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Aim: Alzheimer's disease (AD) is the most common neurodegenerative disease. In 2000, Mendiondo et al. reported on a model predicting that AD progresses at an accelerating rate and cognitive function worsens rapidly. Recently, anti-AD drugs and non-pharmacological intervention have been established, but the effect of intervention is unclear and might depend on the stage of AD progression. Here, we examined the prediction of Mendiondo's model in patients with different severities of AD., Methods: A total of 163 new outpatients with AD at four memory clinics were retrospectively analyzed. The Revised Hasegawa Dementia Scale (HDS-R) and Mini-Mental State Examination (MMSE) were administered to all AD patients at the first visit and after approximately 12 months. We divided the patients into three groups according to scores at the first visit: mild, moderate and moderate-to-severe. We compared the scores at the first visit with those obtained after 12 months of anti-AD drug and non-pharmacological interventions., Results: The HDS-R score improved from 14.5 to 15.0, and the MMSE score improved from 18.8 to 19.1 after 12 months of intervention. Also, the HDS-R and MMSE scores at the first visit were significantly associated with the annual change in the scores. Among the three groups, lower HDS-R and MMSE scores at the first visit were associated with significantly greater annual improvement in the scores after 12 months of intervention., Conclusions: Contrary to the prediction of Mendiondo's model, mild or moderate AD progressed more rapidly than moderate-to-severe AD under pharmacological and non-pharmacological interventions. Geriatr Gerontol Int 2020; 20: 324-328., (© 2020 Japan Geriatrics Society.)

Aim: Alzheimer's disease causes loss of appetite, resulting in bodyweight reduction. This, in turn, causes progression of cognitive dysfunction and physical complications that hasten death. Earlier care for loss of appetite is essential in Alzheimer's disease management. Rivastigmine is a therapeutic agent for Alzheimer's disease that has dual inhibition effects on acetylcholine esterase and butyrylcholine esterase. Butyrylcholine esterase is known to degrade the gastric hormone, ghrelin, which regulates appetite; therefore, we considered that rivastigmine might have an effect on appetite. The present study aimed to evaluate the hypothesis that rivastigmine improves appetite in Alzheimer's disease patients., Methods: Rivastigmine was given to mild-to-moderate Alzheimer's disease patients for 16 weeks. We evaluated the effects of rivastigmine on food intake, bodyweight, motivation (estimated by the vitality index), cognition function (estimated by the Hasegawa Dementia Scale-Revised), plasma butyrylcholine esterase activity, active ghrelin and inactive ghrelin., Results: Plasma butyrylcholine esterase activity significantly decreased over time (percent change: -18.9 ± 27.0%, P < 0.05 at week 8; percent change: -33.4 ± 45.4%, P < 0.05 at week 16). Negative correlations were detected between percent changes in butyrylcholine esterase activity and active ghrelin (r s  = -0.62, P = 0.033) or active/inactive ghrelin ratio (r s  = -0.73, P = 0.007). Furthermore, motivation (including appetite) improved significantly (percent change: 17.9 ± 18.6%, P < 0.05 at week 16)., Conclusions: The present study suggests that rivastigmine might improve appetite in mild-to-moderate Alzheimer's disease patients by suppressing degradation of plasma active ghrelin through the inhibition of plasma butyrylcholine esterase. Geriatr Gerontol Int 2018; 18: 886-891., (© 2018 Japan Geriatrics Society.)

Aim: To examine the clinical effect of four antidementia drugs (donepezil, galantamine, rivastigmine and memantine) in Alzheimer's disease patients who were divided into subgroups based on their periventricular hyperintensity (PVH) severity., Methods: A total of 551 Alzheimer's disease patients (201 men and 350 women) were divided into four subgroups based on their PVH severity (0-III). They received monotherapy for 12 months. We compared the clinical effects at the baseline, and at 3, 6 and 12 months after initiation., Results: The baseline age became higher with PVH grades, and the Mini-Mental State Examination and Hasegawa Dementia Scale-Revised showed a decrease that was dependent on white matter severity. Although the PVH 0 subgroup showed stable cognitive, affective and ADL functions until 12 months in all four drug groups, the PVH I subgroup showed an improved Apathy Scale from the baseline in response to memantine at 3 and 9 months (P < 0.05), and galantamine at 9 months (P < 0.01). In the PVH II subgroup, the Mini-Mental State Examination showed a significant improvement from the baseline in response to galantamine (P < 0.05) at 9 months and Hasegawa Dementia Scale-Revised (P < 0.05) at 3 months. In the PVH III subgroup, cognitive and affective functions were preserved in all four drug groups until 12 months, but activities of daily living deteriorated in the riverstigmine group at 6 and 12 months (P < 0.05)., Conclusions: The present study shows that these four drugs showed sensitivity dependent on white matter severity that clinically affected cognitive, affective and activities of daily living functions. Geriatr Gerontol Int 2017; 17: 1991-1999., (© 2017 Japan Geriatrics Society.)

Aim: To evaluate the therapeutic effects of switching from one acetylcholinesterase inhibitor (ChEI), donepezil, galantamine or rivastigmine, to another in Alzheimer's disease patients., Methods: We retrospectively enrolled 171 Alzheimer's disease patients, whose ChEI medication was changed. The patients were evaluated on three major aspects of dementia - cognitive, affective and activities of daily living (ADL) measures - at 6 months (M) before the drug switch, at the time of drug switch (baseline), and at 3 M and 6 M after the drug switch., Results: The doses of the three ChEI were significantly lower at 6 M after the switch compared with the pre-switch doses. Improvements in apathy were found at 3 M when switching from donepezil to galantamine, but not to rivastigmine, but this switch had adverse effects on ADL. Improvements in cognitive scores at 3 M were also found when switching from galantamine to rivastigmine, but not to donepezil. However, both of these changes improved Abe's Behavioral and Psychological Symptoms of Dementia scores (ABS), except ADL. Switching from rivastigmine to donepezil worsened ABS at 6 M, but preserved cognitive and ADL scores., Conclusions: The present study suggests that despite a relatively lower dose of ChEI after the switch, switching from donepezil or rivastigmine preserved cognitive functions for at least 6 M. Switching from galantamine to rivastigmine improved Mini-Mental State Examination and ABS at 3 M, but did not improve ADL scores. Geriatr Gerontol Int 2017; 17: 1843-1848., (© 2017 Japan Geriatrics Society.)

Aim: To investigate whether the inhibitory rate of serum butyrylcholinesterase (BuChE) activity in Japanese patients with Alzheimer's disease is correlated with cognitive function, behavioral symptoms and caregiver burden., Methods: A total of 61 patients with mild to moderately severe Alzheimer's disease who were not undergoing cholinesterase enzyme inhibitor/memantine combinatorial treatment received a rivastigmine (18 mg) patch for 24 weeks. The rate of inhibition of BuChE was correlated with scores obtained on cognitive (Mini-Mental State Examination), behavioral (the Japanese version of the modified Crichton Geriatric Behavioral Rating Scale [CGBRS] and Vitality Index [VI]) and burden (the Japanese version of Zarit Burden Inventory [ZBI]) scales; and the Clinical Global Impression of Change scale., Results: The serum BuChE activity showed a significant decrease after 24 weeks compared with baseline (P < 0.001). Overall, significant effects were found in the Mini-Mental State Examination score, VI score and modified CGBRS score. We then divided patient groups into a high inhibitory rate (≥40%) group and a low inhibitory rate (<40%) group; there were significant improvements in the Mini-Mental State Examination score, VI score and modified CGBRS score in both groups. However, favorable results were seen in cooperation, restlessness and leisure on modified CGBRS subscales in the high inhibitory rate group (P < 0.001, P = 0.007, P < 0.001, respectively), and rehabilitation and other activities on VI subscales in the high inhibitory rate group (P = 0.005) compared with those in the low inhibitory rate group., Conclusions: Demonstrable significant improvements in behavioral symptoms, such as low cooperation, restlessness or low activities in patients with Alzheimer's disease, were achieved on inhibition of BuChE at a rate of 40% or more. Geriatr Gerontol Int 2017; 17: 1306-1312., (© 2016 Japan Geriatrics Society.)