- Email: [email protected]
Cerebral autoregulation and ageing
Journal of Clinical Neuroscience (2005) 12(6), 643–646 0967-5868/$ - see front matter ª 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.jocn.2004.08.017
Clinical study
Cerebral autoregulation and ageing Alan T Yam1 MBBS, Erhard W Lang1 MD PHD, Jim Lagopoulos2,4 PHD, Kwok Yip1 MBBS, Jane Griffith1 RN CNS, Yugan Mudaliar3 FFARACS FRACP, Nicholas W C Dorsch1 FRCS FRACS 1 Departments of Neurosurgery, 2Neurophysiology, and 3Intensive Care, Westmead Hospital, 4School of Psychiatry, University of Sydney, Westmead, New South Wales, Australia
Summary Little is known about the effects of ageing on cerebral autoregulation (CA). To examine the relationship between age and CA in adults, we conducted a prospective study using a non-invasive protocol without external stimuli. We studied 32 subjects, aged 23–68 years. They were assigned to a young group (28 ± 5 years) and an old group (54 ± 8 years). The groups were sex-matched. Transcranial Doppler ultrasonography (TCD) was used to record bilateral middle cerebral artery flow velocities (CBFV, cm/sec). Noninvasive beat-to-beat tonometric arterial blood pressure (ABP) measurement of the radial artery was used to record spontaneous blood pressure fluctuations. The Mx, an index of dynamic cerebral autoregulation (dCA), was calculated from a moving correlation between ABP and CBFV. We did not find a correlation between age and Mx. No statistically significant difference in the Mx between the groups (0.27 ± 0.23, young, vs. 0.37 ± 0.24, old) was demonstrated. Age does not affect dynamic cerebral autoregulation assessed by the Mx index in healthy adult subjects. This study supports findings from previous papers wherein CA was measured with protocols which require external stimuli. Further studies are needed to determine CA in subjects above 70 years of age. ª 2005 Elsevier Ltd. All rights reserved. Keywords: Comparative study, cerebral autoregulation, ageing, cerebral blood flow velocity, transcranial Doppler ultrasound
INTRODUCTION
SUBJECTS AND METHODS
Cerebral autoregulation (CA) is the ability of the brain’s vasculature to react to changes in arterial blood pressure (ABP) and cerebral perfusion pressure (CPP) in order to achieve stable cerebral blood flow (CBF). The response of mean middle cerebral artery blood flow velocity (CBFV) measured by transcranial Doppler ultrasound (TCD) to changes in ABP or CPP indicates cerebral autoregulatory capacity and is used to quantify CA in clinical practice.1–4 CA is impaired in traumatic brain injury and cerebrovascular pathology such as subarachnoid hemorrhage and ischemic strokes.5–7 Impairment of CA is linked to poor prognosis.1,2,8 The physiological effects of ageing on CA in humans are not clear. 9–11 Comparative studies on adolescents showed less CA capacity in adolescents than adults.11 Czosnyka et al have developed an index which can be used to quantify CA, called Mx (mean index of autoregulation).1 The Mx is derived from spontaneous fluctuations of CPP and CBFV.1,12 This index is attractive for CA monitoring because it is derived from spontaneous fluctuations and it does not require an external stimulus to produce blood pressure change.1,13–15 We have recently demonstrated that the Mx can also be monitored and reliably graded when ABP is used instead of CPP which eliminates the need for invasive intracranial pressure measurements.7 This study was designed to assess the effect of ageing on CA in reaction to spontaneous arterial blood pressure changes by noninvasively measuring the dynamic CA of healthy subjects in a range of ages.
Subjects
Received 2 July 2004 Accepted 10 August 2004 Correspondence to: Dr. Erhard W. Lang, Neurosurgery Oce, Rotes Kreuz Krankenhaus, Bergmannstrasse 32, 34121 Kassel, Germany. Tel.: +49 561 3163990; Fax: +49 561 3163992; E-mail: [email protected]
With approval from the human research ethics committee, healthy volunteers were recruited in the neurosurgical unit in a teaching hospital and enrolled in this study. All subjects were normotensive, without a history of cerebrovascular or cardiovascular diseases. They did not take medications that may affect the cerebral vascular or cardiovascular system or had previous cranial or cardiac surgery. Each subject was given information about the study and written informed consent was obtained. Methods The study was performed at the neurosurgical unit of a teaching hospital. Each subject was positioned on a reclined couch in a designated room with minimal stimuli. A rigid head frame (the “Arthur Lam TCD probe holder”) was used to secure each TCD transducer over the temporal fossa by attaching at the nasion and the ears. Bilateral middle cerebral arteries (MCAs) were identified and CBFV were recorded using standard transcranial Doppler (TCD) ultrasound equipment (Multi-Dop T, DWL, Sipplingen, Germany). Calculated mean flow velocity (cm/sec) from both sides was used (Vmca). Continuous ABP measurement recordings were obtained on the right radial artery using a non-invasive beat-tobeat blood pressure (NIBP) monitor (Model 7000 NIBP Monitor, Colin Medical Instruments Corp, Aichi, Japan). Recording commenced when satisfactory and stable TCD and NIBP signals were achieved. TCD and NIBP signals were recorded and stored digitally in the TCD units. Mx calculation used 10,000 data points sampled at 57.4 Hz and further data analysis was performed off-line. All recording sessions were consistently performed by two examiners (ATY, EWL). The left-right averaged Mx from each subject was used for ageCA correlation analysis. We also compared the Mx from a subgroup of subjects composing of the ten youngest and ten oldest in the groups. 643
644 Yam et al.
not show a statistically significant CA difference between the young and old groups. One of the important parameters in regulating stable cerebral blood flow is the vasculature’s reactivity to fluctuating systemic blood pressure and cerebral perfusion pressure.16 This combination of reactivity and ability constitutes cerebral autoregulation (CA) as shown in Fig. 2. Vavilala et al demonstrated a significantly lower CA in adolescents when compared with adults.11 Their study compared two age groups, 12–17 years (n = 8) and 25–45 years (n = 9) and showed lower autoregulatory index (ARI) in healthy adolescent volunteers than adult volunteers. A higher ARI indicates better autoregulation. In a study comparing two older age groups experiencing an external BP stimulus, Carey’s group used dynamic pressor BP stimuli: lower body negative pressure release, Valsalva maneuver and spontaneous BP rises at rest and dynamic depressor BP stimuli: thigh cuff release and spontaneous BP drops at rest.9 Carey et al showed ageing has no effect on cerebral autoregulation by comparing ARI in a young group (29 € 5 years, n = 27) and an old group (68 € 5 years, n = 27).9 Rosengarten et al performed TCD on the posterior cerebral artery on healthy male subjects of three age groups between ages 10 to 60 years using a visual stimulation protocol.10,17 Rather than using indices like Mx and ARI, Rosengarten’s group analyzed changes in flow velocity in a control system approach. The parameters used in the control system approach, which are also measures of cerebral vasoreactivity, were time delay, attenuation, natural frequency, rate time and gain.18 Comparing the three age groups,
Statistical analysis was performed using independent t-test and Levene’s Test for equality of variance. Correlational analysis used Pearson’s correlation and Spearman’s correlation. Significance was set at P < 0.05. RESULTS Thirty-two volunteer subjects were recruited and enrolled in this study. Mean age of the young group (n = 16) was 28 € 5 years. Mean age of the old group (n = 16) was 54 € 8 years. Information and baseline data for the young and old group are shown in Table 1. Although there was a nominal Mx difference of 0.1 between the two groups (0.27 € 0.23, young group; 0.37 € 0.24, old group) this was not statistically significant (independent t-test, t = 1.24; df = 30, p > 0.05). There was no statistically significant correlation between age and Mx (Pearson correlation, p = 0.23; Spearman correlation, p = 0.19, Fig. 1). Within a subset comprised of the ten youngest (23–28 years, mean 25.6 € 1.43) and ten oldest subjects (48–68 years, mean 58.45 € 6.03), no significant difference in Mx was found either (independent t-test, t = 1.515; df = 18, p = 0.15). We report that no correlation between age and Mx was found. DISCUSSION This study does not demonstrate a correlation between age and dynamic cerebral autoregulation between age 23–68 years. It does
Table 1 Demographic details and characteristics
n mean age (range) mean ABP (range) Mx left side Mx right side Mx l/r average (range) CBFV MCA left CBFV MCA right CBFV MCA l/r average (range)
Young Group
Old Group
16 28 ± 5 (23–42) 80 ± 18 (50–102) 0.24 ± 0.24 0.29 ± 0.23 0.27 ± 0.23 ( 0.08 – 0.75) 57 ± 16 54 ± 15 55 ± 15 (34–75)
16 54 ± 8 (42–68) 82 ± 21 (47–104) 0.39 ± 0.26 0.34 ± 0.24 0.37 ± 0.24 ( 0.09 – 0.75) 58 ± 14 57 ± 16 57 ± 15 (34–86)
Age: years. ABP: mean arterial blood pressure (mm Hg). CBFV: cerebral blood flow velocity (cm/sec). MCA: middle cerebral artery. Yr: left/right.
average left/right Mx vs Age 80 70
Age (years)
60 50 40 30 20 10 0 -0.2
-0.1
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
average left/right Mx
Fig. 1 The average left/right index plotted against age. No correlation was found.
Journal of Clinical Neuroscience (2005) 12(6), 643–646
ª 2005 Elsevier Ltd. All rights reserved.
Cerebral autoregulation and ageing
Pressure Passive Dilatation
645
Pressure Passive Dilatation
Zone of Autoregulation • Vasoconstriction
100
Cerebral Blood Flow (ml/100g/min)
Cerebral Blood Volume Compartment
75
50
ICP 25
0 0
25
50
75
100
125
150
Arterial Blood Pressure (mmHg)
Fig. 2 Intact cerebral autoregulation where, within the autoregulatory range between 50 and 150mm Hg ABP (x-axis), cerebral blood flow (y-axis) remains stable. There is no correlation between pressure and flow. The Mx is less than 0.3.
Rosengarten et al found the parameters to be statistically unchanged between groups but did note a decrease in resting flow velocity with advancing age.10 Vavilala et al reported significantly increased Vmca in the young group (age 12–17 years) than in the old group.11 Carey and Rosengarten also reported increased Vmca in the young group compared with the old group but no difference in CA.9,10,18 In our study, however, we found no significant difference in Vmca between the two age groups studied. All three studies cited above used techniques that require some form of external stimuli. Both the Vavilala and Carey studies employed manipulative techniques such as Valsalva maneuver and thigh blood pressure cuff deflation to obtain pressor and depressor stimuli.9,11 The Rosengarten study used visual stimulation. Studies using methods involving visual stimulation, maneuvers and thigh cuff deflation techniques did not yield significantly different results from our approach.9,18 It should be noted that among the external stimulus used in the Carey study, thigh cuff release produces significantly greater ARI values than other stimulus.9 This present study confirmed findings in two other reports and showed no effect from normal moderate aging on CA in healthy adults.9,10 An observable effect of aging on CA from children to adults was demonstrated by Vavilala.11 Taken together this suggests there are observable age related CA changes in earlier part of life11 but after adolescence CA remains stable over much of adult life in a healthy person.9,10 LIMITATIONS AND FUTURE RESEARCH Several of the study subjects had an Mx that was around the cutoff value between normal and abnormal CA, an Mx of 0.3. This cutoff value was chosen because it provided the best cutoff for data analysis in head injury outcome studies in patients receiving sedation, analgesia and vasoactive medications. Data from this group of study subjects shows that apparently normal people can exhibit an Mx that would be considered indicative of abnormal CA if found in a group of head injury patients. In studies like this one involving normal subjects, we may need to revise the cutoff value for normal and abnormal CA. There were several smokers among the test subjects, as history of tobacco smoking was not among the exclusion criteria. It is likely that long term use of tobacco has an effect on the cerebral ª 2005 Elsevier Ltd. All rights reserved.
vasculature that will affect cerebral autoregulation. Acute increases in Vmca of 19% have been detected in subjects who were smoking.19 Larger increases in Vmca were detected in male subjects than female subjects.19 Previous reports on the effects of aging on CA did not exclude smokers from study population.9–11 A future study to test the correlation of the number of pack years smoked with CA index such as Mx would be interesting to see the effects of chronic tobacco smoking on cerebral autoregulation. The issue of the influence that interactions of age and gender combined have on CA is interesting and should be explored in future studies. Also, as this is the first study we know of which uses non-invasive tonometric ABP recordings, we are uncertain whether Mx differs when calculated with data from invasive and non-invasive recordings. A comparative study of Mx calculated from invasive and non-invasive ABP recordings is needed to clarify this issue. Data from Vavilala suggests that cerebral autoregulation may be lower at the 12–17 years age range while Carey’s and our study showed relatively stable values in the middle spectrum of age.9,11 A study comparing a young group with healthy subjects aged above 70 years might yield a more complete picture of how the process of ageing affects CA. Another limitation of this study is the number of subjects. While the number of subjects is comparable to other reports, we cannot rule out the possibility that with a larger number of subjects the insignificant difference between groups would become wider and eventually, significant. But given that the difference between groups we found is very small, we do not think this is likely to occur. CONCLUSIONS In this study we have provided further evidence that normal aging does not affect dynamic cerebral autoregulation regardless of the method by which CA is assessed. No correlation between age and dynamic cerebral autoregulation and no significant difference in dynamic cerebral autoregulation were found between the young and old group. Further studies will need to isolate the mechanisms in the “normal” ageing process from the abnormal or pathological processes in cerebrovascular parameters, which are responsible for changes in CA. Journal of Clinical Neuroscience (2005) 12(6), 643–646
646 Yam et al.
ACKNOWLEDGEMENTS This study was made possible by a grant from the Ian Tucker Foundation and the Australian Brain Foundation.
REFERENCES 1. Czosnyka M, Smielewski P, Kirkpatrick P, Menon DK, Pickard JD. Monitoring of cerebral autoregulation in head-injured patients. Stroke 1996; 27: 1829–1834. 2. Czosnyka M, Smielewski P, Piechnik S, Pickard JD. Clinical significance of cerebral autoregulation. Acta Neurochir Suppl 2002; 81: 117–119. 3. Sundgreen C, Larsen FS, Herzog TM, et al. Autoregulation of cerebral blood flow in patients resuscitated from cardiac arrest. Stroke 2001; 32: 128–132. 4. Tiecks FP, Lam AM, Aaslid R, Newell DW. Comparison of static and dynamic cerebral autoregulation measurements. Stroke 1995; 26: 1014–1019. 5. Eames PJ, Blake MJ, Dawson SL, Panerai RB, Potter JF. Dynamic cerebral autoregulation and beat to beat blood pressure control are impaired in acute ischaemic stroke. J Neurol Neurosurg Psychiatry 2002; 72: 467–472. 6. Choi JY, Morris JC, Hsu CY. Aging and cerebrovascular disease. Neurol Clin 1998; 16: 687–711. 7. Lang EW, Lagopoulos J, Griffith J, et al. Noninvasive cerebrovascular autoregulation assessment in traumatic brain injury: validation and utility. J Neurotrauma 2003; 20: 69–75. 8. Dawson SL, Panerai RB, Potter JF. Serial changes in static and dynamic cerebral autoregulation after acute ischaemic stroke. Cerebrovasc Dis 2003; 16: 69–75.
Journal of Clinical Neuroscience (2005) 12(6), 643–646
9. Carey BJ, Eames PJ, Blake MJ, Panerai RB, Potter JF. Dynamic cerebral autoregulation is unaffected by aging. Stroke 2000; 31: 2895–2900. 10. Rosengarten B, Aldinger C, Spiller A, Kaps M. Neurovascular coupling remains unaffected during normal aging. J Neuroimaging 2003; 13: 43–47. 11. Vavilala MS, Newell DW, Junger E, et al. Dynamic cerebral autoregulation in healthy adolescents. Acta Anaesthesiol Scand 2002; 46: 393–397. 12. Steinmeier R, Bauhuf C, Hubner U, et al. Slow rhythmic oscillations of blood pressure, intracranial pressure, microcirculation, and cerebral oxygenation. Dynamic interrelation and time course in humans. Stroke 1996; 27: 2236–2243. 13. Lang EW, Mehdorn HM, Dorsch NW, Czosnyka M. Continuous monitoring of cerebrovascular autoregulation: a validation study. J Neurol Neurosurg Psychiatry 2002; 72: 583–586. 14. Panerai RB, White RP, Markus HS, Evans DH. Grading of cerebral dynamic autoregulation from spontaneous fluctuations in arterial blood pressure. Stroke 1998; 29: 2341–2346. 15. Piechnik SK, Yang X, Czosnyka M, et al. The continuous assessment of cerebrovascular reactivity: a validation of the method in healthy volunteers. Anesth Analg 1999; 89: 944–949. 16. Aaslid R, Lindegaard KF, Sorteberg W, Nornes H. Cerebral autoregulation dynamics in humans. Stroke 1989; 20: 45–52. 17. Gomez SM, Gomez CR, Hall IS. Transcranial Doppler ultrasonographic assessment of intermittent light stimulation at different frequencies. Stroke 1990; 21: 1746–1748. 18. Rosengarten B, Huwendiek O, Kaps M. Neurovascular coupling in terms of a control system: validation of a second-order linear system model. Ultrasound Med Biol 2001; 27: 631–635. 19. Boyajian RA, Otis SM. Acute effects of smoking on human cerebral blood flow: a transcranial Doppler ultrasonography study. J Neuroimaging 2000; 10: 204–208.
ª 2005 Elsevier Ltd. All rights reserved.
Clinical study
Cerebral autoregulation and ageing Alan T Yam1 MBBS, Erhard W Lang1 MD PHD, Jim Lagopoulos2,4 PHD, Kwok Yip1 MBBS, Jane Griffith1 RN CNS, Yugan Mudaliar3 FFARACS FRACP, Nicholas W C Dorsch1 FRCS FRACS 1 Departments of Neurosurgery, 2Neurophysiology, and 3Intensive Care, Westmead Hospital, 4School of Psychiatry, University of Sydney, Westmead, New South Wales, Australia
Summary Little is known about the effects of ageing on cerebral autoregulation (CA). To examine the relationship between age and CA in adults, we conducted a prospective study using a non-invasive protocol without external stimuli. We studied 32 subjects, aged 23–68 years. They were assigned to a young group (28 ± 5 years) and an old group (54 ± 8 years). The groups were sex-matched. Transcranial Doppler ultrasonography (TCD) was used to record bilateral middle cerebral artery flow velocities (CBFV, cm/sec). Noninvasive beat-to-beat tonometric arterial blood pressure (ABP) measurement of the radial artery was used to record spontaneous blood pressure fluctuations. The Mx, an index of dynamic cerebral autoregulation (dCA), was calculated from a moving correlation between ABP and CBFV. We did not find a correlation between age and Mx. No statistically significant difference in the Mx between the groups (0.27 ± 0.23, young, vs. 0.37 ± 0.24, old) was demonstrated. Age does not affect dynamic cerebral autoregulation assessed by the Mx index in healthy adult subjects. This study supports findings from previous papers wherein CA was measured with protocols which require external stimuli. Further studies are needed to determine CA in subjects above 70 years of age. ª 2005 Elsevier Ltd. All rights reserved. Keywords: Comparative study, cerebral autoregulation, ageing, cerebral blood flow velocity, transcranial Doppler ultrasound
INTRODUCTION
SUBJECTS AND METHODS
Cerebral autoregulation (CA) is the ability of the brain’s vasculature to react to changes in arterial blood pressure (ABP) and cerebral perfusion pressure (CPP) in order to achieve stable cerebral blood flow (CBF). The response of mean middle cerebral artery blood flow velocity (CBFV) measured by transcranial Doppler ultrasound (TCD) to changes in ABP or CPP indicates cerebral autoregulatory capacity and is used to quantify CA in clinical practice.1–4 CA is impaired in traumatic brain injury and cerebrovascular pathology such as subarachnoid hemorrhage and ischemic strokes.5–7 Impairment of CA is linked to poor prognosis.1,2,8 The physiological effects of ageing on CA in humans are not clear. 9–11 Comparative studies on adolescents showed less CA capacity in adolescents than adults.11 Czosnyka et al have developed an index which can be used to quantify CA, called Mx (mean index of autoregulation).1 The Mx is derived from spontaneous fluctuations of CPP and CBFV.1,12 This index is attractive for CA monitoring because it is derived from spontaneous fluctuations and it does not require an external stimulus to produce blood pressure change.1,13–15 We have recently demonstrated that the Mx can also be monitored and reliably graded when ABP is used instead of CPP which eliminates the need for invasive intracranial pressure measurements.7 This study was designed to assess the effect of ageing on CA in reaction to spontaneous arterial blood pressure changes by noninvasively measuring the dynamic CA of healthy subjects in a range of ages.
Subjects
Received 2 July 2004 Accepted 10 August 2004 Correspondence to: Dr. Erhard W. Lang, Neurosurgery Oce, Rotes Kreuz Krankenhaus, Bergmannstrasse 32, 34121 Kassel, Germany. Tel.: +49 561 3163990; Fax: +49 561 3163992; E-mail: [email protected]
With approval from the human research ethics committee, healthy volunteers were recruited in the neurosurgical unit in a teaching hospital and enrolled in this study. All subjects were normotensive, without a history of cerebrovascular or cardiovascular diseases. They did not take medications that may affect the cerebral vascular or cardiovascular system or had previous cranial or cardiac surgery. Each subject was given information about the study and written informed consent was obtained. Methods The study was performed at the neurosurgical unit of a teaching hospital. Each subject was positioned on a reclined couch in a designated room with minimal stimuli. A rigid head frame (the “Arthur Lam TCD probe holder”) was used to secure each TCD transducer over the temporal fossa by attaching at the nasion and the ears. Bilateral middle cerebral arteries (MCAs) were identified and CBFV were recorded using standard transcranial Doppler (TCD) ultrasound equipment (Multi-Dop T, DWL, Sipplingen, Germany). Calculated mean flow velocity (cm/sec) from both sides was used (Vmca). Continuous ABP measurement recordings were obtained on the right radial artery using a non-invasive beat-tobeat blood pressure (NIBP) monitor (Model 7000 NIBP Monitor, Colin Medical Instruments Corp, Aichi, Japan). Recording commenced when satisfactory and stable TCD and NIBP signals were achieved. TCD and NIBP signals were recorded and stored digitally in the TCD units. Mx calculation used 10,000 data points sampled at 57.4 Hz and further data analysis was performed off-line. All recording sessions were consistently performed by two examiners (ATY, EWL). The left-right averaged Mx from each subject was used for ageCA correlation analysis. We also compared the Mx from a subgroup of subjects composing of the ten youngest and ten oldest in the groups. 643
644 Yam et al.
not show a statistically significant CA difference between the young and old groups. One of the important parameters in regulating stable cerebral blood flow is the vasculature’s reactivity to fluctuating systemic blood pressure and cerebral perfusion pressure.16 This combination of reactivity and ability constitutes cerebral autoregulation (CA) as shown in Fig. 2. Vavilala et al demonstrated a significantly lower CA in adolescents when compared with adults.11 Their study compared two age groups, 12–17 years (n = 8) and 25–45 years (n = 9) and showed lower autoregulatory index (ARI) in healthy adolescent volunteers than adult volunteers. A higher ARI indicates better autoregulation. In a study comparing two older age groups experiencing an external BP stimulus, Carey’s group used dynamic pressor BP stimuli: lower body negative pressure release, Valsalva maneuver and spontaneous BP rises at rest and dynamic depressor BP stimuli: thigh cuff release and spontaneous BP drops at rest.9 Carey et al showed ageing has no effect on cerebral autoregulation by comparing ARI in a young group (29 € 5 years, n = 27) and an old group (68 € 5 years, n = 27).9 Rosengarten et al performed TCD on the posterior cerebral artery on healthy male subjects of three age groups between ages 10 to 60 years using a visual stimulation protocol.10,17 Rather than using indices like Mx and ARI, Rosengarten’s group analyzed changes in flow velocity in a control system approach. The parameters used in the control system approach, which are also measures of cerebral vasoreactivity, were time delay, attenuation, natural frequency, rate time and gain.18 Comparing the three age groups,
Statistical analysis was performed using independent t-test and Levene’s Test for equality of variance. Correlational analysis used Pearson’s correlation and Spearman’s correlation. Significance was set at P < 0.05. RESULTS Thirty-two volunteer subjects were recruited and enrolled in this study. Mean age of the young group (n = 16) was 28 € 5 years. Mean age of the old group (n = 16) was 54 € 8 years. Information and baseline data for the young and old group are shown in Table 1. Although there was a nominal Mx difference of 0.1 between the two groups (0.27 € 0.23, young group; 0.37 € 0.24, old group) this was not statistically significant (independent t-test, t = 1.24; df = 30, p > 0.05). There was no statistically significant correlation between age and Mx (Pearson correlation, p = 0.23; Spearman correlation, p = 0.19, Fig. 1). Within a subset comprised of the ten youngest (23–28 years, mean 25.6 € 1.43) and ten oldest subjects (48–68 years, mean 58.45 € 6.03), no significant difference in Mx was found either (independent t-test, t = 1.515; df = 18, p = 0.15). We report that no correlation between age and Mx was found. DISCUSSION This study does not demonstrate a correlation between age and dynamic cerebral autoregulation between age 23–68 years. It does
Table 1 Demographic details and characteristics
n mean age (range) mean ABP (range) Mx left side Mx right side Mx l/r average (range) CBFV MCA left CBFV MCA right CBFV MCA l/r average (range)
Young Group
Old Group
16 28 ± 5 (23–42) 80 ± 18 (50–102) 0.24 ± 0.24 0.29 ± 0.23 0.27 ± 0.23 ( 0.08 – 0.75) 57 ± 16 54 ± 15 55 ± 15 (34–75)
16 54 ± 8 (42–68) 82 ± 21 (47–104) 0.39 ± 0.26 0.34 ± 0.24 0.37 ± 0.24 ( 0.09 – 0.75) 58 ± 14 57 ± 16 57 ± 15 (34–86)
Age: years. ABP: mean arterial blood pressure (mm Hg). CBFV: cerebral blood flow velocity (cm/sec). MCA: middle cerebral artery. Yr: left/right.
average left/right Mx vs Age 80 70
Age (years)
60 50 40 30 20 10 0 -0.2
-0.1
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
average left/right Mx
Fig. 1 The average left/right index plotted against age. No correlation was found.
Journal of Clinical Neuroscience (2005) 12(6), 643–646
ª 2005 Elsevier Ltd. All rights reserved.
Cerebral autoregulation and ageing
Pressure Passive Dilatation
645
Pressure Passive Dilatation
Zone of Autoregulation • Vasoconstriction
100
Cerebral Blood Flow (ml/100g/min)
Cerebral Blood Volume Compartment
75
50
ICP 25
0 0
25
50
75
100
125
150
Arterial Blood Pressure (mmHg)
Fig. 2 Intact cerebral autoregulation where, within the autoregulatory range between 50 and 150mm Hg ABP (x-axis), cerebral blood flow (y-axis) remains stable. There is no correlation between pressure and flow. The Mx is less than 0.3.
Rosengarten et al found the parameters to be statistically unchanged between groups but did note a decrease in resting flow velocity with advancing age.10 Vavilala et al reported significantly increased Vmca in the young group (age 12–17 years) than in the old group.11 Carey and Rosengarten also reported increased Vmca in the young group compared with the old group but no difference in CA.9,10,18 In our study, however, we found no significant difference in Vmca between the two age groups studied. All three studies cited above used techniques that require some form of external stimuli. Both the Vavilala and Carey studies employed manipulative techniques such as Valsalva maneuver and thigh blood pressure cuff deflation to obtain pressor and depressor stimuli.9,11 The Rosengarten study used visual stimulation. Studies using methods involving visual stimulation, maneuvers and thigh cuff deflation techniques did not yield significantly different results from our approach.9,18 It should be noted that among the external stimulus used in the Carey study, thigh cuff release produces significantly greater ARI values than other stimulus.9 This present study confirmed findings in two other reports and showed no effect from normal moderate aging on CA in healthy adults.9,10 An observable effect of aging on CA from children to adults was demonstrated by Vavilala.11 Taken together this suggests there are observable age related CA changes in earlier part of life11 but after adolescence CA remains stable over much of adult life in a healthy person.9,10 LIMITATIONS AND FUTURE RESEARCH Several of the study subjects had an Mx that was around the cutoff value between normal and abnormal CA, an Mx of 0.3. This cutoff value was chosen because it provided the best cutoff for data analysis in head injury outcome studies in patients receiving sedation, analgesia and vasoactive medications. Data from this group of study subjects shows that apparently normal people can exhibit an Mx that would be considered indicative of abnormal CA if found in a group of head injury patients. In studies like this one involving normal subjects, we may need to revise the cutoff value for normal and abnormal CA. There were several smokers among the test subjects, as history of tobacco smoking was not among the exclusion criteria. It is likely that long term use of tobacco has an effect on the cerebral ª 2005 Elsevier Ltd. All rights reserved.
vasculature that will affect cerebral autoregulation. Acute increases in Vmca of 19% have been detected in subjects who were smoking.19 Larger increases in Vmca were detected in male subjects than female subjects.19 Previous reports on the effects of aging on CA did not exclude smokers from study population.9–11 A future study to test the correlation of the number of pack years smoked with CA index such as Mx would be interesting to see the effects of chronic tobacco smoking on cerebral autoregulation. The issue of the influence that interactions of age and gender combined have on CA is interesting and should be explored in future studies. Also, as this is the first study we know of which uses non-invasive tonometric ABP recordings, we are uncertain whether Mx differs when calculated with data from invasive and non-invasive recordings. A comparative study of Mx calculated from invasive and non-invasive ABP recordings is needed to clarify this issue. Data from Vavilala suggests that cerebral autoregulation may be lower at the 12–17 years age range while Carey’s and our study showed relatively stable values in the middle spectrum of age.9,11 A study comparing a young group with healthy subjects aged above 70 years might yield a more complete picture of how the process of ageing affects CA. Another limitation of this study is the number of subjects. While the number of subjects is comparable to other reports, we cannot rule out the possibility that with a larger number of subjects the insignificant difference between groups would become wider and eventually, significant. But given that the difference between groups we found is very small, we do not think this is likely to occur. CONCLUSIONS In this study we have provided further evidence that normal aging does not affect dynamic cerebral autoregulation regardless of the method by which CA is assessed. No correlation between age and dynamic cerebral autoregulation and no significant difference in dynamic cerebral autoregulation were found between the young and old group. Further studies will need to isolate the mechanisms in the “normal” ageing process from the abnormal or pathological processes in cerebrovascular parameters, which are responsible for changes in CA. Journal of Clinical Neuroscience (2005) 12(6), 643–646
646 Yam et al.
ACKNOWLEDGEMENTS This study was made possible by a grant from the Ian Tucker Foundation and the Australian Brain Foundation.
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