Table 1.

Common sleep and wake characteristics of neurodegenerative diseases.

	Brain areas, neurons damaged	General	Putative predictive factors	Circadian	NREM	REM	Wake	Therapeutic interventions
Age-associated degeneration	Basal forebrain, LC, cerebral cortex; DA, orexin1,2,3; cholinergic receptors4	Phase advanced, fragmented sleep and wake, EDS5,6	Disrupted melatonin system7,8	Altered circadian rest-activity rhythms9,10; altered peripheral resynchronization11	Decreased SWS12	Decreased REM12,13,14	Fragmented wake, increased napping, EDS6,10	Phototherapy15
Alzheimer’s disease	Basal forebrain; cerebral cortex; ACh16,17	Decreased total sleep time18	REM density13	Disrupted core-body temperature rhythm19; disrupted melatonin system20	Decreased SWS18; decreased sleep spindles21	Decreased REM13; increased iNOS during REM22	Fragmented wake, increased napping23	Phototherapy, exercise24; orexin/hypocretin antagonist in mice25
Parkinson’s disease	Substantia nigra pars compacta; DA26; Orexin27	Sleep fragmentation28; RBD29	REM behavior disorder29,30	Decreased diurnal variation of cortisol31; altered circadian rest-activity rhythms9	Decreased SWS, decreased sleep spindles32	RBD29; intrusion of REM into NREM33	EDS34	Phototherapy35
Huntington’s disease	Basal ganglia; DA36,37	Fragmented sleep and wake, decreased REM38	Increased sleep spindles32	Disruption associated with increased nocturnal activity39; delayed sleep phase42	Chorea during stage 140; increased stage 138; increased sleep spindles32,41	Decreased REM, increased latency to REM38	Wake is impaired but reports that are different from age-matched controls are not consistent 41,42	Food entrainment43; alprazolam to restore circadian rhythms slows cognitive decline44
Amyotrophic lateral sclerosis	Motor neurons of the motor cortex, brainstem, and spinal cord; progressive degeneration of 5HT neurons contributes to decreased motoneuron activity45	SDB, insomnia46,47; reduced quality of sleep correlated with the severity of the disease48; degeneration leads to muscle weakness and SDB46	SDB (predictive of early respiratory failure)46	Disrupted cortisol circadian rhythm49	Decreased SWS48	Decreased and fragmented REM sleep48; sleep disordered breathing46	EDS48,50	CPAP50, 51; BiPAP52; melatonin supplementation53

DA, dopamine; iNOS, inducible nitric oxide synthase.

¹Sturrock and Rao (1985), ²Zhang et al. (2005), ³Naidoo et al. (2011), ⁴van der Zee et al. (1991), ⁵Carskadon et al. (1982), ⁶Foley et al. (2007), ⁷Magri et al. (1997), ⁸Touitou (1995), ⁹Whitehead et al. (2008), ¹⁰Huang et al. (2002), ¹¹Davidson et al. (2008), ¹²Turek et al. (1995), ¹³Dykierek et al. (1998), ¹⁴Feinberg et al. (1967), ¹⁵Myers and Badia (1995), ¹⁶Brun and Englund (1981), ¹⁷Teipel et al. (2005), ¹⁸Vitiello et al. (1991), ¹⁹Satlin et al. (1995), ²⁰Wu et al. (2007), ²¹Montplaisir et al. (1995), ²²Tseng et al. (2010), ²³Bonanni et al. (2005), ²⁴Wu and Swaab (2007), ²⁵Kang et al. (2009), ²⁶Braak et al. (2004), ²⁷Thannickal et al. (2007), ²⁸Factor et al. (1990), ²⁹Schenck et al. (1996), ³⁰Postuma and Montplaisir (2009), ³¹Hartmann et al. (1997), ³²Emser et al. (1988), ³³Mouret (1975), ³⁴Diederich et al. (2005), ³⁵Willis and Turner (2007), ³⁶Vonsattel et al. (1985), ³⁷Kremer et al. (1991), ³⁸Arnulf et al. (2008), ³⁹Morton et al. (2005), ⁴⁰Fish et al. (1991), ⁴¹Wiegand et al. (1991), ⁴²Aziz et al. (2010), ⁴³Maywood et al. (2010), ⁴⁴Pallier et al. (2007), ⁴⁵Sandyk (2006), ⁴⁶Kimura et al. (1999), ⁴⁷Atalaia et al. (2007), ⁴⁸Lo Coco et al. (2011), ⁴⁹Patacchioli et al. (2003), ⁵⁰Barthlen and Lange (2000), ⁵¹Howard et al. (1989), ⁵²David et al. (1997), ⁵³Weishaupt et al. (2006).