BRAIN and NERVE－神経研究の進歩68巻7号

2016年07月発行

増大特集 認知症の危険因子と防御因子

認知症の早期徴候とリスク要因としての睡眠問題

著者： 三島和夫¹

所属機関： ¹国立精神・神経医療研究センター精神保健研究所・精神生理研究部

ページ範囲：P.779 - P.791

文献概要

アルツハイマー病をはじめとする認知症では，睡眠および覚醒系神経核や視交叉上核の器質障害により，極めて高い頻度で不眠，過眠，リズム障害，睡眠時呼吸障害，睡眠不足などの睡眠障害や概日リズム異常が併存する。これら睡眠障害は認知症患者の生活の質を低下させ，介護負担を増大させる。最近の研究により，睡眠障害は認知症の早期マーカーであり，かつ発症の危険因子となっていることも明らかになってきた。

参考文献

1)Benca RM, Obermeyer WH, Thisted RA, Gillin JC: Sleep and psychiatric disorders. A meta-analysis. Arch Gen Psychiatry 49: 651-668, 1992

2)Ohayon MM, Carskadon MA, Guilleminault C, Vitiello MV: Meta-analysis of quantitative sleep parameters from childhood to old age in healthy individuals: developing normative sleep values across the human lifespan. Sleep 27: 1255-1273, 2004

3)Bliwise DL: Normal aging. Kryger M, Roth T, Dement WC (eds): Principles and Practice of Sleep Medicine 4th edition. Elsevier Saunders, Philadelphia, 2005, pp24-38

4)van Coevorden A, Mockel J, Laurent E, Kerkhofs M, L'Hermite-Balériaux M, et al: Neuroendocrine rhythms and sleep in aging men. Am J Physiol 260: E651-E661, 1991

5)Kräuchi K, Cajochen C, Werth E, Wirz-Justice A: Warm feet promote the rapid onset of sleep. Nature 401: 36-37, 1999

6)Kräuchi K, Wirz-Justice A: Circadian rhythm of heat production, heart rate, and skin and core temperature under unmasking conditions in men. Am J Physiol 267: R819-R829, 1994

7)Lushington K, Dawson D, Lack L: Core body temperature is elevated during constant wakefulness in elderly poor sleepers. Sleep 23: 504-510, 2000

8)Horne JA, Shackell BS: Slow wave sleep elevations after body heating: proximity to sleep and effects of aspirin. Sleep 10: 383-392, 1987

9)Dorsey CM, Teicher MH, Cohen Zion M, Stefanovic L, Satlin A, et al: Core body temperature and sleep of older female insomniacs before and after passive body heating. Sleep 22: 891-898, 1999

10)Mishima Y, Hozumi S, Shimizu T, Hishikawa Y, Mishima K: Passive body heating ameliorates sleep disturbances in patients with vascular dementia without circadian phase-shifting. Am J Geriatr Psychiatry 13: 369-376, 2005

11)Echizenya M, Mishima K, Satoh K, Kusanagi H, Sekine A, et al: Heat loss, sleepiness, and impaired performance after diazepam administration in humans. Neuropsychopharmacology 28: 1198-1206, 2003

12)Echizenya M, Mishima K, Satoh K, Kusanagi H, Sekine A, et al: Enhanced heat loss and age-related hypersensitivity to diazepam. J Clin Psychopharmacol 24: 639-646, 2004

13)Gilbert SS, van den Heuvel CJ, Dawson D: Daytime melatonin and temazepam in young adult humans: equivalent effects on sleep latency and body temperatures. J Physiol 514: 905-914, 1999

14)Mishima K, Okawa M, Shimizu T, Hishikawa Y: Diminished melatonin secretion in the elderly caused by insufficient environmental illumination. J Clin Endocrinol Metab 86: 129-134, 2001

15)Schmid HA, Requintina PJ, Oxenkrug GF, Sturner W: Calcium, calcification, and melatonin biosynthesis in the human pineal gland: a postmortem study into age-related factors. J Pineal Res 16: 178-183, 1994

16)Vgontzas AN, Bixler EO, Wittman AM, Zachman K, Lin HM, et al: Middle-aged men show higher sensitivity of sleep to the arousing effects of corticotropin-releasing hormone than young men: clinical implications. J Clin Endocrinol Metab 86: 1489-1495, 2001

17)Mishima K, Okawa M, Hozumi S, Hishikawa Y: Supplementary administration of artificial bright light and melatonin as potent treatment for disorganized circadian rest-activity, and dysfunctional autonomic and neuroendocrine systems in institutionalized demented elderly persons. Chronobiol Int 17: 419-432, 2000

18)Mishima K, Tozawa T, Satoh K, Matsumoto Y, Hishikawa Y, et al: Melatonin secretion rhythm disorders in patients with senile dementia of Alzheimer's type with disturbed sleep-waking. Biol Psychiatry 45: 417-421, 1999

19)Davis FC, Viswanathan N: Stability of circadian timing with age in Syrian hamsters. Am J Physiol 275: R960-R968, 1998

20)Czeisler CA, Duffy JF, Shanahan TL, Brown EN, Mitchell JF, et al: Stability, precision, and near-24-hour period of the human circadian pacemaker. Science 284: 2177-2181, 1999

21)Klerman EB, Duffy JF, Dijk DJ, Czeisler CA: Circadian phase resetting in older people by ocular bright light exposure. J Investig Med 49: 30-40, 2001

22)Tozawa T, Mishima K, Satoh K, Echizenya M, Shimizu T, et al: Stability of sleep timing against the melatonin secretion rhythm with advancing age: clinical implications. J Clin Endocrinol Metab 88: 4689-4695, 2003

23)Duffy JF, Zeitzer JM, Rimmer DW, Klerman EB, Dijk DJ, et al: Peak of circadian melatonin rhythm occurs later within the sleep of older subjects. Am J Physiol Endocrinol Metab 282: E297-E303, 2002

24)Kawakami F, Okamura H, Tamada Y, Maebayashi Y, Fukui K, et al: Loss of day-night differences in VIP mRNA levels in the suprachiasmatic nucleus of aged rats. Neurosci Lett 222: 99-102, 1997

25)Wise PM, Cohen IR, Weiland NG, London ED: Aging alters the circadian rhythm of glucose utilization in the suprachiasmatic nucleus. Proc Natl Acad Sci U S A 85: 5305-5309, 1988

26)Satinoff E, Li H, Tcheng TK, Liu C, McArthur AJ, et al: Do the suprachiasmatic nuclei oscillate in old rats as they do in young ones? Am J Physiol 265: R1216-R1222, 1993

27)Benloucif S, Masana MI, Dubocovich ML: Light-induced phase shifts of circadian activity rhythms and immediate early gene expression in the suprachiasmatic nucleus are attenuated in old C3H/HeN mice. Brain Res 747: 34-42, 1997

28)Swaab DF, Fliers E, Partiman TS: The suprachiasmatic nucleus of the human brain in relation to sex, age and senile dementia. Brain Res 342: 37-44, 1985

29)Hofman MA, Fliers E, Goudsmit E, Swaab DF: Morphometric analysis of the suprachiasmatic and paraventricular nuclei in the human brain: sex differences and age-dependent changes. J Anat 160: 127-143, 1988

30)Saper CB, Fuller PM, Pedersen NP, Lu J, Scammell TE: Sleep state switching. Neuron 68: 1023-1042, 2010

31)Lim AS, Ellison BA, Wang JL, Yu L, Schneider JA, et al: Sleep is related to neuron numbers in the ventrolateral preoptic/intermediate nucleus in older adults with and without Alzheimer's disease. Brain 137: 2847-2861, 2014

32)Vitiello MV, Prinz PN: Alzheimer's disease. Sleep and sleep/wake patterns. Clin Geriatr Med 5: 289-299, 1989

33)Bliwise DL, Tinklenberg J, Yesavage JA, Davies H, Pursley AM, et al: REM latency in Alzheimer's disease. Biol Psychiatry 25: 320-328, 1989

34)Prinz PN, Vitiello MV: Dominant occipital (alpha) rhythm frequency in early stage Alzheimer's disease and depression. Electroencephalogr Clin Neurophysiol 73: 427-432, 1989

35)Hassainia F, Petit D, Nielsen T, Gauthier S, Montplaisir J: Quantitative EEG and statistical mapping of wakefulness and REM sleep in the evaluation of mild to moderate Alzheimer's disease. Eur Neurol 37: 219-224, 1997

36)Hita-Yañez E, Atienza M, Cantero JL: Polysomnographic and subjective sleep markers of mild cognitive impairment. Sleep 36: 1327-1334, 2013

37)Gillin JC, Sitaram N, Mendelson WB: Acetylcholine, sleep, and depression. Hum Neurobiol 1: 211-219, 1982

38)Siegel JM: Mechanisms of sleep control. J Clin Neurophysiol 7: 49-65, 1990

39)Vitiello MV, Bokan JA, Kukull WA, Muniz RL, Smallwood RG, et al: Rapid eye movement sleep measures of Alzheimer's-type dementia patients and optimally healthy aged individuals. Biol Psychiatry 19: 721-734, 1984

40)Prinz PN, Vitaliano PP, Vitiello MV, Bokan J, Raskind M, et al: Sleep, EEG and mental function changes in senile dementia of the Alzheimer's type. Neurobiol Aging 3: 361-370, 1982

41)Prinz PN, Peskind ER, Vitaliano PP, Raskind MA, Eisdorfer C, et al: Changes in the sleep and waking EEGs of nondemented and demented elderly subjects. J Am Geriatr Soc 30: 86-93, 1982

42)Markowska AL, Stone WS, Ingram DK, Reynolds J, Gold PE, et al: Individual differences in aging: behavioral and neurobiological correlates. Neurobiol Aging 10: 31-43, 1989

43)Stone WS, Altman HJ, Berman RF, Caldwell DF, Kilbey MM: Association of sleep parameters and memory in intact old rats and young rats with lesions in the nucleus basalis magnocellularis. Behav Neurosci 103: 755-764, 1989

44)Stone WS, Wenk GL, Olton DS, Gold PE: Poor blood glucose regulation predicts sleep and memory deficits in normal aged rats. J Gerontol 45: B169-B173, 1990

45)Furuta H, Yamamori S, Nakagawa K, Maeda Y, Ishiguro N, et al: Effects of lecithin and physostigmine on REM sleep in Alzheimer's disease. Racagni G, Brunello N, Fukuda T (eds): Proceedings of the 5th World Congress of Biological Psychiatry. Florence, Italy, June 9-14, 1991. Elsevier Science Publishing, Amsterdam, 1991, pp833-836

46)Schredl M, Weber B, Leins ML, Heuser I: Donepezil-induced REM sleep augmentation enhances memory performance in elderly, healthy persons. Exp Gerontol 36: 353-361, 2001

47)Riemann D, Gann H, Dressing H, Müller WE, Aldenhoff JB: Influence of the cholinesterase inhibitor galanthamine hydrobromide on normal sleep. Psychiatry Res 51: 253-267, 1994

48)Dunn NR, Pearce GL, Shakir SA: Adverse effects associated with the use of donepezil in general practice in England. J Psychopharmacol 14: 406-408, 2000

49)Rogers SL, Doody RS, Mohs RC, Friedhoff LT: Donepezil improves cognition and global function in Alzheimer disease: a 15-week, double-blind, placebo-controlled study. Donepezil Study Group. Arch Intern Med 158: 1021-1031, 1998

50)Stahl SM, Markowitz JS, Gutterman EM, Papadopoulos G: Co-use of donepezil and hypnotics among Alzheimer's disease patients living in the community. J Clin Psychiatry 64: 466-472, 2003

51)Yorston GA, Gray R: Hypnopompic hallucinations with donepezil. J Psychopharmacol 14: 303-304, 2000

52)Ross JS, Shua-Haim JR: Aricept-induced nightmares in Alzheimer's disease: 2 case reports［letter］. J Am Geriatr Soc 46: 119-120, 1998

53)Kondratova AA, Kondratov RV: The circadian clock and pathology of the ageing brain. Nat Rev Neurosci 13: 325-335, 2012

54)Haimov I, Laudon M, Zisapel N, Souroujon M, Nof D, et al: Sleep disorders and melatonin rhythms in elderly people. BMJ 309: 167, 1994

55)Hajak G, Rodenbeck A, Staedt J, Bandelow B, Huether G, et al: Nocturnal plasma melatonin levels in patients suffering from chronic primary insomnia. J Pineal Res 19: 116-122, 1995

56)Uchida K, Okamoto N, Ohara K, Morita Y: Daily rhythm of serum melatonin in patients with dementia of the degenerate type. Brain Res 717: 154-159, 1996

57)Dori D, Casale G, Solerte SB, Fioravanti M, Migliorati G, et al: Chrono-neuroendocrinological aspects of physiological aging and senile dementia. Chronobiologia 21: 121-126, 1994

58)Skene DJ, Vivien-Roels B, Sparks DL, Hunsaker JC, Pévet P, et al: Daily variation in the concentration of melatonin and 5-methoxytryptophol in the human pineal gland: effect of age and Alzheimer's disease. Brain Res 528: 170-174, 1990

59)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: 323-327, 1999

60)Tohgi H, Abe T, Takahashi S, Kimura M, Takahashi J, et al: Concentrations of serotonin and its related substances in the cerebrospinal fluid in patients with Alzheimer type dementia. Neurosci Lett 141: 9-12, 1992

61)Satlin A, Volicer L, Stopa EG, Harper D: Circadian locomotor activity and core-body temperature rhythms in Alzheimer's disease. Neurobiol Aging 16: 765-771, 1995

62)Harper DG, Volicer L, Stopa EG, McKee AC, Nitta M, et al: Disturbance of endogenous circadian rhythm in aging and Alzheimer disease. Am J Geriatr Psychiatry 13: 359-368, 2005

63)Stopa EG, Volicer L, Kuo-Leblanc V, Harper D, Lathi D, et al: Pathologic evaluation of the human suprachiasmatic nucleus in severe dementia. J Neuropathol Exp Neurol 58: 29-39, 1999

64)Zhou JN, Hofman MA, Swaab DF: VIP neurons in the human SCN in relation to sex, age, and Alzheimer's disease. Neurobiol Aging 16: 571-576, 1995

65)Liu RY, Zhou JN, Hoogendijk WJ, van Heerikhuize J, Kamphorst W, et al: Decreased vasopressin gene expression in the biological clock of Alzheimer disease patients with and without depression. J Neuropathol Exp Neurol 59: 314-322, 2000

66)Wu YH, Swaab DF: Disturbance and strategies for reactivation of the circadian rhythm system in aging and Alzheimer's disease. Sleep Med 8: 623-636, 2007

67)Ancoli-Israel S, Klauber MR, Jones DW, Kripke DF, Martin J, et al: Variations in circadian rhythms of activity, sleep, and light exposure related to dementia in nursing-home patients. Sleep 20: 18-23, 1997

68)Campbell SS, Kripke DF, Gillin JC, Hrubovcak JC: Exposure to light in healthy elderly subjects and Alzheimer's patients. Physiol Behav 42: 141-144, 1988

69)Bliwise DL, Carroll JS, Lee KA, Nekich JC, Dement WC: Sleep and “sundowning” in nursing home patients with dementia. Psychiatry Res 48: 277-292, 1993

70)Hinton DR, Sadun AA, Blanks JC, Miller CA: Optic-nerve degeneration in Alzheimer's disease. N Engl J Med 315: 485-487, 1986

71)Yaffe K, Falvey CM, Hoang T: Connections between sleep and cognition in older adults. Lancet Neurol 13: 1017-1028, 2014

72)Tate B, Aboody-Guterman KS, Morris AM, Walcott EC, Majocha RE, et al: Disruption of circadian regulation by brain grafts that overexpress Alzheimer beta/A4 amyloid. Proc Natl Acad Sci U S A 89: 7090-7094, 1992

73)Wisor JP, Edgar DM, Yesavage J, Ryan HS, McCormick CM, et al: Sleep and circadian abnormalities in a transgenic mouse model of Alzheimer's disease: a role for cholinergic transmission. Neuroscience 131: 375-385, 2005

74)Liu C, Gillette MU: Cholinergic regulation of the suprachiasmatic nucleus circadian rhythm via a muscarinic mechanism at night. J Neurosci 16: 744-751, 1996

75)Bina KG, Rusak B: Muscarinic receptors mediate carbachol-induced phase shifts of circadian activity rhythms in Syrian hamsters. Brain Res 743: 202-211, 1996

76)Kang JE, Lim MM, Bateman RJ, Lee JJ, Smyth LP, et al: Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle. Science 326: 1005-1007, 2009

77)Roh JH, Huang Y, Bero AW, Kasten T, Stewart FR, et al: Disruption of the sleep-wake cycle and diurnal fluctuation of β-amyloid in mice with Alzheimer's disease pathology. Sci Transl Med 4: 150ra122, 2012

78)Mander BA, Marks SM, Vogel JW, Rao V, Lu B, et al: β-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation. Nat Neurosci 18: 1051-1057, 2015

79)Tranah GJ, Blackwell T, Stone KL, Ancoli-Israel S, Paudel ML, et al: Circadian activity rhythms and risk of incident dementia and mild cognitive impairment in older women. Ann Neurol 70: 722-732, 2011

80)Schlosser Covell GE, Dhawan PS, Lee Iannotti JK, Hoffman-Snyder CR, Wellik KE, et al: Disrupted daytime activity and altered sleep-wake patterns may predict transition to mild cognitive impairment or dementia: a critically appraised topic. Neurologist 18: 426-429, 2012

81)Lim AS, Kowgier M, Yu L, Buchman AS, Bennett DA: Sleep Fragmentation and the Risk of Incident Alzheimer's Disease and Cognitive Decline in Older Persons. Sleep 36: 1027-1032, 2013

82)Tsapanou A, Gu Y, Manly J, Schupf N, Tang MX, et al: Daytime Sleepiness and Sleep Inadequacy as Risk Factors for Dementia. Dement Geriatr Cogn Dis Extra 5: 286-295, 2015

83)Lim AS, Saper CB: Sleep, circadian rhythms, and dementia. Ann Neurol 70: 677-679, 2011

84)Rongve A, Boeve BF, Aarsland D: Frequency and correlates of caregiver-reported sleep disturbances in a sample of persons with early dementia. J Am Geriatr Soc 58: 480-486, 2010

85)American Academy of Sleep Medicine(ed): The lnternational Classification of Sleep Disorders, Diagnostic and Coding Manual, second edition (ICSD-2). American Academy of Sleep Medicine, Westchester, 2005

86)Boeve BF, Silber MH, Saper CB, Ferman TJ, Dickson DW, et al: Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease. Brain 130: 2770-2788, 2007

87)Mahowald MW, Bornemann MA, Schenck CH: When and where do synucleinopathies begin? Neurology 75: 488-489, 2010

88)Braak H, Del Tredici K, Bratzke H, Hamm-Clement J, Sandmann-Keil D, et al: Staging of the intracerebral inclusion body pathology associated with idiopathic Parkinson's disease (preclinical and clinical stages). J Neurol 249 (Suppl 3): III/1-5, 2002

89)Luppi PH, Clement O, Sapin E, Gervasoni D, Peyron C, et al: The neuronal network responsible for paradoxical sleep and its dysfunctions causing narcolepsy and rapid eye movement (REM) behavior disorder. Sleep Med Rev 15: 153-163, 2011

90)Décary A, Rouleau I, Montplaisir J: Cognitive deficits associated with sleep apnea syndrome: a proposed neuropsychological test battery. Sleep 23: 369-381, 2000

91)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: 1-16, 2002

92)Lavie L: Oxidative stress in obstructive sleep apnea and intermittent hypoxia—revisited—the bad ugly and good: implications to the heart and brain. Sleep Med Rev 20: 27-45, 2015

93)Yaffe K, Laffan AM, Harrison SL, Redline S, Spira AP, et al: Sleep-disordered breathing, hypoxia, and risk of mild cognitive impairment and dementia in older women. JAMA 306: 613-619, 2011

94)Elie M, Cole MG, Primeau FJ, Bellavance F: Delirium risk factors in elderly hospitalized patients. J Gen Intern Med 13: 204-212, 1998

95)Fick DM, Agostini JV, Inouye SK: Delirium superimposed on dementia: a systematic review. J Am Geriatr Soc 50: 1723-1732, 2002

96)Lerner AJ, Hedera P, Koss E, Stuckey J, Friedland RP: Delirium in Alzheimer disease. Alzheimer Dis Assoc Disord 11: 16-20, 1997

97)Robertsson B, Blennow K, Gottfries CG, Wallin A: Delirium in dementia. Int J Geriatr Psychiatry 13: 49-56, 1998

98)Bedrosian TA, Nelson RJ: Sundowning syndrome in aging and dementia: research in mouse models. Exp Neurol 243: 67-73, 2013

99)Cohen-Mansfield J, Werner P, Freedman L: Sleep and agitation in agitated nursing home residents: an observational study. Sleep 18: 674-680, 1995

100)Evans LK: Sundown syndrome in institutionalized elderly. J Am Geriatr Soc 35: 101-108, 1987

101)Martin J, Marler M, Shochat T, Ancoli-Israel S: Circadian rhythms of agitation in institutionalized patients with Alzheimer's disease. Chronobiol Int 17: 405-418, 2000

102)Volicer L, Harper DG, Manning BC, Goldstein R, Satlin A: Sundowning and circadian rhythms in Alzheimer's disease. Am J Psychiatry 158: 704-711, 2001