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Increased neocortical neurofibrillary tangle density in subjects with Alzheimer disease and psychosis.

Abstract

BACKGROUND

Psychosis is common in patients with Alzheimer disease. While the relationship between psychosis and clinical variables has been examined frequently, few studies have examined the relationship between psychosis and the 2 major neuropathological hallmarks of Alzheimer disease: neurofibrillary tangles and senile plaques. We characterized the occurrence of psychosis in relation to dementia severity and determined if subjects with Alzheimer disease and psychosis had a greater neurofibrillary tangle or senile plaque burden than subjects with Alzheimer disease and no psychosis.

METHODS

One hundred nine subjects with Alzheimer disease were followed longitudinally with semistructured assessments in order to assign a Clinical Dementia Rating and determine whether psychosis was present. After the subjects died, their brains were obtained for histological examination. Analysis of variance was used to compare the densities of neurofibrillary tangles, total senile plaques, and cored senile plaques in subjects with psychosis vs subjects without psychosis, in several neocortical regions, the hippocampus, and the entorhinal cortex.

RESULTS

Psychosis occurred commonly in Alzheimer disease, affecting 63% of subjects. The frequency of psychosis increased with increasing dementia severity. More importantly, we found that subjects with psychosis had a 2.3-fold (95% confidence interval, 1.2-3.9) greater density of neocortical neurofibrillary tangles than did subjects without psychosis. The increase was independent of dementia severity. No similar relationship with psychosis was seen for total senile plaques or cored senile plaques.

CONCLUSIONS

The increase in psychosis frequency that occurs with the progression of dementia severity and the independent association between psychosis and neurofibrillary tangle density suggest the possibility that some common underlying process or processes specific to Alzheimer disease may regulate both phenomena. Arch Gen Psychiatry. 2000;57:1165-1173.

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  • Authors+Show Affiliations

    ,

    Washington University, Department of Psychiatry, Campus Box 8134, 660 S Euclid Ave, St Louis, MO 63110-1009, USA. farbern@psychiatry.wustl.edu

    , , , , , ,

    Source

    Archives of general psychiatry 57:12 2000 Dec pg 1165-73

    MeSH

    Aged
    Alzheimer Disease
    Comorbidity
    Delusions
    Entorhinal Cortex
    Female
    Hallucinations
    Hippocampus
    Humans
    Longitudinal Studies
    Male
    Neocortex
    Neurofibrillary Tangles
    Plaque, Amyloid
    Psychiatric Status Rating Scales
    Psychotic Disorders
    Severity of Illness Index

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    11115331

    Citation

    Farber, N B., et al. "Increased Neocortical Neurofibrillary Tangle Density in Subjects With Alzheimer Disease and Psychosis." Archives of General Psychiatry, vol. 57, no. 12, 2000, pp. 1165-73.
    Farber NB, Rubin EH, Newcomer JW, et al. Increased neocortical neurofibrillary tangle density in subjects with Alzheimer disease and psychosis. Arch Gen Psychiatry. 2000;57(12):1165-73.
    Farber, N. B., Rubin, E. H., Newcomer, J. W., Kinscherf, D. A., Miller, J. P., Morris, J. C., ... McKeel, D. W. (2000). Increased neocortical neurofibrillary tangle density in subjects with Alzheimer disease and psychosis. Archives of General Psychiatry, 57(12), pp. 1165-73.
    Farber NB, et al. Increased Neocortical Neurofibrillary Tangle Density in Subjects With Alzheimer Disease and Psychosis. Arch Gen Psychiatry. 2000;57(12):1165-73. PubMed PMID: 11115331.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Increased neocortical neurofibrillary tangle density in subjects with Alzheimer disease and psychosis. AU - Farber,N B, AU - Rubin,E H, AU - Newcomer,J W, AU - Kinscherf,D A, AU - Miller,J P, AU - Morris,J C, AU - Olney,J W, AU - McKeel,D W,Jr PY - 2000/12/15/pubmed PY - 2001/3/3/medline PY - 2000/12/15/entrez SP - 1165 EP - 73 JF - Archives of general psychiatry JO - Arch. Gen. Psychiatry VL - 57 IS - 12 N2 - BACKGROUND: Psychosis is common in patients with Alzheimer disease. While the relationship between psychosis and clinical variables has been examined frequently, few studies have examined the relationship between psychosis and the 2 major neuropathological hallmarks of Alzheimer disease: neurofibrillary tangles and senile plaques. We characterized the occurrence of psychosis in relation to dementia severity and determined if subjects with Alzheimer disease and psychosis had a greater neurofibrillary tangle or senile plaque burden than subjects with Alzheimer disease and no psychosis. METHODS: One hundred nine subjects with Alzheimer disease were followed longitudinally with semistructured assessments in order to assign a Clinical Dementia Rating and determine whether psychosis was present. After the subjects died, their brains were obtained for histological examination. Analysis of variance was used to compare the densities of neurofibrillary tangles, total senile plaques, and cored senile plaques in subjects with psychosis vs subjects without psychosis, in several neocortical regions, the hippocampus, and the entorhinal cortex. RESULTS: Psychosis occurred commonly in Alzheimer disease, affecting 63% of subjects. The frequency of psychosis increased with increasing dementia severity. More importantly, we found that subjects with psychosis had a 2.3-fold (95% confidence interval, 1.2-3.9) greater density of neocortical neurofibrillary tangles than did subjects without psychosis. The increase was independent of dementia severity. No similar relationship with psychosis was seen for total senile plaques or cored senile plaques. CONCLUSIONS: The increase in psychosis frequency that occurs with the progression of dementia severity and the independent association between psychosis and neurofibrillary tangle density suggest the possibility that some common underlying process or processes specific to Alzheimer disease may regulate both phenomena. Arch Gen Psychiatry. 2000;57:1165-1173. SN - 0003-990X UR - https://www.unboundmedicine.com/medline/citation/11115331/Increased_neocortical_neurofibrillary_tangle_density_in_subjects_with_Alzheimer_disease_and_psychosis_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=11115331.ui DB - PRIME DP - Unbound Medicine ER -