Mini mental Parkinson test: standardization and normative data on an Italian sample

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1 Neurol Sci (2013) 34: DOI /s ORIGINAL ARTICLE Mini mental Parkinson test: standardization and normative data on an Italian sample Alberto Costa Eriola Bagoj Marco Monaco Silvia Zabberoni Salvatore De Rosa Ciro Mundi Carlo Caltagirone Giovanni Augusto Carlesimo Received: 30 November 2012 / Accepted: 19 February 2013 / Published online: 12 March 2013 Ó Springer-Verlag Italia 2013 Abstract The mini mental Parkinson (MMP) is a test built to overcome the limits of the mini mental state examination (MMSE) in the short-time screening of cognitive disorders in individuals with Parkinson s disease (PD). In fact, in this scale, items tapping executive functioning are included to better capture PD-related cognitive changes. Some data sustain the sensitivity and validity of the MMP in the short neuropsychological screening of these individuals. Here, we report normative data on the MMP we collected on a Electronic supplementary material The online version of this article (doi: /s ) contains supplementary material, which is available to authorized users. A. Costa (&) M. Monaco S. Zabberoni IRCCS Fondazione Santa Lucia, Via Ardeatina 306, Rome, Italy a.costa@hsantalucia.it M. Monaco m.monaco@hsantalucia.it S. Zabberoni s.zabberoni@hsantalucia.it E. Bagoj S. De Rosa C. Mundi Azienda Ospedaliero-Univeristaria O.O.R.R, Ospedali Riuniti Foggia, Viale Luigi Pinto 1, Foggia, Italy eriolabagoj@libero.it S. De Rosa sderosa@ospedaliriunitifoggia.it C. Mundi cmundi@ospedaliriunitifoggia.it C. Caltagirone G. A. Carlesimo IRCCS Fondazione Santa Lucia and Università di Roma Tor Vergata, Rome, Italy c.caltagirone@hsantalucia.it G. A. Carlesimo memolab@hsantalucia.it sample of 307 Italian healthy subjects ranging from 40 to 91 years. The results document a detrimental effect of age and an ameliorative effect of education on the MMP total performance score. We provide for correction grids for age and literacy that derive from results of the regression analyses. Moreover, we also computed equivalent scores in order to allow a direct and fast comparison between the performance on the MMP and on other psychometric measures that can be administered to the subjects. Keywords Mini mental Parkinson Parkinson s disease Dementia Cognitive disorders Neuropsychological assessment Introduction Parkinson s disease (PD) is frequently associated with cognitive deficits. Dementia occurs in a large proportion of PD patients, prevalence varying between 20 and 30 % in cross-sectional studies and 80 % in longitudinal trials [1]. Beyond dementia, subtle cognitive deficits have also been shown to be an early neuropsychological feature in this neurological population [2 4]. Recent guidelines to screen cognitive functioning in PD patients have been proposed in a series of studies by the Task Force of the Movement Disorder Society [5]. A twostep procedure was proposed that includes (a) a first-level assessment of dementia by means of global screening scales, and (b) a second-level detailed investigation of specific neuropsychological deficits using a battery of tests. The first-level assessment is a critical step since it is at this time that (risk of) dementia should be correctly recognized. In this regard, Kulisevsky et al. [6] pointed-out the importance to use scales that are specific for PD such as the mini

2 1798 Neurol Sci (2013) 34: mental Parkinson (MMP) [7], the Scale for Outcomes of Parkinson s Disease-Cognition [8], the Parkinson Neuropsychometric Dementia Assessment [9] and the Parkinson s Disease-Cognitive Rating Scale [10]. However, for no of above instruments psychometric properties have been investigated in the Italian population. In fact, among scales recommended to be used for the first-level assessment of cognitive functioning, Italian normative data are available solely for the Frontal Assessment Battery [11, 12] and the mini mental state examination (MMSE) [13, 14]. Indeed, the Frontal Assessment Battery is a useful bedside scale for the investigation of executive abilities with the advantage of short-time assessment and good construct validity. Nevertheless, the Frontal Assessment Battery has the relevant limit to not investigate declarative memory functioning at all. Moreover, a recent study also revealed that, although the total score on this scale was able to discriminate between PD and healthy individuals, the two groups actually differed on only two subtests scores (i.e., Similarities and Go-no-Go subtests) [15]. The MMSE is a reliable scale to be used for the short screening of Alzheimer s type cognitive deficits; nevertheless, it is less sensitive to cognitive impairments in the PD population [16 18]. Indeed, Mamikonyan et al. [18] documented that significant cognitive impairments may occur in PD subjects with MMSE scores in the higher limit of normal range. In fact, MMSE items do not investigate executive functions such as, abstract reasoning, planning, and set-shifting, all capacities that are commonly impaired in PD patients since the early stages of disease [16, 19]. To address MMSE limits in detecting cognitive decline in PD individuals, MMP [7] was proposed. In respect to MMSE, the MMP adds visual declarative memory, verbal fluency, set-shifting and abstract reasoning subtests. Although the validity of the MMP has been poorly explored, some data appear promising in this regard. In a pivotal study, in which the MMP, the MMSE and an extensive neuropsychological battery were administered to a PD sample (n = 50) [7], the MMP, compared to the MMSE, had higher correlation coefficients with performance scores on tests tapping cognitive deficits frequently associated to PD (i.e., the Wisconsin Card Sorting Test, the Stroop test, the verbal fluency and the Benton Line Orientation tests) [7]. In this study, the authors also found good content and construct validity and high inter-rater reliability (r = 0.84). Subsequent studies consistently verified the psychometric characteristics of this test and evidenced satisfying levels of sensitivity and specificity to be applied to the investigation of global cognitive impairment in PD [20 22]. In summary, MMP is a potential useful instrument for the first-level screening of cognitive functioning in PD patients thus helping the clinician to individuate those subjects who need a specialist neuropsychological exam. However, its applicability in the Italian population is limited by the absence of data on the score distribution in healthy individuals. The present study was aimed at collecting normative data on the MMP in the Italian population. For this purpose, the effects of some socio-demographic factors (i.e., age, education and gender) have been investigated in a sample of 307 healthy individuals ranging from 40 to 91 years to achieve criteria for raw scores correction and to define cut-off scores. Moreover, equivalent scores were also computed to permit a direct comparison of MMP scores with subject s performance on other psychometric instruments used for the cognitive screening such as, for instance, the Frontal Assessment Battery and the Mental Deterioration Battery. Subjects and methods Subjects Subjects included in this study derived from two different cities of Italy (Roma, Foggia). Three-hundred and seven volunteers (148 females and 159 males) participated in the study. Mean age for the whole sample was 62.8 ± 13.9 (range 40 91) and average years of formal education was 10.6 ± 4.8 (range 1 23). Subjects were recruited from the following sources: (a) among partners of patients with neurological diseases; (b) among volunteers in a senior centre; (c) among individuals belonging to sanitary and administrative staff. Subjects stratification according to age, years of formal education and gender is reported in Table 1. The following inclusion criteria were adopted: (a) absence in the history of psychiatric disorders, alcohol or drug abuse according to DSM-IV-TR [23] criteria, as evaluated by a clinical examination and by the administration of the Mini International Neuropsychiatric Interview [24], (b) no history of neurological disorders, traumatic brain injury, stroke, transient ischemic attacks or seizures and (c) absence of dementia or memory complaints as resulted from a clinical assessment according to DSM-IV- TR [23] criteria, and confirmed by a adjusted score on the MMSE [23.8 [14]. All participants were explained the purpose of the study and written informed consent was collected. The mini mental Parkinson test The Italian version of the MMP was not different from the original one [7] with the exception of the backward spelling task in which the word carne (meat) was used. The test is reported in ESM appendix 1. The test is composed of

3 Neurol Sci (2013) 34: Table 1 Socio-demographical characteristics distribution of the sample Decade Total Number Mean years of education (range 1 23) and SD (4.58) (4.9) (4.94) 9.36 (3.93) 9.29 (4.93) (4.80) M/F 27/37 28/46 26/37 33/18 45/10 159/148 the following seven subtests: temporo-spatial orientation, visual memory immediate and delayed recall, attention/ mental control, verbal fluency, set-shifting and concept processing. The procedure of administration and criteria for scoring are presented below for the seven subtests according to their canonical order of administration. Spatial temporal orientation The subjects are requested to answer at the following questions: What is the year? date? day of the week? month? and without looking it s watch, what time it is? (one-hour tolerance is allowed). In which State, Country, Town, Place and Floor are we? One point is given to each correct item, the score ranging between 0 and 10. Visual memory immediate recall The subjects are asked to look for a subsequent recall three pairs of figures representing concrete stimuli and geometric figures. Each pair is presented in one stimulus card one at a time (first card: glasses and a ring with an horizontal line inside; second card: a cube and letter m ; third card: a triangle and a flower) that the subject has to name. After the three cards presentation, the subject is required to recall the six individual stimuli independently from their order of administration. Three presentations of the three cards are allowed. Three points are given if the subject recalls all six figures after the first presentation, two points if he/she recalls stimuli after the second presentation and one point after the third one. A score of zero is attributed if the subject is not able to recall all six figures even after the third presentation. Attention and mental control This subtest is the same as in the MMSE. The subject is required to count backwards from 100 in five 7-point steps. In the case the subject has difficulties with this test, he is asked to spell out backward the word Carne (meat in English). One point is given to each correct single computation (or to each letter spelled out in the right order), the score ranging varying from 0 to 5. The subject is attributed the higher score he/she obtained out of the two tasks. Verbal fluency The subject is required to name three animals each beginning with letter L within 30 s. One point is given to each correct item, the score ranging between 0 and 3. Visual memory delayed recall The three stimulus cards presented in the previous visual memory immediate recall subtest are presented again in a different order. In this case, however, in each card only one of the two previously paired stimuli is presented. The subject is asked to recall the missing stimulus in each card. One point is given to each correct recall and another point is attributed to the remembering of the correct order of card presentation. The score ranges between 0 and 4. Shifting abilities One card reporting four isosceles triangles that vary as for dimension, orientation, colour (black/white) and the geometric figure in which it is included is presented. The subject is required to individuate all characteristics that differentiate each triangle from the others. One point is given to each correctly identified variable, the score ranging from 0 to 4. Abstract reasoning Three word-triplets are verbally presented in three different trials [first trial: treno, borsa, barca (train, bag, boat); second trial: guanti, cappello, rastrello (glove, hat, rake); third trial: arancia, carota, uva (orange, carrot, grapes)]. In each trial the subject is required to individuate the two more closely semantically related words in the triplet. One point is given to each correct response, the score ranging between 0 and 3. The subjects were assessed in one single session. Total score on the MMP was computed as the sum of scores in each individual subtest (range 0 32). Statistical analysis As a first step of the statistical analysis we calculated the effects of demographic variables (age, education and

4 1800 Neurol Sci (2013) 34: gender) on healthy subjects total score on the MMP test. Pearson s correlation coefficients were performed between the score and age and education. Various transformations of the row age and education values (i.e., quadratic, logarithmic, inverted) were tested to verify which was the most effective in reducing residual variance. The effect of gender (males vs. female) on test scores was, instead, investigated by using Student s t test statistic. A multiple linear regression analysis was then performed with test score as the dependent variable and age, education (or most convenient transformations) and gender as explicative factors. According to the Bonferroni s correction, the independent variables entered in the definitive regression model only if their significance was at least p = (p = 0.05/2). Based on the results of multiple regression analyses, regression equations were built up to calculate the adjusted performance scores for each combination of significant demographic variables [25]. Then, we calculated the adjusted scores for each subject and we determined the lower limit of the tolerance interval for the test performance. Using a nonparametric procedure [26], we set the ninth scalar observation as the tolerance limit, leaving above at least 95 % of the normal population (with 95 % confidence). A score below this tolerance limit was considered not normal with 95 % confidence. Conversely, a score above the tolerance limit was declared normal with 95 % confidence. To make scores comparable with other neuropsychological tests, we classified adjusted scores into five categories (equivalent scores) endowed with an ordinal relationship: 0, scores lower than the 95 % tolerance limit; 4, scores higher than the median value of the sample; 1, 2 and 3, scores lower than 10.4, 26.4 and 50 % of the normative sample distribution, respectively [25]. Results The average MMP total score was 28.3 (SD = 2.6, range = 19 32), the median and moda values being 29 and 30, respectively. As shown in Fig. 1a, performance scores on the MMP test are inversely correlated with age (r = -0.41; p \ 0.001). This means that increasing age is associated with progressively decreasing performance on the MMP. Figure 1b also illustrates MMP scores distribution as a function of the years of formal education. In this case, a significant positive correlation was found indicating that increasing MMP score is significantly associated with increasing years of education (r = 0.39; p \ 0.001). As for the effect of gender, females were significantly more accurate than males [t (1,305) = 3.21; p = 0.024]. In Tables 2 and 3 the results of the multiple regression analyses with gender, age and education as independent variables are reported. In the first regression model only the age and education factors predicted MMP scores (p \ 0.001), while the effect of gender was not significant (p = 0.45). Therefore, the definitive regression model was built with only age and education as explicative variables (F = 36.9; p \ 0.001). Table 4 reports equation and correction grid by age and education. Table 5 reports equivalent scores for adjusted scores on the test. Discussion The assessment of cognitive functioning is being increasingly recognized as an important clinical issue in individuals with PD. Indeed, cognitive decline that includes dementia and MCI involves a significant proportion of patients and is associated with worse prognosis and poorer quality of life [27, 28]. Recent guidelines have been proposed that suggest procedures and tools to evaluate cognitive impairment and the risk of developing dementia in this population [5, 16]. In particular, a two-step procedure with a first level of assessment, in which a general screening of cognitive functioning is performed, followed by a specialist exam of the neuropsychological profile is generally suggested. As previously mentioned, the screening level is critical for the detection of initial cognitive impairment. At this regard, Litvan et al. [5] points out the need for the use of psychometric measures that have acceptable specificity and sensitivity for the detection of neuropsychological changes due to PD. In fact, cognitive decline in PD patients is typically characterized by a dysexecutive syndrome associated declarative memory and visual-spatial deficits [19], symptoms that are not reliably investigated by some instruments that are widely used in the ambulatory services for dementia or memory disorders (e.g., the mini mental state examination). Various tools sensitive to frontal-striatal like cognitive disorders have been proposed to be used in the screening phase with PD patients. These include the MMP [7], the Scale for Outcomes of Parkinson s Disease-Cognition [8], the Parkinson Neuropsychometric Dementia Assessment [9] and the Parkinson s Disease-Cognitive Rating Scale [10]. However, the use of these tests is limited in the Italian population because of the lack of normative data. The aim of this study was to provide standardization and normative data on the MMP to make available for the clinician a brief test for the global cognitive screening in individuals with PD. For this purpose, the effects of age, years of formal education and gender on the performance score of a relatively large group of healthy Italian

5 Neurol Sci (2013) 34: a MMP average accuracy score Age Decades b MMP average accuracy score Years of formal education Fig. 1 The figure illustrates, in the whole sample, MMP scores distribution as a function of aging (a) and of years of formal education (b) Table 2 Results of the multiple regression analyses with age, years of formal education and gender as explicative variables Table 3 Results of the multiple regression analysis with age and years of formal education as explicative variables Independent variables B Standard error Degree of freedom t test p level Independent variables B Standard error Degree of freedom t test p level Constant Sex Age Education B regression coefficient individuals were investigated. No subject showed difficulties in performing the test that took about min to be executed. As expected, age was inversely correlated with subjects MMP performance and higher education predicted better scores on the MMP. The effect of gender, that was revealed by the first level analysis that compared group Constant Age Education B regression coefficient means (i.e., females more accurate than males), was not confirmed by the multiple regression model. Therefore, we computed correction parameters to adjust raw scores and inferential cut-off scores on the basis of a regression equation including solely age and years of formal education. Data were further elaborated in order to calculate

6 1802 Neurol Sci (2013) 34: Table 4 Regression equation and correction grid according to age and education for raw scores on the MMP Age/education Best linear model: 28.3? (Age-62.86) (School-10.61) Significance: age t =-6.75, p \ 0.001; school t = 6.22, p \ Table 5 Equivalent scores computed according to procedure described by Spinnler and Tognoni [25] Equivalent scores % distr del campione a sinistra del limite indicato MMPSE \22.85 \25.42 \27.20 \28.53 [28.53 equivalent scores [25] that allow a direct and fast comparison between the performance on the MMP and on other on other psychometric instruments used for the cognitive screening such as, for instance, the Frontal Assessment Battery and the Mental Deterioration Battery. The MMP test was built to overcome the limits of the MMSE in the brief screening of cognitive disorders in PD [7]. In fact, substantial difference between the two scales are represented by the inclusion, in the former, of items sensitive to executive disorders such as shifting aptitude, conceptualization capacities and the ability to access stored information. These deficits are frequently reported in PD patients even in the early stages of disease and the relationship with altered activity of prefrontal-striatal pathways was suggested [29, 30]. However, the validity of the MMP in the PD population is not been well established yet. After the pivotal study by Mahieux et al. [7], very few studies have been published on this issue. As previously discussed, results by Mahieux et al. [7] document that MMP scores in patients with PD are associated to performance on some external measures of executive and visual-spatial abilities sensitive to cognitive dysfunction in these patients (i.e., Wisconsin Card Sorting Test, the Stroop test, verbal fluency and the Benton Line Orientation tasks). Parrao-Diaz et al. [21] also demonstrated that the MMP score discriminated between PD patients with a diagnosis of dementia, PD patients without dementia but with cognitive impairment and PD individuals without cognitive deficit at all. Moreover, Caslake et al. [20] showed that a MMP score of 28 has high sensitivity (86 %) and specificity (73 %) in detecting the presence of cognitive disorders in the PD population. However, the authors did not specify whether they used raw or adjusted scores. Interesting data on the psychometric properties of the MMP test have been recently published by Serrano-Dueñas [22] on a sample of PD individuals. In this study the MMP test had good validity with high internal consistency (Cronbach s alpha value = 0.75) and fair capacity to discriminate individuals according to the severity of disease (validity for Known Groups). Moreover, the reliability of the MMP test was substantially comparable to that of the Scale for Outcomes of Parkinson s Disease- Cognition while score distribution appeared to be less skewed than that observed for the MMSE. In particular, a ceiling effect for MMP score was observed in the 2.4 % of subjects whereas for the MMSE the same effect occurred in the 32.5 % of the individuals. The authors argued that this latter finding could be due to the relatively low sensitivity of the MMSE to executive dysfunction associated with PD. The psychometric properties of the MMP has been also investigated in a general neurological population. In one study, Larner et al. [31] showed that, in a sample of 201 individuals with neurological diseases, the MMP has good level of sensitivity and specificity in classifying subjects affected by cognitive impairments. The authors also commented that the MMP was easy to administer and was quite acceptable by all patients. In conclusion, this study was aimed at providing the clinician for a reliable and easy instrument to be administered for the brief screening of cognitive impairment in individuals with PD. Indeed, the results of various study on the MMP in non-italian samples sustain its sensitivity, validity and reliability in the assessment of cognitive changes associated to PD. The application of our normative data to the performance of Italian PD individuals on the MMP test is necessary to clarify the clinical usefulness of this tool and its relationship with other psychometric measures of cognitive and functional abilities in this neurological population.

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