executive dysfunction using behavioral assessment of the dysexecutive syndrome in parkinson's...

Executive Dysfunction Using Behavioral Assessment of theDysexecutive Syndrome in Parkinson’s Disease

Satoshi Kamei, MD,1* Motohiko Hara, MD,1 Kan Serizawa, MD,1 Masato Murakami, MD,2

Tomohiko Mizutani, MD,1 Motoko Ishiburo, PhD,2 Ritsuko Kawahara, PhD,2 Yukiko Takagi, PhD,2

Katsuhiko Ogawa, MD,1 Hirokazu Yoshihashi, MD,1 Satoru Shinbo, MD,1 Yutaka Suzuki, MD,1

Mai Yamaguchi, MD,1 Akihiko Morita, MD,1 Jun Takeshita, MD,1 and Kaname Hirayanagi, MD3

1Division of Neurology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan2Clinic of Psychosomatic Medicine, Nihon University Itabashi Hospital, Tokyo, Japan

3Department of Hygiene and Public Health, Nihon University of Physical Education, Tokyo, Japan

Abstract: The objective of this study was to evaluate theexecutive dysfunction (ExD) in Parkinson’s disease (PD) usingthe Behavioral Assessment of the Dysexecutive Syndrome(BADS), which provides a wide-range assessment of ExD. TheBADS and the Unified Parkinson’s Disease Rating Scale (UP-DRS) were investigated in 63 nondemented PD patients whorevealed scores of �24 points on the Mini-Mental State Ex-amination based on the DSM-IV. Multiple logistic regressionanalysis was performed to evaluate the predisposing factors toExD, which was defined as �70 points on the age-controlledstandardized score. The total score on the UPDRS was asignificant independent predisposing factor to ExD. Among thevarious parts of the UPDRS, part II was the significant factorfor ExD. The profile scores of all subtests on the BADS in

patients with ExD were significantly lower than those of pa-tients without ExD. All profile scores decreased with severityof PD, but the changes among these scores differed. ExD innondemented PD predisposed to a greater severity of PD,particularly as regards the activity of daily living impairment.Nondemented PD revealed wide-range components of ExD. Allcomponents of ExD were impaired with severity of PD, but thepatterns of each component exhibited variety. © 2007 Move-ment Disorder Society

Key words: executive function; Parkinson’s disease; predis-posing factor; behavioral assessment of the dysexecutive syn-drome (BADS); Unified Parkinson’s Disease Rating Scale(UPDRS).

Executive dysfunction (ExD) in Parkinson’s disease(PD) has been described in many previous studies, butthe reported tasks for evaluation of the ExD were able todetect one or several components of ExD. The ExD inPD has been widely assessed by the Wisconsin CardSorting test (WCST).1–5 The WCST was designedmainly to detect the ability for set shifting.6 In previousstudies employing the WCST,1–5 the frequency of im-pairment of shifting conceptual sets of ExD at the early

stage of PD was found to be higher than that in age-matched normal control subjects. However, the earlystage of PD in these previously reported subjects con-sisted of Hohen & Yahr (H&Y) stage I and II, or stage Ito III. There was only one reported comparative study onExD estimated by the WCST among different H&Ystages in PD.7 Although the number of subjects in thisprevious study7 was small, the ExD did not present atH&Y stage I but was evident at more than stage II. Theimpairment of set shifting, as estimated by the Trail-Making test or Stroop Color-Word test, had also beenreported to present at the early stage of PD8,9 and to berelated to the UPDRS score for the severity of PD.10

Moreover, Tower tasks such as the Tower of Londontask (TOL) mainly detect the ability for set elaborationand planning.6 In previous studies2,11,12 that employedthe TOL, the initial thinking time was impaired at the

The authors report no conflicts of interest.*Correspondence to: Dr. Satoshi Kamei, Division of Neurology,

Department of Medicine, Nihon University School of Medicine,30–1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan.E-mail: [email protected]

Received 25 May 2007; Revised 3 October 2007; Accepted 8 No-vember 2007

Published online 20 December 2007 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/mds.21890

Movement DisordersVol. 23, No. 4, 2008, pp. 566–573© 2007 Movement Disorder Society

566

stage of mild PD and the minimum move solution wasrevealed at the severe stage of PD. Impairment of themotor set had also been found to be evident at the mildto moderate stage of PD, but providing an external cue atthe start of the examination could improve the perfor-mance.13 On the other hand, patients with advanced PDhave been described as exhibiting the disturbance ofevery cognitive measure.14,15

Wilson et al. developed a new test battery providing awide-range assessment of ExD, the Behavioral Assess-ment of the Dysexecutive Syndrome (BADS).16 Lezak etal. recently indicated that the BADS was appropriate asa wide-range assessment for ExD.17 Bennett et al. alsoreported that the BADS was more sensitive to ExD thanmany traditional tests including the WCST, Trail MakingTest, Porteus Maze Test, Controlled Oral Word Associ-ation Test, and Tinker Toy Test.18 However, the impor-tant issue is not whether the BADS is more sensitive orspecific than other well-established batteries or not, butthat the BADS has a notable ability to examine with onlyone scale all aspects of the dysexecutive syndrome: it isthis which gives special relevance to the BADS. In thepresent study, we therefore employed the BADS for thefirst time to estimate the ExD.

The BADS consists of 6 different subtests as follows:the Rule Shift Cards Test, Action Program Test, KeySearch Test, Temporal Judgement Test, Zoo Map Test,and Modified Six Elements Test. The BADS offers amore comprehensive assessment of ExD, in that it in-volves not only set shifting and inhibition control (e.g.,the Rule Shift Cards Test), but also the planning ofbehavior under concept formation to novel situations(e.g., the Action Program Test), problem solving (e.g.,the Key Search Test and Zoo Map Test), even the rea-soning (the Temporal Judgement Test), and problemsolving under planning in the face of several competingtasks (e.g., the Modified Six Elements Test).16,19 TheBADS is thus considered to provide a more integratedbattery with “ecological validity” based on the simula-tion of problem-solving situations that patients may con-front in actual daily life.20–22

Performance on each of the 6 subtests in the BADS isscored according to the BADS manual. These scores aresummed to derive a composite total profile score, pro-viding an overall measure of ExD. The total profile scoreis then converted into a standardized score with a mean(M) of 100 and a standard deviation (SD) of 15 based ondata obtained from normal control subjects in the samemanner as for IQ scores on the Wechsler Adult Intelli-gence Scale, Revised.16 In 2003, Kashima et al. trans-lated and revised the Japanese version of the BADS,which was adapted for validity and normalization in

Japanese people, under the supervision of Wilson.23 Thetotal profile score and profile scores of each subtest inthis Japanese version were confirmed to have an identicalpotential against the original version of the BADS.23

Moreover, Ihara et al. reported that the Japanese versionwas consistent with the original version of the BADSbased on comparative data for Japanese and English ExDpatients.24 It is therefore possible to classify the standard-ized score on the BADS into five grades: impaired,borderline, low average, average, high average, and su-perior, in the same manner as in the traditional IQ test.Since executive function decreases even in normal, agedsubjects, a controlled standardized score is also providedfor the BADS based on data obtained from different agegroups of normal control subjects.16,23 In the presentassessments, we thus employed the age-controlled stan-dardized score of the BADS to estimate the ExD ofnondemented PD patients.

Most previous studies on ExD in PD have, however,utilized single variable analysis. Such analysis tests thesignificance of each variable separately, whereas multi-ple logistic regression analysis tests the independent ef-fect of each variable after considering the associationsamong the variables. A predisposing factor for ExD inPD using multiple logistic regression analysis has beenreported in only one study: Muslimovic et al. found thatpatient’s age was the only significant predisposing factoremploying such analysis.25 Although many earlier stud-ies using two-paired comparisons indicated that the ExDin PD was associated with the severity or motor disabil-ity of PD,5,10,12,14 axial impairment and speech disorderas motor symptoms were only enrolled in this previousmultiple logistic regression analysis.25

The present study therefore represents the first evalu-ation of predisposing factors to ExD based on multiplelogistic regression analysis, which included the totalscore and score of part III on the Unified Parkinson’sDisease Rating Scale (UPDRS) as measures of the se-verity and motor disability of PD.

METHODS

Patient Definitions

The number of consecutive patients in this study aftergiving informed written consent was 106 out of 146, whowere diagnosed as having sporadic form PD at the Neu-rology Clinic of our hospital during the period betweenDecember 2004 and May 2006. The diagnosis of spo-radic PD was made according to the UK Parkinson’sDisease Brain Bank criteria.26 Based on the clinical fea-tures and neuroradiological findings, we excluded otherforms of Parkinsonism that included (1) dementia with

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Lewy bodies (DLB),27,28 (2) drug-induced Parkinsonism,(3) vascular Parkinsonism, and (4) atypical Parkinsonismwith absent or minimal responses to anti-parkinsoniandrugs. Thus, the enrolled patients with PD in the presentstudy did not become demented within 1 year of onset ofmotor manifestations and also lacked any history ofvisual hallucinations or fluctuating cognitive ability sug-gestive of a clinical diagnosis of DLB.

One of us (S.K.) diagnosed 96 out of the 106 patientsas having sporadic PD, and excluded the remaining 10patients from the present study.

Assessments

All 96 registered patients underwent the same assess-ments, including a detailed PD history, family history ofneurological diseases, assessment of educational back-ground, drug history, H&Y stage, and UPDRS evalua-tions for the severity of PD, and a Mini-Mental StateExamination (MMSE) of their mental state. The UPDRS,H&Y stage, and MMSE in all patients were evaluated atthe Neurology Clinic by S.K. Nondemented PD wasdefined as patients with a score of �24 points on theMMSE based on the Diagnostic and Statistical Manualof Mental Disorders, 4th ed. (DSM-IV) criteria for de-mentia according to a previously reported study.29 Forthe estimation of ExD, the BADS (Japanese version) wasperformed in 71 nondemented PD patients by 3 neuro-psychologists (M.I., R.K., and Y.T.) at the Clinic ofPsychosomatic Medicine. Since 7 patients demonstrateda wearing-off phenomenon in their parkinsonism, theassessments including the UPDRS, H&Y stage, MMSE,and BADS were undertaken at the time of the on-periodof PD. The assessments of the BADS were performedwithin one week after those of the UPDRS, H&Y stage,and MMSE. The BADS in all patients was rated accord-ing to the BADS manual16 by M.I., R.K. or Y.T.

Statistical Analysis

SPSS software version 12.0 (SPSS, Chicago, Illinois)was used. At the end of May 2006, the statistical analyst(K.H.) at another independent institute collected the datafor the clinical parameters from S.K. and those for theneuropsychological parameters from M.M.. ExD wasdefined as “impaired” when it showed a value of below70 on the age-controlled standardized score in accor-dance with the BADS manual.16,23 Since the SD for thatstandardized score was 15, this criterion represented twoSD below when compared to the age-controlled normalsubjects. The level of statistical significance in this studywas defined as 0.05.

Estimation of the Inter-Rater Reliability of BADS.

Wilson et al. stated that the inter-rater reliability of theBADS was high based on results for the correlationcoefficient of two different raters.16 We also tested theinter-rater reliability in the present study by estimatingstatistically the intraclass correlation coefficient using atwo-way mixed effects model among the 3 raters. At thebeginning of the present study, the above 3 raters as-sessed the first 15 registered patients independently inorder to evaluate the inter-rater reliability of the BADS.The total profile scores, i.e., the sums for the 6 compo-nent tasks of the BADS, were compared among theseraters.

Assessment of Differences in Each VariableBetween Patients With and Without ExD.

Fisher’s exact probability test was employed for esti-mating the difference of sex between patients with andwithout ExD, for comparing the frequency of ExD pa-tients at different H&Y stages, and for assessing thedifferences in frequency of drug administration. TheMann-Whitney U test was also performed for estimatingthe differences of M-values between 2 groups in terms ofthe age at assessment, duration from onset, educationallevel, and UPDRS scores.

Multiple Logistic Regression Analysis forPredisposing Factors to ExD in Nondemented PD.

Multiple logistic regression analysis was employed toassess the predisposing factors to ExD in PD. A dichot-omous dependent variable of ExD was assigned a valueof 1 when the age-controlled standardized BADS scorewas �70, and 0 when the score was �70. The indepen-dent variables were assigned as (1) sex (male � 0,female � 1), (2) patient’s age at this assessment (years;real number), (3) duration from onset (months; real num-ber), (4) educational level (years; real number), and (6)total score or score on each part of the UPDRS (realnumber). Since the number of patients at H&Y stage I,which was a reference categorical variable, was too small(only 6 patients), the H&Y stage [variable (5)] wasdeleted from the present analysis. The UPDRS [variable(6)] was thus utilized for assessment of the severity ofPD in the present analysis. Moreover, since 33 out of the63 enrolled patients with nondemented PD were alsoexamined for their Zung Self-Rating Depression Scale(SDS), multiple logistic regression analysis including thescore on the SDS as an independent variable was alsoundertaken.

568 KAMEI ET AL.


Assessment of Differences in Each Profile Score ofthe 6 BADS Subtests Between Patients With andWithout ExD, and Changes in Each Profile ScoreWith Progression of H&Y Stage.

The Mann-Whitney U test was performed to estimatethe differences in M-values of the 6 profile scores on theBADS between patients with and without ExD. More-over, the change in each profile score of the 6 subtests onthe BADS according to the progression of the H&Ystage was evaluated from the difference the M-value inthe percentage of the maximum profile score amongdifferent H&Y stages (Mann-Whitney U test).

RESULTS

Six out of the 10 excluded patients in the present studyhad possible vascular parkinsonism (4 patients) or DLB(2 patients). In the other 4 patients, the severity of PDcould not be evaluated clinically because of disability inthe postoperative state following transcervical fracture ofthe femur (2 patients), and pain due to lumbar compres-sion fracture (1 patient) and osteoporosis (1 patient).Ninety-six patients were thus confirmed with a diagnosisof sporadic PD. Among these 96 patients, 71 patientswere diagnosed as having nondemented PD based on theabove-mentioned MMSE and DSM-IV criteria. Amongthe 71 serial patients, 8 were unable to complete theBADS: 5 patients became too fatigued to continue theexamination, 2 patients failed to complete because ofmarked tremor of their right hands, and 1 patient enteredthe off-period during the examination. The remaining 63consecutive patients were thus enrolled for the presentstudy. According to the BADS manual, it takes about 30minutes to complete the examination. However, since thePD patients had motor disability, approximately 1 hourwas required.

ExD, defined as less than 70 points on the aged-controlled standardized score in accordance with theBADS manual, was revealed in 13 out of the 63 patientsstudied (20.6%). The demographic and clinical featuresof the groups of patients which were separated by scoresof �70 and �70 on the age-controlled standardizedBADS are summarized in Table 1. The 63 nondementedPD patients included 40 males and 23 females [mean ageat this assessment, 65.8 � 9.8 years (range, 46–87), withdisease duration 67.1 � 51.1 months (range, 6–228), and13.0 � 2.9 years (range, 6–16) of education].

Inter-Rater Reliability of BADS

The intraclass correlation coefficient for the total pro-file scores in the first 15 registered patients among the 3raters was 0.994 (95% CI: 0.985 to 0.998). The clinical

profile of these 15 patients was included: 10 males and 5females (mean age at this assessment, 64.0 � 11.1 years(range, 46–87), with disease durations 68.5 � 50.9months (range, 12–228) and 13.5 � 2.6 years (range9–16) of education].

Differences in Each Variable Between Patients Withand Without ExD

The differences in each variable between the patientswith and without ExD are summarized in Table 1. Theage at assessment with ExD was greater than that withoutExD. The frequency of ExD at H&Y stage III was higherthan that at stage II. Moreover, the total scores and scoreson part II (Activities of daily living; ADL) and part III(Motor examination) of the UPDRS were also higher inthe patients with ExD than in those without ExD.

Predisposing Factors to ExD in Nondemented PD

The results of the multiple logistic regression analysisin relation to ExD indicated that the only significantindependent variable related to the presence of ExD inPD was the total score on the UPDRS [odds ratio �1.117 (95%CI: 1.040 to 1.200), P � 0.0025]. The otherfactors including sex, age at assessment, duration fromonset, and educational level were not significant. Theresults for each part of the UPDRS employing multiplelogistic regression analysis against the presence of ExDin PD revealed that the only significant independentvariable was the score on part II (ADL) of the UPDRS[odds ratio � 1.115 (95%CI: 1.183–3.100), P � 0.0082].The other factors including the UPDRS part I, part III,and part IV were not significant.

Furthermore, the results of the multiple logistic regres-sion analysis including the SDS score in 33 patients alsoindicated that the only significant independent variablerelated to the presence of ExD in PD was the total scoreon the UPDRS [odds ratio � 1.117 (95%CI: 1.036 to1.209), P � 0.0145]. The correlation between the SDSscore and aged-controlled standardized score of theBADS in these 33 patients was not significant (r �0.263, P � 0.197).

Differences in Each Profile Score of the 6 BADSSubtests Between Patients With and Without ExD,

and Changes in Each Profile Score WithProgression of H&Y Stage

The results for the differences in each profile score ofthe 6 subtests on the BADS between patients with andwithout ExD are summarized in Table 2. Every profilescore of the 6 subtests on the BADS in the ExD patientswas significantly lower than that in those without ExD.Since the clinical severity of PD, which was indicated by



the total score on the UPDRS, was identified as a sig-nificant predictor for ExD in the present study, we alsoassessed the changes in each profile score of the 6subtests with the progression of H&Y stage. The resultsfor the changes in each profile score among the differentH&Y stages are summarized in Figure 1. The profilescores of all 6 subtests decreased with progression of theH&Y stages. However, the patterns of these changeswere not uniform among the subcomponents of the ex-ecutive function. The profile scores for the Rule ShiftCards Test and Action Program Test were relativelypreserved at H&Y stage I, whereas those for the other 4subtests which consisted of the Key Search Test, Tem-poral Judgement Test, Zoo Map Test, and Modified SixElements Test tended to be impaired even at H&Y stageI. Another notable finding was that the profile scores for

the Rule Shift Cards Test decreased markedly from H&Ystage I to IV plus V stage.

DISCUSSION

Patient’s age, severity of PD, and scores on part III(Motor examination) of the UPDRS have been reportedas predisposing factors to ExD in PD based on two-paircomparisons.5,10,12,14 Our results for the correlation ofvariables against ExD demonstrated that patient’s age,H&Y stage, total score, and scores on parts II and III ofthe UPDRS represented significant factors. Our findingswere thus consistent with these earlier results using two-pair comparisons.5,10,12,14

However, PD is a slowly progressive disease thatadvances with increase in the patient’s age. Moreover,since the majority of traditional neuropsychological tests

TABLE 1. Demographic and clinical characteristics of the nondemented PD patients studied

Parameter

Age-controlled standardized score of BADS

Statistical methods and results P value�70 (ExD) (number

of patients: 13)�70 (number of

patients: 50)

(1) Male (%) 8 patients (61.5) 32 patients (64.0) Frequency of males between the 2 groupsa NS(2) Age at assessment (years)

(minimum, mean, median,and maximum)

58, 73.6, 74, 87 46, 63.7, 67, 81 Difference of mean valuesb: patients withExD were older than patients withoutExD

0.0033c

(3) Months after onset(minimum, mean, median,and maximum)

6, 61.2, 52, 156 7, 68.6, 60, 228 Difference of mean valuesb NS

(4) Educational level (years)(minimum, mean, median,and maximum)

9, 12.9, 12, 16 6, 13.0, 12, 16 Difference of mean valuesb NS

(5) Hohen & Yahr stage (%) I: 0 patients (0) I: 6 patient (12.0) Frequency of patients with ExD at differentstagesa:

II: 1 patient (7.7) II: 29 patients (58.0) Stage III was higher than stage II 0.0021c

III: 8 patients (61.5) III: 13 patients(26.0)

Comparisons between other pairs ofstages

NS

IV: 3 patients (23.1) IV: 2 patients (4.0)V: 1 patient (7.7) V: 0 patients (0)

(6) UPDRS (minimum, mean,median, and maximum)

Difference of mean valuesb:

Total score 35, 51.4, 48, 80 8, 30.4, 28, 62 Patients with ExD exhibited higher scoresthan patients without ExD

�0.0001c

Part I (Mentation,behavior, mood)

0, 3.0, 3, 7 0, 2.0, 2, 7 NS

Part II (Activities of dailyliving)

9, 17.5, 17, 25 1, 8.7, 8, 20 Patients with ExD exhibited higher scoresthan patients without ExD

�0.0001c

Part III (Motorexamination)

16, 28.8, 27, 50 6, 18.6, 16, 38 Patients with ExD exhibited higher scoresthan patients without ExD

0.0011c

Part IV (Complications oftherapy)

1, 2.0, 1, 7 0, 1.2, 1, 5 NS

(8) Treatments(a) Dopaminergic drugs (%) 11 patients (84.6) 45 patients (90.0) Frequency of administration between the 2

groupsaNS

(b) Anticholinergic drug (%) 1 patient (7.7) 12 patients (24.0) Frequency of administration between the 2groups#

NS

aFisher’s exact probability test.bMann-Whitney U test.cStatistically significant (P � 0.01).dStatistically significant (0.01 � P � 0.05).UPDRS, Unified Parkinson’s Disease Rating Scale; BADS, behavioral assessment of the dysexecutive syndrome; NS, not significant.

570 KAMEI ET AL.


concentrate on building blocks or card sorting, ExD inPD cannot always be readily assessed because of theconfounding motor disability.30 Nevertheless, in view ofthe fact that ExD constitutes a nonmotor symptom, sincepart III (Motor examination) of the UPDRS had beenreported previously to be a predisposing factor,5,10,12,14

doubt existed as to whether or not ExD in PD reflectedonly the difficulty in tasks for executive function due tothe motor disability in PD. We therefore evaluated thepredisposing factors for ExD by multiple logistic analy-sis including patient’s age and motor disability (part IIIon the UPDRS) as independent variables. Since otherparts of the UPDRS except for part III had not been

estimated in the previous studies, the total score and eachpart of the UPDRS were examined in the present study.The results obtained revealed first that the total score ofthe UPDRS was a significant predisposing factor for thepresence of ExD. Moreover, they also demonstrated thatwhile part II (ADL) was a significant predisposing factor,part III (Motor examination) was not a significant pre-disposing factor. These findings suggested that ExD innondemented PD patients did not predispose to motordisability of PD, but affected the impairment of actualdaily life based on wide-range disturbances of ExD.

Since the BADS provides an integrated assessment ofExD, it has the ability to detect many different aspects of

TABLE 2. Results for differences in profile score on the BADS between patients with and without executive dysfunction (ExD)

Age-controlled standardized scoreof BADS

Statistical methods and results (Difference ofmean valuesa) P value�70 (ExD) �70

Profile score on BADS (minimum, mean, median, and maximum)Total profile score 7, 9.1, 9, 11 11, 16.5, 17, 23 Patients with ExD exhibited lower scores than

patients without ExD in both their totalprofile score and profile scores for eachsubtest

�0.0001b

Rule Shift Cards test 0, 1.6, 1, 4 0, 3.2, 3, 4 0.0004b

Action Program test 0, 2.5, 3, 4 2, 3.6, 4, 5 �0.0001b

Key Search test 0, 0.9, 1, 2 0, 2.0, 2, 4 0.0110c

Temporal Judgement test 0, 1.5, 2, 3 0, 2.5, 2, 4 0.0028b

Zoo Map test –1, 0.5, 0, 2 0, 2.2, 2, 4 �0.0001b

Modified Six Elements test 0, 2.0, 2, 3 0, 3.0, 3, 4 0.0011b

aMann-Whitney U test.bStatistically significant (P � 0.01).cStatistically significant (0.01 � P � 0.05).BADS, behavioral assessment of the dysexecutive syndrome; NS, not significant.

FIG. 1. Mean (and standard deviation)percentage of the maximum possiblescore on each profile of the BADS forpatients with different Hohen & Yahrstages of nondemented PD.



ExD at the same time. The present results for the subtestson the BADS in nondemented PD patients revealed thatevery profile score of the 6 subtests in the patients withExD was significantly lower than that in those withoutExD. The data for the subtests indicated that ExD innondemented PD was seen for set shifting, inhibitioncontrol, reasoning, planning, and problem solving. More-over, the impairments of ExD occurred on the test with atime constraint (Modified Six Elements Test) and the testthat involved a reaction time measure (Rule Shift CardsTest). These observations support the previous findingthat PD patients exhibited a prolonged thinking time.2,15

Nondemented PD patients thus suffer from many differ-ent aspects of ExD.

Although there have been many reported investiga-tions of ExD in relation to the severity of PD, the detailedchanges in different subcomponents of ExD in nonde-mented PD according to the progression of PD are farfrom being established. One notable result of the presentstudy was that ExD in nondemented PD presented non-uniform findings with different patterns among the sub-components of the executive function according to pro-gression of the H&Y stage. This might reflect certaindifferences in the affected lesions and/or disturbance ofneurotransmitters among the subcomponents of ExD. Insummary, the present study on nondemented PD re-vealed a wide-range ExD which was related to the se-verity of PD, although some different patters of progres-sion were evident among the subcomponents of theexecutive function.

Acknowledgments: This work was supported by a grantfrom the Ministry of Education, Culture, Sports, Science, andTechnology of Japan for the promotion of industry–universitycollaboration at Nihon University, Japan; a grant for an “Aca-demic Frontier” Project for Private Universities (matching fundsubsidy from MEXT); and Grants-in-Aid from the ResearchCommittee of CNS Degenerative Diseases, the Ministry ofHealth, Labor and Welfare of Japan. We are indebted to Prof.Mitsuru Kawamura, MD, and Dr. Hiroko Mochizuki, MD,Department of Neurology, Showa University School of Medi-cine, Tokyo, Japan, and Professor Michio Yamada, MD, Pres-ident, Ube Frontier University, Ube, Japan for their invaluablecomments regarding this study.

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