Simple and choice reaction time in dementia: Clinical implications

Neurobiology of Aging, Vol. 2, pp. 113--117, 1981. Printed in the U.S.A.

Simple and Choice Reaction Time in Dementia: Clinical Implications F R A N C I S J. P I R O Z Z O L O 1, K A T H Y J. C H R I S T E N S E N , K A T H L E E N M. O G L E E D W A R D C. H A N S C H A N D W. G A R Y T H O M P S O N

Geriatric Research, Education, and Clinical Center (GRECC), Minneapolis V.A. Medical Center Departments o f Neurology, Psychiatry, and Psychology, University o f Minnesota Minneapolis, M N R e c e i v e d 20 F e b r u a r y 1981 PIROZZOLO, F. J., K. J. CHRISTENSEN, K. M. OGLE, E. C. HANSCH AND W. G. THOMPSON. Simple andchoice reaction time in dementia: Clinical implications. NEUROBIOL. AGING 2(2) 113-117, 1981.--The present study investigated differences between normal elderly subjects matched for age and education and patients with dementia of the Alzheimer's type (DAT) on two measures of reaction time (RT). Statistically significant group differences clearly demonstrate that normal elderly subjects have faster RT than subjects with senile dementia on all RT tasks. The DAT patients were most clearly differentiated in terms of overall group means and clinical classification from their age-matched counterparts on the choice RT task. Eleven of 12 (92%) DAT patients displayed choice RT's 2 or more standard deviations above those of age-matched normals. While both RT measures were discriminative between patients and normals, the overall results argue for increased sensitivity when choice is required in RT in accessing the cognitive deficits in DAT.

Dementia of the Alzheimer's type (DAT)

Choice reaction time

DEMENTIA of the Alzheimer's type (DAT) is clinically characterized by a slowly progressing intellectual decline. DAT is morphologically characterized by ventricular dilitation and cortical atrophy, with in Vivo evaluations showing a strong correlation between the severity of dementia and the width of the third ventricle [12]. The neuropsychological features of DAT include disturbances of memory, spatial orientation and psychomotor speed. Recent studies [13,20] have shown that measures of reaction time can be useful in psychophysiological assessments of dementia. Reaction time (RT), a simple motor response to a sensory stimulus, has been thought to reflect the speed of nervous conduction since the mid-nineteenth century [16,29]. RT is known to be sensitive to a variety of subject and experimental variables. An early experimental finding was that there is a slowing of all volitional movements with aging [15]. Studies of age effects on RT have examined the interaction of such factors as general health [6], cardiovascular status [1, 8, 17], motivation [7,28], practice [8], and the use of warning signals [27]. In all cases, greater age is associated with slower RT. Regular exercise habits in the elderly have been found to eliminate age differences in RT [9, 25], although others have found no effect [8]. It is also well established that psychomotor speed is adversely affected by organic disease of the brain. Patients with focal cerebral disease [5], with transient ischemic attacks [17], and with unilateral cerebral lesions [3] have been found to have slower response times than age-matched con-

Simplereaction time

Reaction time

trois. Age has been shown to interact with brain disease producing a more pronounced slowing of RT in elderly subjects with acquired brain lesions [2]. Studies examining the relationship between complexity of the RT task and impairment in speed of response in patients with brain disease have produced inconsistent results. A positive relationship between the complexity of a verbal association task and the degree of retardation of RT in postencephalitic patients was noted by Steck [26] as early as 1924. Other studies [5, 10, 24] of RT in neurologic patients have found equal or even superior group differentiation using simple RT over more complex discriminative RT tasks. Interactions between laterality of lesion and greater diagnostic sensitivity with increased number of choices in RT have been described [11]. Ferris et al. [13] have recently described RT increases on warned simple and three choice disjunctive RT tasks for cognitively impaired "senile" patients compared to a group of normal elderly individuals. The authors concluded that the group differences in simple RT could be accounted for by the larger disjunctive RT differences and that consequently simple RT depends to some extent on the cardinal variable of "cognitive involvement" tapped most directly in the disjunctive measure. The aforementioned studies suggest that the relative efficacy of simple and choice RT tasks in discriminating between patients with brain disease and controls is likely to be a function of age, specific neuroiogic diagnosis, and the number of choices on the RT task. The purpose of

1Address correspondence and reprint requests to Dr. Francis J. Pirozzolo, GRECC (127F), Veterans Administration Medical Center, 54th Street and 48th Avenue South, Minneapolis, MN 55417.

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METHOD Twelve male outpatients with presumptive diagnoses of dementia of the Alzheimer's type (DAT) followed at the Geriatric Research, Education and Clinical Center of the Veterans Administration Medical Center in Minneapolis served as the patient group. This group had a mean age of 67.4 years with 12.7 years of education. Presumptive diagnoses of DAT were made after neurological examination, psychiatric interview, neuropsychoiogical testing, CT scan, EEG and standard screening for reversible causes of dementia [18]. In addition, twelve normal age- and education-matched (within one year) elderly male volunteers were selected from groups of retired VAMC employees, VAMC volunteers and members of a community-based senior citizens organization. Exclusions for both patients and'volunteers were: history of psychiatric hospitalization, coronary heart disease, neurological disease (other than DAT in the patient group), chemical dependency, limiting motor disability, or uncorrected visual or auditory acuity defects. All subjects were tested in mid-morning to minimize effects of fatigue. No patients or controls were taking neuroleptic or sedative medication, although two DAT patients were on antidepressants at the time of the study. All patients and normal control subjects underwent extensive neuropsychological evaluation in order to document each subject's mental status. This evaluation [19, 21, 22] includes measures of language abilities, perception, verbal and non-verbal memory, concept set shifting, oculomotor scanning, fund of information, graphomotor transcoding, and depression. Control subjects had cognitive abilities that were rated "normal." DAT patients were rated minimally, mildly, moderately or severely impaired. In the present study, most of the DAT subjects came from the moderately impaired group. Simple auditory and visual reaction times and four-choice visual reaction times were obtained by means of a commercially available Lafayette Instrument Company Visual Choice Reaction Time Apparatus Model 63035 and Digital Display Stop Clock Model 54030. The reaction time apparatus consisted of a subject panel with four stimulus lamps (red, white, blue and green), an audio speaker, and five circular 20.5 mm diameter response buttons. The response buttons were situated 28.5 mm apart in a horizontal row below their respective stimuli with the auditory response button in the middle. Stop clock timing was activated by stimulus onset and terminated by appropriate button press. In the simple auditory RT task, the subject rested his index fmger on the button below the audio speaker. Upon hearing the tone, the subject pressed the button as quickly as possible to extinguish the tone. In the simple visual RT task, the subject rested his index finger on the button below the white light before each trial. Subjects pressed the button as quickly as possible after seeing the light in order to extinguish it. Eight trials were recorded with each hand on the simple RT tasks. In the four-choice visual RT task, the subject rested his index finger on the center response button before each RT trial. Subjects were instructed to lift off this " h o m e " button and press the response button corresponding to the trial-determined illuminated lamp as quickly as possible. As in the

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simple visual RT task, the stimulus lamp illumination continued until the subject made a correct response. A total of sixteen responses were required from each ~ d with each light position represented randomly four times. A minimum of five practice trials were ~ s t e r e d for each hand on all RT tasks. The starting ~ d was alternated on each successive task, with s ~ ~ on the first task counterbalanced between fight and left =cross subjects. A variable intertrial interval was employed with m ~ ~ o f 10 seconds. Trials in which the response time exceeded 20 sec, onds without a correct response were not included in the analysis. RESULTS Individual subject mean and median RT's were obtained by collapsing across the eight trials and response hand for both patients and normals. All analyses were performed using both the mean and median for raw data summarization, with similar results obtained for each measure o f central tendency. The statistical analyses to be discussed here were based on the individual subject median RT as the data for each group showed some positive skewing. Mean (across group members) RT values for controls and Alzheimer patients on the three RT tasks are displayed in Fig. I. A two-way analysis of variance (group membership x task) revealed significant main effects for group membership, F=28.27, p<0.001, and task, F=196.9,p<0.001. Analysis of simple main effects of group membership for each RT measure demonstrated that RT of the normal controls was significantly shorter than that of Alzheimer patients (simple auditory mean RT=233, 393 msec, F-7.38, p<0.05; simple

REACTION TIME IN DEMENTIA

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TABLE 1 CLINICAL CLASSIFICATIONOF NORMAL CONTROLS AND BAT PATIENTSBASEDON RT

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visual mean RT=283, 594 msec, F=12.17, p<0.01; choice mean RT=535, 1603 msec, F=29.91, p<0.001 for normals and patients, respectively). In addition, a significant interaction occurred between group membership and task, F= 120.85,p<0.001. Significance in the interaction was explained by the simple auditory and visual RT tasks demonstrating relatively similar differences between the controls and Alzheimer patients, while the choice RT task produced a more pronounced RT advantage for normal controls compared to Alzheimer patient values. Planned comparisons examining the sources of significance in this two-way interaction revealed that the four-choice RT task produced significantly greater group differences than either the simple auditory RT task, F= 123.6, p<0.001, or simple visual RT procedure, F=85.8, p<0.001, while the two simple RT tasks failed to differ significantly when contrasted against each other on their pattern of group differences in RT. Linear regression of median RT on age in the normal controls failed to demonstrate a significant relationship between these variables for all three tasks, r=.48, r=.23, r = - . 3 1 for choice, simple visual, and simple auditory RT tasks, respectively. As correlations with age were small and heterogenous between tasks, age correction for deviation of patient RT values around normals using the standard errors of estimate around the regression line was deemed unreliable and not used for clinical classification. Instead, + 1.5 and +2 standard deviation (SD) points above mean RT of the normal age-matched group served as cutoff criterion values to assess clinical diagnostic utility of each RT measure. Table 1 presents the numbers of DAT patients and normals exceeding these established cutoff points for the three experimental measures. Classification based on the fourchoice RT task was superior to that based on either simple RT task. Using a criterion of 2 SD's above mean median of choice RT time of normals, 92% of the patients were correctly classified. The simple RT measures correctly classified smaller percentages (50 and 75 for auditory and visual, respectively) of DAT patients than did the choice RT task. Only in the auditory RT task did the lowered + 1.5 SD criterion result in increased patient diagnostic yield without increasing the number of false positives. While the +2 SD criterion for choice RT correctly identified all but one DAT patient without misclassifying any normals, the distribution of patient RT values suggested that a

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FIG. 2. Individual four-choice median RT's plotted against age for DAT patients and normals.

more stringent classification cutoff would not result in an appreciable diminuition of diagnostic "hits." Individual median choice RT's for normals and patients are displayed as a function of age in Fig. 2. The extremely clear separation of DAT patients from age-matched normals is clearly evident in this figure, with 10 of 12 patients falling 3 or more SD's above normal values. DISCUSSION

As a human psychological entity readily extrapolated from experimental designs, reaction time has received consider'able attention in the laboratory over the last one hundred years. The dependence of RT on sensory, motor, and cognitive variables suggests that performance on RT tasks would be largely influenced by the structural integrity of the central nervous system. The significantly increased simple and choice RT of patients with DAT over age-matched normal counterparts in the present study confirmed the prediction that RT would be increased in this patient group with clinical neurologically and neuropsychologically-established cognitive dysfunction. While the DAT patients had significantly higher mean RT on all three RT measures, the group differences were most pronounced when choice was required in the response. The imposition of information processing demands in the choice measure, by adding selective signal detection and discriminative responding to task performance, disproportionately increased RT in DAT patients as compared to

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the normal controls. An increased sensitivity of the fourchoice task over the simple RT measures in indexing cognitive impairment in Alzheimer patients is implied by these results. The steepness of the RT gradient as the number of choices increase in choice RT has been postulated to serve as an index of intellectual functioning in normals [14]. The lack of significant regressions of age on the RT measures in the normal group in the present study can be accounted for by the small number of individuals studied over an attenuated (51-84) age span. Increased classification accuracy using a +2 SD cutoff criterion with the four-cboice measure (92% of patients correctly classified) over simple auditory (50%) and simple visual (75%) RT lent support to preferential employment of choice RT for clinical diagnostic purposes. These percentages compared favorably with those obtained for simple visual (60%) and three-choice disjunctive (65%) RT in cognitively impaired "senile" patients obtained by discriminant analysis in the Ferris et al. [13] study without increasing the occurrences of "false positives." Several differences between these studies probably account for the increased diagnostic yield for four-choice RT in the present investigation. The patient population in the present study was more homogenous in neurologic diagnosis, consisting entirely of patients carrying the presumptive diagnosis of DAT, based on neurologic, psychiatric, neuropsycbologic, electroencephalographic and neuroradiologic test results. Secondly, Fen-is et al. [13] employed a "warned" RT paradigm, as opposed to the "unwarned" task used in the current study; that normals and DAT patients alike showed shorter response latencies on both their simple and choice RT tasks is likely due to facilitation by the warning signal. The use of warning stimuli is known to decrease response time in young normals, especially when the preparation interval is held constant [4], with an optimal interval of between 0.2 and 0.5 seconds [22]. Alertness and preparatory demands are probably maximized in the unwarned paradigm where no external stimuli serve to direct attention to an impending event, thus the enhanced group differences in our study may stem from an underlying difference in non-specific attentional or arousal processes characterizing the patients with dementia. In a component analysis of choice RT, attentional factors may be viewed to interact with central cognitive processing demands in modulating group differences, since increased group differentiation when choice is added to RT may well be due to selective group incapacity to increase non-specific attentional processes above some "fixed" baseline level. Use of a warning stimulus might serve to mask group differences in what Posner [23] has described as a preliminary "alertness or preparation" stage of decisional processes, thus reducing overall choice RT discrepancy between the groups. A third possible contributing factor to enhanced group differentiation on the choice RT measure in the pres-

ent study involved the task characteristics of "choice" m each study. Ferris et al. [13] studied three-cboice "disjunctive RT" in a paradigm where subjects made a unitary key release response when one of three stimulus conditions occurred. Although the task can be considered "disjunctive" in that subjects responded differentially according to stimulus type, Ferris et al. [13] averaged RT only to the one "responded to" stimulus, with the alternative stimulus-response contingencies denoted by non-response. The four-choice RT task in the present study required 4 separate responses to 4 discrete stimuli with all stimulus types contributing to overall median RT; greater central cognitive involvement can be assumed/n selecting differential motor response output dependent on stimulus type when "choice" is defined in this context. Increasing the numbers of cboices from 3 to 4 would serve to increase cognitive demands as well. Thus, it appears that the four-choice RT measure in our study increased the difficulty of the cognitive decisional component as well as maximizing attentional demands by not having a warning signal. The extremely clear separation of normals from DAT patients on "choice" RT may reflect both nonspecific attentional or more specific dimensions of cognitive information processing deficits characterizing the latter group. Parametric manipulation of warning intervals and number of choices would seem fruitful in determination of the contributions of various components of overall choice RT in modulating response time increase in patients with DAT. Recently, increases in ocnlomotor RT in patients with dementia of presumed Alzheimer's etiology have been described, correlating with severity of dementia based on clinical neurologic tests and neuropsychological evaluation [20]. The non-homogenous distribution of RT values on the choice measure of DAT patients in the present study, where some patients fell 10 or more SD's above normal control values, may stem from underlying variance in mean severity of cognitive impairment. Quite different patient distributions for choice RT would be expected depending on whether severity bears a linear, monotonic relationship with RT or whether a nonlinear sharp increase in RT occurs at some critical level of cognitive impairment. Attention to this variable in further research would be helpful in improving diagnostic utility of choice RT in the differential diagnosis of dementia where mild cognitive impairment would tend to prevail.

ACKNOWLEDGEMENTS This research was supported, in part, by a Merit Review Grant (71853) from the Veterans Administration to the first author. We would like to thank Dr. Patrick Irvine and the Program in Geriatric Medicine of the University of ~ s o t a for their support of this project. The assistance of Barbara Johnson and Marlys Anderson in the preparation of this manuscript is also gratefully acknowledged.

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