J7ournal ofNeurology, Neurosurgery, and Psychiatry 1996;60:91-93 91 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.60.1.91 on 1 January 1996. Downloaded from SHORT REPORT Executive dysfunction in early Alzheimer's disease G Binetti, E Magni, A Padovani, S F Cappa, A Bianchetti, M Trabucchi Abstract have been related to frontal lobe dysfunction. Twenty five patients with probable mild It has been suggested that in addition to more Alzheimer's disease were assessed for direct involvement with selected aspects of deficits in executive functioning and the memory, such as remote memory, confabula- impact ofthese deficits on performance in tion, and memory for temporal sequences, other neuropsychological domains. The the frontal lobes play a strategic part as a Wisconsin card sorting test, the release "cognitive mediation" system in the encoding from proactive interference paradigm, and retrieval of memories.4 Frontal lobe the verbal fluency test, and the Stroop test involvement in the clinical heterogeneity were adopted to classify patients with of Alzheimer's disease, however, has not (AD+) and without (AD -) executive been fully investigated and it is still unclear deficits. Seven of the patients showed an whether frontal lobe related neuropsychologi- impairment in executive function (AD+), cal impairments are integral to Alzheimer's defined as a performance below the cut disease in the early phase, and whether they off score in at least two of these tests. are associated with a differential pattern of There were no significant differences neuropsychological impairment. The aim of in clinical assessments, demographic this study was to evaluate executive function features, or other cognitive functions in patients with mild Alzheimer's disease and between patients. to investigate the relation between executive Executive dysfunction may be an early dysfunction and performance in other neuro- additional feature in a subgroup of psychological domains such as language, patients with mild Alzheimer's disease. memory, attention, abstract reasoning, and Impairment on frontal lobe tests does not visuospatial abilities. For this purpose, the seem to be related to the severity or dura- Wisconsin card sorting test,5 the release tion of disease, or to a different pattern of from proactive interference,6 the verbal fluency impairment in other cognitive domains. test,7 and Stroop test8 were adopted to classify http://jnnp.bmj.com/ patients with (AD+) and without (AD-) _J Neurol Neurosurg Psychiatry 1996;60:91-93) executive deficits. Keywords: Alzheimer's disease; executive function Subjects and methods All patients included in this study were Alzheimer's disease is characterised by impair- evaluated in the Alzheimer's disease unit at ment of multiple memory related systems. In S Couore Fatebenefratelli Hospital in Brescia, on September 26, 2021 by guest. Protected copyright. Alzheimer's Disease addition patients with Alzheimer's disease Italy, and were drawn from a consecutive Unit, Istituto S Cuore have disturbances in several other cognitive series of patients included in a longitudinal Fatebenefratelli, Brescia, Italy and domains such as language, visuospatial skills, programme on mild Alzheimer's disease Geriatric Research praxis, and abstraction.' In addition to clinical, (MADI project). Group, Brescia, Italy epidemiological, biological, and neuroimaging Twenty five consecutive patients, affected G Binetti E Magni findings, the evidence of distinct profiles of by probable Alzheimer's disease according to A Padovani cognitive deficits has led some authors to sug- currently accepted clinical criteria,9 and with A Bianchetti gest the existence of heterogeneous subtypes a questionable or mild form of dementia (clin- M Trabucchi of patients with Alzheimer's disease.' 2 For ical dementia rating (CDR) 0-5 or 1)10 were Department of example, there is evidence that in individual included in the study. All patients had CT or Neurology, University of Brescia, Italy patients the presenting symptom may not be MRI to exclude other possible aetiologies of S F Cappa the usual memory loss but one or more of a dementia. Correspondence to: number of deficits involving other cognitive Twenty five normal elderly subjects, either Dr Giuliano Binetti, par- correlated volunteers or spouses of patients, Alzheimer's Disease Unit, functions. As there is growing evidence, Istituto S Cuore ticularly from imaging studies, suggesting a were also included in the study. History of Fatebenefratelli, Via cortex disabilities, Pilastroni, 4, 25123 Brescia, considerable involvement of the frontal alcoholism, drug abuse, learning Italy. in Alzheimer's disease,3 study of executive and serious neurological or psychiatric ill- Received 25 August 1994 dsyfunction is essential to the understanding nesses were considered as exclusion criteria. and in final revised form of the disease. Written informed consent was obtained from 30 August 1995 of heterogeneity Accepted 1 September 1995 Various aspects of memory and learning all subjects (patients and controls), or care- 92 Binetti, Magni, Padovani, Cappa, Bianzchetti, Trabucchi givers where appropriate. Patients and con- version of WCST5 with 64 cards was adopted, J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.60.1.91 on 1 January 1996. Downloaded from trols were assessed on the geriatric depression computing an index of perserveration (IP; scale (GDS)" to exclude subjects with severe number of errors/number of perseveration). depressive symptoms (GDS score > 20). The The verbal fluency for letters (PFL) was mini mental state examination (MMSE)"2 was assessed by recording the number of words given to characterise the global cognitive level. produced in the course of one minute for each letter.7 The Stroop colour word test' is an NEUROPSYCHOLOGICAL ASSESSMENT executive task for the assessment of the The following neuropsychological tests were ability to change perceptual sets to conform to given to both groups (for details of tests see changing task requirement. The interference Binetti et al). score (IS) was calculated by subtracting the Short term memory was assessed by audi- predicted colour word score from the raw tory-verbal forward digit span and visuospatial colour word scores. The higher the resultant span (Corsi's block tapping test). Episodic score, the less susceptible the patient is to memory was tested with the logical memory interference. The release from proactive inter- test (recall of a short story) and with the 20 ference (RPI) paradigm was evaluated using minutes delayed recall of the Rey complex the Wickens'6 modification of the Peterson figure. A 30 item version of the Boston naming and Peterson'3 distractor technique according test provided a measure of naming and seman- to Freedman and Cermak.'4 The stimuli, con- tic memory. Remote memory was assessed sisting of five trials of words triads grouped in with the Q60 questionnaire. The Street test four blocks, were presented on a 23 x 18 cm and the copy of the Rey figure were used to monitor. After the presentation of each triad assess visuospatial abilities. The Raven's subjects were asked to count backwards from coloured progressive matrices test, the a random number as rapidly as possible, to attentional matrices test, and the token test preclude rehearsal of the triad. After counting were also included in the neuropsychological for 10 seconds, the patient was asked to recall battery. the three words he had just read. Each block "Executive" function was evaluated by the of five trials consisted of the presentation of Wisconsin card sorting test (WCST), PFL four triads of words from the same semantic verbal fluency test,7 Stroop test,' and the category, followed by a fifth triad of words release from proactive interference paradigm.6 from a different semantic category (shift con- The WCST is a problem solving task dition (SC)). Each block consisted of high that measures the ability to identify abstract lexical frequency words from four categories categories and shift cognitive set. A shortened taken from Battig and Montague Connecticut category norms." The categories were, in sequence, animals, fruits, colours, and vegeta- Table I Perfonnance ofpatients with (AD+) anid without (AD-) executive functions bles. The SC effect was calculated by sub- deficits tracting the fourth trial score from the score of AD- AD+ each fifth trial throughout the blocks. (n = 18) (n = 7) No ofpatients As an arbitrary cut off value to identify (mcan (SD)) (meani (SD)) below the cut off (0) patients with prominent executive dysfunc- Demographic data: tion, we adopted the criterion of a score 1SD http://jnnp.bmj.com/ Age (y) 72-1 (9 5) 73 7 (6 9) Education (y) 7-4 (4-1) 5-7 (1-6) below the controls' mean on at least two out MJF 3/15 F7 - of the four measures of frontal lobe function CDR (0 5/1) 4/14 3/4 - MMSE 21 5 (2 2) 21 4 (2 4) (IP, PFL, IS, SC). Duration of illness (months) 30 7 (18 9) 36.8 (24-1) Geriatric depression scale 12-0 (7 6) 10 4 (6-8) Tests: Verbal fluency (PFL)t 17 5 (7-9) 10 0 (9-4) 3 (12) Results Wisconsin card sorting test: Index of perseveration 0-3 (0-14) 0-5 (0 17)* 7 (28) According to the described cut off, we Stroop test interference - 31 (12-7) - 3-8 (9-4) 5 (29) identified two subgroups of patients with on September 26, 2021 by guest. Protected copyright. Release from proactive interference 1 5 (3 1) -0-8 (30)* 12 (48) (block 5-block 4) Alzheimer's disease: seven patients (AD+) were considered to show executive dysfunc- *p < 0 05. tScores are not corrected for age and education. tion and 18 patients (AD -) not. Table 1 CDR = Clinical dementia rating. shows the number of patients below the cut off for each test. The AD+ and AD - groups were com- Table 2 Performance ofpatients with Alzheimer's disease with (AD+) and without parable in terms of age, education, sex, and (AD -) frontal lobe dysfunction on tests of memory, language, attention, abstract thinking, and visuospatial abilities depressive synptoms (table 1).