questions were too demanding even for mildly deteriorated patients and generated performances characterized by insufficient test- reasoning about the consequences of voting. We have also calculated the reliability of the test and its relation to retest and inter-rater reliabilities. Interpreting subjects’ per- dementia severity. formance remains, however, problematic even when analyses are restricted to the questions inherent in the Doe standard On the basis of our results, a full capacity to vote (as expressed by integrity of all above mentioned decision- (understanding and choice). Clearly, performances at the making abilities) appears to be retained by a small minority extremes of the spectrum are not controversial, so that a of AD subjects (3/38), and exclusively at mild-stage disease performance generating the minimum score unequivocally (MMSE ≥ 20). indicates absence of voting capacity and, by contrast, a performance generating the maximum score indicates a full However, when we applied less restrictive criteria for determining voting competence, as those identified in the compliance with the Doe standard. However, intermediate Doe standard (a legal standard based on a 2001 federal scores need a judgement to be made, the basis of which is not obvious and deserves further comments. For example, district court decision in Maine (US), which solely requires an intact ability to understand and make a choice) [10], in both the US and our study, almost all of the participants subjects’ voting capacity was not completely predicted by with intermediate scores appeared to be invariably capable MMSE scores. On understanding and choice measures, in to make a choice, while what varied was their ability to fact, only 58% of our less deteriorated subjects (MMSE ≥ understand the nature and effect of voting. Consequently, if 20) obtained the maximum score but, remarkably, over one- we had applied more liberal criteria than those identified in third of those who scored the maximum were beyond mild- the Doe standard for determining voting competence and, stage disease (MMSE 13–19). As a result, the relation of for example, we had deemed a patient to retain the capacity to vote if he/she was able to express a choice regardless these measures to severity of cognitive impairment was only moderate (r = 0.61). of understanding, the great majority of AD subjects (90% Of note, over two-thirds of our AD patients, although in our study and 88% in the US study) would have been categorized as such. still able to express a choice, did not appear to be entirely able to understand the nature and, especially, the effect of The limitations of this study relate to lack of data from the vote, thereby failing to meet the Doe standard. A similar nondemented persons, whose availability would have been pattern (choice considerably less impaired than understand- extremely helpful in interpreting intermediate scores by the ing) has previously been reported by US investigators [5]. identification of appropriate cutoffs and of more detailed In their study, however, the percentage of AD patients who neuropsychological information than that provided by the failed to fulfil the Doe standard was lower than that seen MMSE. Other issues are the relatively small sample size, the in our study (55% versus 68%), and there was a much relatively narrow range of cognitive impairment, and the more substantial link between declining voting capacity and presence of significant behavioural and psychopathological increasing dementia severity (r = 0.87 versus 0.61). symptoms (although their severity did not appear to influ- There are several possible reasons for the discrepancy ence the performance of our patients on the CAT-V). Since between our results and those previously reported by the this study was restricted to persons with mild-moderate US investigators. For example, compared to these authors, disease, and most of them had significant behavioural we examined a sample characterized by more advanced age disturbances, its results may be not entirely representative (81.1 versus 77.7 years), greater female preponderance (76% of all patients with AD. Despite these flaws, the primary versus 52%), less severe impairment (mean MMSE 18.2 hypothesis of the present study has been tested and verified. versus 16.4), and considerably lower education (5.6 versus 14 There was an inverse relationship between voting capacity years). Furthermore, since we excluded patients with severe and dementia severity but, somewhat unexpectedly, the AD from analyses, the range of cognitive impairment was strength of this association was not substantial. However, more compressed in our sample (MMSE 11–27) than in as predicted, the single decision-making abilities evaluated the US sample (MMSE 2–28). The exclusion of patients by the CAT-V were unequally impaired by the dementing MMSE Score International Journal of Alzheimer’s Disease 5 Table 5 for example watching TV, listening to their campaign issues, ask: What already known on this topic is “Well, that is how you might decide who you like to be People with dementia are underrepresented at the polls. the Prime Minister. But how would actually express your Many of them are denied the opportunity to vote even when choice?”) retaining the mental capacity to do so. Score of 2: Entirely correct response, for example, “I will Methods that address voting capacity of demented people, go to the polls and vote” or “I will cast my vote for one or the such as the Competence Assessment Tool for Voting other”, and so forth. (CAT-V), have been proposed and tested in the US, but never Score of 1: Ambiguous or partially correct response, for elsewhere. example, “That is why we have Election Day”, and so forth. Using the CAT-V in patients with Alzheimer Disease (AD), Score of 0: Incorrect response, for example, ”There is US investigators have shown a robust association between nothing you can do; the TV guys decide”, and so forth. declining voting capacity and increasing dementia severity. What this study adds Understanding the Effect of Voting. “Once the election for Using a modified version of the CAT-V, we found only a Prime Minister is over, how is it going to be decided who moderate association between declining voting capacity and is the winner?” increasing dementia severity in AD. Score of 2: Entirely correct response, for example, “The The capacity to express a choice is largely preserved even in votes will be counted and the candidate with more votes will moderate-stage AD. be the winner.” Many patients with AD, although no longer capable of Score of 1: Ambiguous or partially correct response, for understanding the nature and importance of voting, are still example, “The better between the two candidates will be the able to express a choice. Their right to vote should therefore winner”, and so forth. be respected. Score of 0: Incorrect or irrelevant response. process (reasoning > understanding > choice). On the basis Choice. Hand patient a card with the information in the of these data, the use of a structured interview, such as following paragraph in large print; allow to retain and the CAT-V, may offer advantages over unstructured or consult this card for the remainder of the interview. clinical assessments, especially in light of the fact that global “For the sake of simplicity, the first candidate (of the measures of cognitive functioning, such as the MMSE, do not right party) is willing to lower taxes by decreasing the burden appear to be strong predictors of the capacity to vote. Further of bureaucracy and public administration, in order to make studies are needed to refine the clinicians’ approaches to people spend more as a result of higher income. The second identifying demented people who are still capable to vote candidate (of the left party) is willing to either raise taxes or, from those who are no longer capable. Nevertheless, a tool by fighting tax elusion, keep them unchanged getting every like the CAT-V can adequately assist in this distinction citizen to pay, so that the rights to education and welfare (Table 5). remain protected. Based on either what I have just told you or what you already knew about the candidates, do you think you are able to choose between the two? Mind that I do not Appendix want to know from you which candidate you would vote for, but only if you have made your choice?” Italian Version of the Competency Score of 2: The patient clearly indicates the choice, Assessment Tool for Voting including a reasoned choice not to vote or a manifestation “I will ask you a few questions about next elections. This it is of indetermination (“I still do not know which candidate to going to take five minutes or less. If you do not understand vote for”). something of what I am saying or asking, please let me know Score of 0: No choice is stated because the patient is and I will repeat it. Some of the questions might seem very unable to choose, does not understand what is asked, and so simple to you, but do not worry about that. We only need forth. straightforward answers. Do you have any questions before we start?” Reasoning Understanding. “Next elections will take place within few Comparative Reasoning. If the patient identifies a choice, ask: weeks. Two candidates are running for Prime Minister (make “Why do you think that it is worth voting for either of the the patient name the candidates or, if he/she does not candidates?” or “Why do you think neither of the candidates remember, remind him/her of their names).” deserves to be voted for?” Score of 2: Entirely correct response, for example, Understanding the Nature of Voting. “What will you do to “Because it is right to maintain the welfare state”, “Because pick the Prime Minister on Election Day?” it is right that everybody pays taxes”, “Because the State (if patient gives an indirect answer, describing how he/she should not empty the citizen’s pockets with too high taxes”, or people in general would choose between the candidates, “Because, despite different views, neither of the candidates 6 International Journal of Alzheimer’s Disease will fulfill the promises made before Election Day”, and so Professionals, Oxford University Press, New York, NY, USA, forth. [2] The President’s Commission for the Study of Ethical Problems Score of 1: Ambiguous or partially correct response, for in Medicine and Biomedical and Behavioral Research. Making example, “Healthcare”, “it is better to spend more than spend Health Care Decisions, US Government Printing Office, Wash- less”, and so forth. ington, DC, USA, 1982. Score of 0: The patient fails to mention a comparative [3] J. H. Karlawish, R. J. Bonnie, P. S. Appelbaum et al., attribute of the respective candidates. “Addressing the ethical, legal, and social issues raised by voting by persons with dementia,” Journal of the American Medical Reasoning on Consequences. If the patient is able to make Association, vol. 292, no. 11, pp. 1345–1350, 2004. [4] J. Karlawish, R. J. Bonnie, P. Appelbaum et al., “Identifying his/her choice for either of the candidates or even in the case the barriers and challenges to voting by residents in nursing he/she wants to abstain from voting, ask: “In your opinion, homes and assisted living settings,” Journal of Aging and Social should the first candidate, that one who wants to lower Policy, vol. 20, no. 1, pp. 65–79, 2008. taxes by decreasing the burden of bureaucracy, or second [5] M. Redley, J. C. Hughes, and A. Holland, “Voting and mental candidate, that one who wants to maintain the welfare state capacity,” British Medical Journal, vol. 341, p. c4085, 2010. by fighting against tax elusion, be elected, how could that [6] P. S. Appelbaum, R. J. Bonnie, and J. H. Karlawish, “The affect your life?” capacity to vote of persons with Alzheimer’s disease,” American Score of 2: Entirely correct response, for example, “I Journal of Psychiatry, vol. 162, no. 11, pp. 2094–2100, 2005. will have more money to spend”, “Public Services won’t be [7] M. F. Folstein, S. E. Folstein, and P. R. McHugh, ““Mini mental reduced”, “I cannot predict what will happen, because they state”: a practical method for grading the cognitive state of won’t do what they promised to do”, and so forth. patients for the clinician,” Journal of Psychiatric Research, vol. Score of 1: Ambiguous or partially correct response, for 12, no. 3, pp. 189–198, 1975. [8] G. McKhann, D. Drachman, M. Folstein, R. Katzman, D. example, “Health will improve”, and so forth. Price, and E. M. Stadlan, “Clinical diagnosis of Alzheimer’s Score of 0: The patient does not give a consequence for disease: report of the NINCDS-ADRDA work group under the his/her life or a reason for saying that there are no personally auspices of Department of Health and Human Services Task relevant consequences. Force on Alzheimer’s disease,” Neurology, vol. 34, no. 7, pp. 939–944, 1984. [9] J. L. Cummings, M. Mega, K. Gray, S. Rosenberg-Thompson, Authors’ Contribution D. A. Carusi, and J. Gornbein, “The neuropsychiatric in- All authors contributed to the design of the study. C. A. ventory: comprehensive assessment of psychopathology in dementia,” Neurology, vol. 44, no. 12, pp. 2308–2314, 1994. Defanti and L. Sacco identified the participants. M. Sala [10] Doe v Rowe, 156 F, supplement 2d 35(DMe), 2001. and E. Chito` did the individual interviews. S. Stefanini, L. Sacco, and C. Defanti administered the neuropsychological and neurobehavioural scales. All authors contributed to the analysis and interpretation of data. P. Tiraboschi drafted the article, and all authors revised it critically for important intellectual content. P. Tiraboschi is the guarantor. Conflict of Interests All authors have completed the Unified Competing Interest form (available on request from the corresponding author) and declare that P. Tiraboschi, E. Chito, ` L. Sacco, M. Sala, S. Stefanini, C. A. Defanti, their spouses, partners, and children have not had any supports or relationships with companies that might have an interest in the submitted work. All authors also declare that they have no nonfinancial interest that may be relevant to the submitted work. Ethical Approval The study was approved by our local institutional review board. Each participant (or his/her caregiver) provided a written informed consent. References [1] T.Grisso andP.S.Appelbaum, Assessing Competence to Consent to Treatment: A Guide for Physicians and Other Health MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 International Journal of Journal of Immunology Research Endocrinology Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Submit your manuscripts at http://www.hindawi.com BioMed PPAR Research Research International Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Research and Treatment Cellular Longevity Neurology Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014

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International Journal of Alzheimer's DiseaseHindawi Publishing Corporation

Published: Jul 14, 2011

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