Nl230001621p

A frontal assessment battery at bedside
B. Dubois, MD; A. Slachevsky, MD; I. Litvan, MD; and B. Pillon, PhD Article abstract—Objective: To devise a short bedside cognitive and behavioral battery to assess frontal lobe functions.
Methods: The designed battery consists of six subtests exploring the following: conceptualization, mental flexibility, motor
programming, sensitivity to interference, inhibitory control, and environmental autonomy. It takes approximately 10
minutes to administer. The authors studied 42 normal subjects and 121 patients with various degrees of frontal lobe
dysfunction (PD, n ϭ 24; multiple system atrophy, n ϭ 6; corticobasal degeneration, n ϭ 21; progressive supranuclear
palsy, n ϭ 47; frontotemporal dementia, n ϭ 23). Results: The Frontal Assessment Battery scores correlated with the
Mattis Dementia Rating Scale scores (rho ϭ 0.82, p Ͻ 0.01) and with the number of criteria (rho ϭ 0.77, p Ͻ 0.01) and
perseverative errors (rho ϭ 0.68, p Ͻ 0.01) of the Wisconsin Card Sorting Test. These variables accounted for 79% of the
variance in a stepwise multiple regression, whereas age or Mini-Mental State Examination scores had no significant
influence. There was good interrater reliability (␬ ϭ 0.87, p Ͻ 0.001), internal consistency (Cronbach’s coefficient alpha ϭ
0.78), and discriminant validity (89.1% of cases correctly identified in a discriminant analysis of patients and controls).
Conclusion: The Frontal Assessment Battery is easy to administer at bedside and is sensitive to frontal lobe dysfunction.
Assessing frontal lobe function and thus being able and patients with various degrees of executive dys- to identify a dysexecutive syndrome are helpful for function, and 3) interrater reliability.
the diagnosis and prognosis of brain diseases such asfrontotemporal dementias1 and for evaluation of the Methods.
Description of the Frontal Assessment Battery severity of brain injuries. It can also help to identify According to current theories, the frontal lobes vascular dementias2 and parkinsonian disorders, control conceptualization and abstract reasoning, mental particularly progressive supranuclear palsy (PSP), in flexibility, motor programming and executive control of ac- which the presence of frontal lobe dysfunction sup- tion, resistance to interference, self-regulation, inhibitory ports the diagnosis.3 It may also be useful for differ- control, and environmental autonomy.6,10-14 Each of these entiating between degenerative disorders involving processes is needed for elaborating appropriate goal- subcortical structures and for evaluating the pro- directed behaviors and for adapting the subject’s response to new or challenging situations—functions that are medi- The functions of the frontal lobes are difficult to ated by the prefrontal cortex. For that reason, the designed assess clinically. There is no test that reliably identi- battery consists of six subtests, each exploring one of theaforementioned functions related to the frontal lobes.
fies a dysexecutive syndrome.5 In practice, extensive Moreover, these subtests were chosen because the score of neuropsychological batteries are needed to assess the each of them significantly correlated with frontal metabo- frontal lobe processes.6,7 Given the modular func- lism, as measured in terms of the regional distribution of tional organization of the frontal lobes,8,9 searching 18-fluorodeoxyglucose in a PET study of patients with for a possible dysexecutive syndrome requires time- frontal lobe damage of various etiologies.9 The processes consuming tests exploring functions associated with studied and the corresponding subtests of the FAB are different frontal areas. Therefore, there is a need for a presented below. The content, instructions and scoring of brief tool exploring different domains of executive func- each subtest are provided in the Appendix. The total scores tion that are impaired in several neurologic diseases.
are calculated by adding the notes of the six subtests. The We devised a bedside battery to assess the pres- overall duration of the battery is approximately 10 ence and severity of a dysexecutive syndrome affect- ing both cognition and motor behavior, and toevaluate it for 1) content and concurrent validity, 2) 1. Conceptualization: Abstract reasoning is impaired in discriminant validity, comparing normal controls frontal lobe lesions.11 This function is currently investi- See also pages 1601, 1609, and 1613
From INSERM EPI 007 and Fédération de Neurologie (Drs. Dubois, Slachevsky, and Pillon), Hôpital de la Salpêtrière, Paris, France; and CognitiveNeuropharmacology Unit (Dr. Litvan), Henry M. Jackson Foundation, Bethesda, MD.
Supported by INSERM. Funded by a grant from Mideplan-Chile (A.S.).
Received June 12, 2000. Accepted in final form September 13, 2000.
Address correspondence and reprint requests to Dr. Bruno Dubois, Fédération de Neurologie, Hôpital de la Salpêtrière, 47 Boulevard de l’Hôpital, 75651Paris cedex 13, France; e-mail: [email protected] Copyright 2000 by AAN Enterprises, Inc.
Table Study group characteristics
Values are presented as mean Ϯ SD. Significantly different at p Ͻ 0.05 for: acontrols and patients; bfrontotemporal dementia (FTD) andcorticobasal degeneration (CBD) patients; cPD and CBD patients; dprogressive supranuclear palsy (PSP) and CBD patients; eFTD andmultiple system atrophy (MSA) patients; fPSP and MSA patients; gPD and PSP patients; hFTD and PSP patients; iPD and FTD pa-tients; jPD and MSA patients.
MMSE ϭ Mini-Mental State Examination; DRS ϭ Dementia Rating Scale; FAB ϭ Frontal Assessment Battery.
gated by card-sorting tasks, proverb interpretation, or tend to execute echopractic movements, imitating the similarities.15 The last task is easier for bedside assess- ment and scoring. Subjects have to conceptualize the Inhibitory control: Withholding a response may be links between two objects from the same category (e.g., difficult for patients with damage to the ventral part of an apple and a banana). Patients with frontal lobe dys- the frontal lobes.21 In tasks anticipated to elicit a false- function may be unable to establish an abstract link alarm motor response, these patients are often unable between the items (i.e., fruit), adhering to the concrete to inhibit inappropriate responses.22 This difficulty in aspects of objects (i.e., both are yellow), or may be un- controlling impulsiveness can be assessed with the able to establish a link of similarity (i.e., one is round go–no go paradigm,23 in which the subjects must inhibit a response that was previously given to the same stim- 2. Mental flexibility: Patients with frontal lobe lesions are ulus, e.g., not tapping when the examiner taps twice.
specifically disturbed in nonroutine situations in which Environmental autonomy: Patients with frontal lobe self-organized cognitive strategies have to be built lesions are excessively dependent on environmental up.16,17 Literal fluency tasks are unusual, require self- cues.24 Sensory stimuli can activate patterns of re- organized retrieval from semantic memory, and are sponses that are normally inhibited in normal controls.
easy to score. Frontal lesions, regardless of side, tend to For example, the patient conceives the sight of a move- decrease verbal fluency, with left frontal lesions result- ment as an order to imitate (imitation behavior); the ing in lower word production than right frontal le- sight of an object implies the order to use it (utilization sions.18 In this task, subjects need to recall as many behavior); and the sight or sensory perception of the words as they can beginning with a given letter in a examiner’s hands compels the patient to take them (prehension behavior). In some cases, the patients can 3. Motor programming: Patients with frontal lobe lesions elicit these behaviors even if they have been explicitly are also impaired in tasks requiring temporal organiza- told not to do so. These abnormal behaviors (the sponta- tion, maintenance, and execution of successive ac- neous tendency to adhere to the environment) express tions.12,13,19 In Luria’s motor series, such as “fist–palm– the lack of inhibition normally exerted by the prefrontal edge,” less severely impaired patients are unable to cortex on the activation of patterns of behavior trig- execute the series in correct order, whereas the most severely affected are unable to learn the series. Simpli-fication of the task (two gestures instead of three) and Subjects gave informed written consent to perseveration (inappropriate repetition of the same ges- participate. Forty-two normal control subjects (mean Ϯ SD; age, 58 Ϯ 14.4 years), without any neurologic or psy- Sensitivity to interference: Deficits in behavioral self- chiatric history, were included (table). All control subjects regulation may be observed in tasks in which verbal had a Mattis Dementia Rating Scale (DRS)25 score Ͼ136 or commands conflict with sensory information. This oc- a Mini-Mental State Examination (MMSE)26 score Ͼ27.
curs in the Stroop test, in which the subject must name To evaluate the discriminative power of the FAB, 121 the colors of words while inhibiting the natural ten- patients with mild (PD, n ϭ 24; multiple system atrophy dency to read the words. This also occurs in the case of [MSA], n ϭ 6), moderate (corticobasal degeneration [CBD], conflicting instructions, in which subjects must provide n ϭ 21), or severe (frontotemporal dementia [FTD], n ϭ 23; an opposite response to the examiner’s alternating sig- progressive supranuclear palsy [PSP], n ϭ 47) frontal lobe nal, e.g., tapping once when the examiner taps twice.
dysfunction27,28 were included (see table). All patients un- Thus, subjects should obey verbal commands and re- derwent an extensive clinical evaluation to confirm their frain following what they see.20 Patients with a frontal diagnosis and all met currently accepted diagnostic crite- lobe lesion usually fail to obey the verbal command and ria. The diagnostic criteria for PD were based on the pres- December (1 of 2) 2000
ence of a parkinsonian syndrome with unilateral onset the extent to which the six items of the FAB reflect the characterized by a resting tremor or an akinetorigid syn- same underlying construct, by calculating the Cronbach’s drome, a good response to levodopa that persisted at the time of evaluation, and the absence of exclusion criteria(e.g., supranuclear gaze palsy).29,30 The diagnostic criteria Results.
Technical properties of the battery. for MSA included the presence of an extrapyramidal syn- drome poorly responsive to levodopa, associated with an FAB scores and the Mattis DRS performance in 121 pa- autonomic or urinary dysfunction in the absence of exclu- tients (r ϭ 0.82, p Ͻ 0.001). Similarly, the FAB scores sion criteria.31 The diagnostic criteria for CBD included a correlated with the number of criteria (r ϭ 0.77, p Ͻ 0.001) slowly progressive asymmetric akinetorigid syndrome and and perseverative errors (rho ϭ 0.68, p Ͻ 0.001) achieved one or more of the following signs of cortical involvement: in the Wisconsin CST. A stepwise multiple regression was ideomotor apraxia, myoclonus, cortical sensory deficit, or used to evaluate the influence on the FAB performance of alien limb syndrome.32 The criteria for PSP included the the following independent variables: age of patient, MMSE presence of a gradually progressive disorder with an age at and Mattis DRS scores, and the number of criteria and onset of 40 years or later; a supranuclear limitation of perseverative errors in the Wisconsin CST. The Mattis vertical gaze; a prominent postural instability, with falls DRS score and number of criteria achieved in the Wiscon- occurring in the first year of symptom onset; and no evi- sin CST accounted for 79% of variance in the FAB (F [2,82] dence of another disease that could explain the symptoms; ϭ 152.9; p Ͻ 0.001; r2 ϭ 0.79). Interestingly, age and in the absence of exclusion criteria.33 The diagnosis of FTD MMSE scores had no significant influence.
was based on a progressive onset of behavioral changes fulfilling the Lund and Manchester criteria,1 a severe dys- tween controls and patients after adjusting for age as a executive syndrome on neuropsychological evaluation, and covariate (analysis of covariance: F[1,131] ϭ 17. 24; p Ͻ the absence of any other neurologic disorder sufficient to 0.001). The performance on the FAB correctly identified explain the frontotemporal cortical deficit.1 The neuropsy- 89.1% of the cases (Wilke’s lambda ϭ 0.43, F[1,135] ϭ chological evaluation of patients consisted of the MMSE26 176.2; p Ͻ 0.001). A stepwise discriminant analysis in pa- and Mattis DRS for all patients,25 and the Wisconsin Card tients with FTD and PSP using the six FAB subscores as Sorting Test (CST)34 for 86 patients. The MMSE ranges independent variables showed that similarities and pre- were 30 to 24 for patients with PD, 30 to 21 for patients hension behavior correctly classified 69.7% of the patients with MSA, 30 to 13 for patients with CBD, 30 to 17 for (Wilke’s lambda ϭ 0.865; ␹2 [ddl ϭ 2] ϭ 10.6; p ϭ 0.005).
patients with PSP, and 30 to 6 for patients with FTD.
subset of 17 patients with the FAB achieved an optimal Technical properties of the battery. interrater reliability (␬ ϭ 0.87, p Ͻ 0.001). The Cronbach’s coefficient alpha between the items of the FAB of 121 the battery evaluates the existence of a frontal lobe syn- patients was 0.78, suggesting good internal consistency.
drome,35 was analyzed by correlating the FAB total scorewith the patient’s performance on 1) the Wisconsin CST, atest considered to be sensitive to executive dysfunction36; and Discussion.
2) the Mattis DRS, a global scale reported to be correlated assessing frontal lobe function that could be applied with the degree of executive dysfunction in neurodegenera- by any practitioner, we designed a short assessment tive diseases.4,25 For the Wisconsin CST, the number of crite- battery, the FAB, based on our experience with focal ria achieved and the number of perseverative errors were frontal lobe lesions24 and movement disorders associ- considered because both have been shown to be sensitive to ated with striatofrontal dysfunction.4 Other tools frontal lobe dysfunction.34 We performed a correlational va- have already been designed to evaluate frontal lobe lidity study because there is no “gold standard” that deter- function at the bedside.38-41 A brief assessment of mines the existence and severity of a frontal lobe syndrome.35 frontal and subcortical functions was proposed for patients with suspected subcortical pathology, but the FAB to discriminate between normal control subjects patients with AD scored significantly lower on this and patients with cognitive impairment according to the scale than those with Huntington’s disease or PD.38 Mattis DRS scale. Patients without cognitive impairment The EXIT 25, an executive interview, correlates not were excluded for this analysis. Only 95 patients with a only with tests sensitive to frontal lobe dysfunction Mattis DRS score below 136 were included.
but also with the MMSE (r ϭ Ϫ0.85). This suggests The ability of the FAB to differentiate the frontal dys- function of patients with cortical and subcortical lesions that the EXIT 25 is also sensitive to functions that was studied by using a stepwise discriminant analysis in are not executive.39 Another brief tool sensitive to two groups of patients with frontal lobe dysfunction of executive control, the CLOX (a clock drawing test),40 different origins—subcortical (47 patients with PSP) and has been proposed, but only investigates one domain of cognitive function: drawing. Lastly, Ettlin and Kischka41 proposed the “frontal lobe score,” which is, comparing the scores of two independent raters who were however, not convenient for bedside assessment be- present during the administration of the FAB by one of cause it includes tasks such as the Trail-Making them. Each rater was blind to the ratings made by the Test and takes up to 40 minutes to complete. The other. Interrater reliability was conducted in 17 patients FAB is an easy test to administer, requires less than and determined by calculating the kappa value.
10 minutes to complete, and is well accepted by pa- We studied the internal consistency of the battery, i.e., tients. The six FAB subtests explore both cognitive December (1 of 2) 2000
and behavioral domains under the control of the Appendix
frontal lobes, each of them having been shown to be Content, instructions, and scoring of the FAB
significantly correlated with frontal lobe metabolic 1. Similarities (conceptualization)
activity measured by 18-fluorodeoxyglucose using PET scan.9 Moreover, each subtest is associated with A banana and an orange (In the event of total failure: “they are specific areas of the frontal lobes on the basis of not alike” or partial failure: “both have peel,” help the patient bysaying: “both a banana and an orange are.”; but credit 0 for the neuropsychological, electrophysiologic, and func- item; do not help the patient for the two following items) tional arguments: conceptualization with dorsolat- eral areas,42,43 word generation with medial areas,44,45 and inhibitory control with orbital or medial frontal Score (only category responses [fruits, furniture, flowers] are areas.46,47 Therefore, performance on the six subtests of the FAB can give a composite global score, which evaluates the severity of the dysexecutive syndrome and may suggest a descriptive pattern of executive 2. Lexical fluency (mental flexibility)
“Say as many words as you can beginning with the letter ‘S,’ The FAB presents good metric properties. The any words except surnames or proper nouns.” study demonstrated good internal consistency (Cron- If the patient gives no response during the first 5 seconds, say: “for instance, snake.” If the patient pauses 10 seconds, stimulate bach’s alpha was 0.78),37 optimal interrater reliabil- him by saying: “any word beginning with the letter ‘S.’ The time ity (␬ ϭ 0.87), and concurrent validity. Indeed, the FAB score was strongly associated with the perfor- Score (word repetitions or variations [shoe, shoemaker], sur- mance of patients on the Mattis DRS (rho ϭ 0.82) names, or proper nouns are not counted as correct responses) and Wisconsin CST (rho ϭ 0.77 for the number of criteria), both of which evaluate different cognitive functions under frontal lobe control. These functions include initiation, conceptualization, and attention 3. Motor series (programming)
“Look carefully at what I’m doing.” for the Mattis DRS scale25 and conceptualization and The examiner, seated in front of the patient, performs alone cognitive flexibility for the Wisconsin CST. Several three times with his left hand the series of Luria “fist– edge– recent studies have demonstrated that performance palm.” “Now, with your right hand do the same series, first with in the Wisconsin CST is related to functional activity me, then alone.” The examiner performs the series three timeswith the patient, then says to him/her: “Now, do it on your own.” in the prefrontal cortex.42,48-50 In contrast, the FAB score is correlated neither with the MMSE score, a Patient performs six correct consecutive series alone: 3 measure of more general cognitive function, nor with Patient performs at least three correct consecutive series alone: 2 age (see the results of the stepwise multiple regres- Patient fails alone, but performs three correct consecutive se- sion). The battery also presents good discriminant Patient cannot perform three correct consecutive series even validity, allowing differentiation to be made between control subjects and patients with frontal or subcor- 4. Conflicting instructions (sensitivity to interference)
ticofrontal cognitive impairment. However, the FAB To be sure that the patient has understood the instruction, a global score does not allow discrimination between series of three trials is run: 1-1-1. “Tap once when I tap twice.” To patients with predominantly subcortical (PSP) or be sure that the patient has understood the instruction, a series of cortical (FTD) dysfunction. Only two subtests dis- three trials is run: 2-2-2. The examiner performs the followingseries: 1-1-2-1-2-2-2-1-1-2.
criminated between these patients to some extent— prehension behavior (more severely impaired in patients with PSP) and similarities (more severely impaired in patients with FTD). This result is not More than two errors: 1Patient taps like the examiner at least four consecutive times: 0 unexpected because patients with frontal and sub- 5. Go–No Go (inhibitory control)
corticofrontal lesions usually present similar cogni- tive deficits and share only subtle neuropsychological To be sure that the patient has understood the instruction, a series of three trials is run: 1-1-1. “Do not tap when I tap twice.”To be sure that the patient has understood the instruction, a Some points should be stressed, however. Test– series of three trials is run: 2-2-2. The examiner performs the retest reliability was not assessed. The anatomic cor- following series: 1-1-2-1-2-2-2-1-1-2.
relation of the different subtests of the battery was derived from data obtained with similar tests, but not from the subtests themselves. Finally, although highly significant correlations were shown between Patient taps like the examiner at least four consecutive times: 0 the FAB and tests sensitive to frontal lobe functions, 6. Prehension behavior (environmental autonomy)
but not between the FAB and MMSE, it would be The examiner is seated in front of the patient. Place the pa- necessary to demonstrate that patients with non– tient’s hands palm up on his/her knees. Without saying anything frontal lobe injuries perform at a higher level than or looking at the patient, the examiner brings his/her hands close that observed for patients with frontal lobe injuries, to the patient’s hands and touches the palms of both the patient’shands, to see if he/she will spontaneously take them. If the patient to definitively consider the FAB as a measure of takes the hands, the examiner will try again after asking him/her: December (1 of 2) 2000
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Hippocampal and cortical atrophy predict
dementia in subcortical ischemic
vascular disease
G. Fein, PhD; V. Di Sclafani, MPH; J. Tanabe, MD; V. Cardenas, PhD; M.W. Weiner, MD; W.J. Jagust, MD; B.R. Reed, PhD; D. Norman, MD; N. Schuff, PhD; L. Kusdra; T. Greenfield; and H. Chui, MD Article abstract—Background: The cause of dementia in subcortical ischemic vascular disease (SIVD) is controversial.
Objectives: To determine whether cognitive impairment in SIVD 1) correlates with measures of ischemic brain injury or
brain atrophy, and/or 2) is due to concomitant AD. Methods: Volumetric MRI of the brain was performed in 1) elderly
subjects with lacunes (L) and a spectrum of cognitive impairment—normal cognition (NCϩL, n ϭ 32), mild cognitive
impairment (CIϩL, n ϭ 26), and dementia (DϩL, n ϭ 29); 2) a comparison group with probable AD (n ϭ 28); and 3) a
control group with normal cognition and no lacunes (NC). The authors examined the relationship between the severity of
cognitive impairment and 1) volume, number, and location of lacunes; 2) volume of white matter signal hyperintensities
(WMSH); and 3) measures of brain atrophy (i.e., hippocampal, cortical gray matter, and CSF volumes). Results: Among the
three lacune groups, severity of cognitive impairment correlated with atrophy of the hippocampus and cortical gray
matter, but not with any lacune measure. Although hippocampal atrophy was the best predictor of severity of cognitive
impairment, there was evidence for a second, partially independent, atrophic process associated with ventricular dilation,
cortical gray matter atrophy, and increase in WMSH. Eight autopsied SIVD cases showed variable severity of ischemic
and neurofibrillary degeneration in the hippocampus, but no significant AD pathology in neocortex. The probable AD
group gave evidence of only one atrophic process, reflected in the severity of hippocampal atrophy. Comparison of regional
neocortical gray matter volumes showed sparing of the primary motor and visual cortices in the probable AD group, but
relatively uniform atrophy in the DϩL group. Conclusions: Dementia in SIVD, as in AD, correlates best with hippocampal
and cortical atrophy, rather than any measure of lacunes. In SIVD, unlike AD, there is evidence for partial independence
between these two atrophic processes. Hippocampal atrophy may result from a mixture of ischemic and degenerative
pathologies. The cause of diffuse cortical atrophy is not known, but may be partially indexed by the severity of WMSH.
Subcortical ischemic vascular disease (SIVD) is char- port risk of dementia to be higher among subjects acterized by lacunar infarcts and deep white matter with lacunar infarcts versus other subtypes of changes. The proportion of vascular dementia (VaD) stroke,4 and among patients with AD with concomi- attributed to SIVD ranges from 36 to 50%, with tant lacunar versus large-artery infarcts.5 Thus, higher rates noted among African Americans1 and SIVD is an important subtype of VaD either alone or Asian Americans2 than whites.3,4 A few studies re- From Neurobehavioral Research, Inc. (Dr. Fein and V. Di Sclafani); Psychiatry Research (Dr. Cardenas) and Magnetic Resonance Unit (Drs. Tanabe, Weiner,and Schuff, and L. Kusdra and T. Greenfield), Department of Veterans Affairs Medical Center; the Departments of Radiology (Drs. Tanabe, Cardenas,Weiner, Norman, and Schuff) and Psychiatry (Dr. Weiner), University of California, San Francisco; the Center for Functional Imaging (Dr. Jagust), LawrenceBerkeley Laboratory, the Department of Neurology (Drs. Jagust and Reed), University of California, Davis; and the Department of Neurology (Dr. Chui),University of Southern California, Los Angeles.
Supported by the National Institutes of Health (P01-AG12435, P50-AG10129, R01-AG10897), the State of California Department of Health ServicesAlzheimer Program, a National Research Service Award (DA-05683-02), and a Career Scientist Award (G.F.) from the Department of Veterans Affairs.
Received August 5, 1999. Accepted in final form October 2, 2000.
Address correspondence and reprint requests to Dr. Helena Chui, Geriatric Neurobehavior and Alzheimer Center, 800 Annex West, 7601 East ImperialHighway, Downey, CA 90242; e-mail: [email protected] Copyright 2000 by AAN Enterprises, Inc.

Source: http://www.gakushu-ryoho.jp/member/pdf/fab_eg.pdf