Efficacy, Safety, and Tolerability of Switching from Oral Cholinesterase Inhibitors to Rivastigmine Transdermal Patch with 1-Step Titration in Patients with Mild to Moderate Alzheimer's Disease: A 24-Week, Open-Label, Multicenter Study in Japan.

BACKGROUND: Few studies have investigated treatment options for patients with Alzheimer's disease (AD) showing a poor response to oral cholinesterase inhibitors (ChEIs) in Japan. OBJECTIVE: To investigate the efficacy and safety of switching from oral ChEIs to rivastigmine transdermal patch in patients with AD. METHODS: In this multicenter, open-label, phase IV study in outpatient clinics in Japan, patients with mild-moderate AD who had a poor response to or experienced difficulty in continuing donepezil or galantamine were switched to rivastigmine transdermal patch (5 cm2; loaded dose 9 mg, delivery rate 4.6 mg/24 h) with a 1-step titration in week 4 (10 cm2; loaded dose 18 mg, delivery rate 9.5 mg/24 h), which was continued for 4 weeks in the titration period and 16 weeks in a maintenance period. The primary endpoint was the change in Mini-Mental State Examination (MMSE) total score from baseline to week 24. RESULTS: A total of 118 patients were enrolled and switched to rivastigmine, of which 102 completed the 24-week study. The MMSE total score was essentially unchanged during the study, with a least-square mean change (SD) of -0.35 (2.64) at week 24 (p = 0.1750). Exploratory analysis with a mixed-effect model comparing changes in MMSE between the pre- and post-switch periods suggested that switching to rivastigmine prevented a worsening of MMSE. Application site skin reactions/irritations occurred in 30.5% of patients overall, in 22.0% in the 8-week titration period, and in 10.2% in the 16-week maintenance period. CONCLUSION: Within-class switching from an oral ChEI to rivastigmine transdermal patch might be an efficacious and tolerable option for AD patients showing a poor or limited response to a prior oral ChEI.

Stress-buffering Effect of Coping Strategies on Interrole Conflict among Family Caregivers of People with Dementia.

OBJECTIVES: To examine the stress-buffering effect of coping strategies on the adverse effects of interrole conflict on the mental health of employed family caregivers, and clarify the moderating role of attentional control on this stress-buffering effect. METHODS: Data were drawn from a two-wave longitudinal online survey of employed Japanese family caregivers of people with dementia (263 males, 116 females; age 51.54 ± 9.07 years). We assessed interrole conflict, coping strategies, attentional control, mental health variables (psychological strain and quality of life), and confounding factors. RESULTS: Hierarchical regression analyses controlled for sociodemographic factors found formal support seeking had a stress-buffering effect for strain- and behavior-based caregiving interfering with work (CIW) only on psychological strain, and was moderated by attentional control. Single slope analysis showed higher CIW was related to higher psychological strain in those with greater use of formal support seeking and lower attentional control, but not in those with higher attentional control. CONCLUSIONS: Greater use of formal support seeking weakens the adverse effects of strain- and behavior-based CIW on psychological strain in people with high attentional control. CLINICAL IMPLICATIONS: Attentional control is a key factor in the stress-buffering effect of formal support seeking on strain- and behavior-based CIW.

Can self-efficacy ameliorate interrole conflict among employed family caregivers? A moderated mediation approach.

OBJECTIVES: This study examined the moderation effect of different dimensions of self-efficacy on the way in which various types of interrole conflict mediate between caregiving demands and the mental health of employed family caregivers. METHOD: Using a moderated mediation approach, we examined the moderation effect of self-efficacy on interrole conflict's mediation between caregiving demands and mental health (psychological strain and quality of life) in a sample of Japanese employed family caregivers who regularly provide care at home (263 males aged 53.14 ± 8.28 years and 116 females aged 47.92 ± 9.77 years). RESULTS: Increased self-efficacy in managing dementia and in self-care were correlated with lower caregiving demands and better mental health among family caregivers. Self-efficacy in managing dementia was also positively correlated with increased interrole conflict. Increased caregiving demands were related to higher psychological strain in those with higher (+1SD), but not lower (-SD) self-efficacy in managing dementia. CONCLUSION: Self-efficacy does not play a protective role in managing the effect of caregiving demands on interrole conflict. It also does not appear to protect against any indirect effects of caregiving demands on the mental health of employed family caregivers.

[Treatments of sleep disorders in dementia patients].

In elderly, biological changes cause circadian rhythm disturbance, and sleep disorders are often observed. The risk of sleep disorders is higher in dementia patients, sleep disorders are causes of care burden increase. In treatments of sleep disorders in dementia patients, it is important to evaluate correctly about sleep disorders and to check BPSD which merges to insomnia. In clinical, nonpharmacological therapies, such as an improvement of a lifestyle and cause removal of insomnia, are first choices. In medication, when other psychological symptoms and BPSDs merge, use of an easy sleeping drug is avoided, and medication of antidepressants or atypical antipsychotics is considered, but these medications use requires cautions about insurance adaptation and side effects.

Progressive supranuclear palsy combined with Alzheimer's disease: a clinicopathological study of two autopsy cases.

We present here the clinicopathological characteristics of two autopsy-confirmed cases comorbid of progressive supranuclear palsy (PSP) and Alzheimer's disease (AD). Histopathologically, the amount and distribution of neurofibrillary tangles (NFTs) in the basal ganglia and brainstem fulfilled the pathological criteria of PSP proposed by the National Institute of Neurological Disorders and Stroke--The Society for PSP (NINDS-SPSP). The Braak stages of senile plaques and NFTs were stage C and stage V in Case 1, and stage C and stage IV in Case 2. These neuropathological findings confirmed that the two patients had combined PSP with AD. Our patients presented clinically with executive dysfunction prior to memory disturbance as an early symptom. Not only neurological symptoms such as gait disturbance, supranuclear ophthalmoplegia and pseudobulbar palsy, but emotional and personality changes and delirium were prominent. Therefore, symptoms of subcortical dementia of PSP were more predominant than AD-related symptoms in the present two patients. Comorbid PSP and AD further complicates the clinical picture and makes clinical diagnosis even more difficult.

Diffusion abnormality in the posterior cingulum and hippocampal volume: correlation with disease progression in Alzheimer's disease.

The purpose of this study was to determine correlations among disease progression, diffusion abnormalities in the posterior cingulum and hippocampal volume in patients with Alzheimer's disease (AD). We studied 25 AD patients by neuropsychological testing, including the Mini-Mental State Examination (MMSE), and by magnetic resonance imaging, including diffusion tensor imaging (DTI) and high-resolution three-dimensional T1-weighted imaging. The MMSE score was used as an indicator of disease progression. Diffusion tensor tractography of the posterior cingulum was generated from the DTI; mean diffusivity (MD) and fractional anisotropy (FA) were measured in co-registered voxels along the posterior cingulum. Hippocampal volume was measured using automated voxel-based morphometry. The relationships among MMSE score, hippocampal volume and MD and FA of the posterior cingulum were evaluated by bivariate correlation analysis. MD in the posterior cingulum correlated significantly with the MMSE score. No significant correlation was seen between FA and MMSE score and between hippocampal volume and MMSE score, FA or MD. Our results suggest that MD in the posterior cingulum is a more sensitive indicator of progression of AD than FA of the posterior cingulum and hippocampal volume.

Diffusion abnormality in posterior cingulate fiber tracts in Alzheimer's disease: tract-specific analysis.

PURPOSE: The aim of this study was to determine diffusion abnormalities in the posterior cingulate fiber tracts (PCFTs) in patients with Alzheimer's disease (AD) by diffusion tensor tractography (DTT). MATERIALS AND METHODS: We studied 23 AD patients and 18 age-matched normal controls who underwent magnetic resonance imaging using diffusion tensor imaging (DTI). DTT of PCFTs was generated from DTI. Mean diffusivity (MD) and fractional anisotropy (FA) were measured in co-registered voxels along with DTT of PCFTs. Student's t-test was used to compare results between the AD patients and normal controls. RESULTS: The MD in PCFTs was significantly higher in AD patients than in normal controls (P = 0.019). The FA in PCFTs was significantly lower in AD patients than in normal controls (P = 0.007). CONCLUSION: The abnormal MD increase and FA decrease, which is considered to indicate a net loss of barriers that restrict water molecular motion and tissue anisotropy of white matter, is consistent with neuropathological data that demonstrate partial loss of myelin, axons, and oligodendrial cells in white matter of AD brains. Our results suggest that MD and FA reflect progression of AD-related histopathological changes in the PCFTs and may represent a useful biological index for monitoring AD.

Diffusion abnormalities of the uncinate fasciculus in Alzheimer's disease: diffusion tensor tract-specific analysis using a new method to measure the core of the tract.

INTRODUCTION: Our aim was to determine diffusion abnormalities in the uncinate fasciculus (UF) in Alzheimer's disease (AD) by diffusion tensor tractography (DTT) using a new method for measuring the core of the tract. METHODS: We studied 19 patients with AD and 19 age-matched control subjects who underwent MRI using diffusion tensor imaging (DTI). DTT of the UF was generated. The mean diffusivity (MD) and fractional anisotropy (FA) of the core of the tract were measured after voxelized tract shape processing. Student's t-test was used to compare results between patients with AD and controls. Intraobserver correlation tests were also performed. RESULTS: FA was significantly lower (P < 0.0001) in the UF of patients with AD than of controls. There was no significant difference in MD along the UF between the two groups. Intraobserver reliability (intraclass correlation coefficient) for the first and second measurement was r > 0.93 for measured FA and r > 0.92 for measured MD. CONCLUSION: Our results suggest that FA reflects progression of AD-related histopathological changes in the UF of the white matter and may represent a useful biological index in monitoring AD. Diffusion tensor tract-specific analysis with voxelized tract shape processing to measure the core of the tract may be a sensitive tool for evaluation of diffusion abnormalities of white matter tracts in AD.