Drug Use In The Elderly: Risk or Protection?

Christel Cornelius

Disclosures

Curr Opin Psychiatry. 2004;17(6) 

In This Article

Abstract and Introduction

Purpose of Review: Medication in the elderly is often complicated because of multimorbidity. Dementia is common in old age, and finding effective therapy is challenging. This review focuses on drug use in the elderly, with special attention paid to the prevention and treatment of Alzheimer's disease and dementia.
Recent Findings: Increasing drug use makes polypharmacy a common problem in the elderly, and indications of inappropriate medication were often found in the studies reviewed. Inappropriate medication also includes undertreatment, for example with antidepressants. Patients with Alzheimer's disease, as well as those with vascular or mixed dementia, could benefit from the symptomatic treatment of acetylcholinesterase inhibitors. Possible neuroprotective therapy may prevent Alzheimer's disease/dementia, including nonsteroidal antiinflammatory drugs, and treatment against hypertension and vascular risk factors. Whether calcium channel blockers protect against dementia in patients without hypertension remains unclear. Estrogen failed to protect against dementia in a recent randomized trial.
Summary: Increasing drug use emphasizes the importance of optimizing medication in the elderly and reviewing their drug consumption on a regular basis. Optimum drug use also includes avoiding undertreatment, for example in depressive and cognitively impaired individuals. Depressed mood and impaired memory should not be dismissed as the normal state of ageing. Controlling vascular risk factors and hypertension seems to be of great importance in trying to avoid dementia. Preventing an inflammatory reaction in the brain may also have an impact on the disease progression. Future drugs that treat dementia will hopefully target the pathological events causing the disease. There is still hope of a vaccine against Alzheimer's disease.

With increasing age, multimorbidity becomes more frequent, leading to higher occurrence of medication and a higher risk of adverse drug reactions due to polypharmacy, chronic diseases, and age-related changes in pharmacokinetics (absorption, distribution, and elimination of a drug in the body) and pharmacodynamics (the pharmacologic effect and clinical response to the drug).[1**] In general, older people are more sensitive to drugs than younger people. The age-related changes in the functions and composition of the human body require adjustments of drug selection and dosage for older individuals.[2**] First, ageing leads to a decline in renal function, which affects the elimination of many drugs. In addition, muscle mass decreases with age, making serum creatinine an unreliable measure of renal function in elderly people, hence, creatinine clearance should be used. Second, reduction in total body water with age results in a relative increase in body fat, which influences water-soluble and lipid-soluble drugs, respectively. A lower volume of distribution can result in higher serum levels of a water-soluble drug (i.e. digoxin), consequently requiring a lower dose of the drug. The relative increase in body fat increases the volume of distribution for a lipid-soluble drug (i.e. diazepam), resulting in a prolonged half-life of the drug, which can sustain the effect. Third, the central nervous system undergoes substantial changes with age, including a reduction in neurotransmitters such as acetylcholine. Deficiency in the cholinergic system is involved in cognitive dysfunction and dementia. Thus, sensitivity to anticholinergic drugs is especially pronounced in the elderly. Finally, psychotropics represent a group of centrally active drugs that older people are more vulnerable to, for example increased and prolonged sedation of hypnotics/sedatives.

Age is a major risk factor for dementing disorders, and after 60 years of age dementia incidence increases exponentially.[3] Hence, finding an effective treatment against dementia would be of utmost importance in the ageing populations worldwide, decreasing the burden of disease for patients and relatives, as well as for health care and social service systems. Alzheimer's disease is the most common type of dementia, accounting for more than 50% of all dementia cases, followed by vascular dementia in 15-20% of cases.[4] Alzheimer's disease is a slowly progressive disorder characterized by neurofibrillary tangles and the aggregation of β-amyloid in senile plaques in the brain, as well as the presence of inflammation and oxidative stress in connection to these changes.[5] According to the amyloid cascade hypothesis,[6] the accumulation of β-amyloid is followed by a sequence of pathogenic events, leading to neuronal loss, for example in the cholinergic system. Stroke episodes usually precede the development of vascular dementia with a stepwise deterioration, while a subtype of subcortical vascular dementia shows a more slowly progressive cognitive decline. Furthermore, Alzheimer's disease and vascular dementia share the same vascular risk factors, like hypertension, hypercholesterolemia, atherosclerosis, and cardio- and cerebrovascular diseases.[7] Consequently, possible preventive measures against both Alzheimer's disease and vascular dementia include control of blood pressure and other vascular risk factors.[8] In addition, various existing drugs have been discussed as possible neuroprotective agents against dementia, for example antiinflammatory drugs that may reduce the inflammatory reaction in the brain,[9] and affect the accumulation of β-amyloid.[10] Treatment with the calcium channel blocker nitrendipine against hypertension has shown a protective effect against dementia in an extended follow-up study within the Syst-Eur trial,[11] thus supporting the hypothesis that calcium dysregulation and increased levels of intracellular calcium may be involved in neurodegenerative disorders like dementia.[12] The actions of estrogen in the brain include improving cerebral blood flow, stimulating cholinergic markers, and exercising antioxidant effects, thus estrogen has been suggested to have neuroprotective properties. However, this could not be confirmed in a randomized controlled trial of postmenopausal women treated with estrogen and progestin or placebo.[13] On the contrary, the risk of dementia was higher in the active treated group.

To date, the established treatment of dementia is symptomatic, showing effects on cognition, behaviour and function. Acetylcholinesterase inhibitors (AChEIs) strengthen the cholinergic system, and the noncompetitive N-methyl-D-aspartate receptor antagonist, memantine, affects the excitotoxicity of glutamate in the central nervous system. Newer psychotropic drugs, including atypical antipsychotics and serotonergic agents, are useful in the treatment of behavioural and psychological symptoms in dementia, such as sleeping disorder, anxiety, depressed mood, agitation, and psychotic symptoms.

This review is based on articles from English-language journals published since April 2003, identified through PubMed (MEDLINE), and focusing on drug use in the elderly with special attention paid to the prevention and treatment of Alzheimer's disease and dementia.

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