Key words : REM REM. tauopathy AD. α synucleinopathy - DLB. REM on REM off - I. Table 1 OSAS. 26 Japanese Journal of Cognitive Neuroscience

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1 1 2 Key words : REM REM REM 1 2 I. Table tauopathy AD 3 α synucleinopathy DLB PD REM on REM off 4 REM RBD ; REM DLB OSAS REM 26 Japanese Journal of Cognitive Neuroscience

2 Table 1. Changes in sleep parameters/circadian rhythm in respective dementia disorders Alzheimer s disease 2 Dementia with lewy bodies Parkinson s disease with dementia Vascular dementia Subjective sleep quality subjective sleep quality time to fall asleep Daytime sleepiness Sleep architecture awakenings light sleep (stage 1/2) deep sleep (stage 3/4) REM sleep 24 hour sleep patterns sleep/wake fragmentation daytime napping Circadian rhythms circadian rhythm amplitude Delayed circadian rhythms = ; = ; = OSAS OSAS II. α synucleinopathy RBD RBD 0.5 1% RBD RBD 5 α synucleinopathy RBD RBD RBD PD DLB 6 Fig. 1 RBD RBD REM without atonia RWA ; REM 7 RBD mild cognitive impairment MCI REM α θ 8 RBD DLB 60 80% RBD PD RBD PD 40 50% RBD RWA RBD 60% 9 PD RBD REM 10 PD RBD AD tauopathy RBD RBD Vol. 17 No

3 Neurological disease free survival (%) Time from IRBD diagnosis (years) Time from RBD onset (years) Fig. 1 Rates of neurological disease free survival according to the time of A IRBD diagnosis and B estimated RBD onset 6 IRBD=idiopathic rapid eye movement REM sleep behaviour disorder. RBD=REM sleep behaviour disorder. III. AD AD apolipoprotein E ε4 carrier 11 AD Fig BZ Fig. 2 The relationship between dementia severity and stability of the amplitude of circadian ampitude 12 AD ω1 28 Japanese Journal of Cognitive Neuroscience

4 13 AD BZ 6 sulphatoxymelatonin IV. β V. OSAS OSAS 18 OSAS AHI OSAS 80 AHI 20 AD apolipoprotein E ε4 carrier AHI Rey Auditory Verbal Learning Test 21 Fig. 3 OSAS 20 OSAS nasal CPAP Fig. 3 Graph of the Rey Auditory Verbal Learning Test 21 RAVLT plotted against the apnea/hypopnea index per hour of estimated sleep AHI/hour in APOE ε4 carriers compared to non carriers. Vol. 17 No

5 OSAS MCI CPAP OSAS OSAS MCI OSAS 10 translational breakthrough 1 Okajima I, Komada Y, Nomura T, Nakashima K, Inoue Y Insomnia as a risk for depression : a longitudinal epidemiologic study on a Japanese rural cohort. J Clin Psychiatry 73 3, Knutson KL, Spiegel K, Penev P, Van Cauter E The metabolic consequences of sleep deprivation. Sleep Med Rev 11 3, Gehrman P, Marler M, Martin JL, Shochat T, Corey Bloom J, Ancoli Israel S The relationship between dementia severity and rest/activity circadian rhythms. Neuropsychiatr Dis Treat 1 2, Luppi PH, Clément O, Sapin E, Gervasoni D, Peyron C, Léger L, Salvert D, Fort P The neuronal network responsible for paradoxical sleep and its dysfunctions causing narcolepsy and rapid eye movement REM behavior disorder. Sleep Med Rev 15 3, Kang SH, Yoon IY, Lee SD, Han JW, Kim TH, Kim KW REM sleep behavior disorder in the Korean elderly population : prevalence and clinical characteristics. Sleep 36 8, Iranzo A, Tolosa E, Gelpi E, Molinuevo JL, Valldeoriola F, Serradell M, Sanchez Valle R, Vilaseca I, Lomeña F, Vilas D et al Neurodegenerative disease status and post mortem pathology in idiopathic rapid eye movement sleep behaviour disorder : an observational cohort study. Lancet Neurol 12 5, Postuma RB, Gagnon JF, Vendette M, Desjardins C, Montplaisir JY Olfaction and color vision identify impending neurodegeneration in rapid eye movement sleepbehavior disorder. Ann Neurol 69 5, Sasai T, Matsuura M, Inoue Y Electroencephalographic findings related with mild cognitive impairment in idiopathic rapid eye movement sleep behavior disorder. Sleep 36 12, Nomura T, Inoue Y, Högl B, Uemura Y, Yasui K, Sasai T, Namba K, Nakashima K Comparison of the clinical features of rapid eye movement sleep behavior disorder in patients with Parkinson s disease and multiple system atrophy. Psychiatry Clin Neurosci 65 3, Nomura T, Inoue Y, Mitani H, Kawahara R, Miyake M, Nakashima K Visual hallucinations as REM sleep behavior disorders in patients with Parkinson s disease. Mov Disord 18 7, Liu RY, Zhou JN, van Heerikhuize J, Hofman MA, Swaab DF Decreased melatonin levels in postmortem cerebrospinal fluid in relation to aging, Alzheimer s disease, and apolipoprotein E epsilon4/4 genotype. J Clin Endocrinol Metab 84, Gehrman P, Marler M, Martin JL, Shochat T, Corey Bloom J, Ancoli Israel S The relationship between dementia severity and rest/activity circadian rhythms. Neuropsychiatr Dis Treat 2, Pascual B, Prieto E, Arbizu J, Marti Climent JM, Peñuelas I, Quincoces G, Zarauza R, Pappatà S, Masdeu JC Decreased carbon 11 flumazenil binding in early Alzheimer s disease. Brain 135 Pt 9, Obayashi K, Saeki K, Iwamoto J, Okamoto N, Tomioka K, Nezu S, Ikada Y, Kurumatani N Positive effect of daylight exposure on nocturnal urinary melatonin excretion in the elderly : a cross sectional analysis of the HEIJO KYO study. J Clin Endocrinol Metab 97 11, McCurry SM, Pike KC, Vitiello MV, Logsdon RG, Larson EB, Teri L Increasing walking and bright light exposure to improve sleep in community dwelling persons with Alzheimer s disease : results of a randomized, controlled trial. J Am Geriatr Soc 59 8, Kang JE, Lim MM, Bateman RJ, Lee JJ, Smyth LP, Cirrito JR, Fujiki N, Nishino S, Holtzman DM Amyloid beta dynamics are regulated by orexin and the sleep wake cycle. Science , Japanese Journal of Cognitive Neuroscience

6 17 Billioti de Gage S, Moride Y, Ducruet T, Kurth T, Verdoux H, Tournier M, Pariente A, Begaud B Benzodiazepine use and risk of Alzheimer s disease : case control study. BMJ 349, g Buratti L, Viticchi G, Falsetti L, Cagnetti C, Luzzi S, Bartolini M, Provinciali L, Silvestrini M Vascular impairment in Alzheimer s disease : the role of obstructive sleep apnea. J Alzheimers Dis 38 2, Beebe DW, Gozal D Obstructive sleep apnea and the prefrontal cortex : towards a comprehensive model linking nocturnal upper airway obstruction to daytime cognitive and behavioral deficits. J Sleep Res 11, Aoki K, Matsuo M, Takahashi M, Murakami J, Aoki Y, Aoki N, Mizumoto H, Namikawa A, Hara H, Miyagawa M et al Association of sleep disordered breathing with decreased cognitive function among patients with dementia. J Sleep Res 23 5, O Hara R, Schröder CM, Kraemer HC, Kryla N, Cao C, Miller E, Schatzberg AF, Yesavage JA, Murphy GM Jr Nocturnal sleep apnea/hypopnea is associated with lower memory performance in APOE epsilon4 carriers. Neurology 65, Relationship between sleep disorders and dementia Yuichi Inoue Department of Somnology, Tokyo Medical University 2 Japan Somnology Center, Neuropsychiatric Research Institute, Tokyo, Japan Key words : Alzheimer type dementia, Lewy body dementia, circadian rhythm, hypnotics, obstructive sleep apnea syndrome, REM sleep behavior disorder Sleep disorder is very common in population affected with dementia. Although fragmentation and shallowing of nocturnal sleep are relatively common among dementia disorders, some specific abnormalities are present in respective dementia disorders, i.e. patients with Alzheimer type dementia are likely to show decreased amplitude of circadian rhythm leading to irregular sleep awake schedule and patients with Lewy body dementia frequently have dysfunction of the control of muscle tonus during REM sleep which may cause dream enactment abnormal behavior in this sleep stage. For prevention of the appearance as well as the development of dementia, appropriate management of insomnia would be necessary. However, usage of hypnotics benzodiazepines and its agonists in demented population may become a risk factor for falls, nocturnal delirious behavior and enhancement of cognitive dysfunction in the affected population. In addition, we want to emphasize the necessity of proper management of obstructive sleep apnea syndrome, a common disorder in the elderly, would be desirable in individuals with dementia, since the disorder may become a risk factor for causing cerebrovascular events during sleep and for the aggravation of cognitive decline in this population. Vol. 17 No