Alzheimer's Disease
Alzheimer's disease is a chronic neurodegenerative disorder. It is the most common cause of dementia in patients older than 65 years of age, and the fourth most common cause of death from disease in patients older than 65. Diffuse amyloid-rich senile plaques and neurofibrillary tangles are the hallmark pathologic findings. There are also changes in synapses and the activity of multiple major neurotransmitters, especially involving acetylcholine and central nervous system nicotinic receptors. Two types of Alzheimer's disease have been described: early onset and late onset. Early-onset Alzheimer's disease usually presents before age 60 and is thought to be due to missense mutations on up to three genes leading to an autosomal dominant mode of transmission. Late-onset Alzheimer's disease usually develops after age 60, and genetic transmission appears to play a relatively minor role in the risk of developing this disorder. With both forms of the disease, patients typically develop progressive cognitive impairment that can consist of problems with memory as well as apraxia, aphasia, and agnosia. Definitive diagnosis is usually made on postmortem examination, usually making premortem diagnosis of Alzheimer's disease one of exclusion. There is currently no cure for Alzheimer's disease, and treatment usually focuses on control of symptoms. Pharmacologic options include cholinesterase inhibitors, such as tacrine, donepezil, rivastigmine, and galantamine. Pharmacologic therapy should be combined with nonpharmacologic therapy including caregiver education and family support. Despite treatment, the prognosis for patients with Alzheimer's disease is poor.
Alzheimer's disease is a chronic neurodegenerative disorder. It is the most common cause of dementia in patients older than 65 years of age, and the fourth most common cause of death from disease in patients older than 65. Diffuse amyloid-rich senile plaques and neurofibrillary tangles are the hallmark pathologic findings. There are also changes in synapses and the activity of multiple major neurotransmitters, especially involving acetylcholine and central nervous system nicotinic receptors. Two types of Alzheimer's disease have been described: early onset and late onset. Early-onset Alzheimer's disease usually presents before age 60 and is thought to be due to missense mutations on up to three genes leading to an autosomal dominant mode of transmission. Late-onset Alzheimer's disease usually develops after age 60, and genetic transmission appears to play a relatively minor role in the risk of developing this disorder. With both forms of the disease, patients typically develop progressive cognitive impairment that can consist of problems with memory as well as apraxia, aphasia, and agnosia. Definitive diagnosis is usually made on postmortem examination, usually making premortem diagnosis of Alzheimer's disease one of exclusion. There is currently no cure for Alzheimer's disease, and treatment usually focuses on control of symptoms. Pharmacologic options include cholinesterase inhibitors, such as tacrine, donepezil, rivastigmine, and galantamine. Pharmacologic therapy should be combined with nonpharmacologic therapy including caregiver education and family support. Despite treatment, the prognosis for patients with Alzheimer's disease is poor.
Patients with Alzheimer's disease may present for a variety of surgical interventions that are common in the elderly population. Patients are often confused and sometimes uncooperative, making monitored anesthesia care or regional anesthesia challenging. However, there is probably no one single anesthesia technique or agent that is superior in this group of patients. Shorter acting sedative/hypnotic drugs, anesthetic agents, and narcotics are preferred since they may allow a more rapid return to baseline mental status. Finally, one should be aware of potential drug interactions, especially prolongation of the effect of succinylcholine and relative resistance to nondepolarizing muscle relaxants due
to the use of cholinesterase inhibitors.
to the use of cholinesterase inhibitors.
Clinical aspects related to anaesthetic management
The percentage of aged and older patients that require surgical procedures is increasing and, generally, their cases may be considered more complex than those regarding adult and young patients. Impairment of one or more systems or organs may cause enduring disability and loss of autonomy. For this reason, elderly patients require a careful evaluation of their physical and mental status. Indeed, a careful mental status evaluation seems mandatory in the light of evidence that long life expectancy exposes the elderly to the risk of developing dementia or mild cognitive impairments (MCI). These patients have more systemic impairments (e.g. cardiovascular, pulmonary, renal, endocrine and metabolic) and clinically evident or borderline organ failure. In addition to age-related changes, a chronic disease, smoking, alcohol and environmental toxins may contribute to the difficulties in managing these patients.
Patients affected by AD or MCI require careful management which takes into account such potential problems as informed consent, preoperative progression of disease and postoperative care and support. Patients with impaired mental function are probably not able to sign an informed consent, so relatives should be consulted, where possible. Anaesthetists should also be aware of the possibility of pharmacokinetic and pharmacodynamic changes for administered drugs, and of unfavourable drug interactions. For instance, the cholinesterase inhibitor donepezil and its metabolites block acetylcholine hydrolysis and antagonize the effects of atracurium. Galantamine, which has been approved for the symptomatic treatment of senile dementia of the Alzheimer's type, has been used in anaesthesia to reverse neuromuscular paralysis induced by turbocurarine-like neuromuscular blocking agents. Chronic use of tacrine, an anticholinesterase drug used to manage Alzheimer's dementia, could affect response to nondepolarizing neuromuscular blocking agents, as chronic tacrine therapy in rats causes resistance to D-tubocurarine, probably because of the down-regulation of postsynaptic acetylcholine receptors.
All these aspects, taken together, account for both the different susceptibility of the aged patient to anaesthetics and the increased attention that anaesthesiologists must apply when confronted with a patient with AD requiring anaesthesia or sedation.
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