Effect of neuropsychiatric symptoms of Alzheimer's disease on Chinese and American caregivers.

BACKGROUND: In Chinese culture, extended family support, acceptance of age-related cognitive changes and filial tradition of caring for elders may decrease caregiver burden and distress in the context of dementia. OBJECTIVE: To study cross-regional and cross-cultural differences in symptom-related caregiver distress due to the behavioral problems of Chinese and American patients with Alzheimer's disease. METHOD: Caregivers of patients with Alzheimer's disease at Taipei Veterans General Hospital, Taiwan (n = 89), Chinese University of Hong Kong (n = 31) and the UCLA Alzheimer's Disease Research Center, Los Angeles, California (n = 169) reported the neuropsychiatric symptoms of patients and their corresponding distress on the Neuropsychiatric Inventory. RESULT: Presence or absence of distress due to the neuropsychiatric symptoms of the patients with Alzheimer's disease was assessed. The three centers differed significantly in the proportions of caregivers with distress caused by depression (p < 0.05) and apathy (p < 0.001). UCLA had higher proportions of caregivers with depression-related distress than Taipei. UCLA caregivers were also more stressed by apathy than caregivers in Taipei and Hong Kong. Logistic regression further supported the findings that depression-related and apathy-related caregiver distress differed between Chinese and American caregivers (p < 0.05). CONCLUSIONS: The results were surprising, in that American and Chinese (Taipei and Hong Kong) caregivers exhibited similar distress or lack of distress in response to delusions, hallucinations, agitation, anxiety, euphoria, disinhibition, irritability, aberrant motor behavior, sleep and appetite symptoms of Alzheimer's disease patients. Chinese caregivers were less affected by depression and apathy in patients with Alzheimer's disease than Caucasian caregivers.     

Cost-effectiveness analysis of donepezil for mild to moderate Alzheimer's disease in Taiwan

BACKGROUND: Donepezil is a drug used for treatment in patients with Alzheimer's disease (AD). Information regarding the cost-effectiveness of this medication was previously rare in Asia. We used techniques of decision analysis and economic evaluation in conjunction with available local epidemiological and clinical data on costs of mild to moderate AD to assess the cost-effectiveness of donepezil in Taiwan. METHODS: A four-state Markov model was built to simulate the disease progression of AD patients. Local transition probabilities and costs of different stages were from the studies published earlier. RESULTS: Over a 5-year span, donepezil treatment for mild or moderate AD patients is predicted to result in the gain of 0.505 QALYs when comparing to usual care, while at the same time reducing the cost by US$7,691. The incremental cost was US$3,647 from the payer perspective; thus, the incremental cost-effectiveness ratio was estimated to be US$7,226 when considering only the medical expenditures. CONCLUSIONS: Under some assumptions, donepezil treatment might be a cost saving strategy for mild to moderate AD patients in Taiwan from a societal perspective. It is inconclusive from the payer's part since we still lack a consensus for judging the cost-effectiveness of a new health care technology.     

Quality of Life in relation to neuropsychiatric symptoms in Alzheimer's disease: 5‐year prospective ALSOVA cohort study

Objective

To examine the association between neuropsychiatric symptoms (NPS) with self‐ and caregiver‐rated Quality of Life (QoL) for patients with Alzheimer's disease (AD) during a 5‐year follow‐up.

Methods

The ALSOVA 5‐year follow‐up study included, at baseline, 236 patients with either very mild (Clinical Dementia Rating Scale (CDR) 0.5), or mild (CDR 1) AD, together with their caregivers from three Finnish hospital districts. QoL was evaluated using patient self‐reported, and caregiver‐rated, QoL in AD (QoL‐AD) scores. NPS were assessed using the Neuropsychiatric Inventory (NPI), and AD severity was evaluated using the CDR, with cognition tested by the mini‐mental state examination. The performance of daily activities was assessed using the Alzheimer's Disease Cooperative Study–Activities of Daily Living Inventory.

Results

Over the 5‐year follow‐up period, patient self‐reported QoL‐AD scores did not change significantly (p = 0.245), despite increases in their NPS. However, caregiver‐rated patient QoL‐AD scores declined significantly (p ≤ 0.001), as total NPI scores increased during follow‐up. No NPS at baseline, and only apathy at follow‐up, correlated significantly (p = 0.007) with patient self‐rated QoL‐AD scores. Caregiver‐rated patient QoL‐AD scores correlated significantly with most NPS, especially (p ≤ 0.001) apathy, agitation, anxiety, irritability, depression, and delusions at baseline, and delusions, hallucinations, apathy, appetite disturbances, and anxiety during follow‐up.

Conclusions

Patient rated QoL‐AD scores are an unreliable tool with which to evaluate the success of therapy for NPS. Instead, caregiver‐rated scores for patients correlated well with NPI scores, and health care professionals in the clinic should preferentially use these. Copyright © 2017 John Wiley & Sons, Ltd.     

Clinically significant depressive symptoms and very mild to mild dementia of the Alzheimer type

OBJECTIVE: To compare depressive symptoms reported by persons with very mild or mild dementia of the Alzheimer type (DAT) with those reported for the person by a collateral source. DESIGN: Cross-sectional evaluation. SETTING: Washington University Alzheimer's Disease Research Center. PARTICIPANTS: Consecutive series of elderly volunteers (n = 156) enrolled in longitudinal studies with a Clinical Dementia Rating (CDR) of 0.5 (very mild) or 1 (mild). Twenty-one per cent (n = 33) exhibited clinically significant depressive symptoms for which treatment was recommended. MAIN OUTCOME MEASURES: Presence and frequency of DSM-IV depressive symptoms within the last year and last month reported by the participant or collateral source as ascertained by clinical examination and structured interviews. RESULTS: Collateral source information is essential in diagnosing clinically significant depressive symptoms. The Geriatric Depression Scale scores correlate with participant information only and therefore may substantially underestimate depression. Depressive symptoms fluctuate in individuals with DAT. The most consistent depressive symptoms are depressed mood, fatigue and indecision. CONCLUSIONS: Clinically significant depressive symptoms may be common in individuals with very mild or mild DAT, although they may fluctuate. Information from both a knowledgeable collateral source and the participant is important for detection of depressive symptoms.     

APOE genotype predicts depression in women with Alzheimer's disease: a retrospective study

OBJECTIVE: The association between the APOE epsilon4 allele and depression was investigated in a retrospective study of 323 AD patients. METHODS: Patients were divided into demographically comparable groups based on the presence or absence of depression. RESULTS: Results showed that the frequency of APOE epsilon4 allele was significantly higher in the depressed vs non-depressed AD patients (72% and 58%, respectively), and an interaction revealed that women possessing the APOE epsilon4 allele were almost four times more likely to be depressed than those without the epsilon4 allele. CONCLUSION: Results are consistent with recent suggestions that the APOE epsilon4 genotype may be over-represented among depressed women with AD and highlight the need for additional research investigating the links between APOE genotype, mood, and gender.     

Improvement in behavioural symptoms in patients with moderate to severe Alzheimer's disease by memantine: a pooled data analysis

INTRODUCTION: Behavioural disturbances are a common and distressing aspect of Alzheimer's disease (AD). This pooled analysis evaluated the specific benefits of memantine on behavioural disturbances in patients with moderate to severe AD. METHODS: Data were pooled from six 24/28-week, randomised, placebo-controlled, double-blind studies. Of the 2,311 patients included in these studies, 1,826 patients with moderate to severe AD (MMSE <20) were included in this analysis, corresponding to the extended indication for memantine in Europe. In this subgroup, 959 patients received memantine 20 mg/day and 867 received placebo. Behavioural symptoms were rated using the Neuropsychiatric Inventory (NPI) total and single-item scores at weeks 12 and 24/28. RESULTS: At weeks 12 and 24/28, ITT analysis demonstrated that memantine treatment produced statistically significant benefits over placebo treatment in NPI total score (p=0.001 and p=0.008), and in NPI single items: delusions (p=0.007 week 12, p=0.001 week 24/28), hallucinations (p=0.037 week 12), agitation/aggression (p=0.001 week 12, p=0.001 week 24/28), and irritability/lability (p=0.005 week 24/28), LOCF population. Analysis of the patients without symptoms at baseline indicated reduced emergence of agitation/aggression (p=0.002), delusions (p=0.047), and disinhibition (p=0.011), at week 12, and of agitation/aggression (p=0.002), irritability/lability (p=0.004), and night-time behaviour (p=0.050) at week 24/28 in those receiving memantine. OC analyses yielded similar results. CONCLUSIONS: The data suggest that memantine is effective in treating and preventing the behavioural symptoms of moderate to severe AD. Specific persistent benefits were observed on the symptoms of delusions and agitation/aggression, which are known to be associated with rapid disease progression, increased caregiver burden, early institutionalisation, and increased costs of care.     

Frequency of behavioral symptoms characterizes agitation in Alzheimer's disease

This study describes two well-characterized groups of Alzheimer's disease (AD) patients with similar levels of cognitive functioning, but with different overall behavioral disturbance levels. We sought to determine the nature of this difference-whether AD patients with higher levels of behavioral disturbance (n = 148) differ from less disturbed AD patients (n = 235) in terms of (a) the range of symptoms exhibited, (b) the frequency of occurrence of these symptoms, or (c) both of these. We defined and operationalized 'diversity of behaviors' and 'frequency' with respect to the item-level responses on the Cohen-Mansfield agitation inventory (CMAI). We found that, in these two samples of AD patients, differences occurred in the frequency of 10 out of 21 behaviors, rather than in a variety of endorsed behaviors. These 10 behaviors, observed at different frequencies in both groups, may be useful for monitoring change in studies of drugs or behavioral interventions for behavioral disturbance in persons with AD.     

Olanzapine does not enhance cognition in non-agitated and non-psychotic patients with mild to moderate Alzheimer's dementia

OBJECTIVE: This was an exploratory study of olanzapine as potential treatment for improvement in cognition in patients with Alzheimer's disease without prominent psychobehavioral symptoms. METHODS: Non-psychotic/non-agitated patients (n = 268) with Alzheimer's disease, who had baseline Mini-Mental State Examination (MMSE) scores of 14-26 were randomized to treatment with olanzapine (2.5 to 7.5 mg/d) or placebo for 26 weeks. The primary objectives were to determine if treatment with olanzapine improved cognition as indexed by the Alzheimer's disease Assessment Scale for Cognition (ADAS-Cog) and the Clinician's Interview-Based Impression of Change (CIBIC) after 26 weeks of therapy. RESULTS: Patients treated with olanzapine vs placebo experienced significant worsening ADAS-Cog scores at weeks 12 (p = 0.03) and 26 (p = 0.004). Changes in CIBIC scores were not significantly different between treatment groups at either assessment. A post hoc analysis revealed that olanzapine-treated patients with more cognitive impairment at baseline (MMSE scores of 14-18) (n = 35) experienced significantly greater deterioration in ADAS-Cog performance than patients in the placebo group (n = 24; p < 0.001); whereas in patients with less cognitive impairment (n = 78, baseline MMSE scores of 23-26) between-group ADAS-Cog changes were not significant. CONCLUSIONS: In this 26-week study non-psychotic/non-agitated patients with Alzheimer's disease treated with olanzapine experienced significant worsening of cognition as compared to placebo.     

Parkinson's disease: The quintessential neuropsychiatric disorder

Although diagnosed by characteristic motor features, Parkinson's disease may be preceded, and is frequently accompanied by, a wide range of cognitive and neuropsychiatric features. In addition to the most commonly studied disorders of dementia, depression, and psychosis, other relatively common and clinically significant psychiatric complications include impulse control disorders, anxiety symptoms, disorders of sleep and wakefulness, and apathy. These problems may be underrecognized and are frequently undertreated. The emergent focus on nonmotor aspects of Parkinson's disease over the past quarter of a century is highlighted by a nonlinear increase in the number of articles published devoted to this topic. Although the development of newer antidepressants, atypical antipsychotics, and cholinesterase inhibitors in recent years has had a positive benefit on the management of these troublesome and distressing symptoms, responses are frequently suboptimal, and this remains an area of major unmet therapeutic need. © 2011 Movement Disorder Society