Hostname: page-component-cd9895bd7-fscjk Total loading time: 0 Render date: 2024-12-28T03:06:05.524Z Has data issue: false hasContentIssue false
  • English
  • Français

Autonomic dysfunction in older people

Published online by Cambridge University Press:  15 October 2010

J Richard G Marigold ,
Monica Arias ,
Michael Vassallo ,
Stephen C. Allen  and
Joseph SK Kwan
J Richard G Marigold*
Affiliation:
Department of Medicine for Older People, Royal Bournemouth Hospital
Monica Arias
Affiliation:
School of Health and Social Care, Bournemouth University, UK
Michael Vassallo
Affiliation:
Department of Medicine for Older People, Royal Bournemouth Hospital School of Health and Social Care, Bournemouth University, UK
Stephen C. Allen
Affiliation:
Department of Medicine for Older People, Royal Bournemouth Hospital School of Health and Social Care, Bournemouth University, UK
Joseph SK Kwan
Affiliation:
Department of Medicine for Older People, Royal Bournemouth Hospital
*
Address for correspondence: Dr J Richard G Marigold, Department of Medicine for Older People, Royal Bournemouth Hospital, Castle Lane East, Bournemouth BH7 7DW, UK. Email: rmarigold@hotmail.com
Get access Rights & Permissions [Opens in a new window]

Summary

The autonomic nervous system comprises the sympathetic, parasympathetic and enteric nervous systems and plays an integral role in homeostasis. This includes cardiovascular and temperature control, glucose metabolism, gastrointestinal and reproductive function and increasing evidence to support its involvement in the inflammatory response to infection and cancer. Ageing is associated with autonomic dysfunction, and many clinical syndromes associated with older adults are due to inadequate autonomic responses to physiological stressors. The aim of this review is to explore the relationship between autonomic dysfunction and ageing illustrated with examples of maladaptive autonomic responses in a variety of different clinical syndromes including an exploration of autonomic cellular changes. Appropriate investigation and management strategies are outlined, recognizing the fine balance needed to improve symptoms without creating further medical complications.

Keywords

autonomic nervous systemelderlydysfunctionfailuregeriatrics
Type
Clinical geriatrics
Information
Reviews in Clinical Gerontology , Volume 21 , Issue 1 , February 2011 , pp. 28 - 44
Copyright
Copyright © Cambridge University Press 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1Langley, JN. The autonomic nervous system. Brain 1903; 26: 1–26.CrossRefGoogle Scholar
2Myllyla, V, Tulppo, M. Cardiovascular Autonomic Dysfunction. In Bolis, CL, Licinio, J, Govoni, S (eds). Handbook of Autonomic Nervous System in Health and Disease. Marcel Dekker Inc, New York, 2003.Google Scholar
3Saenz de Tejada, I, Kim, N, Lagan, I, Krane, RJ, Goldstein, I. Regulation of adrenergic activity in penile corpus cavernosum. J Urol 1989; 142: 1117–21.CrossRefGoogle ScholarPubMed
4Collins, KJ. Low indoor temperatures and morbidity in the elderly. Age Ageing 1986; 15: 212–20CrossRefGoogle ScholarPubMed
5Widicombe, JG, Sterling, GM. Autonomic nervous system and breathing. Arch Intern Med 1970; 126: 311–29.CrossRefGoogle Scholar
6Fagius, J. Sympathetic nerve activity in metabolic control – some basic concepts Acta Physiol Scand 2003; 177: 337–43.CrossRefGoogle ScholarPubMed
7Kopp, UC, DiBona, GF. Neural regulation of renin secretion. Semin Nephrol 1993; 13: 543–51.Google ScholarPubMed
8Bulygin, IA. A consideration of the general principles of organization of sympathetic ganglia. J Auton Nerv Syst 1983; 8: 303–30.CrossRefGoogle ScholarPubMed
9Woodcock, EA, Du, XJ, Reichelt, ME, Graham, RM. Cardiac a1-adrenergic drive in pathological remodelling. Cardiovasc Res 2008; 77: 452–62.CrossRefGoogle Scholar
10Kvietys, PR, Granger, DN. Physiology and pathophysiology of the colonic circulation. Clin Gastroenterol 1986; 15: 967–83.Google ScholarPubMed
11Lewis, MJ, Short, AL, Lewis, KE. Autonomic nervous system control of the cardiovascular and respiratory systems in asthma. Respir Med 2006; 100: 1688–705.CrossRefGoogle ScholarPubMed
12Johnson, RH, Spaulding, JM. Disorders of the Autonomic Nervous System, chapter 11, The Eyes. Contemp Neurol Ser 1974; 11: 199–219.Google Scholar
13Rampin, O. Neural control of erection. J Soc Biol 2004; 198: 217–30.CrossRefGoogle ScholarPubMed
14Collins, KJ, Exton-Smith, AN, James, MH, Oliver, DJ. Functional changes in autonomic nervous responses with ageing. Age Ageing 1980; 9: 17–24.CrossRefGoogle ScholarPubMed
15Oliver, DJ. Heart rate response to standing as a test for autonomic neuropathy BMJ 1978; 1: 1349–50.CrossRefGoogle Scholar
16National Diabetes Data Group. Diabetes in America, 2nd edition. Bethesda, MD, National Institutes of Health, 1995.Google Scholar
17Abrass, IB, Schwartz, RS. Special presentation of endocrine disease in the elderly. In Fitzgerald, FT (ed), Current Practice of Medicine, vol 1, no 2. Philadelphia, PA, Current Medicine Inc, 1998, pp. 415–18.Google Scholar
18Ewing, DJ, Campbell, IW, Clarke, BF. Heart rate changes in diabetes mellitus. Lancet 1981; 1: 183–86.CrossRefGoogle ScholarPubMed
19Low, PA, Walsh, JC, Huang, CY, McLeod, JG. The sympathetic nervous system in diabetic neuropathy: a clinical and pathological study. Brain 1975; 98: 341–56.CrossRefGoogle ScholarPubMed
20Langer, A, Freeman, MR, Josse, RG, Steiner, G, Armstrong, PW. Detection of silent myocardial ischaemia in diabetes mellitus. Am J Cardiol 1991; 67: 1073–78.CrossRefGoogle ScholarPubMed
21Burgos, LG, Ebert, TJ, Asiddao, C, Turner, LA, Pattison, CZ, Wang-Cheng, R, Kampine, JP. Increased intraperative cardiovascular morbidity in diabetics with autonomic neuropathy. Anaesthesiology 1989; 70: 591–97.CrossRefGoogle Scholar
22Veglio, M, Sivieri, R, Chinaglia, A, Scaglione, L, Cavallo-Perin, P. QT interval prolongation and mortality in type 1 diabetic patients: a 5 year cohort prospective study. Diabetes Care 2000; 23: 1381–83.CrossRefGoogle ScholarPubMed
23Stevens, MJ, Raffel, DM, Allman, KC, Dayanikli, F, Ficaro, E, Sandford, T, Wieland, DM, Pfeifer, MA, Schwaiger, M. Cardiac sympathetic dysinnervation in diabetes: implications for enhanced cardiovascular risk. Circulation 1998; 98: 961–68.CrossRefGoogle ScholarPubMed
24Gavazzi, I. Collateral sprouting and responsiveness to nerve growth factor of ageing neurones. Neurosci Lett 1995; 189: 47–50.CrossRefGoogle Scholar
25Cotman, CW, Gomez-Pinilla, F. Basic fibroblast growth factor in the mature brain and its possible role in Alzheimer's disease. Ann NY Acad Sci 1991; 638: 221–31.CrossRefGoogle ScholarPubMed
26Vlassara, H, Bucula, R, Striker, L. Pathological effects of advanced glycosylation: Biochemical, biological and clinical implications for diabetes and ageing. Lab Invest 1994; 70: 138–51.Google Scholar
27Arima, K, Uéda, K, Sunohara, N, Hirai, S, Izumiyama, Y, Tonozuka-Uehara, H, Kawai, M. Immunoelectron-microscopic demonstration of NACP/alpha-synuclein-epitopes on the filamentous component of Lewy bodies in Parkinson's disease and in dementia with Lewy bodies. Brain Res 1998; 808: 93–100.CrossRefGoogle ScholarPubMed
28Trojanowski, JQ. Tauists, Baptists, Syners, Apostates and new data. Ann Neurol 2002; 52: 263–65CrossRefGoogle ScholarPubMed
29Rüb, U, Del Tredici, K, Schultz, C, Ghebremedhin, E, de Vos, RA, Jansen Steur, E, Braak, H. Parkinson's disease: the thalamic components of the limbic system are severly impaired by alpha synuclein staining immunopositive inclusion body pathology. Neurobiol Aging 2002; 23: 245–54.CrossRefGoogle Scholar
30Yoshida, M. Multiple system atrophy: alpha synuclein and neuronal degeneration. Neuropathology 2007; 27: 484–93.CrossRefGoogle ScholarPubMed
31Daniel, S. The neuropathology and neurochemistry of multiple system atrophy. In Matthias, C, Bannister, R (eds). Autonomic Failure: a textbook of clinical disorders of the autonomic nervous system. Oxford, Oxford University Press. 1999; pp. 321–328.Google Scholar
32Minguez-Castellanos, A, Chamorro, CE, Escamilla-Sevilla, F, Ortega-Moreno, A, Rebollo, AC, Gomez-Rio, M, Concha, A, Munoz, DG. Do alpha synuclein aggregates in autonomic plexuses predate Lewy body disorders? A cohort study. Neurology 2007; 68: 2012–18.CrossRefGoogle ScholarPubMed
33Rittirsch, D, Flierl, MA, Ward, PA. Harmful molecular mechanisms in sepsis. Nat Rev Immunol 2008; 8: 776–87.CrossRefGoogle ScholarPubMed
34Medzhitov, R, Janeway, C Jr. Innate immunity. N Engl J Med 2000; 343: 338–44.CrossRefGoogle ScholarPubMed
35Hawlisch, H, Belkaid, Y, Baelder, R, Hildeman, D, Gerard, C, Köhl, J. C5a negatively regulates Toll-like receptor-4-induced immune responses. Immunity 2005; 22: 415–26.CrossRefGoogle ScholarPubMed
36Munford, RS, Tracey, KJ. Is severe sepsis a neuroendocrine disease? Mol Med 2002; 8: 437–42.CrossRefGoogle ScholarPubMed
37Barajon, I, Serrao, G, Arnaboldi, F, Opizzi, E, Ripamonti, G, Balsari, A, Rumio, C. Toll-like receptors 3, 4, and 7 are expressed in the enteric nervous system and dorsal root ganglia. J Histochem Cytochem 2009; 57: 1013–23.CrossRefGoogle Scholar
38Schmidt, H, Hoyer, D, Hennen, R, Heinroth, K, Rauchhaus, M, Prondzinsky, R, Hottenrott, K, Buerke, M, Müller-Werdan, U, Werdan, K. Autonomic dysfunction predicts both 1- and 2-month mortality in middle-aged patients with multiple organ dysfunction syndrome Crit Care Med 2008; 36: 967–70.CrossRefGoogle ScholarPubMed
39Sayk, F, Vietheer, A, Schaaf, B, Wellhoener, P, Weitz, G, Lehnert, H, Dodt, C. Endotoxemia causes central downregulation of sympathetic vasomotor tone in healthy humans. Am J Physiol Regul Integr Comp Physiol 2008; 295: R891–98.CrossRefGoogle ScholarPubMed
40Zhao, A, Bossone, C, Piñeiro-Carrero, V, Shea-Donohue, T. Colitis-induced alterations in adrenergic control of circular smooth muscle in vitro in rats. J Pharmacol Exp Ther 2001; 299: 768–74.Google ScholarPubMed
41Guichard, A, Vignon, G. La Polyradiculoneurite cancereuse metastatique. Le J Médecine de Lyon 1949; 30: 197–207.Google Scholar
42Anderson, NE, Rosenblum, MK, Graus, F. Autoantibodies in paraneoplastic syndromes associated with small-cell lung cancer. Neurology 1988; 38: 1391–98.CrossRefGoogle ScholarPubMed
43Ficker, DM, Hammack, JE. Primary central nervous system lymphoma presenting as autonomic dysfunction. J Neurooncol 1995; 23: 245–48.CrossRefGoogle ScholarPubMed
44Oskarsson, BE, Quan, D, Wiley, RG. Paraneoplastic autonomic neuropathy. E-medicine – last updated 3 January 2009. Available at: http://emedicine.medscape.com/article/1156808-overview (accessed 10 June 2010).Google Scholar
45Lorusso, L, Hart, IK, Ferrari, D, Ngonga, GK, Gasparetto, C, Ricevuti, G. Autonomic paraneoplastic neurological syndromes. Autoimmun Rev 2007; 6: 162–68.CrossRefGoogle ScholarPubMed
46Oh, SJ, Dropcho, EJ, Claussen, GC. Anti-Hu-associated paraneoplastic sensory neuropathy responding to early aggressive immunotherapy: report of two cases and review of literature. Muscle Nerve 1997; 20: 1576–82.3.0.CO;2-Z>CrossRefGoogle ScholarPubMed
47Ewing, DJ, Clarke, BF. Diagnosis and management of diabetic autonomic neuropathy BMJ 1982; 285: 916–18.CrossRefGoogle ScholarPubMed
48Eckberg, DL. Physiological basis for human autonomic rhythms. Ann Med 2000; 32: 341–49.CrossRefGoogle ScholarPubMed
49Ewing, DJ, Campbell, IW, Murray, A, Neilson, JM, Clarke, BF. Immediate heart rate response to standing: simple test for autonomic neuropathy in diabetes. BMJ 1978; 1: 145–47.CrossRefGoogle ScholarPubMed
50Ewing, DJ. Cardiovascular reflexes and autonomic neuropathy. Clin Sci Mol Med 1978; 55: 321–27.Google ScholarPubMed
51Risk, M, Bril, V, Broadbridge, C, Cohen, A. Heart rate variability measurement in diabetic neuropathy: review of methods. Diabetes Technol Ther 2001; 3: 63–76.CrossRefGoogle ScholarPubMed
52Ewing, DJ, Irving, JB, Kerr, F, Wildsmith, JA, Clarke, BF. Cardiovascular responses to sustained handgrip in normal subjects and in patients with diabetes mellitus: a test of autonomic function. Clin Sci Mol Med 1974; 46: 295–306.Google ScholarPubMed
53Ebert, TJ, Stowe, DF, Barney, JA, Kalbfleisch, JH, Smith, JJ. Summated circulatory responses of thermal and baroreflexes in humans. J Appl Physiol 1982; 52: 184–89.CrossRefGoogle ScholarPubMed
54Callister, R, Suwarno, NO, Seals, DR. Sympathetic activity is influenced by task difficulty and stress perception during mental challenge in humans. J Physiol 1992; 454: 373–87.CrossRefGoogle ScholarPubMed
55Birklein, F, Spitzer, A, Riedl, B. The assessment of sudomotor function for diagnosis of autonomic diseases. Principles and methods. Fortschr Neurol Psychiatr 1999; 67: 287–95.CrossRefGoogle ScholarPubMed
56Low, PA, Caskey, PE, Tuck, RR, Fealey, RD, Dyck, PF. Quantitative sudomotor axon reflex test in normal and neuropathic subjects. Ann Neurol 1983; 14: 573–80.CrossRefGoogle ScholarPubMed
57Schatz, IJ, Bannister, R, Freeman, RL et al. Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. Neurology 1996; 46: 1470.Google Scholar
58Harris, T, Lipsitz, LA, Kleinman, JC, Cornoni-Huntley, J. Postural change in blood pressure associated with age and systolic blood pressure: The National Health and Nutrition Examination Survey II. J Gerontol 1991; 46: M159–63.CrossRefGoogle ScholarPubMed
59Lipsitz, LA. Orthostatic hypotension in the elderly. N Engl J Med 1989; 321: 952–57.Google ScholarPubMed
60James, MA, Potter, JF. Orthostatic blood pressure changes and arterial baroreflex sensitivity in elderly subjects. Age Ageing 1999; 28: 522–30.CrossRefGoogle ScholarPubMed
61Low, PA, Opfer-Gehhrking, TL, McPhee, BR et al. Prospective evaluation of clinical characteristics of orthostatic hypotension. Mayo Clin Proc 1995; 70: 617–22.CrossRefGoogle ScholarPubMed
62Ooi, W. The association between orthostatic hypotension and recurrent falls in nursing home residents. Am J Med 2000; 108: 106–11.CrossRefGoogle ScholarPubMed
63Bulpitt, CJ, Peters, R, Staessen, JA, Thijs, L, De Vernejoul, MC, Fletcher, AE, Beckett, NS. Fracture risk and the use of a diuretic (indapamide SR) +/– perindopril: a substudy of the Hypertension in the Very Elderly Trial (HYVET). Trials 2006; 19: 7–33.Google Scholar
64Landi, G, Perrone, P, Guidotti, M. Bilateral TIAs and unilateral seizures due to orthostatic hypotension. A case report. Ital J Neurol Sci 1983; 2: 239–41.CrossRefGoogle Scholar
65Luukinen, H, Koski, K, Laippala, P, Airaksinen, KE. Orthostatic hypotension and the risk of myocardial infarction in the home-dwelling elderly. J Intern Med 2004; 255: 486–93.CrossRefGoogle ScholarPubMed
66Román, GC. Brain hypoperfusion: a critical factor in vascular dementia. Neurol Res 2004; 26: 454–58.CrossRefGoogle ScholarPubMed
67van Lieshout, JJ, ten Harkel, AD, Wieling, W. Fludrocortisone and sleeping in the head-up position limit the postural decrease in cardiac output in autonomic failure. Clin Auton Res 2000; 10: 35–42.CrossRefGoogle ScholarPubMed
68Petrella, RJ, Cunningham, DA, Smith, JJ. Influence of age and physical training on postural adaptation. Can J Sport Sci 1989; 14: 4–9.Google ScholarPubMed
69Freeman, R. Current pharmacologic treatment for orthostatic hypotension. Clin Auton Res 2008; 18: 14–18.CrossRefGoogle ScholarPubMed
70Decaux, G. Fludrocortisone in orthostatic hypotension. N Engl J Med 1979; 301: 1121–22.Google ScholarPubMed
71Wittbrodt, ET, Kovalick, LJ. The use of oral vasopressors in the management of autonomic dysfunction and orthostatic hypotension. Ann Pharmacother 1999; 33: 565–71.CrossRefGoogle ScholarPubMed
72McClellan, KJ, Wiseman, LR, Wilde, MI. Midodrine. A review of its therapeutic use in the management of orthostatic hypotension. Drugs Aging 1998; 12: 76–86.Google ScholarPubMed
73Masuo, K, Mikami, H, Ogihara, T, Tuck, ML. Changes in frequency of orthostatic hypotension in elderly hypertensive patients under medications. Am J Hypertens 1996; 9: 263–68.CrossRefGoogle ScholarPubMed
74Hoeldtke, RD, Streeten, DH. Treatment of orthostatic hypotension with erythropoietin. N Engl J Med 1993; 329: 611–15.CrossRefGoogle ScholarPubMed
75Dewey, RB Jr, Rao, SD, Holmburg, SL, Victor, RG. Ergotamine/caffeine treatment of orthostatic hypotension in parkinsonism with autonomic failure. Eur J Neurol 1998; 5: 593–99.CrossRefGoogle ScholarPubMed
76Woo, J, Or, KH, Teoh, R, Nicholls, MG. Treatment of severe orthostatic hypotension with the somatostatin analogue octreotide. Aust NZ J Med 1990; 20: 822–23.CrossRefGoogle ScholarPubMed
77Shannon, J, Jordan, J, Costa, F, Robertson, RM, Biaggioni, I. The hypertension of autonomic failure and its treatment. Hypertension 1997; 30: 1062–67.CrossRefGoogle ScholarPubMed
78Robertson, D, Wade, D, Robertson, RM. Postprandial alterations in cardiovascular hemodynamics in autonomic dysfunctional states. Am J Cardiol 1981; 48: 1048–52.CrossRefGoogle Scholar
79Jordan, J, Shannon, JR, Black, BK, Ali, Y, Farley, M, Costa, F, Diedrich, A, Robertson, RM, Biaggioni, I, Robertson, D. The pressor response to water drinking in humans: a sympathetic reflex? Circulation 2000; 101: 504–9.CrossRefGoogle ScholarPubMed
80Biaggioni, I, Robertson, RM. Hypertension in orthostatic hypotension and autonomic dysfunction. Cardiol Clin 2002; 20: 291–301.CrossRefGoogle ScholarPubMed
81Wilcox, CS, Puritz, R, Lightman, SL, Bannister, R, Aminoff, MJ. Plasma volume regulation in patients with progressive autonomic failure during changes in salt intake and posture. J Lab Clin Med 1984; 104: 331–39.Google ScholarPubMed
82Naschitz, JE, Slobodin, G, Elias, N, Rosner, I. The patient with supine hypertension and orthostatic hypotension: a clinical dilemma. Postgrad Med J 2006; 82: 246–53.CrossRefGoogle ScholarPubMed
83Singer, W, Sandroni, P, Opfer-Gehrking, TL, Suarez, GA, Klein, CM, Hines, S, O'Brien, PC, Slezak, J, Low, PA. Pyridostigmine treatment trial in neurogenic orthostatic hypotension. Arch Neurol 2006; 63: 513–18.CrossRefGoogle ScholarPubMed
84Paulson, OB, Strandgaard, S, Edvinsson, L. Cerebral autoregulation. Cerebrovasc Brain Metab Rev 1990; 2: 161–92.Google ScholarPubMed
85Yam, AT, Lang, EW, Lagopoulos, J, Yip, K, Griffith, J, Mudaliar, Y, Dorsch, NW. Cerebral autoregulation and ageing. J Clin Neurosci 2005; 12: 643–46.CrossRefGoogle ScholarPubMed
86Brooks, DJ, Redmond, S, Matthias, CJ, Bannister, R, Symon, L. The effect of orthostatic hypotension on cerebral blood flow and middle cerebral artery velocity in autonomic failure, with observations on the action of adrenaline. J Neurol Neurosurg Psychiatry 1989; 52: 962–66.CrossRefGoogle Scholar
87Novak, V, Novak, P, Spies, JM, Low, PA. Autoregulation of cerebral blood flow in orthostatic hypotension. Stroke 1998; 29: 104–11.CrossRefGoogle ScholarPubMed
88Sutton, R, Petersen, M, Brignole, M et al. Proposed classification for tilt induced vasovagal syncope. Europace 1992; 2: 180–83.Google Scholar
89Wayne, HH. Syncope: physiologic considerations and an analysis of the clinical characteristics in 510 patients. Am J Med 1961; 30: 418–38.CrossRefGoogle Scholar
90Zaqqa, M, Massumi, A. Neurally mediated syncope. Tex Heart Inst J 2000; 27: 268–72.Google ScholarPubMed
91Wieling, W, van Lieshout, J. Maintenance of postural normotension in humans. In Low, PA (ed), Clinical Autonomic Disorders: evaluation and management, 2nd edn.Philadelphia: Lippincott-Raven, 1997; 73–82.Google Scholar
92Samoil, D, Grubb, BP. Vasovagal (neurally mediated) syncope: pathophysiology, diagnosis and therapeutic approach. Europace 1992; 2: 234–41.Google Scholar
93The Task Force on Syncope, European Society of Cardiology. Guidelines on Management (Diagnosis and Treatment) of Syncope – Update 2004. Eur Heart J 2004; 25: 2054–72.CrossRefGoogle Scholar
94Benditt, DG, Ferguson, DW, Grubb, BP, Kapoor, WN, Kugler, J, Lerman, BB, Maloney, JD, Raviele, A, Ross, B, Sutton, R, Wolk, MJ, Wood, DL. ACC expert consensus document: tilt table testing for assessing syncope. J Am Coll Cardiol 1996; 28: 263–75.CrossRefGoogle Scholar
95Bloomfield, D, Maurer, M, Bigger, JT Jr. Effects of age on outcome of tilt-table testing. Am J Cardiol 1999; 83: 1055–58.CrossRefGoogle ScholarPubMed
96Krediet, CT, van Dijk, N, Linzer, M, van Lieshout, JJ, Wieling, W. Management of vasovagal syncope: controlling or aborting faints by leg crossing and muscle tensing. Circulation 2002; 106: 1684–89.CrossRefGoogle ScholarPubMed
97Brignole, M, Croci, F, Menozzi, C, Solano, A, Donateo, P, Oddone, D, Puggioni, E, Lolli, G. Isometric arm counter-pressure maneuvers to abort impending vasovagal syncope. J Am Coll Cardiol 2002; 40: 2053–59.CrossRefGoogle ScholarPubMed
98El-Sayed, H, Hainsworth, R. Salt supplement increases plasma volume and orthostatic tolerance in patients with unexplained syncope. Heart 1996; 75: 134–40.CrossRefGoogle ScholarPubMed
99Younoszai, AK, Franklin, WH, Chan, DP, Cassidy, SC, Allen, HD. Oral fluid therapy: a promising treatment for vasodepressor syncope. Arch Pediatr Adolesc Med 1998; 152: 165–68.CrossRefGoogle ScholarPubMed
100Ventura, R, Maas, R, Zeidler, D, Schoder, V, Nienaber, CA, Schuchert, A, Meinertz, T. A randomized and controlled pilot trial of beta-blockers for the treatment of recurrent syncope in patients with a positive or negative response to head-up tilt test. Pacing Clin Electrophysiol 2002; 25: 816–21.CrossRefGoogle ScholarPubMed
101Da Costa, D, McIntosh, S, Kenny, RA. Benefits of fludrocortisone in the treatment of symptomatic vasodepressor carotid sinus syndrome. Br Heart J 1993; 69: 308–10.CrossRefGoogle ScholarPubMed
102Ward, CR, Gray, JC, Gilroy, JJ, Kenny, RA. Midodrine: a role in the management of neurocardiogenic syncope. Heart 1998; 79: 45–49.CrossRefGoogle ScholarPubMed
103Di Girolamo, E, Di Iorio, C, Sabatini, P, Leonzio, L, Barbone, C, Barsotti, A. Effects of paroxetine hydrochloride, a selective serotonin reuptake inhibitor, on refractory vasovagal syncope: a randomized, double-blind, placebo-controlled study. J Am Coll Cardiol 1999; 33: 1227–30.CrossRefGoogle ScholarPubMed
104Connolly, SJ, Sheldon, R, Roberts, RS, Gent, M. The North American Vasovagal Pacemaker Study: a randomised controlled trial of permanent cardiac pacing for the prevention of vasovagal syncope. J Am Coll Cardiol 1999; 33: 16–20.CrossRefGoogle ScholarPubMed
105McIntosh, SJ, Lawson, J, Kenny, RA. Clinical characteristics of vasodepressor, cardioinhibitory, and mixed carotid sinus syndrome in the elderly. Am J Med 1993; 95: 203–8.CrossRefGoogle ScholarPubMed
106Kerr, SR, Pearce, MS, Brayne, C, Davis, RJ, Kenny, RA. Carotid sinus hypersensitivity in asymptomatic older persons: implications for diagnosis of syncope and falls. Arch Intern Med 2006; 166: 515–20.CrossRefGoogle ScholarPubMed
107Brignole, M, Menozzi, C. Carotid sinus syndrome: diagnosis natural history and treatment. Europace 1992; 4: 247–54.Google Scholar
108Davies, AJ, Kenny, RA. Frequency of neurologic complications following carotid sinus massage. Am J Cardiol 1998; 81: 1256–57.CrossRefGoogle ScholarPubMed
109European Society of Cardiology. Guidelines for cardiac pacing and cardiac resynchronization therapy. Eur Heart J 2007; 28: 2256–95.CrossRefGoogle Scholar
110Hussain, RM, McIntosh, SJ, Lawson, J, Kenny, RA. Fludrocortisone in the treatment of hypotensive disorders in the elderly. Heart 1996; 76: 507–9.CrossRefGoogle ScholarPubMed
111NIH Consensus Development Panel on Impotence. NIH Consensus Conference: Impotence. JAMA 1993; 270: 83–90.CrossRefGoogle Scholar
112Johannes, CB, Araujo, AB, Feldman, HA, Derby, CA, Kleinman, KP, McKinlay, JB. Incidence of erectile dysfunction in men 40–69 years old. Longitudinal results from the Massachusetts male aging study. J Urol 2000; 163: 460–63.CrossRefGoogle Scholar
113Morley, JE, Korenman, SG, Kaiser, FE et al. Relationship of brachial penile pressure index to myocardial infarction and cerebrovascular events. Am J Med 1998; 84: 445–48.CrossRefGoogle Scholar
114Wespes, E, Amar, E, Hatzichristou, D, Hatzimouratidis, K, Montorsi, F, Pryor, J, Vardi, Y; EAU. EAU Guidelines on Male Sexual Dysfunction: an update. Eur Urol 2006; 49: 806–15.CrossRefGoogle ScholarPubMed
115Goldstein, I, Lue, TF, Padma-Nathan, H, Rosen, RC, Steers, WD, Wicker, PA. Oral sildenafil in the treatment of erectile dysfunction. N Engl J Med 1998; 338: 1397–404.CrossRefGoogle ScholarPubMed
116Singaram, C, Ashraf, W, Gaumnitz, E et al. Dopaminergic defect of enteric nervous system in Parkinson's disease patients with chronic constipation. Lancet 2005; 346: 861–64.CrossRefGoogle Scholar
117Belmin, J, Auffray, JC, Berbezier, C, Boirin, P, Mercier, S, de Reviers, B, Golmard, JL. Level of dependency: a simple marker associated with mortality during the 2003 heatwave among French dependent elderly people living in the community or in institutions. Age Ageing 2007; 36: 298–303.CrossRefGoogle ScholarPubMed
118Cheshire, WP, Freeman, R. Disorders of sweating. Semin Neurol 2003; 23: 399–406.Google ScholarPubMed
119Simon, HB. Hyperthermia. New Engl J Med 1993; 329: 483–87.Google ScholarPubMed
120Wilson, TE, Sauder, CL, Kearney, ML, Kuipers, NT, Leuenberger, UA, Monahan, KD, Ray, CA. Skin-surface cooling elicits peripheral and visceral vasoconstriction in humans. J Appl Physiol 2007; 103: 1257–62.CrossRefGoogle ScholarPubMed
121Kenney, WL. Thermoregulation at rest and during exercise in healthy older adults. Exerc Sport Sci Rev 1997; 25: 41–76.CrossRefGoogle ScholarPubMed
122Kenney, WL, Morgan, AL, Farquar, WB et al. Decreased active vasodilator sensitivity in aged skin. Am J Physiol 1991; 260: H855–61.Google Scholar
123Danzl, DF, Pozos, RF. Accidental hypothermia. New Eng J Med 1994; 331: 1756–60.CrossRefGoogle ScholarPubMed
124National Center for Health Statistics. Compressed mortality file. Hyattsville, Maryland: US Department of Health and Human Services, CDC, National Center for Health Statistics, 2003.Google Scholar
125Chantler, C, Kelly, S. Deaths from hypothermia in England and Wales. Health Statistics Quart 1999; 02: 50–52.Google Scholar
126Collins, KJ, Exton-Smith, AN, Dore, C. Urban hypothermia: Preferred temperature and thermal perception in old age. Br Med J 1981; 282: 175–77.CrossRefGoogle ScholarPubMed
127Kenney, WL, Buskirk, ER. Functional consequences of sarcopenia: Effect on thermoregulation. J Gerontol A Biol Sci Med Sci 1995; 50: 78–85.Google ScholarPubMed
128Collins, KJ, Dore, C, Exton-Smith, AN, Fox, RH, MacDonald, IC, Woodward, PM. Accidental hypothermia and impaired temperature homeostasis in the elderly. Br Med J 1977; 1: 353–56.CrossRefGoogle ScholarPubMed
129Richardson, D, Tyra, J, McCray, A. Attenuation of the cutaneous vasoconstrictor response to cold in elderly men. J Gerontol 1992; 47: M211–14.CrossRefGoogle ScholarPubMed