Increased striatal dopamine (D2/D3) receptor availability and delusions in Alzheimer disease
Open accessAbstract
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 [11C]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 (BPND) measures. Results: Mean [11C]RAC BPND was higher in patients with delusions (n = 7; 5 men) than in patients without delusions (n = 16; 6 men) (p = 0.006). When women were excluded from the analysis, [11C]RAC BPND was higher in men with delusions than in men without delusions (p = 0.05). Apathy measures showed no association with [11C]RAC BPND. Conclusions: Striatal dopamine (D2/D3) receptor availability is increased in Alzheimer disease patients with delusions, to an extent comparable to that observed in drug-naive patients with schizophrenia. Whether this represents up-regulation of dopamine (D2) or possibly dopamine (D3) receptors and how this relates to responsivity of the striatal dopaminergic system merit further exploration. AD = Alzheimer disease; AI = Apathy Inventory; AST = associative striatum; BPND = binding potential; CAMCOG = Cambridge Cognitive Examination; DA = dopamine; LS = limbic striatum; MMSE = Mini-Mental State Examination; MRC = Medical Research Council; non-AC = non–attenuated corrected; NPI = Neuropsychiatric Inventory; RAC = raclopride; ROI = region of interest; SMST = sensorimotor striatum.
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Apathy in Alzheimer's disease is not associated with D2/D3 dopamine receptor density.
“Of the two reports involving neurochemical imaging, one reported decreased bilateral putamen dopamine transporter density (David et al., 2008) while the other reported no association with D2/D3 dopamine receptor density (Reeves et al., 2009).”
From Neuropsychiatric symptoms in Alzheimer's disease: what might be associated brain circuits? (2015) · cites this paper as Reeves et al., 2009
Delusions in Alzheimer's disease are associated with increased D2/D3 receptor density.
“One neurochemical study with raclopride PET imaging found an association between delusions and increased D2/D3 receptor density (Reeves et al., 2009).”
From Neuropsychiatric symptoms in Alzheimer's disease: what might be associated brain circuits? (2015) · cites this paper as Reeves et al., 2009
There was no association between dopamine D2/D3 receptor density and apathy in Alzheimer's disease.
“there was no association between dopamine D2/ D3 receptor density and apathy in AD (Reeves et al., 2009)”
From Neuropsychiatric symptoms in Alzheimer's disease: what might be associated brain circuits? (2015) · cites this paper as Reeves et al., 2009
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- Authors
- Reeves, S., Brown, R., Howard, R., & Grasby, P.
- Affiliations
- Hammersmith Hospital (GB)
- Venue
- Neurology
- Published
- 2009-02-10
- Volume
- 72
- Issue
- 6
- Pages
- 528-534
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC2818181
- OpenAlex
- W2039588423
- Cited by
- 98
- References
- 39
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 9 · 2023: 3 · 2022: 6 · 2021: 9 · 2020: 5 · 2019: 7 · 2018: 1 · 2017: 4 · 2016: 4 · 2015: 7 · 2014: 7 · 2013: 8 · 2012: 7
- FWCI
- 4.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Pfizer
- GlaxoSmithKline
- Wellcome Trust (078946)
- Eisai
- H. Lundbeck A/S
- Medical Research Council
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- Alzheimer's disease, delusions, [11C]raclopride PET, apathy, neuropsychiatric symptoms, sex differences
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Corpus Striatum, Delusions, Female, Humans, Male, Up-Regulation, Receptors, Dopamine D2, Positron-Emission Tomography, Receptors, Dopamine D3
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