A Review of the Pharmacological Management of Cognition and Behaviour Problems in Older Adults with Advanced Dementia

The accredited CME learning activity based on this article is offered under the auspices of the CE department of the University of Toronto. Participating physicians are entitled to one (1) MAINPRO-M1 credit by completing this program, found online at www.geriatricsandaging.ca/cme.htm

Ann Schmidt Luggen, PhD, GNP, Professor, Department of Nursing and Health Professions, Northern Kentucky University, Highland Heights, KY; Gerontological Nurse Practitioner, Evercare, Cincinnati, OH, USA.

Medical management of Alzheimer’s disease patients involves drugs that temporarily relieve or stabilize symptoms, or lessen the expected decline in cognition, function, and behaviour, but ultimately fail to halt progression of the disease. Commonly used agents in the management of early- to mid-stage dementias--albeit with modest outcomes--are the cholinesterase inhibitors (ChEIs). Antipsychotics have been used with mixed success to treat psychiatric symptoms that occur in 30-60% of patients with moderate-to-severe AD. In the terminal stages of dementia, palliation of symptoms and a focus on comfort care is important. Management of pain and relief from depression and anxiety are useful.

Key words: dementia, Alzheimer’s disease, cholinesterase inhibitors, behaviour, antipsychotics.

Introduction
Dementia is a growing global health problem. Worldwide, 18 million people have dementia¹ and approximately 60-70% of adults aged 65 and over with dementia have Alzheimer’s disease (AD).³ Other common dementias include Lewy body dementia (DLB) and vascular dementia (VaD), and many patients have more than one form of dementia.

About four million people in the U.S., most of whom are 65 or older, have AD.2 An estimated 420,000 Canadians over age 65 (or 8% of all seniors) have AD or a related dementia (NACA, 2005:2.1/2). Though the prevalence of AD doubles every five years after age 65 in the U.S., little is known about the pathophysiology and medical management of this disease. At best, we can treat AD patients with drugs that relieve some of the symptoms but fail to halt progression of the disease.¹

Advanced Dementia
Symptoms of the advanced dementias are similar,³ and in many cases it is difficult to distinguish between the different types. Patients have significant impairment of language skills with little meaningful speech; some of them become mute. It is common in the U.S. to place the older patient with advanced dementia in a long-term care facility, as she/he has difficulty with even the most basic activities of daily living (ADL). Many patients are unable to feed themselves and are incontinent of bladder and bowel. They become wheelchair bound and may become bed bound. Patients with advanced dementia have much comorbidity, such as malnutrition, pressure ulcers, and frequent urinary tract and pulmonary infections. Seizures may also be seen in late-stage dementia.³

Pharmacological Management of Dementia
Mild-to-Moderate Dementia
Commonly used agents in the treatment of primary symptoms of early- to mid-stage dementias--albeit with modest outcomes--are the cholinesterase inhibitors (ChEIs). At early stages of the disease, ChEIs act to improve or stabilize cognitive function and delay symptom progression by preventing the hydrolysis of acetylcholine (ACh) in the synaptic cleft. These agents do little to protect cholinergic neurons from cell death, though, and as the disease progresses and endogenous ACh levels decline, ChEIs become less effective. Second-generation ChEIs have been approved for the treatment of mild-to-moderate AD.

Cholinesterase inhibitors have shown some efficacy in forms of dementias other than AD. Galantamine, for example, has been shown to be effective in managing DLB.⁴ Rivastigmine has been shown to improve cognition and behaviour in DLB,⁵ as has donepezil in a small number of patients.⁶

The ChEIs are also effective in