INECO Frontal Screening

Journal of the International Neuropsychological Society (2009), Page 1 of 10. Copyright © 2009 INS. Published by Cambridge University Press.Printed in the USA. doi:10.1017/S1355617709990415 INECO Frontal Screening (IFS): A brief, sensitive, and specific tool to assess executive functions in dementia TERESA TORRALVA,1,2 MARÍA ROCA,1,2 EZEQUIEL GLEICHGERRCHT,1 PABLO LÓPEZ,1,2 and FACUNDO MANES1,2 1Institute 2Institute of Cognitive Neurology (INECO), Buenos Aires, Argentina of Neurosciences Favaloro University, Buenos Aires, Argentina (Received January 1, 2009; Final Revision June 16, 2009; Accepted June 16, 2009) Abstract Although several brief sensitive screening tools are available to detect cognitive dysfunction, few have been developed to quickly assess executive functioning (EF) per se. We designed a new brief tool to evaluate EF in neurodegenerative diseases. Patients with an established diagnosis of behavioral variant frontotemporal dementia (bvFTD; n = 22), Alzheimer disease (AD; n = 25), and controls (n = 26) were assessed with a cognitive screening test, the INECO Frontal Screening (IFS), and EF tests. Clinical Dementia Rating Scale (CDR) scores were obtained for all patients. Internal consistency of the IFS was very good (Cronbach’s alpha = .80). IFS total (out of 30 points) was 27.4 (SD = 1.6) for controls, 15.6 (SD = 4.2) for bvFTD, and 20.1 (SD = 4.7) for AD. Using a cutoff of 25 points, sensitivity of the IFS was 96.2%, and specificity 91.5% in differentiating controls from patients with dementia. The IFS correlated significantly with the CDR and executive tasks. The IFS total discriminated controls from demented patients, and bvFTD from AD. IFS is a brief, sensitive, and specific tool for the detection of executive dysfunction associated with neurodegenerative diseases. The IFS may be helpful in the differential diagnosis of FTD and AD. (JINS, 2009, 1–10.) Keywords: Neuropsychology, Cognition, Dysexecution, Frontotemporal dementia, Alzheimer disease, Differential diagnosis INTRODUCTION Executive functioning (EF) refers to the end result of a coordinated sequence of cognitive processes aimed at achieving a particular goal in a flexible manner. The prefrontal cortex is essential for these processes (Funahashi, 2001; Fuster, 1997; Stuss & Benson, 1986), and several neurological (Cummings, 1993; Graham, Bak, & Hodges, 2003; WilliamsGray, Foltynie, & Brayne, 2007; Zakzanis, Leach, & Freedman, 1998) and psychiatric disorders (Reichenberg et al., 2008; Roth & Saykin, 2004) are characterized by deficits in EF. However, it is now well established that different pathologies typically classified within the same umbrella, such as various types of dementia, are not equally impaired in this domain. For example, it is known that patients who develop the behavioral variant of frontotemporal dementia (bvFTD) have early and prominent impairments in executive functions due to early changes in frontal lobe structure (for Correspondence and reprint requests to: Teresa Torralva, Instituto de Neurología Cognitiva (INECO), Castex 3293 (1425), Buenos Aires, Argentina. E-mail: [email protected] 1 review, see Hodges & Miller, 2001a, 2001b). On the contrary, patients with Alzheimer’s disease (AD), can present very mild executive dysfunction but are not characterized, at least during the early stages, by prominent executive problems. Rather, they tend to present deficits in episodic memory due to early changes in medial temporal lobe structures (for review, see Nestor, Scheltens, & Hodges, 2004). While an accurate evaluation of executive functions is critical for accurate differential diagnosis of a range of conditions, the detection of a dysexecutive syndrome typically requires an extensive neuropsychological battery. A brief screening tool which is easy to administer, yet shows high sensitivity, specificity, and predictive value would be of great importance to clinicians. Several cognitive screening tools have desirable diagnostic and statistical properties (Cullen, O’Neill, Evans, Coen, & Lawlor, 2007), but few have been designed to specifically assess executive functioning. As evidence of the intrinsic difficulties that arise with the development of such tools, various screening batteries that have attempted to measure executive dysfunction, fail to exhibit reasonable psychometric properties. For instance, Rothlind and Brandt (1993) proposed a brief screening test for detecting Abstraction Working Memory Central Executive . Manes et al. which would be better regarded as a neurological sign of disinhibition (“grasping sign”) than as an index of neuropsychological impairment and is only affected in patients with extremely severe frontal T. easy-to-administer. IFS = INECO Frontal Screening *Predominantly verbal (Phonological Loop). 2002. motor inhibitory control. such as AD and FTD (Castiglioni et al.. To design a more sensitive and specific tool. which is involved in the control and regulation of the Working Memory System. Mahurin. Given the aforementioned difficulties and based on our previous research studies on executive tests (Clark. This screening test was designed to provide health professionals with a sensitive and specific executive screening test to determine frontal dysfunction in patients with dementia. Lipton et al. Table 1. Santangelo et al. proposed by Baddeley and Hitch (1974).. sensitivity to interference.. Ettlin and Kischka developed the Frontal Lobe Score. For various clinical and practical reasons. patients with AD showed worse performance on this test than patients with frontal dysfunction showing low specificity of the tool. we also included new subtests that have been shown to be sensitive to executive dysfunction: numerical working memory (backward digit span). 2005) in the early stages. and Gray (1992) developed an executive functioning interview reflecting a similar problem. Considering this. (2000) showed no correlation between the FAB and general cognitive measures. 2004.. we refrained from including the following subtests of the FAB: verbal fluency. Torralva et al. (2005) while conflicting instructions and inhibitory control are. but administration of this tool requires at least 40 min (Ettlin & Kischka. We incorporated some of the FAB subtests which showed the highest sensitivity in our everyday clinical experience: motor programming. although the original study by Dubois et al. Subtests grouped into the different executive functions tapped by the IFS Executive function Response inhibition and set shifting IFS subtest Motor programming Conflicting instructions Go–No go Verbal inhibitory control (Modified Hayling test) Proverb interpretation Backwards Digit Span Verbal Working Memory* Spatial Working Memory** Note. The executive domain encompasses several different functions and the IFS was designed to incorporate a few measures that could tap. its ability to actually differentiate types of dementia. has a three component structure including a Central Executive. Manes. one responsible for holding verbal information for short periods (phonological loop) and the other for holding information in visual and spatial form (visuo-spatial sketchpad). Castro. 2007). The Frontal Assessment Battery (FAB. over the last years. By contrast. 2009. we designed a tool aimed at detecting executive dysfunction: the INECO Frontal Screening (IFS). sensitive. 2009). Litvan. has become widely used in neurological research (Guedj et al. 2006.. conflicting instructions. while highlighting the lack of correlation with the Mini Mental State Examination (MMSE). Clark & Manes. and in particular. two subtests that usually pose difficulties to our frontal patients. **Predominantly visual (visuo-spatial sketchpad).. & Robbins. & Pillon. sensitive to frontal dysfunction. and inhibitory control. brief (approximately 10 min). and two “slave systems”. 1997a). cognitive flexibility. 2006. Lipton et al.. dysfunction (Iavarone et al. Burgess & Shallice. Royall. one of the most well known models. Slachevsky. the goal of this study was to evaluate a new. because it is usually administered in general cognitive screening batteries.. The design of the IFS was primarily conceived as representing three groups of tasks. The original authors conclude that the FAB is an easy-to-administer battery. Torralva et al. They report correlations with executive measures such as the Wisconsin Card Sorting Test (WCST) and measures of general cognitive functioning (Mattis Dementia Scale).2 frontal and subcortical dysfunction.. other studies have cast doubts on the sensitivity and specificity of the FAB. and also to distinguish between neurological pathologies such bvFTD and AD (Slachevsky et al. subsequent studies failed to replicate these findings suggesting that performance on the FAB does not reflect frontal function exclusively (Castiglioni et al.. the inclusion of the subtests of the IFS was based on the model presented in Table 1. 2004). as follows: (a) response inhibition and set shifting – evaluates the ability to shift from one cognitive set to another and to inhibit inappropriate response in a verbal and motor way. Overall. 2006. and verbal inhibitory control (modified Hayling test. Antoun. Yoshida et al. being sensitive also to nonexecutive dysfunction. 2005). similarities. and prehension behavior. (b) capacity of abstraction – obtained from proverb interpretation. in a brief way. motor programming has been shown to have the highest sensitivity in a study by Lipton et al. spatial working memory (modified Corsi tapping test). verbal working memory (months backward). Lima. Dubois. 2000) is an executive screening test that. 2008. 2004). Moreover. however. as we included a more complex subtest of conceptualization. It consists of six subtests assessing conceptualization. & Garrett. motor programming. and prehension behavior. Fonseca. Meireles. Of the FAB subtests included in the IFS. with concrete interpretation being typical of frontal lobe damage patients.. 2003. conceptualization (proverbs).. in our experience. The authors of the FAB have proposed this test for the evaluation of different kinds of frontal dysfunction. 1999). Oguro et al. as many of these functions as possible. (c) working memory – referring to a brain system that provides temporary storage and manipulation of the information necessary for other complex cognitive tasks. 2008. Sahakian. . Rakowicz. 1994). if they made one or two errors. 1976). instructions. However. Depending on the extent of frontal lesion or degeneration. a practice trial was performed in which the administrator hit the table once. and others may not even be capable of copying it. three times in succession. edge. we propose that. Two trials were . Data for this study were obtained from the following tests: the IFS. 1975). 1995). three more times. Within the dementia group. For this task. but when the examiner hit twice. and then twice. Coben. in which case the score was 0. three more times. Nestor. IFS Subtests 1. when the test administrator hit the table once. To ensure the subject had clearly understood the task. IFS content. If subjects achieved six consecutive series by themselves. “fist. some patients may not be able to complete the series in the correct order on their own. Overall average administration time is approximately 10 min. they should hit it once as well. If subjects made no errors. Mathuranath. Danzinger. Interference (Dubois et al. All patients with AD diagnosis fulfilled NINCDS-ADRDA criteria (Varma et al. After the practice trial the examiner completed the following series: 1-1-2-1-2-2-2-1-1-2. because of the early and prominent executive impairment of bvFTD. specialists determining diagnoses of patients included in the analysis were blind to their performance on the tool introduced in this study. Go–No Go (3 points) (Dubois et al. 1982). a practice trial was performed in which the administrator first hit the table once. the score was 1. or to hit the table twice when the administrator hit it only once. This subtest asks the patient to perform the Luria series. the score was 3. 3. Specifically. 3 scores. 2000. the score was 2. for more than two errors the score was 1. and had no history of either neurological or psychiatric disorder. the score was 1. bvFTD patients showed frontal atrophy on MRI. This task was administered immediately after test 2. and then twice. Healthy controls were examined with a comprehensive neuropsychological and neuropsychiatry evaluation. 2. if they achieved at least three consecutive series on their own. Backward Digit Span (6 points) (Hodges. 2000). three times in succession. Luria. 2000). If subjects made no errors. unless the subject copied the examiner at least four consecutive times. We hypothesized that a screening tool specifically designed to measure executive functioning may differentiate the executive deficits characteristic of frontal damage (bvFTD) from the subtle executive deficits of the early AD. We also investigated whether the IFS could discriminate executive functioning between bvFTD and AD. Folstein.. Berg. 1949). these patients would perform worse than the AD group on said screening tool. & Martin. and the WCST (Nelson. Subjects were told that now. the Addenbrooke’s Cognitive Examination (ACE. the INECO Frontal Screening (IFS). To ensure the subject had clearly understood the task. & Hodges. Procedure The study was initially approved by the ethics committee at the Institute of Cognitive Neurology (INECO) following international regulations established for human research subjects. Motor Programming (3 points) (Dubois et al. including the verbal phonological fluency (Lezak. if they failed at achieving at least three consecutive series alone. for more than two errors. 1998). 1966). 2000) which also incorporates the MMSE (Folstein. 2000). After the practice trial. when available.. and by subsequently doing the series on his or her own then by repeating the series six times alone. Total IFS score is calculated as the sum of each of the eight subtest 4.INECO frontal screening and specific tool for the assessment of executive functioning. they should do nothing. 22 patients presented with the bvFTD and 25 with a diagnosis of probable AD. but achieved three when copying the examiner. palm” by initially copying the administrator. All participants were evaluated with an extensive neuropsychological battery. and scoring for each of the subtests are included as an appendix to this article. All patients underwent a standard examination battery including neurological. Trail Making Test – Part B (Partington & Leiter. Berrios. in which case the score was 0. Patients with frontal lesions tend to imitate the examiner’s movements. and frontal hypoperfusion on SPECT. the score was 3. and classical executive measures. METHODS Participants A total of 73 participants were included in this study.. while all patients in the bvFTD group fulfilled Lund and Manchester criteria (Neary et al. Conflicting Instructions (3 points) (Dubois et al. and neuropsychological examinations and a MRI-SPECT.. Patients with a Clinical Dementia Rating (CDR) Scale of two points or higher were excluded from this study (Hughes. 26 of which were healthy controls. the score was 3. to avoid circularity. a condition which mainly involves medial temporal lobe structures at early stages. 1999).. the score was 2. unless the subject copied the examiner at least four consecutive times. neuropsychiatric. Subjects were asked to hit the table once when the administrator hit it twice. subjects were asked to repeat a progressively lengthening string of digits in the reverse order. for one or two errors the score was 2. otherwise the score was 0. the examiner completed the following series: 1-1-2-1-2-2-2-1-1-2. and 47 of which were diagnosed with dementia. ignoring the verbal instruction. & McHugh. 72 = 2. p < . . the examiner presented the subject with four cubes and pointed at them in a given sequence.01). In this task.3. When analyzing categorical variables (e.001) differed across the groups (all comparisons. Nonetheless.082) nor gender (χ2 = 0.72 = 91. the Freeman-Halton extension of the Fisher exact probability test for 2 × 3 contingency tables was used. Demographic and clinical information. In the second part (remaining three sentences). AD = Alzheimer’s disease. 2007). The MMSE (F2. starting with December.46) 77. the score was 2. The three proverbs were chosen specifically for this demographic population based on their high frequency in oral speech. three proverbs were read to the subjects and they were asked to explain their meaning. subjects were asked for a completion that was syntactically correct but unrelated to the sentence in meaning.4 (2. the number of items produced on the phonological fluency task. As expected. then the next length was administered. a score of 1 for a word semantically related to the expected completion. Spatial Working Memory (4 points) (Wechsler. MMSE = Mini Mental State Examination. the ACE total score. a tooth for a .0 software package. The score was the number of lengths at which the subject passed either trial.5 for a correct example. Note.6 (9. Patients with frontal lesions show difficulties in abstract reasoning tasks.72 = 48. 1997b). Abstraction Capacity (Proverb interpretation) (3 points) (Hodges. In the first part (three sentences).5 (3. There were four trials. & M. Demographic and general cognitive status information bvFTD (n = 22) AD (n = 25) Control (n = 26) Age Years of education Gender (M : F) MMSE ACE CDR 70. a score of 2 was given for a word unrelated to the sentence. Statistical Analysis Internal consistency was determined with Cronbach’s alpha coefficient. Table 2. To analyze concurrent validity with other tasks shown to be sensitive to damage to the prefrontal cortex.. If subjects made no errors.1) 16. p < . four. This task. 1994). p < . beginning at two and continuing to a maximum of seven. as quickly as possible. the score was 1.93 (0. with either similarities or proverb interpretation tasks.4 (11. Score was number of correctly completed sequences.88) differed significantly between the groups.5 (3.85 (0. Verbal Inhibitory Control (6 points) (Burgess & Shallice. The patient was asked to list the months of the year backward.6 (0.1) 80.5. with sequences of two. significant differences were found for the CDR (F2.001). the MMSE. 5. Values are expressed as Mean (SD).g.5 (2.72 = 60. with AD patients differing from both controls (p < . the number of categories abstracted. Example: “An eye for an eye. maximum 6. for one error.). with controls scoring significantly lower than the dementia groups (both. but no differences between AD and FTD (p = .. Torralva et al. bvFTD = behavioral variant frontotemporal dementia.1) 9 : 13 27. this subtest is potentially capable of efficiently evaluating two executive function components (initiation and inhibition) in relation to a unique symbolic verbal form (Abusamra. Verbal Working Memory (2 points) (Hodges. T. the IFS total score was correlated with the Clinical Dementia Rating (CDR) Scale. as well as neuropsychological test performance were compared between the groups using oneway analyses of variance with Bonferroni post hoc analyses when appropriate. and perseverative errors on the WCST.001).1) 0 8.9) 0.91).5) 0. and a score of 0 for the expected word itself.72 = 10.25. All statistical analyses were performed using the SPSS 15. p = .4 given at each successive list length.63. A significant difference was found for age (F2. 6. 7. Only the second part was scored. three.(table)…” By presenting an identical structure during both phases.2 (8. ACE = Addenbrooke’s Cognitive Examination. The subject was asked to repeat the sequence in reverse order.17) 69.6 (5. For each proverb a score of 1 was given when the subject gave an adequate explanation. neither years of formal education (F2. and five cubes respectively.2) 12 : 14 29. Materials were six sentences. This task evaluates the same function as the previous subtest but with a slightly different load because the series is highly overlearned for most individuals. namely. Reasoning is most frequently clinically assessed in one of two ways. p < .4. Inter-rater reliability was determined using Cohen’s kappa coefficient by two independent raters (T.2) 14.001). For each sentence.6) 68. RESULTS Clinical and Cognitive Profile Demographic profile and total scores on tests of general cognitive status are summarized in Table 2. When data were not normally distributed. gender).6) 12 : 13 24.001) and the ACE (F2.. The ability of the IFS to discriminate healthy controls from patients diagnosed with either form of dementia included in our study (AD or bvFTD) was determined using a receiver operating characteristic (ROC) curve analysis. In this task.001) and bvFTD patients (p < . 1994). inspired by the Hayling test. Miranda. because patients with frontal lesions usually have difficulties in stepping away from the concrete facts to find their abstract meaning. and a score of 0. Otherwise the score was 0.3 (3. subjects were read each sentence and asked to complete it correctly. CDR = Clinical Dementia Rating Scale. p < . and latency to complete Part B of the Trail Making Test (TMT-B).T. 1987).4) 95. The latter was chosen for this screening test. p = .5 (6. otherwise the score was 0.R. p < . measures a subject’s capacity to inhibit an expected response. each missing the last word and constructed to strongly constrain what it should be. & Ferreres. If subjects passed either trial at a given list length.9) 14.01).7.6 (2. Mann-Whitney U tests were used to compare two groups at a time. p = .15 ** . Mean (SD) scores for Controls.04 ** AC . p < .67.95 –1.0. the area under the curve (AuC) of the classical executive tasks was compared with the AuC of the IFS.29 .01 ** .014).4% of the bvFTD patients and the 23 cutoff score set by the MMSE detected only 4.04. when correlations were calculated exclusively within the AD group. and 20. p = .01 . the executive tasks had poor discrimination accuracy (Phonological fluency: AuC = .5. the 88-point cutoff score set by the ACE detected 63. p < .01). CI = Conflicting Instructions.87). the verbal working memory task (U = 174. as shown by the black-filled dots on Figure 2 correlation graphs.01 . when correlations were calculated exclusively within the bvFTD group. p = .01 .09. with a sensitivity of 72.464. 1. p = . further correlations were conducted within the bvFTD group between IFS total score and the subscores of the ACE domains.87). p < . as controls performed significantly better than both bvFTD (p < .17 .57. WCST: AuC = . DISCUSSION In our study.7.29 .71).45 .01). p = .001).89 .01 .01 .84).01) area under the curve of . p < . MP = Motor Programming.90).001). Area under the ROC curve was .55 < . A significant difference was found between the groups on the IFS total score (F2. A ROC curve analysis on the IFS total score between healthy controls and patients (AD and bvFTD) generated a cutoff score of 25 points with sensitivity of 96. 100% of the bvFTD patients were detected as bearing the executive deficits expected for frontotemporal dementia versus 12% of controls. TMT-B: AuC = .001).618. BDS = Backwards Digit Span. significant correlations were found between the IFS total score and the MMSE (r = . Inter-rater reliability was very good (Cohen’s kappa = 0.INECO frontal screening 5 Psychometric Properties Internal consistency of the IFS was very good (Cronbach’s alpha = 0. p < .2) for bvFTD. p < . VIC = Verbal Inhibitory Control. the total number of categories abstracted (r = 0. a ROC curve analysis between both groups generated a cutoff score of 19 points. ACE (r = .01 . p < .55.001).09 .01).5. AC = Abstraction Capacity.45 .16. MIC = Motor Inhibitory Control.43). as previously stated.04.01 ** memory (r = . Go–No Go task (U = 182. However.01 .72 = 63.2% and specificity of 91.01 ** .39 < .001) on the WCST.60 < .99 .34 < . p = . ** −.01 .01 .0% and a specificity of 81. p = . excellent . p < . p < .038).77.41 .05.43 < .62–.09). To further analyze the superior sensitivity of the IFS in differentiating bvFTD patients from AD.04.0. p < . IFS total score was 27. when patient groups were separated based on their form of dementia. The IFS total score also correlated (Figure 2) with classical executive tests: the number of items produced on the phonological fluency task (r = 0. p = .3%.001) and perseverative errors (r = −0. p = . both dementia groups differed significantly between themselves on the IFS total score (p < . Inter-subscale correlation matrix (A) MP r p CI r p MIC r p BDS r p VWM r p SWM r p AC r p VIC r p MP CI MIC BDS VWM SWM .17. With an IFS cutoff score of 26.01 . and time to complete the TMT-B (r = −0. yet significant (p < .6 (SD = 4.487.59. or visuo-construction (r = . VWM = Visual Working Memory.89. fluency (r = . the IFS has demonstrated good psychometric properties: very good internal consistency.40. Note. no significant correlations were found with orientation (r = . SWM = Spatial Working Memory.38 < .43 < .001). or the CDR (r = −.4 (SD = 1. and the verbal inhibitory control Hayling test (U = 144.49 < . no significance was found between the IFS total score and the MMSE (r = . p = . as shown by Figure 1.13 .7) for AD.24 . A similar profile was observed within the control group (MMSE: r = . p < .01 ** 30 25 20 15 10 5 0 CONTROLS * * IFS Total bvFTD AD Fig. A detailed comparison of AD versus bvFTD performance on each of the eight IFS subtests (Figure 3) revealed that the groups differed significantly on the motor inhibitory control.27 . with a smaller.02 .77.01 .5% (Figure 4).1 (SD = 4.50 < . and most subtests correlated significantly between themselves (Table 3).51 < .18.09 . language (r = .55.001) patients.10 . 15.16 .17 .47 .05) as expected.06 . While.09). ACE: r = . ACE (r = . p = .22 .50).41 < . In contrast. To demonstrate the specificity of IFS to executive functioning.776 (CI: .38. p = . p < .6% of the bvFTD patients.75.59 < .98 (CI: . p = . Table 3. the abstraction capacity task (U = 113.42 < . and behavioral variant frontotemporal dementia (bvFTD) groups on the INECO Frontal Screening (IFS). Alzheimer’s disease (AD).001) and AD (p < .40. p = . Interestingly. Moreover.44 < .67).45). While a significant correlation was found with the attention domain (r = .01 .80). Furthermore.01 ** VIC .36.001).001).01 < .20 .6) for controls. the latter was significant (p < .001).01 . Alzheimer’s disease (AD. The excellent correlations found between these well-established frontal tests and the IFS demonstrate a close association between the total IFS score and executive dysfunction in our groups of patients. 2001). Linear fit lines are presented with mean confidence intervals. 3.05. ●). the Addenbrooke’s Cognitive Examination (ACE) total score. *p < . . 1971). verbal fluency tasks. patients with AD from patients with bvFTD. shows that the concurrent validity of the IFS is highly specific for Fig. Stuss and Levine (2002) reported a series of studies where the inclusion of the WCST as a “frontal measure” in neuropsychological batteries was strongly justified. describing frontal activation during the execution of this task.001. as shown by its significant correlation with classical measures of frontal functioning (phonological verbal fluency. and TMT-B). the phonological verbal fluency task is traditionally considered to be capable of reflecting left frontal functioning in particular (Milner. WCST categories and perseverative errors. Torralva et al. One of the most reliable findings of the utility of the IFS is the concurrent validity demonstrated between this test and some of the most classical executive tests available. and. Fig. furthermore.. Data points represent behavioral variant frontotemporal dementia (bvFTD. the weak correlations found between the IFS total score and all subdomains of the ACE (except attention). as revealed by the capability of the IFS to significantly differentiate healthy controls from demented patients. phonological fluency task. Moreover. and the time performance of the Trail Making Test–Part B is sensitive to frontal pathology (Stuss et al. 2. and Trail Making Test B. categories and perseverations).6 T. concurrent validity. and controls (▲). □). and good discriminant validity. latency to complete Trail Making Test-Part B (TMT-B). ***p < . Correlations between the INECO Frontal Screening (IFS) total score and the Mini Mental State Examination (MMSE). Mean (SD) scores for Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD) groups on each subtests of the INECO Frontal Screening (IFS). In this same way. Several studies have shown the close association between neuropsychological tasks such as the WCST. and Wisconsin Card Sorting Test (WCST. and functioning of the prefrontal cortex. Proverbs. to perform within normal ranges on the IFS. the differences on age between the groups results from earlier onset of bvFTD in comparison to AD. is its poor capability for the detection of executive dysfunction. In contrast. as it may be resulting from high variability within the group. In this respect. differences in the clinical profiles. otherwise undetected by general cognitive tests. cube copying. while significant correlations were found on the whole sample (patients and controls) between the IFS total score and general cognitive measures such as the MMSE and the ACE. 2001). Another limitation has to do with the relatively small sample sizes used in this study. In analyzing each IFS subtest independently. AD patients outperformed bvFTD on all except one subtest of the IFS.. when looking at the individual performances on ACE and IFS within the bvFTD group. On the other hand. as expected. all subtests (except the conflicting instructions task) showed a clear trend toward a similar profile. even though the former group was older. The more severe executive dysfunction observed in patients with the bvFTD is consistent with the etiological properties of this condition: predominant frontal atrophy and executive disorders since the early stages (Hodges. Naturally. The different profile observed for the conflicting instruction task. future studies should replicate the present work to strengthen the generalizability of the results. two findings present evidence against this. This difference becomes especially important when considering that the FAB’s initially reported discriminant ability failed to be replicated by other research groups (Castiglioni et al. supporting the idea that minimal general functioning is needed for proper performance on this battery. and clock drawing). Lipton et al. within the bvFTD group. acknowledged even by its original authors.INECO frontal screening 7 There are some limitations to this study. for which AD patients showed a worse performance than the bvFTD group requires further exploration. . We suggest that the administration of both IFS and ACE in the detection of dementia will help overcome this limitation. In fact.. the general cognitive status has a direct impact on IFS performance. IFS still captured the dysexecution of a younger yet selectively impaired bvFTD group. 2005). Verbal Working Memory. as well as between both pathological groups and healthy controls. a variable that could have even a stronger effect than age on executive dysfunction. moderate for the fluency and visuo-spatial domains. no significant correlations were found between the IFS total score and global cognitive measures. executive functions. as revealed by the analysis of the areas under the curve. In fact. On one hand. 4. a significant difference was found between AD and both bvFTD and controls for their mean age. and attention. there were no significant differences on the levels of education between the groups. It is unlikely that this lack of correlation stems from ceiling effects. those correlations were not observed when we split the sample based on their type of dementia. The high specificity for executive functions demonstrated by the IFS is further supported by the larger accuracy in differentiating AD from bvFTD. This could be explained by the fact that. language. The correlations were. patients with low general cognitive functioning (lower scores on ACE) also perform more poorly on the IFS. because of the relatively strong executive component inherent to these tasks of the ACE (phonological fluency. The ACE is a screening tool that has demonstrated to have excellent specificity and sensitivity for patients with dementia. and the Hayling test. 2000). and highlights the inclusion of early-stage patients in the present study. especially for Alzheimer disease (Mathuranath et al.. Unlike controls. It is likely that some patients fail to exhibit high performance on a domain-specific task (IFS) if cognitive areas such as comprehension. First. The lack of correlations found Fig. significant correlations were indeed found between the IFS total score and the MMSE and the ACE. Receiver operating characteristic (ROC) curve analyses for dementia versus controls (left) and between dementia groups (right). most bvFTD patients exhibit high performance on the ACE but poor performance on the IFS. More specifically. the global IFS score was able to differentiate between bvFTD and AD patients. While this is important because of the potential effect of ageing on executive performance. showing that. bvFTD patients exhibited a more severe executive dysfunction. all of which are captured by ACE. As it can be observed in Figure 2. 2006. visuo-spatial abilities. preserved cognitive functioning is needed. Moreover. significant differences were found between AD and bvFTD patients on four particular tasks: Go–No Go. This is especially important because it highlights the fact that the IFS may be specifically capturing executive domains. are not minimally spared. represented by their lower overall IFS scores compared with patients with AD. as one could expect. One of the most remarkable limitations of the ACE. such as attention. or differential performance on other cognitive domains. In addition. when correlations were calculated exclusively within the AD group. In fact. (1975). Burgess. K.D. Berg. T. (2008). (2003). V.. B.. Journal of Neurology. As previously described. The human frontal lobes. Dementia and Geriatric Cognitive Disorders. K. Neurology. N.R. 41.. Galeone. O.M.) In summary. B. R.. The Frontal Assessment Battery (FAB) in Parkinson’s disease and correlations with formal measures of executive functioning. 65.. Loré.A. Burgess. T. The neuropsychology of frontal variant frontotemporal dementia and semantic dementia..R. Introduction to the special topic papers: Part I. Castiglioni. F.L. P.H.P. and Psychiatry. Miranda. 8.. This study was funded by a FINECO grant and a Fundación LyD grant. Bedside frontal lobe testing.. Further studies are needed to explore the different profiles within various types of dementia and control populations. & Hodges.T. Sahakian. Cullen. Hodges. Miller & J. J.. T.) New York: Raven Press. In B. Le Ber.H. NY: The Guilford Press. Neurocase. (1997a).. T. Neurology. Adaptación y normas del test de Hayling]. Tentorio. 726–731. B. 31–35. In G. A. (1999).. Evans. C. Fonseca... & Lacritz. Journal of Psychiatric Research... 50. S6–S10. The Hayling and Brixton Tests.S. Further research is needed to determine the assumption that a combination of the ACE and the IFS will increase the efficiency in differentiating types of dementia. Womack.. & Ferreres. Folstein.. 19–32.. W.B.. E. 191–195. the present study indicates that the IFS is a solid.R. 7. Higher cortical function in man. 84–87. Cognitive assessment for clinicians.A. Torralva et al. Iavarone. J. 189–198. The Hayling Test. Lipton. Hodges.L. 1474–1183. Ohman.. (2001a). 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The Psychiatric Clinics of North America. Williams-Gray.R. Scoring: 6 consecutives series alone: 3 / At least 3 consecutive series alone: 2 / Patient fails at 1 but achieves 3 consecutive series with examiner: 1 / Patient does not achieve 3 series with examiner: 0 /3 Go-No Go (Inhibitory Control) “Hit the desk once when I hit it once”. Heaton. A.. Kishimoto. Schizophrenia Bulletin.. D. J. M. Psychological Assessment. C.. Advances in the early detection of Alzheimer’s disease. (2006). Journal of Neuropsychiatry and Clinical Neurosciences. Evaluation of the NINCDS-ADRA criteria in the differentiation of Alzheimer disease and frontotemporal dementia. (2009) Cognitive dysfunctions and pathological gambling in patients with Parkinson’s disease. New York: Raven Press. T..D. Scheltens.M. Passant.E. Talbot. 313–324. M. D. P. Zakzanis. & Neary.. 53.. S. & Gray. G.. (2004). S. Ohshima. The examiner completes this series: 1-1-21-2-2-2-1-1-2. Berrios. table.. Mann.. 272–277. 130.” The examiner repeats the series 3 times with the patient and then says “Now. hit once on the . (1949). 55. Bokura. Grossi.. S34–S41. H. The relationship between affective decision-making and theory of mind in the frontal variant of frontotemporal dementia. Mathuranath. Aitken. Structural and functional meta-analytic evidence for fronto-subcortical system deficit in progressive supranuclear palsy.. (2000)...J. Neurosurgery. Bedside assessment of executive cognitive impairment: The executive interview.S. Brain. Verde. Stuss. Torralva. 45. C. Hahn-Barma.. Villalpando.J. Stuss. M. & Leiter. 230– 239. 125. B.M.R.. S. J... Reichenberg. Archives of Neurology. & Izukawa. (1976). Scoring: No errors: 3 / One or two errors: 2 / More than two errors: 1 / Patient hits like examiner 4 consecutive times: 0 Motor Series (Programming) “Look carefully at what I’m doing”.... 1.. 342–349.. S. Lloyd. (2004). & Hodges. R..... Snowden. A modified card sorting test sensitive to frontal lobe deficits. C.. & Brayne. Sahakian. P. Brain. APPENDIX The following is a translated version of the original Spanish language screening tool used on the patients included in this study. Adult clinical neuropsychology: Lessons from studies of the frontal lobes. A. 1546–1554. 9–20. & Hodges.. Alexander. and Psychiatry. J. Journal of American Geriatrics Society. Milner.. M.K.. [Epub ahead of print]. & Saykin. J. To ensure the patient has clearly understood the task. (1986). 253. Antoun. 1104–1107. Leach. To ensure the patient has clearly understood the task..... New York: Psychological Corporation. The frontal lobes. Stuss. K.. A. Sato. D. (2007).. Neurology. H. R. Varma. hit once on the table. Evolution of cognitive dysfunction in an incident Parkinson’s disease cohort.. Yamaguchi. Decision-making processes following damage to the prefrontal cortex. D. Executive dysfunction in attention-deficit/hyperactivity disorder: Cognitive and neuroimaging findings..K.INECO frontal screening Manes.. Nestor. Differentiating Alzheimer’s disease from subcortical vascular dementia with the FAB test. 1613–1620. Annual Review of Psychology. 184–188.. (2002). Gustafson. 61. J.. & Benson...R. et al. Pillon. Nature Medicine.. 83–89. & Dubois. L. H.M.. 1787–1798. 1 error = 1... “Still waters run deep” 3. Ask the patient to repeat the series in the reverse order.. Torralva et al.Oct .Feb ...Aug . Different word: 2 / Semantic Relation: 1 / Exact word: 0 point.May .. I want you to tell me a word that makes no sense whatsoever in the context of the sentence.. . quence in the reverse order. inconclusive task) Instruction: Say the months of the year backwards. 1-2 b... 2-4-3 c.. as quickly as possible. a. patient chooses hand of preference.April March .. and it must not be related to the word that actually completes the sentence.. and I tie my . Scoring: Line is considered correct when the patient gets one or both items correct. you must tell me. Move on to the next task when the patient gets both items on the line wrong. I washed my clothes with water and .. Verbal working memory Months backwards: (errors are considered if: wrong order... patient must copy the se- /6 1....Jan.10 Scoring: No errors: 3 / One or two errors: 2 / More than two errors: 1 / Patient hits like examiner 4 consecutive times: 0 T. 1-4-2-3-4 /3 Digits backward Read each series of numbers out load.. Correct explanation: 1 Point 1. > 2 errors = 0) /2 Spatial Working Memory “I will point at the squares in a given order. 2..Jun .Jul . at a speed of one word/ second. /4 Score 1 2 3 4 5 6 Trial I 5-1 4-9-3 3-8-1-4 6-2-9-7-2 7-1-5-2-8-6 4-7-3-9-1-2-8 Correct Trial II 3-8 5-2-6 1-7-9-5 4-8-5-2-7 8-3-1-9-6-4 8-1-2-9-3-6-5 Correct Proverbs: Example: ... (0 errors = 2....... John bought candy at the . omissions. “One swallow does not make a summer” 2.. I put my shoes on. Do it slowly. “A bird in the hand is worth two in the bush” /3 /6 Hayling Test (Abbreviated) Phase 1: Initiation: “Listen carefully to these sentences and as soon as I am done reading them... An eye for an eye. (laces) It was raining cats and ... 3-4-2-1 d. 3..5 points.Nov . (dogs) Phase 2: Inhibition. I want you to point them in the reverse order”. what word completes the sentence”.. a tooth for a . starting with the last month of the year Dec ... “This time.rain”.Sep ... Score is the last line achieved correctly.” “For example: Daniel hit the nail with a.