Skip to main content Accessibility help
×
Hostname: page-component-586b7cd67f-t7fkt Total loading time: 0 Render date: 2024-11-23T03:10:29.276Z Has data issue: false hasContentIssue false

7 - Circadian Rhythm Disruption in Aging and Alzheimer’s Disease

Published online by Cambridge University Press:  07 October 2023

Laura K. Fonken
Affiliation:
University of Texas, Austin
Randy J. Nelson
Affiliation:
West Virginia University
Get access

Summary

Circadian rhythms exhibit many alterations during the normal aging process and more severe disruptions are evident in age-related neurological conditions such as Alzheimer’s disease (AD). Indeed, evidence suggests that circadian rhythm alterations increase susceptibility to AD and conversely that the progressive neuropathological features of AD such as amyloid-beta accumulation further exacerbate circadian rhythm disruption. Impairments in neural function in the master circadian pacemaker in the hypothalamic suprachiasmatic nucleus underlie age- and AD-related alterations in circadian rhythms. Deficits in expression of the clock genes constituting the molecular pathways controlling circadian rhythms also contribute to circadian rhythm impairments and neurodegeneration in senescence and AD. This chapter describes the mechanisms underlying age- and AD-related alterations in circadian rhythms as well as their possible causes and potential strategies for their amelioration.

Type
Chapter
Information
Biological Implications of Circadian Disruption
A Modern Health Challenge
, pp. 165 - 182
Publisher: Cambridge University Press
Print publication year: 2023

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abrahamson, E. E., & Moore, R. Y. (2001). Suprachiasmatic nucleus in the mouse: Retinal innervation, intrinsic organization and efferent projections. Brain Res, 916, 172191.CrossRefGoogle ScholarPubMed
Albers, H. E., Walton, J. C., Gamble, K. L., McNeill, J. K., & Hummer, D. L. (2017). The dynamics of GABA signaling: Revelation from the circadian pacemaker in the suprachiasmatic nucleus. Front Neuroendocrinol, 44, 3582.CrossRefGoogle ScholarPubMed
Albus, H., Vansteensel, M. J., Michel, S., Block, G. D., & Meijer, J. H. (2005). A GABAergic mechanism is necessary for coupling dissociable ventral and dorsal regional oscillators within the circadian clock. Curr Biol, 15(10), 886893.Google Scholar
Aton, S. J., Colwell, C. S., Harmar, A. J., Waschek, J., & Herzog, E. D. (2005). Vasoactive intestinal polypeptide mediates circadian rhythmicity and synchrony in mammalian clock neurons. Nat Neurosci, 8, 476.Google Scholar
Aujard, F., Cayetanot, F., Bentivoglio, M., & Perret, M. (2006). Age-related effects on the biological clock and its behavioral output in a primate. Chronobiol Int, 23(1), 451460.CrossRefGoogle ScholarPubMed
Benloucif, S., Green, K., L’Hermite-Baleriaux, M., Weintraub, S., Wolfe, L. F., & Zee, P. C. (2006). Responsiveness of the aging circadian clock to light. Neurobiol Aging, 27, 18701879.Google Scholar
Benloucif, S., Masana, M. I., & Dubocovich, M. L. (1997). 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(1), 3442.Google Scholar
Bliwise, D. L. (1993). Sleep in normal aging and dementia. Sleep, 161, 4081.Google Scholar
Bliwise, D. L. (2004). Sleep disorders in Alzheimer’s disease and other dementias. Clin Cornerstone, 6(Suppl), S16S28.Google Scholar
Bliwise, D. L., Hughes, M., McMahon, P. M., & Kutner, N. (1995). Observed sleep/wakefulness and severity of dementia in an Alzheimer’s disease special care unit. J Gerontol, 50A, M303M306.Google Scholar
Bliwise, D. L., Mercaldo, N. D., Boever, B. F., Greer, S. A., & Kukull, W. A. (2011). Sleep disturbance in dementia with Lewy bodies and Alzheimer’s disease: A multicenter analysis. Dement Geriatr Cogn Disord, 31, 239246.Google Scholar
Brancaccio, M., Wolfes, A. C., & Ness, N. (2021). Astrocyte circadian timekeeping in brain health and neurodegeneration. Adv Exp Med Biol, 1344, 87110.Google Scholar
Buijs, R. M., La Fleur, S. E., Wortel, J., van Heyningen, C., Zuiddam, L., Mettenleiter, T. C., Kalsbeek, A., Nagai, K., & Niijima, A. (2003). The suprachiasmatic nucleus balances sympathetic and parasympathetic output to peripheral organs through separate preautonomic neurons. J Comp Neurol, 464, 3648.CrossRefGoogle ScholarPubMed
Cain, S. W., Karatsoreos, I., Gautam, N., Konar, Y., Funk, D., McDonald, R. J., & Ralph, M. R. (2004). Blunted cortisol rhythm is associated with learning impairment in aged hamsters. Physiol Behav, 82, 339344.CrossRefGoogle ScholarPubMed
Cermakian, N., Lamont, E. W., Boudreau, P., & Boivin, D. B. (2011). Circadian clock gene expression in brain regions of Alzheimer’s disease patients and control subjects. J Biol Rhythms, 26(2), 160170.CrossRefGoogle ScholarPubMed
Chauhan, R., Chen, K.-F., Kent, B. A., & Crowther, D. C. (2017). Central and peripheral circadian clocks and their role in Alzheimer’s disease. Dis Model Mech, 10, 11871199.Google Scholar
Chen, C.-Y., Logan, R.-W., Ma, T., Lewis, D. A., Tseng, G. C., Sibille, E., & McClung, C. A. (2016). Effects of aging on circadian patterns of gene expression in the human prefrontal cortex. Proc Natl Acad Sci USA, 113(1), 206211.Google Scholar
Colwell, C. S., Michel, S., Itri, J., Rodriguez, W., & Tam, J. (2003). Disrupted circadian rhythms in VIP- and PHI-deficient mice. Am J Physiol, 285, R939.Google ScholarPubMed
Dalm, S., Enthoven, L., Meijer, O. C., van der Mark, M. H., Karssen, A. M., De Kloet, E. R., & Oitzl, M. S. (2005). Age-related changes in hypothalamic-pituitary-adrenal axis activity of male C57BL/6J mice. Neuroendocrinology, 81(6), 372380.CrossRefGoogle ScholarPubMed
Dardente, H., Poirel, V. J., Klosen, P., Pevet, P., & Masson-Pevet, M. (2002). Per and neuropeptide expression in the rat suprachiasmatic nuclei: Compartmentalization and differential cellular induction by light. Brain Res, 958, 261271.Google Scholar
Davidson, A. J., Yamazaki, S., Arble, D. M., Menaker, M., & Block, G. D. (2008). Resetting of central and peripheral circadian oscillators in aged rats. Neurobiol Aging, 29(3), 471477.Google Scholar
Deng, X.-H., Bertini, G., Palomba, M., Xu, Y.-Z., Bonaconsa, M., Nygard, M., & Bentivoglio, M. (2010). Glial transcripts and immune-challenged glia in the suprachiasmatic nucleus of young and aged mice. Chronobiol Int, 27, 742767.Google Scholar
Di Benedetto, S., Muller, L., Wenger, E., Duzel, S., & Pawelec, G. (2017). Contribution of neuroinflammation and immunity to brain aging and the mitigating effects of physical and cognitive interventions. Neurosci Biobehav Rev, 75, 114128.Google Scholar
Duncan, M. J. (2007). Aging of the mammalian circadian timing system: Changes in the central pacemaker and its regulation by photic and nonphotic signals. Neuroembryol Aging, 4, 85101.Google Scholar
Duncan, M. J. (2020). Interacting influences of aging and Alzheimer’s disease on circadian rhythms. Eur J Neurosci, 51(1), 310325.CrossRefGoogle ScholarPubMed
Duncan, M. J., Guerriero, L. E., Kohler, K., Beechem, L. E., Gillis, B. D., Salisbury, F., Wessel, C., Wang, J., Sunderam, S., Bachstetter, A. D., O’Hara, B. F., & Murphy, M. P. (2022). Chronic fragmentation of the daily sleep-wake rhythm increases amyloid-beta levels and neuroinflammation in the 3xTg-AD mouse model of Alzheimer’s disease. Neuroscience, 481, 111122.Google Scholar
Duncan, M. J., Hill, S. A., & Herron, J. M. (2001). Aging selectively suppresses vasoactive intestinal peptide messenger RNA expression in the suprachiasmatic nucleus. Mol Brain Res, 87, 196203.Google Scholar
Duncan, M. J., Prochot, J. R., Cook, D. H., Smith, J. T., & Franklin, K. M. (2013). Influence of aging on Bmal1 and Per2 expression in extra-SCN oscillators in hamster brain. Brain Res, 1491, 4453.Google Scholar
Evans, P. D., Fredhoi, C., Loveday, C., Hucklebridge, F., Aitchison, E., Forte, D., & Clow, A. (2011). The diurnal cortisol cycle and cognitive performance in the healthy old. Int J Psychophysiol, 79(3), 371377.Google Scholar
Farajnia, S., Michel, S., Deboer, T., van der Leest, H. T., Houben, T., Rohling, J. H. T., Ramkisoensing, A., Yasenkov, R., & Meijer, J. H. (2012). Evidence for neuronal desynchrony in the aged suprachiasmatic nucleus clock. J Neurosci, 32, 58915899.CrossRefGoogle ScholarPubMed
Ferrari, E., Cravello, L., Muzzoni, B., Casarotti, D., Paltro, M., Solerte, S. B., Fioravanti, M., Cuzzoni, G., Pontiggia, B., & Magri, F. (2001). Age-related changes of the hypothalamic-pituitary-adrenal axis: Pathophysiological correlates. Eur J Endocrinol, 144, 319329.CrossRefGoogle ScholarPubMed
Fonken, L. K., Kitt, M. M., Gaudet, A. D., Barrientos, R. M., Watkins, L. R., & Maier, S. F. (2016). Diminished circadian rhythms in hippocampal microglia may contribute to age-related neuroinflammatory sensitization. Neurobiol Aging, 47, 102112.CrossRefGoogle ScholarPubMed
Franken, P., & Dijk, D.-J. (2009). Circadian clock genes and sleep homeostasis. Eur J Neurosci, 29, 18201829.Google Scholar
Gehrman, P., Marler, M., Martin, J. L., Shochat, T., Corey-Bloom, J., & Ancoli-Israel, S. (2004). The timing of activity rhythms in patients with dementia is related to survival. J Gerontol A Biol Sci Med Sci, 59(10), 10501055.Google Scholar
Gilhooley, M. J., Pinnock, S. B., & Herbert, J. (2011). Rhythmic expression of per1 in the dentate gyrus is suppressed by corticosterone: Implications for neurogenesis. Neurosci Lett, 489, 177181.Google Scholar
Gilpin, H., Whitcomb, D., & Cho, K. (2008). Atypical evening cortisol profile induces visual recognition memory deficit in healthy human subjects. Mol Brain, 1, 4.CrossRefGoogle ScholarPubMed
Guarnieri, B., Adorni, F., Musicco, M., Appollonio, I., Bonanni, E., Caffarra, P., Caltagirone, C., Cerroni, G., Concari, L., Cosentino, F. I., Ferrara, S., Fermi, S., Ferri, R., Gelosa, G., Lombardi, G., Mazzei, D., Mearelli, S., Morrone, E., Murri, L., … Sorbi, S. (2012). Prevalence of sleep disturbances in mild cognitive impairment and dementing disorders: A multicenter Italian clinical cross-sectional study on 431 patients. Dement Geriatr Cogn Dis, 33(1), 5058.Google Scholar
Harney, J. P., Scarbrough, K., Rosewell, K. L., & Wise, P. M. (1996). In vivo antisense antagonism of vasoactive intestinal peptide in the suprachiasmatic nuclei causes aging-like changes in the estradiol-induced luteinizing hormone and prolactin surges. Endocrinology, 137(9), 36963701.Google Scholar
Harper, D. G., Stopa, E. G., Kuo-LeBlanc, V., McKee, A. C., Asayama, K., Volicer, L., Kowall, N., & Satlin, A. (2008). Dorsomedial SCN neuronal subpopulations subserve different functions in human dementia. Brain, 131, 16091617.CrossRefGoogle ScholarPubMed
Harper, D. G., Volicer, L., Stopa, E. G., McKee, A. C., Nitta, M., & Satlin, A. (2005). Disturbance of endogenous circadian rhythm in aging and Alzheimer disease. Am J Geriatric Psych, 13(5), 359368.CrossRefGoogle ScholarPubMed
Heaney, J. L. J., Phillips, A. C., & Carroll, D. (2012). Ageing, physical function, and the diurnal rhythms of cortisol and dehydroepiandrosterone. Psychoneuroendocrinology, 37(3), 341349.Google Scholar
Hofman, M. A., & Swaab, D. F. (1993). Diurnal and seasonal rhythms of neuronal activity in the suprachiasmatic nucleus of humans. J Biol Rhythms, 8, 283295.Google Scholar
Jilg, A., Lesny, S., Peruzki, N., Schwegler, H., Selbach, O., Dehghani, F., & Stehle, J. H. (2010). Temporal dynamics of mouse hippocampal clock gene expression support memory processing. Hippocampus, 20, 377388.CrossRefGoogle ScholarPubMed
Jones, J. R., Chaturvedi, S., Granados-Fuentes, D., & Herzog, E. D. (2021). Circadian neurons in the paraventricular nucleus entrain and sustain daily rhythms in glucocorticoids. Nat Commun, 12(1), 5763.Google Scholar
Juda, M., Liu-Ambrose, T., Feldman, F., Suvagau, C., & Mistlberger, R. E. (2020). Light in the senior home: Effects of dynamic and individual light exposure on sleep, cognition, and well-being. Clocks Sleep, 2(4), 557576.CrossRefGoogle ScholarPubMed
Kallo, I., Kalamatianos, T., Piggins, H. D., & Coen, C. W. (2004). Ageing and the diurnal expression of mRNAs for vasoactive intestinal peptide and for VPAC2 and PAC1 receptors in the suprachiasmatic nucleus of male rats. J Neuroendocrinol, 16, 758766.Google Scholar
Kang, J. E., Lim, M. M., Bateman, R. J., Lee, J. J., Smyth, L. P., Cirrito, J. R., Jufuki, N., Nishino, S., & Holtzman, D. M. (2009). Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle. Science, 326(5955), 10051007.CrossRefGoogle ScholarPubMed
Katzman, R. (1986). Alzheimer’s disease. N Engl J Med, 314(15), 964973.Google Scholar
Kondratov, R., Kondratova, A. A., Gorbacheva, V. Y., Vykhovanets, O. V., & Antoch, M. P. (2006). Early aging and age-related pathologies in mice deficient in BMAL1, the core component of the circadian clock. Genes Dev, 20, 18681878.Google Scholar
Krajnak, K., Kashon, M. L., Rosewell, K. L., & Wise, P. M. (1998). Aging alters the rhythmic expression of vasoactive intestinal polypeptide mRNA but not arginine vasopressin mRNA in the suprachiasmatic nuclei of female rats. J Neurosci, 18(12), 47674774.Google Scholar
Kress, G. J., Liao, F., Dimitry, J., Cedeno, M. R., FitzGerald, G. A., Holtzman, D. M., & Musiek, E. S. (2018). Regulation of amyloid-beta dynamics and pathology by the circadian clock. J Exp Med, 215, 10591068.Google Scholar
Kwak, Y., Lundkvist, G. B., Brask, J., Davidson, M., Menaker, M., Kristensson, K., & Block, G. D. (2008). Interferon-gamma alters electrical activity and clock gene expression in suprachiasmatic nucleus neurons. J Biol Rhythms, 23, 150159.CrossRefGoogle ScholarPubMed
Leise, T. L., Harrington, M. E., Molyneux, P. C., Song, I., Queenan, H., Zimmerman, E., Lall, G. S., & Biello, S. (2013). Voluntary exercise can strengthen the circadian system in aged mice. Age, 35(6), 21372152.CrossRefGoogle ScholarPubMed
Li, H., & Satinoff, E. (1998). Fetal tissue containing the suprachiasmatic nucleus restores multiple circadian rhythms in old rats. Am J Physiol Regul Integr Comp Physiol, 275(6), R1735R1744.Google Scholar
Li, P., Gao, L., Gaba, A., Yu, L., Cui, L., Fan, W., Lim, A. S. P., Bennett, D. A., Buchman, A. S., & Hu, K. (2020). Circadian disturbances in Alzheimer’s disease progression: A prospective observational cohort study of community-based older adults. Lancet Healthy Longev, 1(3), e96e105.CrossRefGoogle ScholarPubMed
Lim, A. S. P., Kowigier, M., Yu, L., Buchman, A. S., & Bennett, D. A. (2013). Sleep fragmentation and the risk of incident Alzheimer’s Disease and cognitive decline in older persons. Sleep, 36, 10271032.Google Scholar
Liu, R. Y., Zhou, J. N., Hoogendijk, W. J., van Heerikhuize, J., Kamphorst, W., Unmehopa, U. A., Hofman, M. A., & Swaab, D. F. (2000). Decreased vasopressin gene expression in the biological clock of Alzheimer disease patients with and without depression. J Neuropathol Exp Neurol, 59(4), 314322.Google Scholar
Loh, D. H., Abad, C., Colwell, C. S., & Waschek, J. A. (2008). Vasoactive intestinal peptide is critical for circadian regulation of glucocorticoids. Neuroendocrinology, 88, 246255.Google Scholar
van Maanen, A., Meijer, A. M., van der Heijden, K. B., & Oort, F. J. (2016). The effects of light therapy on sleep problems: A systematic review and meta-analysis. Sleep Med Rev, 29, 5262.Google Scholar
Mishima, K., Tozawa, T., Satoh, K., Matsumoto, Y., Hishikawa, Y., & Okawa, M. (1999). Melatonin secretion rhythm disorders in patients with senile dementia of Alzheimer’s type with disturbed sleep-waking. Biol Psychiatry, 45(4), 417421.Google Scholar
Musiek, E. S., Bhimansani, M., Zangrilli, M. A., Morris, J. C., Holtzman, D. M., & Ju, Y.-E. S. (2018). Circadian rest-activity pattern changes in aging and preclinical Alzheimer disease. JAMA Neurol, 75, 582590.Google Scholar
Musiek, E. S., & Holtzman, D. M. (2016). Mechanisms linking circadian clocks, sleep, and neurodegeneration. Science, 354(6315), 10041008.Google Scholar
Musiek, E. S., Lim, M. M., Yang, G., Bauer, A. Q., Qi, L., Lee, Y., Roh, J. H., Ortiz-Gonzalez, X., Dearborn, J. T., Culver, J. P., Herzog, E. D., Hogenesch, J. B., Wozniak, D. F., Dikranian, K., Giasson, B. I., Weaver, D. R., Holtzman, D. M., & FitzGerald, G. A. (2013). Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration. J Clin Invest, 123, 53985400.Google Scholar
Nakamura, T. J., Nakamura, W., Kudo, T., Cutler, T., Colwell, C. S., & Block, G. D. (2011). Age-related decline in circadian output. J Neurosci, 31, 1020110205.CrossRefGoogle ScholarPubMed
Nakamura, T. J., Nakamura, W., Tokuda, I. T., Ishikawa, T., Kudo, T., Colwell, C. S., & Block, G. D. (2015). Age-related changes in the circadian system unmasked by constant conditions. eNeuro, 2, e0064.CrossRefGoogle ScholarPubMed
Palomba, M., Nygård, M., Florenzano, F., Bertini, G., Kristensson, K., & Bentivoglio, M. (2008). Decline of the presynaptic network, including GABAergic terminals, in the aging suprachiasmatic nucleus of the mouse. J Biol Rhythms, 23(3), 220231.CrossRefGoogle ScholarPubMed
Perrin, J. S., Segall, L. A., Harbour, V. L., Woodside, B., & Amir, S. (2006). The expression of the clock protein PER2 in the limbic forebrain is modulated by the estrous cycle. Proc Natl Acad Sci USA, 103(14), 55915596.CrossRefGoogle ScholarPubMed
Prinz, P. N., Peskind, E., Vitaliano, P. P., Raskind, M., Eisdorfer, C., Zemcuznikov, N., & Gerber, C. (1982). Changes in the sleep and waking EEGs in non-demented and demented elderly subjects. J Am Geriatr Soc, 30, 8693.Google Scholar
Roh, J. H., Huang, Y., Bero, A. W., Kasten, T., Stewart, F. R., Bateman, R. J., & Holtzman, D. M. (2012). Disruption of the sleep-wake cycle and diurnal fluctuation of amyloid-beta in mice with Alzheimer’s disease pathology. Sci Transl Med, 4, 150ra122.Google Scholar
Roy, U., Heredia-Munoz, M. T., Stute, L., Hofling, C., Matysik, J., Meijer, J. H., Roßner, S., & Alia, A. (2019). Degeneration of the suprachiasmatic nucleus in an Alzheimer’s disease mouse model monitored by in vivo magnetic resonance relaxation measurements and immunohistochemistry. J Alzheimers Dis, 69(2), 363375.Google Scholar
Satinoff, E., Li, H., Tcheng, T. K., Liu, C., McArthur, A. J., Medanic, M., & Gillette, M. U. (1993). Do the suprachiasmatic nuclei oscillate in old rats as they do in young ones? Am J Physiol Regul Integr Comp Physiol, 265, R1216R1222.Google Scholar
Saurwein-Teissl, M., Blasko, I., Zisterer, K., Neuman, B., Lang, B., & Grubeck-Loebenstein, B. (1998). An imbalance between pro- and anti-inflammatory cytokines, a characteristic feature of old age. Cytokine, 12(7), 11601161.Google Scholar
Scheff, S. W., DeKosky, S. T., & Price, D. A. (1990). Quantitative assessment of cortical synaptic density in Alzheimer’s disease. Neurobiol Aging, 11, 2937.CrossRefGoogle ScholarPubMed
Schmitt, K., Grimm, A., & Eckert, A. (2017). Amyloid-beta-induced changes in molecular clock properties and cellular bioenergetics. Front Neurosci, 11, 124.CrossRefGoogle ScholarPubMed
Schroeder, A. M., Truong, D., Loh, D. H., Jordan, M. C., Roos, K. P., & Colwell, C. S. (2012). Voluntary scheduled exercise alters diurnal rhythms of behaviour, physiology and gene expression in wild-type and vasoactive intestinal peptide-deficient mice. J Physiol, 590, 62136226.Google Scholar
Segall, L. A., Perrin, J. S., Walker, C. D., Stewart, J., & Amir, S. (2006). Glucocorticoid rhythms control the rhythm of expression of the clock protein, Period2, in oval nucleus of the bed nucleus of the stria terminalis and central nucleus of the amygdala in rats. Neuroscience, 140(3), 753757.Google Scholar
Shan, Y., Abel, J. H., Li, Y., Izumo, M., Cox, K. H., Jeong, B., Yoo, S.-H., Olson, D. P., Doyle, F. J., & Takahashi, J. S. (2020). Dual-color single-cell imaging of the suprachiasmatic nucleus reveals a circadian role in network synchrony. Neuron, 108(1), 164179.e167.Google Scholar
Shearman, L. P., Zylka, M. J., Weaver, D. R., Kolakowski, L. F., & Reppert, S. M. (1997). Two period homologs: Circadian expression and photic regulation in the suprachiasmatic nuclei. Neuron, 19, 12611267.Google Scholar
Silver, R., & Kriegsfeld, L. J. (2014). Circadian rhythms have broad implications for understanding brain and behavior. Eur J Neurosci, 39(11), 18661880.CrossRefGoogle ScholarPubMed
Snider, K. H., Dziema, H., Aten, S., Loeser, J., Norona, F., Hoyt, K., & Obrietan, K. (2016). Modulation of learning and memory by the targeted deletion of the circadian clock gene Bmal1 in forebrain circuits. Behav Brain Res, 308, 222235.Google Scholar
Song, H., Moon, M., Choe, H. K., Han, D.-H., Jang, C., Kim, A., Cho, S., Kim, K., & Mook-Jung, I. (2015). A beta-induced degradation of BMAL1 and CBP leads to circadian rhythm disruption in Alzheimer’s disease. Mol Neurodegener, 10, 13.Google Scholar
Strecker, G. J., Wuarin, J. P., & Dudek, F. E. (1997). GABAA-mediated local synaptic pathways connect neurons in the rat suprachiasmatic nucleus. J Neurophysiol, 78(4), 22172220.Google Scholar
Takahashi, J. S. (2015). Molecular components of the circadian clock in mammals. Diabetes Obes Metab, Suppl 1, 6–11.Google Scholar
Tortosa-Martinez, J., Clow, A., Caus-Pertegaz, N., Gonzalez-Caballero, G., Abellan-Miralles, I., & Saenz, M. J. (2015). Exercise increases the dynamics of dirunal cortisol secretion and executive function in people with amnestic mild cognitive impairment. J Aging Phys Activ, 23, 550558.Google Scholar
Tranah, G. J., Blackwell, T., Stone, K. L., Ancoli-Israel, S., Paudel, M. S., Ensrud, K. E., Cauley, J. A., Redline, S., Hillier, T. A., Cummings, S. R., Yaffe, K., & SOF Research Group. (2011). Circadian activity rhythms and risk of incident dementia and mild cognitive impairment in older women. Ann Neurol, 70(5), 722732.CrossRefGoogle ScholarPubMed
Van Cauter, E., Leproult, R., & Kupfer, D. J. (1996). Effects of gender and age on the levels and circadian rhythmicity of plasma cortisol. J Clin Endocr Metab, 81, 24682473.Google Scholar
Van Reeth, O., Zhang, Y., Zee, P. C., & Turek, F. W. (1994). Grafting fetal suprachiasmatic nuclei in the hypothalamus of old hamsters restores responsiveness of the circadian clock to a phase shifting stimulus. Brain Res, 643, 338342.Google Scholar
Venturelli, M., Sollima, A., Ce, E., Limonta, E., Bisconti, A. V., Brasioli, A., Muti, E., & Esposito, F. (2016). Effectiveness of exercise- and cognitive-based treatments on salivary cortisol levels and sundowning syndrome symptoms in patients with Alzheimer’s disease. J Alzheimers Dis, 53(4), 16311640.Google Scholar
Vitiello, M. V., Poceta, J. S., & Prinz, P. N. (1991). Sleep in Alzheimer’s disease and other dementing disorders. Can J Psychol, 45(2), 221239.Google Scholar
Wang, J. L., Lim, A. S., Chiang, W.-Y., Hsieh, W.-H., Lo, M.-T., Schneider, J. A., Buchman, A. S., Bennett, D. A., Hu, K., & Saper, C. B. (2015). Suprachiasmatic neuron numbers and rest-activity circadian rhythms in older humans. Ann Neurol, 78, 317322.Google Scholar
Wang, L. M., Dragich, J. M., Kudo, T., Odom, I. H., Welsh, D. K., O’Dell, T. J., & Colwell, C. S. (2009). Expression of the circadian clock gene Period2 in the hippocampus: Possible implications for synaptic plasticity and learned behaviour. ASN Neuro, 1, e00012.Google Scholar
Watanabe, A., Shibata, S., & Watanabe, S. (1995). Circadian rhythm of spontaneous neuronal activity in the suprachiasmatic nucleus of old hamster in vitro. Brain Res, 695, 237239.CrossRefGoogle ScholarPubMed
Webers, A., Heneka, M. T., & Gleeson, P. A. (2020). The role of innate immune responses and neuroinflammation in amyloid accumulation and progression of Alzheimer’s disease. Immunol Cell Biol, 98(1), 2841.Google Scholar
Weinert, D., & Waterhouse, J. (1999). Daily activity and body temperature rhythms do not change simultaneously with age in laboratory mice. Physiol Behav, 66(4), 605612.Google Scholar
Wolf, O. T., Dziobek, I., McHugh, P., Sweat, V., de Leon, M. J., Javier, E., & Convit, A. (2005). Subjective memory complaints in aging are associated with elevated cortisol levels. Neurobiol Aging, 26, 13571363.CrossRefGoogle ScholarPubMed
Wu, Y. H., Fischer, D. F., Kalsbeek, A., Garidou-Boof, M.-L., van der Vliet, J., van Heijningen, C., Liu, R.-Y., Zhou, J.-N., & Swaab, D. F. (2006). Pineal clock gene oscillation is disturbed in Alzheimer’s disease, due to functional disconnection from the “master clock”. FASEB J, 20(11), 18741876.Google Scholar
Wyse, C. A., & Coogan, A. N. (2010). Impact of aging on diurnal expression patterns of CLOCK and BMAL1 in the mouse brain. Brain Res, 1337, 2131.Google Scholar
Xie, L., Kang, H., Xu, Q., Chen, M. J., Liao, Y., Thiyagarajan, M., O’Donnell, J., Christensen, D. J., Nicholson, C., Iliff, J. J., Takano, T., Deane, R., & Nedergaard, M. (2013). Sleep drives metabolite clearance from the adult brain. Science, 342(6156), 373377.CrossRefGoogle ScholarPubMed
Yamaguchi, Y., Suzuki, T., Mizoro, Y., Kori, H., Okada, K., Chen, Y., Fustin, J. M., Yamazaki, F., Mizuguchi, N., Zhang, J., Dong, X., Tsujimoto, G., Okuno, Y., Doi, M., & Okamura, H. (2013). Mice genetically deficient in vasopressin V1a and V1b receptors are resistant to jet lag. Science, 342(6154), 8590.Google Scholar
Yamazaki, S., Straume, M., Tei, H., Sakaki, Y., Menaker, M., & Block, G. D. (2002). Effects of aging on central and peripheral mammalian clocks. Proc Natl Acad Sci, 99, 1080110806.Google Scholar
Yan, L., & Silver, R. (2002). Differential induction and localization of mPer1 and mPer2 during advancing and delaying phase shifts. Eur J Neurosci, 16, 15311540.Google Scholar
Yang, G., Chen, L., Grant, G. R., Paschos, G., Song, W.-L., Musiek, E. S., Lee, V., McLoughlin, S. C., Grosser, T., Cotsarelis, G., & FitzGerald, G. A. (2016). Timing of expression of the core clock gene Bmal1 influences its effects on aging and survival. Sci Transl Med, 8, 110.CrossRefGoogle ScholarPubMed
Yoo, S.-H., Yamazaki, S., Lowrey, P. L., Shimomura, K., Ko, C. H., Buhr, E. D., Siepka, S. M., Hong, H.-K., Oh, W. J., Yoo, O. J., Menaker, M., & Takahashi, J. S. (2004). PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues. Proc Natl Acad Sci USA, 101, 53395346.Google Scholar
Zhang, R., Lahens, N. F., Ballance, H. I., Hughes, M. E., & Hogenesch, J. B. (2014). A circadian gene expression atlas in mammals: Implications for biology and medicine. Proc Natl Acad Sci USA, 111, 1621916224.Google Scholar
Zhang, Y., Kornhauser, J. M., Zee, P. C., Mayo, K. E., Takahashi, J. S., & Turek, F. W. (1996). Effects of aging on light-induced phase-shifting of circadian behavioral rhythms, Fos expression and CREB phosphorylation in the hamster suprachiasmatic nucleus. Neuroscience, 70, 951961.Google Scholar
Zhou, J.-N., Hofman, M. A., & Swaab, D. F. (1995). VIP neurons in the human SCN in relation to sex, age, and Alzheimer’s disease. Neurobiol Aging, 16, 571576.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×