Annals of Long Term Care

Alzheimer’s disease, the most common form of dementia, is a major factor leading to long-term care (LTC) placement. The current pharmacologic options for treating Alzheimer’s disease are donepezil, galantamine, and rivastigmine, which are cholinesterase inhibitors (CIs), and
memantine, which is an N-methyl-D-aspartate receptor antagonist. In studies of patients with severe Alzheimer’s disease, donepezil has been found to preserve function and cognition, and galantamine and rivastigmine have been found to improve cognition.^1-3 Memantine treatment has been shown to reduce care dependence among patients with severe dementia.⁴ In a randomized controlled trial, combining memantine with donepezil to treat moderate to severe Alzheimer’s disease resulted in improved measures of cognition, activities of daily living (ADLs), and behavior.⁵ Two more recent observational, long-term, real-life studies have demonstrated positive effects for the concomitant use of CI drugs and memantine for patients living at home.^6,7 In one of these studies, which included 943 patients with probable Alzheimer’s disease, time to nursing home admission was significantly extended by adding memantine to CI treatment.⁶ In the other study, which included data comprising 955 patient-years, this combination therapy slowed cognitive and functional decline, with the clinical benefit sustained for at least 2 years.⁷

In Western countries, about 75% of LTC residents have a dementia diagnosis.^8-10 Several studies have shown that concomitant use of CI drugs and memantine is safe for this population,^1,2,4,11,12 and this combination is often used among persons with end-stage dementia.^13,14 Still, less than half of patients with dementia receive medication for the condition in LTC facilities or upon admission to a nursing home or hospice care.^13,15-18 In the months following admission to such facilities, medication is discontinued in about half of residents, depending on the severity of the dementia.^18,19 However, the average time of CI use has been reported to last from 9 months to more than 2 years.^17,20 In a retrospective study by a CI review committee in an LTC facility, one-third of CI users had recommendations to discontinue these agents because of insufficient benefit and most did so.²¹

In light of these data, we sought to determine whether the use of a CI plus memantine would have similar positive results in our nursing home, the Koukkuniemi Home for the Elderly, which is located in Tampere, Finland. We reviewed the literature further and conducted a pilot study using data from the Resident Assessment Instrument (RAI), a validated assessment tool that we have used in our nursing home since 2001.

Literature Review on Agents Used for Severe Dementia

Both CI agents and memantine have been associated with improved cognition and function in LTC residents with severe dementia. Donepezil had positive trends on the Alzheimer’s Disease Cooperative Study–Activities of Daily Living Inventory (ADCS–ADL) at 6 months’ treatment and was associated with less decline on 11 of 13 ADCS–ADL items that are used to score disease severity.^11,22 In other studies with donepezil, cognition improved over a 6-month period, as measured by several tools, including the Severe Impairment Battery examination, the Mini-Mental State Examination (MMSE), and the Clinician’s Interview-Based Impression of Change–Plus Carer Interview.^1,11,22-24 In a study assessing the safety and efficacy of galantamine, cognition was significantly improved in nursing home residents with severe Alzheimer’s disease who were taking this agent, compared with those receiving a placebo.² In a rivastigmine study, no decline in MMSE scores was revealed over 52 weeks of rivastigmine treatment.²⁵ A study of memantine use showed a statistically significant improvement in 8 of 16 ADL measures after 12 weeks of treatment.⁴

LTC setting studies provide evidence that CI agents and memantine are associated with decreased behavioral disturbances. A double-blind, parallel-group, placebo-controlled study showed positive trends as measured by the Neuropsychiatric Inventory (NPI) after 6 months of donepezil use.²² In a study by Tariot and colleagues,¹ however, the use of donepezil revealed no significant differences in behavioral problems compared with placebo in patients with high concomitant medication usage. In an open-label study, patients taking rivastigmine showed significant improvement at 26 weeks in neuropsychiatric and behavioral disturbances, such as delusions, hallucinations, agitation, apathy/indifference, irritability/lability, aberrant motor behavior, night-time disturbances, and appetite/eating changes.²⁶ Rivastigmine also improved 10 of 12 individual NPI-Nursing Home domains at 1-year follow-up.²⁵

Because of the risks and side effects in nursing home residents, the use of antipsychotics should be avoided.²⁷ In one study, 40% of patients taking rivastigmine were able to discontinue previous psychotropic medications or reduce the dosage of these medications.¹² In patients with moderate to severe dementia, 12 weeks of memantine treatment was associated with a positive response in the Clinical Global Impression of Change examination, and the Behavioral Rating Scale for Geriatric Patients subscore of care dependence showed an improvement of 3.1 points, whereas the placebo group had an improvement of 1.1 points.⁴ A 3-month open-label pilot study of memantine in LTC facilities showed significant decrease in agitation/aggression, nursing burden, caregiver distress, and the use of psychotropics.²⁸

Pilot Study

The purpose of our study was to assess residents’ conditions and the outcomes of CI and memantine treatment, either alone or in combination, in a Finnish nursing home environment using information collected with the RAI. The RAI was designed to assess and enhance quality of care, estimate the need for resources, and develop payment systems in nursing home settings. It was introduced in Finland in 2000 and was gradually implemented by the Koukkuniemi Home for the Elderly in 2001.²⁹ The RAI has been tested internationally for validity and reliability,^30-32 and it has been found to be useful for research purposes in nursing home settings.^33,34   

Methods

Our pilot study was conducted in the Koukkuniemi Home for the Elderly in Tampere, Finland. We followed 881 nursing home residents living in Koukkuniemi between the years 2001 and 2009. During the study period, CI and memantine were used for patients with Alzheimer’s disease, mixed dementia, Lewy body dementia, and Parkinson’s disease.

Ethical approval for the study was granted by the nursing home institution and by the city of Tampere. Patients were randomly assigned to one of the following four groups: NO, no memantine or cholinesterase inhibitors; M, memantine only; CI, cholinesterase inhibitor only; and C, combination therapy with memantine and a CI. During the course of the study, a patient could remain in only one group. In the M, CI, and C groups, the results of the RAI assessment conducted before starting the agents, or of the resident’s first RAI assessment if he or she had already been taking the medications, were compared with the results of the previous RAI assessment, whether taken before stopping the medication or at the end of the study follow-up if the medication was still being used. In the NO group, this change was calculated over a comparable follow-up time period. For parametric variables, the chi-square and Fisher exact tests were used whenever possible. To assess statistical differences for nonparametric variables, the Kruskal-Wallis and Mann-Whitney U tests were performed. The first was used to assess overall statistical difference between the groups, and the latter was used to compare results between two groups. Statistical significance was defined at the level of P≤.05.

At the Koukkuniemi Home for the Elderly, the RAI assessment is performed by nursing staff every 6 months after a person becomes a nursing home resident or whenever a marked change in health status occurs. As an assessment summary, the instrument provides various scale reports that combine the results of several Minimum Data Set (MDS) questions. For example, the Cognitive Performance Scale (CPS) consists of five different questions that assess short-term memory, ability to be understood, capacity to make decisions, consciousness, and the ability to eat. Reports include the CPS score, the Activities of Daily Living Hierarchy (ADLH), the Depression Rating Scale (DRS), the Social Engagement Scale (SES), the NREHAB scale (measures the rehabilitation provided by nursing staff), pain level, and body mass index (BMI).

In addition, we studied some specific MDS questionnaire items, including the frequency of wandering, negativity toward care, verbal aggression, physical aggression, and inappropriate behavior, all of which are coded in the MDS from 0 to 3 (0=symptom not occurring, 1= occurring 1-3 days a week, 2=occurring 4-6 days a week, and 3=daily symptom). We also examined the frequency of movement restriction in a chair or with bed rails, which is coded using a scale from 0 to 2 (0=not in use, 1=less than daily, and 2=daily use), and assessed residents’ ability to be understood and of understanding, which is coded using a scale from 0 to 3 (0=always, 1=usually, 2=occasionally, and 3=seldom or never). The use of antipsychotics was studied as well from both medical records and from the MDS, with a score of 0 indicating no use and 1 indicating ongoing use.