Peptides, Vol. 12, pp. 871-876. ©PergamonPress plc, 1991. Printedin the U.S.A.
0196-9781/91 $3.00 + .00
Effects of DDAVP on Movement Planning and Execution Processes in the Healthy Elderly J O H N S. C A R T E R , H A R R I E T G. W I L L I A M S , J. M A R K D A V I S A N D K A R E N E. F R E N C H
Department o f Exercise Science, University o f South Carolina, Columbia, SC 29208 Received 11 October 1990 CARTER, J. S., H. G. WILLIAMS, J. M. DAVIS AND K. E. FRENCH. Effects of DDAVP on movement planning and execution processes in the healthy elderly. PEPTIDES 12(4) 871-876, 1991.--Effects of DDAVP on speed and consistency of planning and executing simple and complex movements in healthy older adults were studied. A simple reaction time (SRT) task, a singleplane movement task, and two tasks involving multiplane movements of distal upper extremities were performed with and/or without a 0.6 ml intranasal dose (60 p.g) of DDAVP or placebo. Results indicated that DDAVP had no significant effect on speed or consistency of SRT processes, or the speed with which simple or complex movements were planned or executed. There was also no effect on retention of motor responses. Behavior
DDAVP
Desmopressin
Motor
Movement
MOST complex movements or motor behaviors undergo change with advancing age; alteration in motor function is characterized by significant losses in speed of performance and in consistency of psychomotor responses (21,32). Critical modifications of motor function occur with age in reflex behaviors, posture and balance control, eye-hand coordination, reaction time, and speed/ variability of movement (13, 16, 28). There is nearly universal agreement that arginine vasopressin (AVP) and AVP analogs, particularly 1-desamino-8-D-arginine vasopressin (DDAVP), affect cognitive functioning, memory processes, and learning in a positive way (10,33). Significant improvements have been seen with AVP treatment in a variety of learning (concept shift, serial, arithmetic, and passive avoidance) and memory (for implicational sentences, free recall, semantically related words, and visual sequential) tasks (1-3, 5, 34). Attention, concentration, mood, and self-confidence have been intensified with AVP/AVP analog treatments (9, 11, 12, 22, 36, 37). It has also been suggested that AVP may be effective in persons with mild cognitive decrements, such as occur in the healthy elderly (10). Since AVP/AVP analogs appear to favorably affect cognitive CNS functions, it seems logical that they may also facilitate neuromotor control processes involved in planning and executing overt motor acts. Little if any attention has been given to the potential mediating effects of AVP or DDAVP on motor functions. Significant increases have been reported in speed of complex movement planning and in velocity and consistency of movement execution processes involved in complex motor tasks among a group of healthy young adults treated with DDAVP (6). No study has been given to the potential facilitatory effects of DDAVP on declining motor functions of older adults. Because a universal characteristic of the aging process is a slowing of psychomotor and other movement-related behaviors, it would seem to be of importance to determine whether or not DDAVP has a positive and/or long-lasting effect on motor functions in
Elderly
Reaction
aging individuals. The primary purpose of this study was to investigate the effects of DDAVP on speed, consistency, and retention of movement planning and movement execution processes in healthy older adults. METHOD
Subjects Participants were sixty healthy, consenting volunteers living independently in metropolitan Columbia and Charleston, SC. Participants ranged in age from 60-85 years (average age=68.9 years). There were fourteen females (average age=66.5 years) and forty-six males (average age = 69.7 years). Participants were physically and emotionally healthy and free of major sensory, neurological, and motor impairments as determined by medical screening and self-report. Individuals with rhinitis, diabetes insipidus, cardiovascular disease or cardiovascular system irregularities, or hypertension were excluded. All subjects had resting blood pressures below 140/90 mmHg and resting heart rates less than 85 bpm.
Tasks Participants were asked to complete four tasks: a simple reaction time task (SRT), a simple movement task (SMT), a moderately complex movement task (CMT1), and a complex (CMT2) movement task. A Lafayette Reaction/Movement Timer Model 63017 was used to record reaction time (RT) and movement time (MT) in milliseconds. Each subject completed ten trials on each task. Simple reaction time (SRT). Individuals were seated facing a motor sequencing apparatus. The subject depressed a " h o m e " telegraph key with the index and third fingers of the dominant hand. After a randomized 1-, 2-, or 3-second forewarning pc-
871
872
riod (signaled by a white light), a red stimulus light appeared. The subject responded to the stimulus light by lifting the fingers as quickly as possible. Simple movement task (SMT). Procedures were similar to those for SRT. However, on appearance of the red stimulus light, the subject lifted the fingers from the "home" key and moved them as quickly as possible to depress a second telegraph key located 60.96 cm to the right. Moderately complex movement task (CMT1). After a randomized 1-, 2-, or 3-second foreperiod, a green stimulus light appeared. The subject lifted the fingers from the "home" key, depressed a lever and turned a knob on the motor sequencing apparatus, and depressed the second key. Complex movement task (CMT2). Procedures were similar to those for CMTI; however, after a randomized foreperiod, a blue stimulus light appeared. The subject lifted the fingers from the "home" key and performed a specific sequence of four actions: pushing a knob, depressing a lever, squeezing a grip handle, and rotating a knob. The second telegraph key was depressed to complete the task.
CARTER, WILLIAMS, DAVIS AND FRENCH
TABLE 1 AVERAGE SPEED AND VARIABILITY OF RT AND MT PERFORMANCES BY GROUP: MEANS AND (STANDARD ERRORS) IN MILLISECONDS
Groups Task
D-D
P-P
Procedures Each subject received either a 0.6 ml dosage (60 Ixg) of DDAVP in a sterile aqueous solution of cholobutanol, sodium chloride, and hydrochloric acid, or an equal volume of saline (placebo) administered intranasally. A double-blind procedure was utilized. Although the test dosage was approximately three times that recommended for adults with diabetes insipidus (0.2 ml/day), both dosage and route of administration are consistent with that used in previous studies and are considered to be safe and effective (1, 3-5). DDAVP is typically absorbed into the bloodstream with peak plasma levels reached within 30-50 minutes. This dosage of DDAVP has a biological effect which lasts 8-12 hours, followed by a gradual loss in effectiveness over an additional 12-hour period. Biphasic half-lives of DDAVP are 7.8 and 75.5 minutes for fast and slow phases; plasma half-lives range between 2.83.6 hours (14,29). Prior to treatment administration, participants were seated and given preliminary blood pressure and resting heart rate checks. Individuals were excluded from the study if blood pressure exceeded 140/90 mmHg or resting heart rate was greater than 85 bpm. Subjects rested in a supine position on a padded table, and a premeasured amount of DDAVP or placebo was administered intranasally by the investigator. Care was taken to insure that none of the dosage entered the throat or was swallowed. Subjects remained supine for 15-20 minutes to allow for absorption. A second blood pressure and heart rate cheek was taken at 20 minutes, and testing began immediately thereafter. A third he-
P-D
Speed of Performance SRT SMT CMT1 CMT2
315(058) 497(156) 544(179) 543(158)
SMT CMT1 CMT2
420(118) 1913(568) 3086(864)
Reaction Time 323(048) 501(143) 606(230) 570(198)
295(035) 490(153) 538(164) 539(153)
332(060) 515(144) 594(193) 590(187)
Movement Time 400(140) 459(131) 1987(584) 2229(658) 3169(829) 3515(950)
389(124) 1936(642) 3034(972)
Variability of Performance
Experimental Conditions Tasks were performed with and/or without DDAVP. Individuals were randomly assigned to one of four treatment groups (n= 15): a control group (P-P) performed all tasks on each of two different days with placebo only; a drug group (D-D) performed all tasks on each of two different days with DDAVP only; and two mixed groups, one of which performed tasks with DDAVP in session 1 and placebo in session 2 (D-P), and the other group that performed under reverse conditions (P-D). All subjects returned for a third (retention) session and performed tasks without placebo or DDAVP. Each session was separated by 5-8 days. Testing was conducted between 0900-1600 hours at the convenience and request of each participant.
D-P
SRT SMT CMT1 CMT2
1.80(002) 7.00(011) 12.0(028) 9.00(014)
Reaction Time 3.60(004) 2.00(003) 12.0(012) 10.0(013) 22.0(038) 13.0(016) 17.0(031) 10.0(0t2)
3.50(004) 12.0(015) 19.0(033) 15.0(187)
SMT CMT1 CMT2
005(007) 102(144) 137(175)
Movement Time 007(013) 006(008) 195(314) 205(313) 223(276) 227(297)
027(182) 251(461) 277(417)
SRT= simple reaction task, SMT= simple movement task, CMT1= moderately complex movementtask, CMT2= complex movementtask.
modynamic check was performed at the completion of testing. No significant changes in either heart rate or blood pressure were observed during or at the conclusion of testing.
Research Design and Statistical Analysis The design of the study was a 4 (Treatment Group) x 3 (Movement Task) × 3 (Session) factorial with repeated measures on the last two factors. Separate repeated measures MANOVAs with appropriate follow-up tests were used to analyze each of four dependent variables: mean RT and MT and variability of RT and MT. SRT performances were analyzed using a 4 (Treatment Group) × 3 (Session) repeated measures ANOVA. RESULTS
Means and standard errors of average speed and variability of performance for each task are shown by group (Table 1), session (Table 2), and treatment (Table 3). The effects of primary interest are the main effect of Group and the Group x Session interaction.
Speed of Reaction Simple reaction time. Neither main effect of Group nor Group x Session interaction were significant [Group: HotellingLawley Trace, F(3,56)= 1.95, p>0.10; Group × Session: F(6,112)=0.75, p>0.60]. These results indicated that, in general, DDAVP had little or no effect on SRT.
MOTOR EFFECTS OF DDAVP IN OLDER ADULTS
873
TABLE 2 AVERAGESPEED AND VARIABILITYOF RT AND MT PERFORMANCES BY SESSION:MEANSAND (STANDARDERRORS)IN MILLISECONDS
TABLE 3 AVERAGESPEED AND VARIABILITYOF RT AND MT PERFORMANCES BY TREATMENT:MEANSAND (STANDARDERRORS)IN MILLISECONDS
Session Task
1
2
Treatment 3 (retention)
Task
DDAVP
Speed of Performance
Placebo
Speed of Performance
SRT SMT CMT1 CMT2
306(048) 527(161) 604(195) 594(188)
Reaction Time 314(053) 496(146) 571(214) 556(178)
328(054) 479(134) 537(167) 531(154)
SRT SMT CMT1 CMT2
Reaction Time 309(054) 509(153) 571(193) 566(175)
311(048) 514(156) 603(216) 585(192)
SMT CMTI CMT2
449(143 ) 2293(688) 3565(997)
Movement Time 415(125) 1976(565) 3161(854)
387(116) 1780(499) 2876(771)
SMT CMT 1 CMT1
Movement Time 435(125) 2128(673) 3335(953)
429(145) 2140(625) 3391(947)
Variability of Performance
Variability of Performance
SRT SMT CMT1 CMT2
1.70(002) 013(016) 022(033) 020(034)
Reaction Time 2.50(003) 009(011) 018(038) 010(015 )
3.90(004) 009(012) 010(013) 008(011 )
SRT SMT CMT1 CMT2
Reaction Time 002(003) 011(009) 018(032) 011 (016)
011(009) 012(010) 022(039) 018(034)
SMT CMT 1 CMT2
022(157) 325(461 ) 340(417)
Movement Time 008(019) 147(240) 185(251 )
004(006) 093(174) 123(147)
SMT CMT 1 CMT2
Movement Time 007(017) 225(319) 224(291)
023(157) 247(429) 301 (40 1)
SRT= simple reaction task, SMT= simple movement task, CMT1 = moderately complex movement task, CMT2 = complex movement task.
SRT= simple reaction task, SMT= simple movement task, CMT1 = moderately complex movement task, CMT 2 = complex movement task.
The main effect of Session was significant, F(2,55)=6.00, p
0196-9781/91 $3.00 + .00
Effects of DDAVP on Movement Planning and Execution Processes in the Healthy Elderly J O H N S. C A R T E R , H A R R I E T G. W I L L I A M S , J. M A R K D A V I S A N D K A R E N E. F R E N C H
Department o f Exercise Science, University o f South Carolina, Columbia, SC 29208 Received 11 October 1990 CARTER, J. S., H. G. WILLIAMS, J. M. DAVIS AND K. E. FRENCH. Effects of DDAVP on movement planning and execution processes in the healthy elderly. PEPTIDES 12(4) 871-876, 1991.--Effects of DDAVP on speed and consistency of planning and executing simple and complex movements in healthy older adults were studied. A simple reaction time (SRT) task, a singleplane movement task, and two tasks involving multiplane movements of distal upper extremities were performed with and/or without a 0.6 ml intranasal dose (60 p.g) of DDAVP or placebo. Results indicated that DDAVP had no significant effect on speed or consistency of SRT processes, or the speed with which simple or complex movements were planned or executed. There was also no effect on retention of motor responses. Behavior
DDAVP
Desmopressin
Motor
Movement
MOST complex movements or motor behaviors undergo change with advancing age; alteration in motor function is characterized by significant losses in speed of performance and in consistency of psychomotor responses (21,32). Critical modifications of motor function occur with age in reflex behaviors, posture and balance control, eye-hand coordination, reaction time, and speed/ variability of movement (13, 16, 28). There is nearly universal agreement that arginine vasopressin (AVP) and AVP analogs, particularly 1-desamino-8-D-arginine vasopressin (DDAVP), affect cognitive functioning, memory processes, and learning in a positive way (10,33). Significant improvements have been seen with AVP treatment in a variety of learning (concept shift, serial, arithmetic, and passive avoidance) and memory (for implicational sentences, free recall, semantically related words, and visual sequential) tasks (1-3, 5, 34). Attention, concentration, mood, and self-confidence have been intensified with AVP/AVP analog treatments (9, 11, 12, 22, 36, 37). It has also been suggested that AVP may be effective in persons with mild cognitive decrements, such as occur in the healthy elderly (10). Since AVP/AVP analogs appear to favorably affect cognitive CNS functions, it seems logical that they may also facilitate neuromotor control processes involved in planning and executing overt motor acts. Little if any attention has been given to the potential mediating effects of AVP or DDAVP on motor functions. Significant increases have been reported in speed of complex movement planning and in velocity and consistency of movement execution processes involved in complex motor tasks among a group of healthy young adults treated with DDAVP (6). No study has been given to the potential facilitatory effects of DDAVP on declining motor functions of older adults. Because a universal characteristic of the aging process is a slowing of psychomotor and other movement-related behaviors, it would seem to be of importance to determine whether or not DDAVP has a positive and/or long-lasting effect on motor functions in
Elderly
Reaction
aging individuals. The primary purpose of this study was to investigate the effects of DDAVP on speed, consistency, and retention of movement planning and movement execution processes in healthy older adults. METHOD
Subjects Participants were sixty healthy, consenting volunteers living independently in metropolitan Columbia and Charleston, SC. Participants ranged in age from 60-85 years (average age=68.9 years). There were fourteen females (average age=66.5 years) and forty-six males (average age = 69.7 years). Participants were physically and emotionally healthy and free of major sensory, neurological, and motor impairments as determined by medical screening and self-report. Individuals with rhinitis, diabetes insipidus, cardiovascular disease or cardiovascular system irregularities, or hypertension were excluded. All subjects had resting blood pressures below 140/90 mmHg and resting heart rates less than 85 bpm.
Tasks Participants were asked to complete four tasks: a simple reaction time task (SRT), a simple movement task (SMT), a moderately complex movement task (CMT1), and a complex (CMT2) movement task. A Lafayette Reaction/Movement Timer Model 63017 was used to record reaction time (RT) and movement time (MT) in milliseconds. Each subject completed ten trials on each task. Simple reaction time (SRT). Individuals were seated facing a motor sequencing apparatus. The subject depressed a " h o m e " telegraph key with the index and third fingers of the dominant hand. After a randomized 1-, 2-, or 3-second forewarning pc-
871
872
riod (signaled by a white light), a red stimulus light appeared. The subject responded to the stimulus light by lifting the fingers as quickly as possible. Simple movement task (SMT). Procedures were similar to those for SRT. However, on appearance of the red stimulus light, the subject lifted the fingers from the "home" key and moved them as quickly as possible to depress a second telegraph key located 60.96 cm to the right. Moderately complex movement task (CMT1). After a randomized 1-, 2-, or 3-second foreperiod, a green stimulus light appeared. The subject lifted the fingers from the "home" key, depressed a lever and turned a knob on the motor sequencing apparatus, and depressed the second key. Complex movement task (CMT2). Procedures were similar to those for CMTI; however, after a randomized foreperiod, a blue stimulus light appeared. The subject lifted the fingers from the "home" key and performed a specific sequence of four actions: pushing a knob, depressing a lever, squeezing a grip handle, and rotating a knob. The second telegraph key was depressed to complete the task.
CARTER, WILLIAMS, DAVIS AND FRENCH
TABLE 1 AVERAGE SPEED AND VARIABILITY OF RT AND MT PERFORMANCES BY GROUP: MEANS AND (STANDARD ERRORS) IN MILLISECONDS
Groups Task
D-D
P-P
Procedures Each subject received either a 0.6 ml dosage (60 Ixg) of DDAVP in a sterile aqueous solution of cholobutanol, sodium chloride, and hydrochloric acid, or an equal volume of saline (placebo) administered intranasally. A double-blind procedure was utilized. Although the test dosage was approximately three times that recommended for adults with diabetes insipidus (0.2 ml/day), both dosage and route of administration are consistent with that used in previous studies and are considered to be safe and effective (1, 3-5). DDAVP is typically absorbed into the bloodstream with peak plasma levels reached within 30-50 minutes. This dosage of DDAVP has a biological effect which lasts 8-12 hours, followed by a gradual loss in effectiveness over an additional 12-hour period. Biphasic half-lives of DDAVP are 7.8 and 75.5 minutes for fast and slow phases; plasma half-lives range between 2.83.6 hours (14,29). Prior to treatment administration, participants were seated and given preliminary blood pressure and resting heart rate checks. Individuals were excluded from the study if blood pressure exceeded 140/90 mmHg or resting heart rate was greater than 85 bpm. Subjects rested in a supine position on a padded table, and a premeasured amount of DDAVP or placebo was administered intranasally by the investigator. Care was taken to insure that none of the dosage entered the throat or was swallowed. Subjects remained supine for 15-20 minutes to allow for absorption. A second blood pressure and heart rate cheek was taken at 20 minutes, and testing began immediately thereafter. A third he-
P-D
Speed of Performance SRT SMT CMT1 CMT2
315(058) 497(156) 544(179) 543(158)
SMT CMT1 CMT2
420(118) 1913(568) 3086(864)
Reaction Time 323(048) 501(143) 606(230) 570(198)
295(035) 490(153) 538(164) 539(153)
332(060) 515(144) 594(193) 590(187)
Movement Time 400(140) 459(131) 1987(584) 2229(658) 3169(829) 3515(950)
389(124) 1936(642) 3034(972)
Variability of Performance
Experimental Conditions Tasks were performed with and/or without DDAVP. Individuals were randomly assigned to one of four treatment groups (n= 15): a control group (P-P) performed all tasks on each of two different days with placebo only; a drug group (D-D) performed all tasks on each of two different days with DDAVP only; and two mixed groups, one of which performed tasks with DDAVP in session 1 and placebo in session 2 (D-P), and the other group that performed under reverse conditions (P-D). All subjects returned for a third (retention) session and performed tasks without placebo or DDAVP. Each session was separated by 5-8 days. Testing was conducted between 0900-1600 hours at the convenience and request of each participant.
D-P
SRT SMT CMT1 CMT2
1.80(002) 7.00(011) 12.0(028) 9.00(014)
Reaction Time 3.60(004) 2.00(003) 12.0(012) 10.0(013) 22.0(038) 13.0(016) 17.0(031) 10.0(0t2)
3.50(004) 12.0(015) 19.0(033) 15.0(187)
SMT CMT1 CMT2
005(007) 102(144) 137(175)
Movement Time 007(013) 006(008) 195(314) 205(313) 223(276) 227(297)
027(182) 251(461) 277(417)
SRT= simple reaction task, SMT= simple movement task, CMT1= moderately complex movementtask, CMT2= complex movementtask.
modynamic check was performed at the completion of testing. No significant changes in either heart rate or blood pressure were observed during or at the conclusion of testing.
Research Design and Statistical Analysis The design of the study was a 4 (Treatment Group) x 3 (Movement Task) × 3 (Session) factorial with repeated measures on the last two factors. Separate repeated measures MANOVAs with appropriate follow-up tests were used to analyze each of four dependent variables: mean RT and MT and variability of RT and MT. SRT performances were analyzed using a 4 (Treatment Group) × 3 (Session) repeated measures ANOVA. RESULTS
Means and standard errors of average speed and variability of performance for each task are shown by group (Table 1), session (Table 2), and treatment (Table 3). The effects of primary interest are the main effect of Group and the Group x Session interaction.
Speed of Reaction Simple reaction time. Neither main effect of Group nor Group x Session interaction were significant [Group: HotellingLawley Trace, F(3,56)= 1.95, p>0.10; Group × Session: F(6,112)=0.75, p>0.60]. These results indicated that, in general, DDAVP had little or no effect on SRT.
MOTOR EFFECTS OF DDAVP IN OLDER ADULTS
873
TABLE 2 AVERAGESPEED AND VARIABILITYOF RT AND MT PERFORMANCES BY SESSION:MEANSAND (STANDARDERRORS)IN MILLISECONDS
TABLE 3 AVERAGESPEED AND VARIABILITYOF RT AND MT PERFORMANCES BY TREATMENT:MEANSAND (STANDARDERRORS)IN MILLISECONDS
Session Task
1
2
Treatment 3 (retention)
Task
DDAVP
Speed of Performance
Placebo
Speed of Performance
SRT SMT CMT1 CMT2
306(048) 527(161) 604(195) 594(188)
Reaction Time 314(053) 496(146) 571(214) 556(178)
328(054) 479(134) 537(167) 531(154)
SRT SMT CMT1 CMT2
Reaction Time 309(054) 509(153) 571(193) 566(175)
311(048) 514(156) 603(216) 585(192)
SMT CMTI CMT2
449(143 ) 2293(688) 3565(997)
Movement Time 415(125) 1976(565) 3161(854)
387(116) 1780(499) 2876(771)
SMT CMT 1 CMT1
Movement Time 435(125) 2128(673) 3335(953)
429(145) 2140(625) 3391(947)
Variability of Performance
Variability of Performance
SRT SMT CMT1 CMT2
1.70(002) 013(016) 022(033) 020(034)
Reaction Time 2.50(003) 009(011) 018(038) 010(015 )
3.90(004) 009(012) 010(013) 008(011 )
SRT SMT CMT1 CMT2
Reaction Time 002(003) 011(009) 018(032) 011 (016)
011(009) 012(010) 022(039) 018(034)
SMT CMT 1 CMT2
022(157) 325(461 ) 340(417)
Movement Time 008(019) 147(240) 185(251 )
004(006) 093(174) 123(147)
SMT CMT 1 CMT2
Movement Time 007(017) 225(319) 224(291)
023(157) 247(429) 301 (40 1)
SRT= simple reaction task, SMT= simple movement task, CMT1 = moderately complex movement task, CMT2 = complex movement task.
SRT= simple reaction task, SMT= simple movement task, CMT1 = moderately complex movement task, CMT 2 = complex movement task.
The main effect of Session was significant, F(2,55)=6.00, p
