Alterations of Striatal Dopamine Receptor Binding in Alzheimer Disease Are Associated With Lewy Body Pathology and Antemortem Psychosis

Sweet, Robert A.; Hamilton, Ronald L.; Healy, Matthew T.; Wisniewski, Stephen R.; Henteleff, Ruth; Pollock, Bruce G.; Lewis, David A.; DeKosky, Steven T.

doi:10.1001/archneur.58.3.466

Cited by 73 publications

(57 citation statements)

References 27 publications

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“…In vitro, a 70% increase in DA (D3) receptor density has been found in the ventral caudate of psychotic (neuroleptic naive or intolerant) compared with nonpsychotic patients with AD. 32 It is not possible to distinguish between DA (D2 and D3) receptors through the use of […”

Section: Results Descriptive and Neuropsychological Testmentioning

confidence: 99%

Increased striatal dopamine (D2/D3) receptor availability and delusions in Alzheimer disease

Reeves¹,

Brown²,

Howard³

et al. 2009

Neurology

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Objective: Dysfunction within corticostriatal dopaminergic neurocircuitry has been implicated in neuropsychiatric symptoms associated with Alzheimer disease (AD). This study aimed to test the hypothesis that the symptom domains delusions and apathy would be associated with striatal dopamine (D2) receptor function in AD. Methods:In vivo dopamine (D2/D3) receptor availability was determined with [ 11 C]raclopride (RAC) PET in 23 patients with mild and moderate probable AD. Behavioral symptoms were measured using the Neuropsychiatric Inventory and the Apathy Inventory. Imaging data were analyzed using a region-of-interest approach. The potential confounding effects of age, sex, and disease stage were explored using a linear mixed model. Correlational and independent samples comparisons were used to examine the relationship between behavioral and binding potential (BP ND ) measures. Results: Mean [11 C]RAC BP ND was higher in patients with delusions (n ϭ 7; 5 men) than in patients without delusions (n ϭ 16; 6 men) (p ϭ 0.006). When women were excluded from the analysis,

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Section: Results Descriptive and Neuropsychological Testmentioning

confidence: 99%

Increased striatal dopamine (D2/D3) receptor availability and delusions in Alzheimer disease

Reeves¹,

Brown²,

Howard³

et al. 2009

Neurology

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“…Forty-five subjects (Table 1) underwent neurologic, neuropsychologic, and psychiatric diagnostic evaluations as part of their participation in the Clinical Core of the Alzheimer Disease Research Center (ADRC) at the University of Pittsburgh [3, 22, 37]. Psychiatrists with specialized training in geriatric psychiatry conducted semi-structured examinations, and the patient, primary caregiver, and all other available informants were interviewed.…”

Section: Methodsmentioning

confidence: 99%

Hyperphosphorylated Tau is Elevated in Alzheimer's Disease with Psychosis

Murray

Kirkwood

Gray

et al. 2014

JAD

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Psychosis occurs in 40–60% of Alzheimer's disease (AD) subjects, is heritable, and indicates amore rapidly progressive disease phenotype. Neuroimaging and postmortem evidence support an exaggerated prefrontal cortical synaptic deficit in AD with psychosis. Microtubule-associated protein tau is a key mediator of amyloid-β-induced synaptotoxicity in AD, and differential mechanisms of progressive intraneuronal phospho-tau accumulation and interneuronal spread of tau aggregates have recently been described. We hypothesized that psychosis in AD would be associated with greater intraneuronal concentration of phospho-tau and greater spread of tau aggregates in prefrontal cortex. We therefore evaluated prefrontal cortex phospho-tau in a cohort of 45 AD cases with and without psychosis. Intraneuronal phospho-tau concentration was higher in subjects with psychosis, while a measure of phospho-tau spread, volume fraction, was not. Across groups both measures were associated with lower scores on the Mini-Mental State Examination and Digit Span Backwards test. These novel findings indicate that tau phosphorylation may be accelerated in AD with psychosis, indicating a more dynamic, exaggerated pathology in AD with psychosis.

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“…Psychotic symptoms are associated with specific patterns of regional cortical metabolism ( fig. 1) [20], as well as with regional neuropathology [21], neurochemistry [22], and neuroreceptor density [23,24], and with particular genetic alleles [25]. These findings suggest a neurobiological substrate for the syndrome and an opportunity to refine pharmacological treatments to address specific physiological alterations that are linked to symptoms.…”

Section: Psychosis In Admentioning

confidence: 99%

Psychosis and Antipsychotic Medications in Alzheimer’s Disease: Clinical Management and Research Perspectives

Sultzer

2003

Dement Geriatr Cogn Disord

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Psychosis is common in patients with Alzheimer’s disease (AD) and contributes substantially to patient morbidity and caregiver distress. Antipsychotic medications are used to treat psychosis and other psychiatric or behavioral symptoms in AD, although optimal treatment guidelines have been elusive. Choosing the most advantageous medication for an individual patient is challenging. This article provides an overview of clinical management principles and medication treatment strategies for patients with AD and psychosis. Effects of individual medications are also described. Medications in the conventional neuroleptic, atypical antipsychotic, cholinesterase inhibitor, and serotonergic classes have been shown to ameliorate psychosis and behavioral symptoms in patients with AD, although the evidence is not conclusive for many medications. Side effects vary substantially across medication classes and modestly among individual patients. Improvement in agitation, aggression, or other behaviors with antipsychotic medication treatment may not depend on distinct antipsychotic effects. In contrast, there is preliminary evidence that delusions and hallucinations may respond to treatment with medications outside the antipsychotic class. Many important clinical questions warrant further research study. In particular, studies to compare how individual symptoms respond to different medications, and to examine how to best manage overlapping symptoms or incomplete treatment response are needed.

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Alterations of Striatal Dopamine Receptor Binding in Alzheimer Disease Are Associated With Lewy Body Pathology and Antemortem Psychosis

Abstract: Alzheimer disease with LB is associated with selective alterations in dopamine receptor density, which may contribute to the distinct clinical profile of this group. The D3 receptor may be an important target of neuroleptic treatment of psychosis in AD.

Cited by 73 publications

References 27 publications

Increased striatal dopamine (D2/D3) receptor availability and delusions in Alzheimer disease

Increased striatal dopamine (D2/D3) receptor availability and delusions in Alzheimer disease

Hyperphosphorylated Tau is Elevated in Alzheimer's Disease with Psychosis

Psychosis and Antipsychotic Medications in Alzheimer’s Disease: Clinical Management and Research Perspectives

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