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Age and Ageing Advance Access originally published online on May 31, 2008
Age and Ageing 2008 37(4):469-473; doi:10.1093/ageing/afn107
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Copyright © The Author 2008. Published by Oxford University Press on behalf of the British Geriatrics Society.

Comprehensive approach of donepezil and psychosocial interventions on cognitive function and quality of life for Alzheimer's disease: the Osaki-Tajiri Project

SIR—There is a major need to develop an appropriate therapy for Alzheimer's disease (AD). Impairment of cholinergic transmission [1, 2] is important for the defects, and cholinesterase inhibitors (e.g. donepezil) [3, 4] cause symptomatic improvement. In Japan, only donepezil is available, and the drug has been reported to maintain cognitive function up to 6 months [5].

Given the lack of a curative treatment for AD, psychosocial interventions have emerged over the years that are directed at optimising the function of patients and supporting their families. One of the most common approaches is reminiscence [6–9]. The primary goal is to facilitate recall of past experiences to promote intra/inter-personal functioning and improve quality of life (QOL). Relatively reserved remote memory [10] can provide a neurological basis to support the effectiveness. Reality orientation (RO) [6, 9, 11] is also used which stimulates time and place orientation. Reminiscence and RO are the most popular interventions [12, 13]. Lai et al. [14] performed a randomised controlled trial (RCT) to investigate whether a reminiscence program leads to higher levels of psychosocial well-being in dementia and found a significant improvement in QOL, although the intervention did not lead to significant cognitive improvement.

Although the effect of donepezil in slowing cognitive decline in AD has been established, and psychosocial interventions were known to exhibit positive effects, a combined effect has not been fully investigated [11]. We hypothesized that donepezil has an effect in slowing cognitive deterioration, and that the additional psychosocial intervention would increase their QOL.

Methods

Patients
We studied institutionalised patients in nursing homes. Inclusion criteria were (1) they met the probable AD criteria (National Institute for Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association) [15]; (2) the Mini-Mental State Examination (MMSE) [16] scores ranged from 10 to 20; (3) magnetic resonance imaging (MRI) showed hippocampal atrophy with only small lacunes. Exclusion criteria were (1) severe aphasia affecting communication with staff members; (2) the presence of severe behavioural and psychological symptoms of dementia (BPSD) which need drug therapy. The BPSD were assessed using the BEHAVE-AD-FW [17], and those with a total score greater than 5 were operationally excluded.

A total of 30 AD patients were recruited, and eventually 28 patients' families agreed to participate in the study. After checking the adverse effects of donepezil following 3 mg/day administration, 24 patients who did not show adverse effects were randomly divided into two groups (Donepezil Group versus Donepezil + Psychosocial Group). We did not randomly allocate any patients to receive only psychosocial intervention as the beneficial effect of donepezil has now been established, so delaying would be unethical. Members of the Psychosocial Group consisted of (1) those who manifested adverse effects with donepezil and had stopped treatment (n = 4), and (2) those who received psychosocial intervention in the same nursing homes before donepezil was licensed in Japan in 1999 (n = 8). Figure 1 illustrates the protocol.


Figure 1
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  		Figure 1. Protocol for selecting patients

 
Since none of the patients had capacity to give consent, written informed consent was received from relatives. The Medical Ethics Committee of the nursing homes approved the study.

Intervention

Donepezil group
The randomly divided 12 patients received donepezil only without psychosocial intervention. They received 3 mg/day of donepezil for 2 weeks to check for any adverse effects, which was then followed by administering 5 mg/day (in Japan, a maximum dose of 5 mg/day had been officially allowed till August 2007).

Donepezil + Psychosocial group
The remaining 12 patients received donepezil and psychosocial intervention. The interventions were performed 40 times in 12 months (every week for 8 months and twice a month for 4 months). This design was based on the clinical practice of our team.


Individual interventions
Three patients went through a reminiscence programme supported by Japanese traditional flower arranging. Before suffering from AD, the patients had had some experience with flower arrangement and one patient was a licensed teacher. A nurse, who is also a teacher (Mitsue Meguro) supported this intervention. We performed this intervention for 1 h for each patient. At the start of the intervention the RO was performed followed by naming the flowers. Past life histories associated with flower arrangement were used for reminiscence.


Group work
Nine patients were divided into three groups. One group consisted of three patients who were urged to cook. An occupational therapist (Mari Kasai) and a dietician led this group for 1 h to promote cooking small traditional dishes. These patients were good at cooking dishes, and past life histories associated with cooking were used for reminiscence. At the start RO for time and place was performed. A recipe was printed and given to the participants each time. Another group comprised of three patients who were urged to perform ancient Japanese calligraphy. These patients had made a hobby of calligraphy and one patient was a licensed teacher in the art. Past life histories associated with calligraphy were used for reminiscence. A speech pathologist (Kyoko Akanuma), also a licensed teacher, supported this group. The third group received a standard reminiscence approach with the RO. The topics of their school days, marriages, etc. were used. Time schedule and the RO in the beginning were the same for the latter groups.

Psychosocial group
This group included four patients who met the inclusion and exclusion criteria but could not tolerate the side-effects of donepezil. There were also eight patients receiving psychosocial intervention before official permission for using the drug was accorded in 1999. Psychosocial intervention included an individual reminiscence approach and RO for the same period, 40 times in 12 months. The content of intervention was considered to be the same, since we had been conducting the same psychosocial intervention independent of an official allowance of donepezil [18].

Mean ages for Donepezil, Donepezil + Psychosocial, and Psychosocial Groups were 78.9, 78.4, and 78.3 years, respectively. Mean educational years were 8.6, 8.8, and 8.4. MMSE scores at baseline were 14.9, 15.5, and 15.2. No significant group differences were noted for all values.

Outcome and analysis
The intervention period was 40 times in 12 months (every week for 8 months and twice a month for 4 months), and all patients could complete all the sessions. Several patients had common cold during the period, but the staff could shift the session within the same week. The MMSE was used to assess cognitive performance before and after the intervention (12 months), and the quality of life-AD scale (QOL-AD) [19] was used to evaluate their QOL. The patients were able to answer the QOL-AD questionnaire by themselves. The reliability and validity of the Japanese version have been reported [20]. One-way analysis of covariance (ANCOVA) with two repeated measures (time) was used for analysis, age and educational levels (years) being used as covariances.

Results

Figure 2, in two parts, shows the mean MMSE (a) and QOL-AD (b) scores at baseline and after the intervention for the three groups. Figure (2a) illustrates the MMSE changes. There was no significant group effect (df = 2, MS = 2.283, F = 0.186, P = 0.831); however, a significant time by group interaction was noted (df = 2, MS = 2.095, F = 5.322, P = 0.012). Then we examined the group effect for the difference of two MMSE scores by one-way ANCOVA. A significant effect (df = 2, MS = 4.191, F = 5.322, P = 0.012) was noted with post hoc test showing a significant larger difference (1.6 score) for the Psychosocial Group compared with the other two groups.


Figure 2
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  		Figure 2. Mean MMSE and QOL-AD scores at baseline (MMSE1, QOL1) and after the intervention (MMSE 2, QOL2) for three groups. (a) MMSE changes, (b) QOL changes

 
Figure (2b) illustrates the QOL-AD changes. There was a significant group effect (df = 2, MS = 55.116, F = 3.537, P = 0.044) with a significant time by group interaction (df = 2, MS = 56.565, F = 6.062, P = 0.007). A post hoc test demonstrated a significant difference between Donepezil + Psychosocial Group versus Donepezil Group (P < 0.05).

Discussion

We should mention methodological limitations. This study was based on a very small sample size. Also, the Psychosocial Group was not randomly allocated. The interventions included not only reminiscence and RO but also several ‘behavioural therapies.’ Although the patients' life histories were mainly used for reminiscence, behavioural stimulation might affect their cognitive function.

For cognitive measure, no group effect for MMSE changes was noted, but the interaction between time and group was noted. Also, the difference between the two MMSE scores was greater in the Psychosocial Group compared with the two other groups. The result can reasonably be said to be due to the donepezil effect of delaying the progression of AD. The effect of donepezil in delaying the progression of AD has been established [2–5]. Previous studies report that the annual decline of MMSE scores were about 1.8–2.3 for AD [21–25]. All the patients exhibited a moderate severity of dementia, and our drug control (Psychosocial Group) also exhibited similar changes. Also, the donepezil effect on apathy has been reported [26]. Therefore, we considered that donepezil could maintain cognitive function and reduce apathy. For psychosocial intervention, no significant effect for cognitive function was noted. However, the outcome measure was MMSE, which assesses global function. A further investigation using frontal lobe function tests would be needed since the intervention might stimulate executive function.

As for QOL measure, a combined positive effect of donepezil and psychosocial intervention was noted when compared with donepezil only. After their attentions were stimulated by donepezil, their preserved functions might be stimulated by psychosocial intervention, leading to an increase in their QOL. Clinically, we know that AD patients who manifest impairment in recent memory, are able to recollect distant memories. We considered the patients' past life histories and designed the intervention programs, which may be associated with their distant memory. Regarding the content, good emotional relationships between the patients and the staff showing excellent participation rate may have positive effects. Namely, for reminiscence supported by Japanese flower arrangement and old calligraphy, one patient and the staff were teachers.

Key points

  • We examined the combined effect of donepezil and psychosocial intervention for cognitive function and QOL for AD patients.
  • Donepezil Group (n = 12) received donepezil without psychosocial intervention, whereas Donepezil + Psychosocial Group (n = 12) received donepezil and psychosocial intervention (RO with reminiscence).
  • There was no group effect for MMSE changes, however, a significant group effect with a time by group interaction was noted for QOL-AD changes.

Conflicts of interest

None

Mitsue Meguro1,2, Mari Kasai1,2, Kyoko Akanuma1,2, Hiroshi Ishii2,3, Satoshi Yamaguchi1,2 and Kenichi Meguro1,2,*

1 Department of Geriatric Behavioral Neurology, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, 980-8575, Sendai, Japan
2 The Osaki-Tajiri SKIP Center, 10-1, Torigi Nakazaki-Higashi, 989-4413, Osaki, Japan
3 Kasawaki Kokoro Hospital, 72, Kita-Kawarayama, Oaza-Kawauchi, 989-1503, Kawasaki, Japan

* To whom correspondence should be addressed E-mail: k-meg{at}umin.ac.jp

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