4 [11] D. G. Harper, E. G. Stopa, A. C. McKee, A. Satlin, D. Fish, and L. Volicer, “Dementia severity and Lewy bodies aﬀect circadian rhythms in Alzheimer disease,” Neurobiology of Aging, vol. 25, no. 6, pp. 771–781, 2004. [12] D. G. Harper, E. G. Stopa, A. C. McKee et al., “Diﬀerential circadian rhythm disturbances in men with Alzheimer disease and frontotemporal degeneration,” Archives of General Psychi- atry, vol. 58, no. 4, pp. 353–360, 2001. [13] D. G. Harper, L. Volicer, E. G. Stopa, A. C. McKee, M. Nitta, and A. Satlin, “Disturbance of endogenous circadian rhythm in aging and Alzheimer disease,” American Journal of Geriatric Psychiatry, vol. 13, no. 5, pp. 359–368, 2005. [14] J. A. Yesavage, A. Noda, B. Hernandez et al., “Circadian clock gene polymorphisms and sleep-wake disturbance in Alzheimer disease,” American Journal of Geriatric Psychiatry, vol. 19, no. 7, pp. 635–643, 2011. [15] A. N. Coogan and J. Thome, “Chronotherapeutics and psychiatry: setting the clock to relieve the symptoms,” World Journal of Biological Psychiatry, vol. 12, supplement 1, pp. 40– 43, 2011. [16] P. Franken and D. J. Dijk, “Circadian clock genes and sleep homeostasis,” European Journal of Neuroscience, vol. 29, no. 9, pp. 1820–1829, 2009. [17] A. N. Coogan, M. M. Papachatzaki, C. Clemens et al., “Haloperidol alters circadian clock gene product expression in the mouse brain,” World Journal of Biological Psychiatry. In press. [18] K. Wulﬀ, S. Gatti, J. G. Wettstein, and R. G. Foster, “Sleep and circadian rhythm disruption in psychiatric and neurodegener- ative disease,” Nature Reviews Neuroscience, vol. 11, no. 8, pp. 589–599, 2010. [19] D. L. Bliwise, N. D. Mercaldo, A. Y. Avidan, B. F. Boeve, S. A. Greer, and W. A. Kukull, “Sleep disturbance in dementia with Lewy bodies and Alzheimer’s disease: amulticenter analysis,” Dementia and Geriatric Cognitive Disorders, vol. 31, no. 3, pp. 239–246, 2011. [20] Y. Song, G. A. Dowling, M. I. Wallhagen, K. A. Lee, and W. J. Strawbridge, “Sleep in older adults with Alzheimer’s disease,” Journal of Neuroscience Nursing, vol. 42, no. 4, pp. 190–198, 2010. [21] E. Mulin, J. M. Zeitzer, L. Friedman et al., “Relationship between apathy and sleep disturbance in mild and mod- erate Alzheimer’s disease: an actigraphic study,” Journal of Alzheimer’s Disease, vol. 25, no. 1, pp. 85–91, 2011. [22] J. Creese, M. Be´dard, K. Brazil, and L. Chambers, “Sleep dis- turbances in spousal caregivers of individuals with Alzheimer’s disease,” International Psychogeriatrics, vol. 20, no. 1, pp. 149– 161, 2008. [23] C. F. Hatﬁeld, J. Herbert, E. J. W. van Someren, J. R. Hodges, and M. H. Hastings, “Disrupted daily activity/rest cycles in relation to daily cortisol rhythms of home-dwelling patients with early Alzheimer’s dementia,” Brain, vol. 127, no. 5, pp. 1061–1074, 2004. [24] K. Hu, E. J. W. van Someren, S. A. Shea, and F. A. J. L. Scheer, “Reduction of scale invariance of activity ﬂuctuations with aging and Alzheimer’s disease: involvement of the circadian pacemaker,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 8, pp. 2490–2494, 2009. [25] E. G. Stopa, L. Volicer, V. Kuo-Leblanc et al., “Pathologic evaluation of the human suprachiasmatic nucleus in severe dementia,” Journal of Neuropathology and Experimental Neu- rology, vol. 58, no. 1, pp. 29–39, 1999. Journal of Aging Research [26] J. N. Zhou, M. A. Hofman, and D. F. Swaab, “VIP neurons in the human SCN in relation to sex, age, and Alzheimer’s disease,” Neurobiology of Aging, vol. 16, no. 4, pp. 571–576, 1995. [27] D. Bachman and P. Rabins, “‘Sundowning’ and other tempo- rally associated agitation states in dementia patients,” Annual Review of Medicine, vol. 57, pp. 499–511, 2006. [28] B. Tate, K. S. Aboody-Guterman, A. M. Morris, E. C. Walcott, R. E. Majocha, and C. A. Marotta, “Disruption of circadian regulation by brain grafts that overexpress Alzheimer beta/A4 amyloid,” Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 15, pp. 7090–7094, 1992. [29] R. Sterniczuk, R. H. Dyck, F. M. Laferla, and M. C. Antle, “Characterization of the 3xTg-AD mouse model of Alzheimer’s disease: part 1. Circadian changes,” Brain Research, vol. 1348, pp. 139–148, 2010. [30] A. W. Bero, P. Yan, J. H. Roh et al., “Neuronal activity regulates the regional vulnerability to amyloid-b deposition,” Nature Neuroscience, vol. 14, pp. 750–756, 2011. [31] D. Craig, D. J. Hart, and A. P. Passmore, “Genetically increased risk of sleep disruption in Alzheimer’s disease,” Sleep, vol. 29, no. 8, pp. 1003–1007, 2006. [32] C. Kissling, W. Retz, S. Wiemann et al., “A polymorphism at the 3 -untranslated region of the CLOCK gene is associated with adult attention-deﬁcit hyperactivity disorder,” American Journal of Medical Genetics Part B, vol. 147, no. 3, pp. 333–338, 2008. [33] N. Cermakian, E. W. Lamont, P. Boudreau, and D. B. Boivin, “Circadian clock gene expression in brain regions of Alzheimer’s disease patients and control subjects,” Journal of Biological Rhythms, vol. 26, no. 2, pp. 160–170, 2011. [34] A. L. Beynon, J. Thome, and A. N. Coogan, “Age and time of day inﬂuences on the expression of transform- ing growth factor-beta and phosphorylated SMAD3 in the mouse suprachiasmatic and paraventricular nuclei,” NeuroIm- munoModulation, vol. 16, no. 6, pp. 392–399, 2009. [35] R. Y. Liu, J. N. Zhou, W. J. G. Hoogendijk et al., “Decreased vasopressin gene expression in the biological clock of Alzheimer disease patients with and without depression,” Journal of Neuropathology and Experimental Neurology, vol. 59, no. 4, pp. 314–322, 2000. [36] A. M. Rosenwasser, “Circadian clock genes: non-circadian roles in sleep, addiction, and psychiatric disorders?” Neuro- science and Biobehavioral Reviews, vol. 34, no. 8, pp. 1249– 1255, 2010. [37] E. I. S. Most, P. Scheltens, and E. J. W. van Someren, “Prevention of depression and sleep disturbances in elderly with memory-problems by activation of the biological clock with light—a randomized clinical trial,” Trials, vol. 11, article 19, 2010. [38] R. F. Riemersma-van der Lek, D. F. Swaab, J. Twisk, E. M. Hol, W. J. G. Hoogendijk, and E. J. W. Van Someren, “Eﬀect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities: a random- ized controlled trial,” JAMA—Journal of the American Medical Association, vol. 299, no. 22, pp. 2642–2655, 2008. [39] A. Wirz-Justice, E. Werth, E. Savaskan, V. Knoblauch, P. F. Gasio, and F. M u¨ller-Spahn, “Haloperidol disrupts, clozapine reinstates the circadian rest-activity cycle in a patient with early-onset Alzheimer disease,” Alzheimer Disease and Associ- ated Disorders, vol. 14, no. 4, pp. 212–215, 2000.