Yasushi Inami

Sleep disturbances and depression in the elderly in Japan

Abstract The purpose of the present study was to evaluate the relationship between sleep disturbances and depression in the Japanese elderly. Methods: These investigations in the Japanese elderly were carried out with the Geriatric Depression Scale, the Pittsburgh Sleep Quality Index, and questions on restless legs syndrome and nocturnal eating disorder. A total of 2023 people (male: 1008; female: 1015; average age: 74.2 ± 6.3 years) were analyzed by χ2 test and simple and multiple logistic regression. The prevalence of sleep disturbance was 37.3% and that of depression was 31.3%. Female gender and/or older (≥75 years) age were significantly associated with depression. Characteristics in depressive elderly were poor sleep efficiency, sleep disturbances due to difficulty of initiating sleep (DIS), breathing discomfort, coldness and pain, poor subjective sleep quality and lack of enthusiasm for activities. Sleep disturbances due to using the bathroom, breathing discomfort and coldness and long sleep latency were associated with depression in younger (65–74 years) men. Sleep disturbance due to DIS was associated with depression in older (≥75 years) men. Sleep disturbance due to pain was associated with depression in younger and older women. Poor sleep efficiency was associated with depression in older women. Poor subjective sleep quality was associated with depression in younger and older men and younger women. Lack of enthusiasm was associated with depression in younger and older men and older women. Restless legs syndrome was statistically significantly associated with depression in younger men. It is concluded that sleep disturbance and depression among the Japanese elderly are closely related symptoms. The features of sleep disturbance with depression differed with sex and age.

Effect of Yi-Gan San on psychiatric symptoms and sleep structure at patients with behavioral and psychological symptoms of dementia.

OBJECTIVE Recently, traditional herbal medicines have been reported to be effective for behavioral and psychological symptoms of dementia (BPSD). This study aims to examine the efficacy of Yi-Gan San (YGS) in the improvement of BPSD and sleep disorders in patients with dementia. METHODS Five patients (1 male and 4 female) with dementia in accordance with DSM-IV criteria were investigated. Participants were treated with YGS for 4 weeks. The Nursing Home version of Neuropsychiatric Inventory (NPI-NH) for the assessment of BPSD, the Mini-Mental State Examination (MMSE) for cognitive function, polysomnography for evaluation of sleep structure, and the Pittsburgh Sleep Quality Index for subjective sleep quality were carried out at baseline and at the end of treatment. RESULTS All patients completed the trial. Significant improvements in the total NPI-NH score (34.0+/-6.5 to 12.8+/-6.6) as well as delusions, hallucinations, agitation/aggression, anxiety, and irritability/lability, whereas MMSE scores were unchanged. PSG revealed increases in total sleep time, sleep efficiency, stage 2 sleep, and decreases in the number of arousals and periodic limb movements. Subjective sleep quality was also improved. No adverse effects were observed. CONCLUSION YGS was effective for BPSD and sleep disturbances, and well tolerated in patients with dementia. Further examinations using a double-blind placebo-controlled design are necessary.

A decrease in N-acetylaspartate and an increase in myoinositol in the anterior cingulate gyrus are associated with behavioral and psychological symptoms in Alzheimer's disease.

BACKGROUND AND PURPOSE The cognitive decline in Alzheimers disease (AD) patients has been reported to involve alterations in the medial temporal lobe and the posterior cingulate gyrus. On the other hand, the neurochemical pathologies of the behavioral and psychological symptoms of dementia (BPSD) have not been sufficiently discussed. The aim of this study was to clarify the pathologies of BPSD in AD patients. METHODS Thirty patients with probable AD were included and underwent the following assessments: Mini Mental State Examination (MMSE), Clock Drawing Test (CDT), Story Recall Test (SRT), Behavioral pathology in Alzheimers disease (BEHAVE-AD) and proton MRS ((1)H-MRS). None of them had been medicated for BPSD. RESULTS The MRS study revealed that MMSE, CDT, and SRT scores were positively related to N-acetyl-aspartate (NAA)/creatine(Cr) and negatively related to myoinositol (mI)/Cr in the posterior cingulate gyrus, but not in the anterior cingulate gyrus. On the other hand, the scores obtained in two categories of BEHAVE-AD (delusional thought/ activity disturbances) were negatively related with NAA/Cr and positively related with mI/Cr in the anterior cingulate gyrus, but not in the posterior cingulate gyrus. CONCLUSION We conclude that BPSD and the decline in cognitive function in AD might have separate pathologies.

Successful treatment with Yi-Gan San for rapid eye movement sleep behavior disorder.

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia observed among the elderly, and is characterized by the absence of REM atonia and the appearance of dream-enacting behaviors. These oneiric behaviors are usually violent or injurious (Mahowald and Schenck, 2005). Clonazepam is an effective first-line agent for RBD treatment (Mahowald and Schenck, 2005). It has been reported that clonazepam is effective in nearly 90% of RBD cases (Schenck et al., 1993). A proportion of RBD patients are refractory to clonazepam because of adverse effects characteristic of benzodiazepines. Yi-Gan San (YGS) contains seven different herbal ingredients Atractylodes lanceae rhizoma, Hoelen, Cnidii rhizoma, Angelicae radix, Bupleuri radix and Glycyrrhizae radix. YGS was developed as a remedy for restlessness and agitation. In Japan, YGS prescription has been approved for patients with insomnia, although the mechanism whereby YGS alleviates sleep disturbances remains to be elucidated. We previously reported that YGS improved sleep quality in patients with dementia (Shinno et al., 2008). We encountered three patients with idiopathic RBD that were successfully treatedwithYGS.Here,wepresent the clinical course of RBD (Fig. 1), and discuss the possible mechanisms of YGS treatment for RBD.

Adverse Reactions to Zolpidem: Case Reports and a Review of the Literature

OBJECTIVE Zolpidem, a nonbenzodiazepine hypnotic, is very effective and widely prescribed in clinical practice for the treatment of insomnia and is thought to have few adverse effects. However, zolpidem-induced adverse effects have begun to be reported in the literature, but few systemic descriptions of the adverse effects (especially for psychotic reactions) of zolpidem have been undertaken. In light of the accumulating reports of adverse reactions to zolpidem, we present 2 case reports of zolpidem-induced adverse effects and review the literature on this subject. DATA SOURCES Articles were selected by the authors on the basis of our experience and by a PubMed search using the terms zolpidem or side effects or adverse effects or adverse reactions. STUDY SELECTION AND DATA EXTRACTION Publications relevant to the objective of this article were obtained (1992-2010), and some adverse neuropsychiatric reactions were summarized. DATA SYNTHESIS Zolpidem has been associated with the development of adverse neuropsychiatric reactions, such as hallucinations/sensory distortion, amnesia, sleepwalking/somnambulism, and nocturnal eating. The following 4 variables should be considered when prescribing zolpidem: (1) gender: women have been found to have a significantly higher serum zolpidem concentration than men; (2) zolpidem dose: the adverse reactions that develop are dose dependent; (3) protein binding affinity: a high proportion of zolpidem is protein bound; therefore, low serum albumin results in a higher level of free zolpidem leading to adverse psychiatric reactions; and (4) cytochrome P450 (CYP) isoenzyme inhibition: concomitant administration of zolpidem and other drugs may cause interactions that lead to increased concentrations of zolpidem. CONCLUSIONS Zolpidem is clinically very effective in treating insomnia. However, while rare, zolpidem-induced unusual complex behavior may develop. Primary care physicians should be alert to the possible unusual complex adverse effects of zolpidem.

NREM Sleep Stage Transitions Control Ultradian REM Sleep Rhythm

STUDY OBJECTIVES The cyclic sequence of NREM and REM sleep, the so-called ultradian rhythm, is a highly characteristic feature of sleep. However, the mechanisms responsible for the ultradian REM sleep rhythm, particularly in humans, have not to date been fully elucidated. We hypothesize that a stage transition mechanism is involved in the determination of the ultradian REM sleep rhythm. PARTICIPANTS Ten healthy young male volunteers (AGE: 22 ± 4 years, range 19-31 years) spent 3 nights in a sleep laboratory. The first was the adaptation night, and the second was the baseline night. On the third night, the subjects received risperidone (1 mg tablet), a central serotonergic and dopaminergic antagonist, 30 min before the polysomnography recording. MEASUREMENTS AND RESULTS We measured and investigated transition probabilities between waking, REM, and NREM sleep stages (N1, N2, and N3) within the REM-onset intervals, defined as the intervals between the onset of one REM period and the beginning of the next, altered by risperidone. We also calculated the transition intensity (i.e., instantaneous transition rate) and examined the temporal pattern of transitions within the altered REM-onset intervals. We found that when the REM-onset interval was prolonged by risperidone, the probability of transitions from N2 to N3 was significantly increased within the same prolonged interval, with a significant delay and/or recurrences of the peak intensity of transitions from N2 to N3. CONCLUSIONS These results suggest that the mechanism governing NREM sleep stage transitions (from light to deep sleep) plays an important role in determining ultradian REM sleep rhythms.

Successful treatment with levothyroxine for idiopathic hypersomnia patients with subclinical hypothyroidism

OBJECTIVE Our objective was to discuss the effect of levothyroxine on excessive daytime sleepiness (EDS) and a prolonged nocturnal sleep at patients with idiopathic hypersomnia who presented with subclinical hypothyroidism. METHODS We present two patients with hypersomnia who complained of EDS and a prolonged nocturnal sleep time. Sleep architecture and subjective daytime sleepiness were estimated by polysomnography (PSG) and Epworth Sleepiness Scale (ESS), respectively. Diagnoses were made using the International Classification of Sleep Disorders, 2nd Edition criteria for idiopathic hypersomnia with long sleep time. RESULTS PSG demonstrated a short sleep latency, a prolonged total sleep time and normal proportions of all non-rapid eye movement (REM) and REM sleep stages. Nocturnal PSG excluded other causes of EDS. No medical, neurological and mental disorders were present. Their laboratory data indicated mildly elevated thyrotropin, despite free thyroxine (T4) and triiodothyronine (T3) estimates within their reference ranges, which is a characteristic of latent hypothyroidism. Levothyroxine (25 microg/day) was administrated orally. After treatment with levothyroxine for 8 weeks, the mean daily sleep times decreased. EDS was also improved, and a significant decrease in the ESS score was observed. Levothyroxine was effective for their hypersomnia and well tolerated. CONCLUSIONS It should be noted that hypersomnia may be associated with subclinical hypothyroidism, although few abnormalities in physical and neurological examinations are present.

A case of neuroleptic-induced unilateral akathisia with periodic limb movements in the opposite side during sleep

We report on a patient with schizoaffective disorder who developed unilateral akathisia. This is the first case report of a patient with neuroleptic‐induced unilateral akathisia on whom an all‐night polysomnogram was recorded. On the polysomnogram we observed right side periodic limb movements (PLM) with left side unilateral akathisia, and after her akathisia disappeared, the PLM also disappeared. Brain MRI findings and neurological findings were within normal limits. The pathogenetic lesion causing akathisia could not be elucidated.

Effect of Donepezil on Sleep and Activity in AlzheimerâÂÂs Disease: Actigraphicand Polysomnographic Assessment

Aim: To examine the effect of donepezil on sleep and daily activity in patients with Alzheimer-type dementia (ATD) using polysomnography and actigraphy. Methods: Ten patients with mild to moderate ATD (mean age: 76 ± 6.2 years) were studied. The Alzheimer’s disease Assessment Scale-cognitive component-Japanese version (ADAS-Jcog),polysomnography, and 7-day recording of actigraphy data were performed. Following this baseline assessment, donepezil (5 mg daily) was administered every morning for 6 weeks, after which the ADAS-Jcog, polysomnography, and actigraphy were repeated. Results: After 6 weeks of treatment with donepezil, daily activity was significantly increased (276.2 ± 89.2 vs. 326.1 ± 98.6; p < 0.05). Similarly, rapid eye movement (REM) sleep (11.3 ± 4.1 vs. 17.1 ± 4.4; p<0.01) and sleep efficiency (76.2 ± 16.3 vs. 82.8 ± 10.6; p<0.05) were significantly increased compared with baseline. Although the ADAS-Jcog score did not decrease significantly (18.5 ± 6.8 vs. 15.9 ± 7.3; P= 0.054), there was a significant positive correlation between the decrease of this score and the increase of daily activity (r= 0.2137, p= 0.4809). Conclusions: An increase of daily activity and cognition were induced by donepezil treatment in patients with ATD, possibly based on improvement of the sleep structure. Trial Registration: Controlled-trials. Com Identifier: UMIN000005018

Effect of levothyroxine on prolonged nocturnal sleep time and excessive daytime somnolence in patients with idiopathic hypersomnia

OBJECTIVE This study aims to examine the effect of levothyroxine, a thyroid hormone, on a prolonged nocturnal sleep and excessive daytime somnolence (EDS) in patients with idiopathic hypersomnia. METHODS In a prospective, open-label study, nine patients were enrolled. All subjects met criteria for idiopathic hypersomnia with long sleep time defined by the International Classification of Sleep Disorders, 2nd edition (ICSD-2). Subjects with sleep apnea syndrome, obesity or hypothyroidism were excluded. Sleep architecture and subjective daytime somnolence were estimated by polysomnography (PSG) and Epworth Sleepiness Scale (ESS), respectively. After baseline examinations, levothyroxine (25μg/day) was orally administered every day. Mean total sleep time, ESS score at baseline were compared with those after treatment (2, 4 and 8 weeks). RESULTS Mean age of participants was 23.8±13.7 years old. At baseline, mean total sleep time (hours) and ESS score were 12.9±0.3 and 17.8±1.4, respectively. Mean total sleep times after treatment were 9.1±0.7 and 8.5±1.0h at 4 and 8 treatment weeks, respectively. Mean ESS scores were 8.8±2.3 and 7.4±2.8 at 4 and 8 treatment weeks, respectively. One patient dropped out at the 2nd week due to poor effect. No adverse effects were noted. CONCLUSIONS After treatment with levothyroxine for over 4 weeks, prolonged sleep time and EDS were improved. Levothyroxine was effective for hypersomnia and well tolerated.