Alterations in the circadian rest-activity rhythm in aging and Alzheimer's disease
Open accessAbstract
The suprachiasmatic nucleus, considered to be the endogenous circadian clock in the mammalian brain, shows morphological changes with aging, which become even more pronounced in Alzheimer's disease (AD). In order to assess possible functional implications of these alterations, circadian rest-activity rhythms of 6 young and 13 old volunteers and of 12 AD patients were studied with a recently developed ambulatory rest-activity monitor (RA24). Young and old volunteers showed no differences in their rest-activity rhythm in any of the variables studied. Comparison of old controls versus AD patients revealed that (1) rest-activity rhythm was markedly disturbed in many of the AD patients and tended to be correlated with the severity of the dementia; (2) disturbances were most pronounced in subjects using sedating drugs; (3) disturbances in the latter group did not result from medication as no differences were found in the rest-activity patterns before and after administration of sedating drugs; (4) negative findings reported in the literature concerning circadian disturbances in AD may well have resulted from selection criteria that excluded the group of patients with the most severely affected rest-activity rhythm; and (5) rest-activity monitors offer a practical and fruitful approach for the study of circadian rhythms in humans.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The idea of combining prolonged-release melatonin with AChEIs came from the observed relation between circadian rhythm dysfunction and neurocognitive disorders, a phenomenon observed as a consequence of decreased circulating melatonin level.
“The idea of the drug combination came from the observed relation between circadian rhythm dysfunction and neurocognitive disorders, a phenomenon that has been observed as consequence of the decreased circulating melatonin (11) level (Figure 6B).76,77”
From From combinations to multitarget-directed ligands: A continuum in Alzheimer’s disease polypharmacology (2021) · cites this paper as [77]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · see citing works
The Global Deterioration Scale for assessment of primary degenerative dementia
Reisberg, ., Ferris, S. H., de Leon, M. J., & Crook, T. H. (1982) · American Journal of Psychiatry · doi:10.1176/ajp.139.9.1136 · Cited by 4,982 · see citing works
The chi square periodogram: Its utility for analysis of circadian rhythms
Sokolove, P. G., & Bushell, W. N. (1978) · Journal of Theoretical Biology · doi:10.1016/0022-5193(78)90022-x · Cited by 972 · see citing works
The suprachiasmatic nucleus of the human brain in relation to sex, age and senile dementia
Swaab, D. F., Fliers, E., & Partiman, T. S. (1985) · Brain Research · doi:10.1016/0006-8993(85)91350-2 · Cited by 847 · see citing works
Self-citationAntidepressant and Circadian Phase-Shifting Effects of Light
Lewy, A. J., Sack, R. L., Miller, L. S., & Hoban, T. M. (1987) · Science · doi:10.1126/science.3798117 · Cited by 709 · see citing works
Optic-Nerve Degeneration in Alzheimer's Disease
Hinton, D. R., Sadun, A. A., Blanks, J. C., & Miller, C. A. (1986) · New England Journal of Medicine · doi:10.1056/nejm198608213150804 · Cited by 700 · see citing works
Winfree, A. T. (1983) · Mathematical Biosciences · doi:10.1016/0025-5564(83)90095-0 · Cited by 541 · see citing works
MILES, L. E., & Wc, D. (1980) · PubMed · Cited by 306 · see citing works
Sanford, J. (1975) · BMJ · doi:10.1136/bmj.3.5981.471 · Cited by 303 · see citing works
Changes in vasopressin cells of the rat suprachiasmatic nucleus with aging
Roozendaal, B., van Gool, W. A., Swaab, D. F., Hoogendijk, J. E., & Mirmiran, M. (1987) · Brain Research · doi:10.1016/0006-8993(87)90710-4 · Cited by 178 · see citing works
Self-citationSleep apnea in Alzheimer's dementia: correlation with mental deterioration.
Reynolds, C. F., Kupfer, D. J., Taska, L. S., Hoch, C. C., Sewitch, D. E., Restifo, K., Spiker, D. G., Zimmer, B., Marin, R. S., & Nelson, J. (1985) · PubMed · Cited by 120 · see citing works
Performance During Frequent Sleep Disruption
Downey, R., & Bonnet, M. H. (1987) · SLEEP · doi:10.1093/sleep/10.4.354 · Cited by 110 · see citing works
Disrupting circadian rhythms in rats induces retrograde amnesia
Fekete, M., van Ree, J. M., Niesink, R. J. M., & de Wied, D. (1985) · Physiology & Behavior · doi:10.1016/0031-9384(85)90008-3 · Cited by 107 · see citing works
Chapter 16 Aging and circadian rhythms
van Gool, W. A., & Mirmiran, M. (1986) · Progress in brain research · doi:10.1016/s0079-6123(08)64309-5 · Cited by 102 · see citing works
Self-citationVasoactive intestinal polypeptide neuron changes in the senile rat suprachiasmatic nucleus
Chee, C. A., Roozendaal, B., Swaab, D. F., Goudsmit, E., & Mirmiran, M. (1988) · Neurobiology of Aging · doi:10.1016/s0197-4580(88)80070-8 · Cited by 101 · see citing works
Self-citationCircadian Temperature Variation in Healthy Aged and in Alzheimer's Disease
Prinz, P. N., Christie, C., Smallwood, R. G., VITALIANO, P. P., Bokan, J. A., Vitiello, M. V., & Martin, D. C. (1984) · Journal of Gerontology · doi:10.1093/geronj/39.1.30 · Cited by 67 · see citing works
Sleep Apnea in Multiinfarct Dementia and Alzheimer's Disease
Erkinjuntti, T., Partinen, M., Sulkava, R. O., Telakivi, T., Salmi, T. K., & Tilvis, R. S. (1987) · SLEEP · doi:10.1093/sleep/10.5.419 · Cited by 65 · see citing works
Electroencephalographic sleep, aging, and psychopathology: new data and state of the art.
Cf, R., Dg, S., Hanin, I., & Dj, K. (1983) · PubMed · Cited by 64 · see citing works
Chapter 2 Cognitive, emotional and behavioral dysfunctions in aging and dementia
JOLLES, J. (1986) · Progress in brain research · doi:10.1016/s0079-6123(08)64295-8 · Cited by 55 · see citing works
Motor activity and sleep duration as a function of age in healthy men
Renfrew, J. W., Pettigrew, K. D., & Rapoport, S. I. (1987) · Physiology & Behavior · doi:10.1016/0031-9384(87)90321-0 · Cited by 52 · see citing works
A simple method for recording and analysing circadian rhythms in man
Mirmiran, M., Overdijk, J., Witting, W., et al. (1988) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(88)90135-5 · Cited by 29 · see citing works
Self-citationSwaab, D. F. (1986) · Data Archiving and Networked Services (DANS) · Cited by 24 · see citing works
Self-citationPrinz, P. N., Vitiello, M. V., Bokan, J. A., et al. (2015) · Interdisciplinary topics in gerontology and geriatrics · doi:10.1159/000413859 · Cited by 10 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Phillips, A. J. K., Clerx, W. M., O’Brien, C. S., Sano, A., Barger, L. K., Picard, R. W., Lockley, S. W., Klerman, E. B., & Czeisler, C. A. (2017) · Scientific Reports · doi:10.1038/s41598-017-03171-4 · Cited by 647 · see citing works
Circadian misalignment and health
Baron, K. G., & Reid, K. J. (2014) · International Review of Psychiatry · doi:10.3109/09540261.2014.911149 · Cited by 645 · see citing works
Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration
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., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci70317 · Cited by 524 · see citing works
Sleep, circadian rhythms, and the pathogenesis of Alzheimer disease
Musiek, E. S., Xiong, D. D., & Holtzman, D. M. (2015) · Experimental & Molecular Medicine · doi:10.1038/emm.2014.121 · Cited by 529 · see citing works
Circadian rest-activity pattern changes in aging and preclinical Alzheimer disease
Musiek, E. S., Bhimasani, M., Zangrilli, M. A., Morris, J. C., Holtzman, D. M., & Ju, Y.-E. S. (2018) · JAMA Neurology · doi:10.1001/jamaneurol.2017.4719 · Cited by 465 · see citing works
Circadian disruption and human health
Fishbein, A. B., Knutson, K. L., & Zee, P. C. (2021) · Journal of Clinical Investigation · doi:10.1172/jci148286 · Cited by 468 · see citing works
Evidence‐Based Recommendations for the Assessment and Management of Sleep Disorders in Older Persons
Bloom, H. G., Ahmed, I., Alessi, C. A., Ancoli‐Israel, S., Buysse, D. J., Kryger, M. H., Phillips, B. A., Thorpy, M. J., Vitiello, M. V., & Zee, P. C. (2009) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2009.02220.x · Cited by 464 · see citing works
Sundowning and Circadian Rhythms in Alzheimer’s Disease
Volicer, L., Harper, D. G., Manning, B. C., Goldstein, R., & Satlin, A. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.5.704 · Cited by 382 · see citing works
Duffy, J. F., Zitting, K.-M., & Chinoy, E. D. (2015) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2015.08.002 · Cited by 367 · see citing works
VIP neurons in the human SCN in relation to sex, age, and Alzheimer's disease
Zhou, J. (1995) · Neurobiology of Aging · doi:10.1016/0197-4580(95)00043-e · Cited by 243 · see citing works
Evidence for Neuronal Desynchrony in the Aged Suprachiasmatic Nucleus Clock
Farajnia, S., Michel, S., Deboer, T., vanderLeest, H. T., Houben, T., Rohling, J. H. T., Ramkisoensing, A., Yasenkov, R., & Meijer, J. H. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.0469-12.2012 · Cited by 230 · see citing works
Sterniczuk, R., Antle, M. C., LaFerla, F. M., & Dyck, R. H. (2010) · Brain Research · doi:10.1016/j.brainres.2010.06.011 · Cited by 228 · see citing works
Hofman, M. A., & Swaab, D. F. (1994) · Brain Research · doi:10.1016/0006-8993(94)90689-0 · Cited by 215 · see citing works
Self-citationA clinical approach to circadian rhythm sleep disorders
Barion, A., & Zee, P. C. (2007) · Sleep Medicine · doi:10.1016/j.sleep.2006.11.017 · Cited by 214 · see citing works
Molecular Mechanisms and Genetics of Oxidative Stress in Alzheimer’s Disease
Cioffi, F., Adam, R. H. I., & Broersen, K. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190863 · Cited by 204 · see citing works
Bravo, R., Matito, S., Cubero, J., Paredes, S. D., Franco, L., Rivero, M., Rodríguez, A. B., & Barriga, C. (2013) · AGE · doi:10.1007/s11357-012-9419-5 · Cited by 199 · see citing works
Bright light therapy for agitation in dementia: a randomized controlled trial
Burns, A., Allen, H., Tomenson, B., Duignan, D., & Byrne, J. (2009) · International Psychogeriatrics · doi:10.1017/s1041610209008886 · Cited by 171 · see citing works
Albertini, C., Salerno, A., de Sena Murteira Pinheiro, P., & Bolognesi, M. L. (2021) · Medicinal Research Reviews · doi:10.1002/med.21699 · Cited by 179 · see citing works
Circadian disruption and human health: A bidirectional relationship
Abbott, S. M., Malkani, R. G., & Zee, P. C. (2020) · European Journal of Neuroscience · doi:10.1111/ejn.14298 · Cited by 161 · see citing works
Assessment of Circadian Rhythms
Reid, K. J. (2019) · Neurologic Clinics · doi:10.1016/j.ncl.2019.05.001 · Cited by 152 · see citing works
Daily rhythm of serum melatonin in patients with dementia of the degenerate type
Uchida, K., Okamoto, N., Ohara, K., & Morita, Y. (1996) · Brain Research · doi:10.1016/0006-8993(96)00086-8 · Cited by 138 · see citing works
Reinertsen, E., & Clifford, G. D. (2018) · Physiological Measurement · doi:10.1088/1361-6579/aabf64 · Cited by 136 · see citing works
Michael Vanderlind, W., Beevers, C. G., Sherman, S. M., Trujillo, L. T., McGeary, J. E., Matthews, M. D., Todd Maddox, W., & Schnyer, D. M. (2014) · Sleep Medicine · doi:10.1016/j.sleep.2013.10.006 · Cited by 117 · see citing works
Levodopa ameliorates learning and memory deficits in a murine model of Alzheimer’s disease
Ambrée, O., Richter, H., Sachser, N., Lewejohann, L., Dere, E., de Souza Silva, M. A., Herring, A., Keyvani, K., Paulus, W., & Schäbitz, W.-R. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.11.010 · Cited by 115 · see citing works
Activity changes and marked stereotypic behavior precede Aβ pathology in TgCRND8 Alzheimer mice
Ambrée, O., Touma, C., Görtz, N., Keyvani, K., Paulus, W., Palme, R., & Sachser, N. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.05.009 · Cited by 93 · see citing works
The relationship between dementia severity and rest/activity circadian rhythms
Gehrman, P., Marler, M., Martin, J. L., Shochat, T., Corey-Bloom, J., & Ancoli-Israel, S. (2005) · Neuropsychiatric Disease and Treatment · doi:10.2147/nedt.1.2.155.61043 · Cited by 82 · see citing works
Hoyt, K. R., & Obrietan, K. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00537-9 · Cited by 77 · see citing works
Swaab, D. F., Van Someren, E. J. W., Zhou, J. N., & Hofman, M. A. (1996) · Progress in Brain Research · doi:10.1016/s0079-6123(08)60418-5 · Cited by 75 · see citing works
Self-citationAn fMRI study of cognitive control in problem gamers
Luijten, M., Meerkerk, G.-J., Franken, I. H. A., van de Wetering, B. J. M., & Schoenmakers, T. M. (2015) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2015.01.004 · Cited by 68 · see citing works
International drive to illuminate delirium: a developing public health blueprint for action
Khachaturian, A. S., Hayden, K. M., Devlin, J. W., Fleisher, L. A., Lock, S. L., Cunningham, C., Oh, E. S., Fong, T. G., Fick, D. M., Marcantonio, E. R., et al. (2020) · Alzheimer's & Dementia · doi:10.1002/alz.12075 · Cited by 60 · see citing works
Carr, O., Saunders, K. E. A., Tsanas, A., Bilderbeck, A. C., Palmius, N., Geddes, J. R., Foster, R., Goodwin, G. M., & De Vos, M. (2018) · Scientific Reports · doi:10.1038/s41598-018-19888-9 · Cited by 57 · see citing works
Diurnal rhythms of wrist temperature are associated with future disease risk in the UK Biobank
Brooks, T. G., Lahens, N. F., Grant, G. R., Sheline, Y. I., FitzGerald, G. A., & Skarke, C. (2023) · Nature Communications · doi:10.1038/s41467-023-40977-5 · Cited by 57 · see citing works
Using behavioral rhythms and multi-task learning to predict fine-grained symptoms of schizophrenia
Tseng, V. W.-S., Sano, A., Ben-Zeev, D., Brian, R., Campbell, A. T., Hauser, M., Kane, J. M., Scherer, E. A., Wang, R., Wang, W., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-71689-1 · Cited by 44 · see citing works
Rest-activity rhythm profiles associated with manic-hypomanic and depressive symptoms
Smagula, S. F., Krafty, R. T., Thayer, J. F., Buysse, D. J., & Hall, M. H. (2018) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2018.04.015 · Cited by 40 · see citing works
Wu, C.-Y., Dodge, H. H., Reynolds, C., Barnes, L. L., Silbert, L. C., Lim, M. M., Mattek, N., Gothard, S., Kaye, J. A., & Beattie, Z. (2021) · Frontiers in Digital Health · doi:10.3389/fdgth.2021.764510 · Cited by 19 · see citing works
Capella, M. D. M., Martinez-Nicolas, A., & Adan, A. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00373 · Cited by 17 · see citing works
The bright and dark side of blue-enriched light on sleep and activity in older adults.
Barroggi Constantino, D., Lederle, K. A., Middleton, B., Revell, V. L., Sletten, T. L., Williams, P., Skene, D. J., & van der Veen, D. R. (2025) · GeroScience · doi:10.1007/s11357-025-01506-y · Cited by 9 · see citing works
Peripheral body temperature impairment in individuals with type 1 diabetes mellitus
Barone, M. T. U., Gonçalves, B., & Menna-Barreto, L. (2018) · Sleep Science · doi:10.5935/1984-0063.20180026 · Cited by 4 · see citing works
- Authors
- Witting, W., Kwa, I. H., Eikelenboom, P., Mirmiran, M., & Swaab, D. F.
- Corresponding author
- Witting, W.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 1990-03
- Volume
- 27
- Issue
- 6
- Pages
- 563-572
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W1983882084
- Cited by
- 621
- References
- 23
- Citations by year
- 2026: 29 · 2025: 38 · 2024: 41 · 2023: 39 · 2022: 35 · 2021: 48 · 2020: 40 · 2019: 37 · 2018: 27 · 2017: 19 · 2016: 17 · 2015: 22 · 2014: 16 · 2013: 16 · 2012: 11
- FWCI
- 7.88
- Type
- journal article
- Language
- en
- Open access
- green
- pure.knaw.nl
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Keywords
- circadian rest-activity rhythm, Alzheimer's disease, aging, suprachiasmatic nucleus, circadian clock, dementia severity, circadian rhythm disruption
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Arousal, Circadian Rhythm, Female, Humans, Male, Middle Aged, Motor Activity, Reference Values, Sleep Stages, Suprachiasmatic Nucleus
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
