Neuropathologic and neurochemical correlates of psychosis in primary dementia

G. S. Zubenko, J. Moossy, A. J. Martinez, G. Rao, D. Claassen, J. Rosen and U. Kopp
Department of Psychiatry, University of Pittsburgh School of Medicine, Pa.

Neuropathologic and neurochemical correlates of psychosis were determined using brain tissue from 27 autopsy-confirmed cases of Alzheimer's disease. The densities of senile plaques and neurofibrillary tangles were determined in the middle frontal and superior temporal cortex, the prosubiculum, and the entorhinal cortex of the hippocampus. The concentrations of norepinephrine, dopamine, and serotonin, the metabolites of these biogenic amines, and the specific activity of choline acetyltransferase were also determined in these four cortical regions as well as in the substantia nigra, thalamus, amygdala, and caudate nucleus. Psychosis was associated with significantly increased densities of senile plaques and neurofibrillary tangles in the prosubiculum and middle frontal cortex, respectively, with trends toward increased densities of these lesions in the other areas examined. This finding is consistent with the increased rate of cognitive decline that accompanies this behavioral disorder. Psychosis was also associated with the relative preservation of norepinephrine in the substantia nigra, with trends in this direction for five of the remaining seven brain regions examined, and a significant reduction of serotonin in the prosubiculum that was accompanied by trends toward reduced levels of serotonin and 5 hydroxyindoleacetic acid in the remaining regions. The profile of neuropathologic and neurochemical changes associated with psychosis is distinct from that previously reported for major depression in the context of primary dementia.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Dementia of the Alzheimer Type
Jalbert et al.
Epidemiol Rev 2008;30:15-34.
ABSTRACT | FULL TEXT  

Aggressive Behavior and Neuroleptic Medication Are Associated With Increased Number of Alpha1-Adrenoceptors in Patients With Alzheimer Disease
Sharp et al.
AJGP 2007;15:435-437.
ABSTRACT | FULL TEXT  

Research Agenda for DSM-V: Diagnostic Categories and Criteria for Neuropsychiatric Syndromes in Dementia
Jeste et al.
J Geriatr Psychiatry Neurol 2006;19:160-171.
ABSTRACT  

Phenomenology and Clinical Correlates of Delusions in Alzheimer Disease
Mizrahi et al.
AJGP 2006;14:573-581.
ABSTRACT | FULL TEXT  

Epidemiology of and Risk Factors for Psychosis of Alzheimer's Disease: A Review of 55 Studies Published From 1990 to 2003
Ropacki and Jeste
Am. J. Psychiatry 2005;162:2022-2030.
ABSTRACT | FULL TEXT  

Delusions and Hallucinations Are Associated With Worse Outcome in Alzheimer Disease
Scarmeas et al.
Arch Neurol 2005;62:1601-1608.
ABSTRACT | FULL TEXT  

The Role of Norepinephrine in the Behavioral and Psychological Symptoms of Dementia
Herrmann et al.
J. Neuropsychiatry Clin. Neurosi. 2004;16:261-276.
ABSTRACT | FULL TEXT  

Neuromotor abnormalities and risk for psychosis in Alzheimer's disease
Caligiuri et al.
Neurology 2003;61:954-958.
ABSTRACT | FULL TEXT  

Treating Depression in Alzheimer Disease: Efficacy and Safety of Sertraline Therapy, and the Benefits of Depression Reduction: The DIADS
Lyketsos et al.
Arch Gen Psychiatry 2003;60:737-746.
ABSTRACT | FULL TEXT  

A Collaborative Study of the Emergence and Clinical Features of the Major Depressive Syndrome of Alzheimer's Disease
Zubenko et al.
Am. J. Psychiatry 2003;160:857-866.
ABSTRACT | FULL TEXT  

Delusional Thoughts and Regional Frontal/Temporal Cortex Metabolism in Alzheimer's Disease
Sultzer et al.
Am. J. Psychiatry 2003;160:341-349.
ABSTRACT | FULL TEXT  

Depression and Alzheimer's disease: Symptom or comorbidity?
Moretti et al.
AM J ALZHEIMERS DIS OTHER DEMEN 2002;17:338-344.
ABSTRACT  

Prevalence of Neuropsychiatric Symptoms in Dementia and Mild Cognitive Impairment: Results From the Cardiovascular Health Study
Lyketsos et al.
JAMA 2002;288:1475-1483.
ABSTRACT | FULL TEXT  

Association between the APOE genotype and psychopathologic symptoms in Alzheimer's disease
Scarmeas et al.
Neurology 2002;58:1182-1188.
ABSTRACT | FULL TEXT  

Apolipoprotein E and Alpha-1-Antichymotrypsin Genotypes Do Not Predict Time to Psychosis in Alzheimer's Disease
Sweet et al.
J Geriatr Psychiatry Neurol 2002;15:24-30.
ABSTRACT  

Role of Serotonin in the Behavioral and Psychological Symptoms of Dementia
Lanctôt et al.
J. Neuropsychiatry Clin. Neurosi. 2001;13:5-21.
ABSTRACT | FULL TEXT  

The Psychotic Phenomenon in Probable Alzheimer's Disease : A Positron Emission Tomography Study
Lopez et al.
J. Neuropsychiatry Clin. Neurosi. 2001;13:50-55.
ABSTRACT | FULL TEXT  

Increased Neocortical Neurofibrillary Tangle Density in Subjects With Alzheimer Disease and Psychosis
Farber et al.
Arch Gen Psychiatry 2000;57:1165-1173.
ABSTRACT | FULL TEXT  

Incidence of and risk factors for hallucinations and delusions in patients with probable AD
Paulsen et al.
Neurology 2000;54:1965-1971.
ABSTRACT | FULL TEXT  

Mental and Behavioral Disturbances in Dementia: Findings From the Cache County Study on Memory in Aging
Lyketsos et al.
Am. J. Psychiatry 2000;157:708-714.
ABSTRACT | FULL TEXT  

Psychosis of Alzheimer's Disease and Related Dementias: Diagnostic Criteria for a Distinct Syndrome
Jeste and Finkel
AJGP 2000;8:29-34.
FULL TEXT  

Apolipoprotein-E (APO-E) Genotype and Symptoms of Psychosis in Alzheimer's Disease
Harwood et al.
AJGP 1999;7:119-123.
ABSTRACT | FULL TEXT  

Delusions in Alzheimer's Disease: A Review
Rao and Lyketsos
J. Neuropsychiatry Clin. Neurosi. 1998;10:373-382.
ABSTRACT | FULL TEXT  

Executive Dysfunction in Alzheimer's Disease: Association With Neuropsychiatric Symptoms and Functional Impairment
Chen et al.
J. Neuropsychiatry Clin. Neurosi. 1998;10:426-432.
ABSTRACT | FULL TEXT  

Dopamine Receptor Genetic Variation, Psychosis, and Aggression in Alzheimer Disease
Sweet et al.
Arch Neurol 1998;55:1335-1340.
ABSTRACT | FULL TEXT  

The Cholinergic Hypothesis of Neuropsychiatric Symptoms in Alzheimer's Disease
Cummings and Back
AJGP 1998;6:64S-78.
ABSTRACT | FULL TEXT  

Differential Neuropsychiatric Symptom Responses to Tacrine in Alzheimer's Disease: Relationship to Dementia Severity
Kaufer et al.
J. Neuropsychiatry Clin. Neurosi. 1998;10:55-63.
ABSTRACT | FULL TEXT  

Biologic Markers and Neurochemical Correlates of Agitation and Psychosis in Dementia
Kirby and Lawlor
J Geriatr Psychiatry Neurol 1995;8:S2-S7.
ABSTRACT