Suprachiasmatic neuron numbers and rest–activity circadian rhythms in older humans
Joshua L. Wang AB
Program in Neuroscience and Division of Sleep Medicine, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
Search for more papers by this authorAndrew S. Lim MD
Program in Neuroscience and Division of Sleep Medicine, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
Search for more papers by this authorWei-Yin Chiang PhD
Medical Biodynamics Program, Division of Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
Center for Dynamical Biomarkers and Translational Medicine, National Central University, Chungli, Taiwan
Search for more papers by this authorWan-Hsin Hsieh PhD
Medical Biodynamics Program, Division of Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
Center for Dynamical Biomarkers and Translational Medicine, National Central University, Chungli, Taiwan
Search for more papers by this authorMen-Tzung Lo PhD
Medical Biodynamics Program, Division of Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
Center for Dynamical Biomarkers and Translational Medicine, National Central University, Chungli, Taiwan
Search for more papers by this authorJulie A. Schneider MD
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL
Search for more papers by this authorAron S. Buchman MD
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL
Search for more papers by this authorDavid A. Bennett MD
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL
Search for more papers by this authorKun Hu PhD
Program in Neuroscience and Division of Sleep Medicine, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
Medical Biodynamics Program, Division of Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
Center for Dynamical Biomarkers and Translational Medicine, National Central University, Chungli, Taiwan
Search for more papers by this authorCorresponding Author
Clifford B. Saper MD, PhD
Program in Neuroscience and Division of Sleep Medicine, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
Address correspondence to Dr Saper, 330 Brookline Avenue, Boston, MA 02215. E-mail: [email protected]Search for more papers by this authorJoshua L. Wang AB
Program in Neuroscience and Division of Sleep Medicine, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
Search for more papers by this authorAndrew S. Lim MD
Program in Neuroscience and Division of Sleep Medicine, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
Search for more papers by this authorWei-Yin Chiang PhD
Medical Biodynamics Program, Division of Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
Center for Dynamical Biomarkers and Translational Medicine, National Central University, Chungli, Taiwan
Search for more papers by this authorWan-Hsin Hsieh PhD
Medical Biodynamics Program, Division of Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
Center for Dynamical Biomarkers and Translational Medicine, National Central University, Chungli, Taiwan
Search for more papers by this authorMen-Tzung Lo PhD
Medical Biodynamics Program, Division of Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
Center for Dynamical Biomarkers and Translational Medicine, National Central University, Chungli, Taiwan
Search for more papers by this authorJulie A. Schneider MD
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL
Search for more papers by this authorAron S. Buchman MD
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL
Search for more papers by this authorDavid A. Bennett MD
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL
Search for more papers by this authorKun Hu PhD
Program in Neuroscience and Division of Sleep Medicine, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
Medical Biodynamics Program, Division of Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
Center for Dynamical Biomarkers and Translational Medicine, National Central University, Chungli, Taiwan
Search for more papers by this authorCorresponding Author
Clifford B. Saper MD, PhD
Program in Neuroscience and Division of Sleep Medicine, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
Address correspondence to Dr Saper, 330 Brookline Avenue, Boston, MA 02215. E-mail: [email protected]Search for more papers by this authorAbstract
The suprachiasmatic nucleus (SCN) of the hypothalamus, the master mammalian circadian pacemaker, synchronizes endogenous rhythms with the external day–night cycle. Older humans, particularly those with Alzheimer disease (AD), often have difficulty maintaining normal circadian rhythms compared to younger adults, but the basis of this change is unknown. We report that the circadian rhythm amplitude of motor activity in both AD subjects and age-matched controls is correlated with the number of vasoactive intestinal peptide–expressing SCN neurons. AD was additionally associated with delayed circadian phase compared to cognitively healthy subjects, suggesting distinct pathologies and strategies for treating aging- and AD-related circadian disturbances. Ann Neurol 2015;78:317–322
Supporting Information
Additional Supporting Information may be found in the online version of this article.
| Filename | Description |
|---|---|
| ana24432-sup-0001-suppinfo.docx76.3 KB |
Supplementary Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1 Saper CB. The central circadian timing system. Curr Opin Neurobiol 2013; 23: 747–751.
- 2 An S, Harang R, Meeker K, et al. A neuropeptide speeds circadian entrainment by reducing intercellular synchrony. Proc Natl Acad Sci U S A 2013; 110: E4355–E4361.
- 3 Yamaguchi Y, Suzuki T, Mizoro Y, et al. Mice genetically deficient in vasopressin V1a and V1b receptors are resistant to jet lag. Science 2013; 342: 85–90.
- 4 Abrahamson EE, Moore RY. Suprachiasmatic nucleus in the mouse: retinal innervation, intrinsic organization and efferent projections. Brain Res 2001; 916: 172–191.
- 5 Kondratova AA, Kondratov RV. The circadian clock and pathology of the ageing brain. Nat Rev Neurosci 2012; 13: 325–335.
- 6 Zhou J-N, Hofman MA, Swaab DF. VIP neurons in the human SCN in relation to sex, age, and Alzheimer's disease. Neurobiol Aging 1995; 16: 571–576.
- 7 Swaab DFF, Fliers E, Partiman TSS. The suprachiasmatic nucleus of the human brain in relation to sex, age and senile dementia. Brain Res 1985; 342: 37–44.
- 8 Bennett DA, Schneider JA, Buchman AS, et al. Overview and findings from the rush Memory and Aging Project. Curr Alzheimer Res 2012; 9: 646–663.
- 9 Lim ASP, Ellison BA, Wang JL, et al. Sleep is related to neuron numbers in the ventrolateral preoptic/intermediate nucleus in older adults with and without Alzheimer's disease. Brain 2014; 137(pt 10): 2847–2861.
- 10 Bennett DA, Schneider JA, Arvanitakis Z, et al. Neuropathology of older persons without cognitive impairment from two community-based studies. Neurology 2006; 66: 1837–1844.
- 11
Huang NE,
Shen Z,
Long SR,
Wu MLC,
Shih HH,
Zheng QN,
Yen NC,
Tung CC,
Liu HH. The empirical mode decomposition and the Hilbert spectrum for nonlinear and non-stationary time analysis. Proc Roy Soc London, Series A-Mathematical Physical and Engineering Sciences 1998; 454: 903–995.
10.1098/rspa.1998.0193 Google Scholar
- 12 Chou TC, Scammell TE, Gooley JJ, et al. Critical role of dorsomedial hypothalamic nucleus in a wide range of behavioral circadian rhythms. J Neurosci 2003; 23: 10691–10702.
- 13 Sokolove PG, Bushell WN. The chi square periodogram: its utility for analysis of circadian rhythms. J Theor Biol 1978; 72: 131–160.
- 14 Hatfield CF, Herbert J, van Someren EJW, et al. Disrupted daily activity/rest cycles in relation to daily cortisol rhythms of home-dwelling patients with early Alzheimer's dementia. Brain 2004; 127(pt 5): 1061–1074.
- 15 Harper DG, Volicer L, Stopa EG, et al. Disturbance of endogenous circadian rhythm in aging and Alzheimer disease. Am J Geriatr Psychiatry 2005; 13: 359–368.
- 16 Harper DG, Stopa EG, Kuo-Leblanc V, et al. Dorsomedial SCN neuronal subpopulations subserve different functions in human dementia. Brain 2008; 131(pt 6): 1609–1617.
- 17 Liu RY, Zhou JN, Hoogendijk WJ, et al. Decreased vasopressin gene expression in the biological clock of Alzheimer disease patients with and without depression. J Neuropathol Exp Neurol 2000; 59: 314–322.
- 18 Pollak CP, Perlick D. Sleep problems and institutionalization of the elderly. J Geriatr Psychiatry Neurol 1991; 4: 204–210.
- 19 Chen CP, Eastwood SL, Hope T, et al. Immunocytochemical study of the dorsal and median raphe nuclei in patients with Alzheimer's disease prospectively assessed for behavioural changes. Neuropathol Appl Neurobiol 2000; 26: 347–355.
- 20 Morin LP. Serotonin and the regulation of mammalian circadian rhythmicity. Ann Med 1999; 31: 12–33.
- 21 Satlin A, Volicer L, Ross V, et al. Bright light treatment of behavioral and sleep disturbances in patients with Alzheimer's disease. Am J Psychiatry 1992; 149: 1028–1032.
- 22 Lovell BB, Ancoli-Israel S, Gevirtz R. Effect of bright light treatment on agitated behavior in institutionalized elderly subjects. Psychiatry Res 1995; 57: 7–12.
Citing Literature
