CoChat
Sign Up
Cited by 265Circadian rhythm and melatoninAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

The DOI matches its Crossref record.

Pathologic Evaluation of the Human Suprachiasmatic Nucleus in Severe Dementia

Stopa, Edward G., Volicer, Ladislav, Kuo-Leblanc, Victoria, Harper, David, Lathi, Devayani, Tate, Barbara, Satlin, Andrew·1999·Journal of Neuropathology and Experimental Neurology
DOI 10.1097/00005072-199901000-00004
Open this paper in CoChat — free account

Abstract

Sleep disruption and other circadian rhythm disturbances are frequently seen in dementia patients. In this study, we examined the suprachiasmatic nucleus (SCN), the putative site of the hypothalamic circadian pacemaker, to determine the nature and degree of pathologic changes caused by severe dementia. Neuropathologic examination indicated that among 30 patients with a clinical history of severe dementia, 22 had Braak and Braak stage V-VI Alzheimer disease, 3 had combined Alzheimer and Parkinson disease, 3 had Pick disease and 2 had severe hippocampal sclerosis. Comparisons were made with a control group composed of 13 age-matched patients with no clinical or pathological evidence of dementia or other CNS disorders. To determine the pathologic involvement within the SCN, human hypothalami were stained with: Nissl, Bielchowsky silver, thioflavin S and specific antibodies directed against vasopressin (VP), neurotensin (NT), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), beta-amyloid (B/A4) and glial fibrillary acidic protein (GFAP). Pathologic damage was primarily limited to neuronal loss and neurofibrillary tangle formation. Only rare diffuse plaques were noted. The pathologic changes within the SCN were less severe than in the other brain regions. Morphometric analysis was accomplished using a stereological approach to sample the average total number of positively stained neurons and astrocytes in 10 different 0.1mm2 microscopic fields in the dorsal subdivision of the SCN. Patients with Alzheimer disease exhibited a significant decrease in vasopressin (9.75 vs 16.7, p < 0.001) and neurotensin (6.82 vs 9.63, p < 0.002) neurons, as well as a corresponding increase in the GFAP-stained astrocyte/Nissl-stained neuron ratio (0.54 vs 0.10, p < 0.009). These studies provide evidence that both vasopressin and neurotensin neurons are lost in Alzheimer disease, and that the astrocyte/neuron ratio is a reliable indicator of disease-related pathology within the SCN. Taken collectively, our data support the hypothesis that damage to the SCN may be an underlying anatomical substrate for the clinically observed changes in circadian rhythmicity that have been observed in Alzheimer patients.

Overview

Integrity signals

Registry

Crossref · 10.1097/00005072-199901000-00004

Cites

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Citations

Cited by

Sorted by citations

Items 201–265 of 265

Related

See all

Metadata

Authors
Stopa, E. G., Volicer, L., Kuo-Leblanc, V., Harper, D., Lathi, D., Tate, B., & Satlin, A.
Affiliations
  • Harvard University (US)
  • Brown University (US)
  • Edith Nourse Rogers Memorial Veterans Hospital (US)
Corresponding author
Stopa, Edward G.
ORCID
Venue
Journal of Neuropathology and Experimental Neurology
Publisher
Oxford University Press (OUP)
Published
1999-01
Volume
58
Issue
1
Pages
29-39
ISSN
0022-3069 (ISSN-L)
DOI
10.1097/00005072-199901000-00004
OpenAlex
W1965668843
Cited by
265
References
0
Citations by year
2026: 8 · 2025: 12 · 2024: 11 · 2023: 11 · 2022: 7 · 2021: 19 · 2020: 20 · 2019: 10 · 2018: 13 · 2017: 11 · 2016: 16 · 2015: 9 · 2014: 11 · 2013: 10 · 2012: 14
FWCI
1.77
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Neuropathology & Experimental Neurology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ag009301-08, 5r01ag010682-06)
  • National Institute on Aging (AG10682, AG-09301)
  • National Institute of Mental Health (MH.NS 31862)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
suprachiasmatic nucleus, advanced dementia, Alzheimer's disease, circadian rhythm disruption, sleep disruption, vasopressin neurons, neurofibrillary tangles, neurodegeneration, hypothalamus, Pick's disease, hippocampal sclerosis, Parkinson's disease
MeSH terms
Circadian Rhythm, Dementia, Evaluation Studies as Topic, Humans, Immunohistochemistry, Male, Middle Aged, Neuroglia, Neurons, Suprachiasmatic Nucleus, Case-Control Studies

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