Key-Points

The process of healthy aging causes several changes in autonomic function that may impair a person's ability to adapt to stress.  However, in the absence of disease and under usual conditions, aging has a relatively small impact on functional ability.  

Autonomic changes due to aging of the cardiovascular system include reduced baroreflex sensitivity, impared beta and alpha adrenergic responses to sympathetic activation, heightened sympathetic nervous system activity, and reduced parasympathetic control of heart rate.  These changes may predispose elderly people to orthostatic, postprandial, and drug-induced hypotension. 

Changes in thermoregulation with aging may predispose elderly people to hypothermia and heat stroke.  These changes include reduced heat generation, conservation, and dissipation, associated with reduced vasoconstriction during cold exposure and impaired vasodilatation and sweating during heat exposure.  

There is a small age-related decline in innervation of the myenteric plexus of the gut and reduction in esophageal and intestinal motility.  However, in the absence of disease or medications, these are rarely symptomatic.  

Common symptoms of consitpation, urinary incontinence, and sexual dysfunction in old age are usually due to medications and diseases outside the autonomic nervous system. 

Aging produces symptoms of autonomic dysfunction:

1. Impaired adaptation to common physiologic stressors

2. Aging of other systems may produce symptoms that mimic autonomic insufficiency.

3. Aging increases the risk of developing diseases that may impair autonomic function.

Age-related changes affecting cardiovascular and cerebrovascular blood flow regulation may predispose elderly people to hypotension in response to medications, posture change, and meal digestion.  These conditions, in turn, may produce dizziness, falls, syncope, cognitive dysfunction, and even stroke. 

Age-related changes in autonomic function may also predispose elderly people to common conditions such as dehydration, heat or cold intolerance, constipation, erectile dysfunction, and urinary incontinence.  It is important to recognize that in healthy elderly persons, symptoms of autonomic dysfunction rarely manifest under the usual demands of everyday life, but may become clinically significant during exposure to a variety of external stressors such as medications, changes in fluid intake, and relatively hot or cold environmental temperature.

Symptoms of autonomic dysfunction such as constipation, urinary incontinence, and impotence may mimic autonomic insufficiency but are caused by conditions outside the autonomic nervous system.  For example, sexual dysfunction and old age is more likely due to vascular disease, diabetes, depression, or medications then to age associated autonomic dysfunction.

Normal aging predisposes older people to diseases that may affect the autonomic nervous system.  These diseases include type 2 diabetes mellitus, amyloidosis, multisystem atrophy, Parkinson disease, and various malignancies.  It is important to differentiate physiologic changes due to aging from changes due to associated diseases or to the medication used to treat these diseases.  For example, orthostatic hypotension may be a manifestation of an age-related impairment in baroreflex control of heart rate, or it may be the result of Parkinson disease and the dopaminergic medications used to treat.

The determination of what symptoms are due to aging and what are due to disease is a difficult clinical challenge.  However, it is never appropriate to attribute autonomic symptoms to aging alone until all potential disease or medication related causes are ruled out.

Causes of hypothermia:

• Cold exposure

• Medications:

  • Phenothiazines

  • Narcotics

  • Vasodilators

  • Barbiturates

• Alcohol

• Inflammatory skin conditions

• Paget's disease

• Endocrine disorders:

  • Hypothyroidism

  • Hypopituitarism

  • Adrenal insufficiency

  • Diabetes mellitus

  • Hypoglycemia

• Sepsis

• Malnutrition/starvation

• Cardiovascular diseases:

  • Congestive heart failure

  • Myocardial infarction

• Uremia

• Hepatic failure

• Neurological diseases:

  • Stroke

  • Parkinson disease

  • Hypothalamic tumors or strokes

  • Warnicke's encephalopathy

  • Spinal cord lesions.

Age related Physiologic Changes Predisposing to Hypotension

Decreased baroreflex sensitivity:

• Diminished heart rate response to hypotensive stimuli

• Reduced alpha-adrenergic vascular responsiveness

Impaired defense of intravascular volume

• Reduced secretion on renin, angiotensin, and aldosterone

• Increased atrial natriuretic peptide, supine and upright

• Decreased plasma vasopressin response to orthostasis

• Reduced thirst after water-deprivation

Impaired early cardiac-ventricular filling (diastolic dysfunction)

Disease related causes of orthostatic and postprandial hypotension

• CNS disorders: MSA, brainstem lesions, multiple cerebral infarctions, Parkinson disease, myelopathy.

• Peripheral and autonomic neuropathies: Pure autonomic failure, diabetes, amyloidosis, tabes dorsalis, alcoholic and nutritional, paraneoplastic syndromes.

• Prolonged immobility

• Medications: Phenothiazines and other neuroleptics, monamine oxidase inhibitors, tricyclic antidepressants, antihypertensives and diuretics, levodopa, vasodilators, beta-blockers, calcium channel blockers, and ACE inhibitors.

Mechanisms of hypotension in the elderly:

Physiologic:

• Impaired adaptive capacity:

  • Associated with hypotension

  • Increase noradrenaline response to posture change

  • Precipitants of hypotension: Hypovolemia, preload reduction, inactivity, other drugs, post-prandial

Pathologic:

• Disease related:

  • Blunted noradrenaline response to posture change or meal digestion

  • Causes:CNS: Stroke, MSA, PD

  • Peripheral nervous system: Diabetes, alcohol

  • Nutritional, amyloid

  • Pure autonomic failure

  • Salt wasting renal disease, 

  • Addison's disease

Reflex:

• Health and cardiovascular disease:

  • Sudden bradycardia and/or hypotension.

  • Causes: Carotid sinus hypersensitivity, neurally mediated syncope, micturition, cough, and swallow syncope.

Blood Pressure Regulation

Normal human aging is associated with several changes in autonomic regulation of BP.  The superimposed cardiovascular diseases and medications often lead to further decrements in autonomic function that manifest as hypotension and syncope.  

Baroreflex Mechansim

• Baroreceptor (stretch) loading > decrease in HR and decrease in PVR

• Baroreceptor (off loading) > increased in HR and increase in PVR.

• Normal human aging is associated with a reduction in baroreflex sensitivity.

  • Blunted cardioacceleratory response to stimuli such as upright posture, nitroprusside infusion, and lower body negative pressure, which lowers arterial pressure, as well as reduced bradycardic response to drugs such as phenylephrine that elevated BP.

  • Baroreflex sensitivity manifests as an increase in BP variability often with potentially dangerous BP reductions during hypotensive stresses such as upright posture or meal digestion. 

  • Both normal aging and hypertension exert independent effects on baroreflex sensitivity.  There is decrease in arterial distensibility with aging and  hypertension resulting in diminished baroreceptor stretch causing less toning inhibition of the brainstem vasomtor center. and increased sympathetic outflow.  Increased sympathetic outflow results in increased circulating noradrenaline which in turn results in further vasoconstriction, BP elevation, and baroreflex impairment.

  • Elevated basal plasma noradrenaline levels and muscle sympathetic nerve activity, as well as a heightened plasma noradrenaline response to baroreceptor unloading in aged subjects supports this hypothesis.