Dopamine and Alzheimer's Disease
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This document discusses dopamine and its relationship to Alzheimer's disease. It provides an overview of dopamine pathways in the brain and its metabolism. Imaging techniques for measuring dopamine like MRI, PET, and tractography are mentioned. Several articles are summarized that show dopamine deficits may be related to cognitive decline in aging and Alzheimer's. Genetic factors like the DAT rs6347 variant and COMT gene are also discussed in the context of dementia severity and psychosis.
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- Delirium is characterized by acute onset of confusion and impaired consciousness. Dementia is a chronic disorder characterized by cognitive decline over months to years. Organic amnestic syndrome specifically involves memory impairment.
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1. Psychosis is a thought disorder characterized by disturbances in reality, perception, cognition, and affect. It encompasses several mental disorders including schizophrenia.
2. Schizophrenia is a type of psychosis characterized by severe personality changes and thought disorders. It has an onset in late teens to early twenties and has both genetic and environmental risk factors.
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I would do the following:
1. Assess for delirium by checking vital signs, mental status, and reviewing the medication list for any recent changes.
2. Taper and discontinue the ropinirole and alprazolam which can worsen hallucinations.
3. Consider reducing the levodopa dose gradually if hallucinations persist after stopping the other medications.
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- Positive symptoms include delusions and hallucinations, while negative symptoms include anhedonia and avolition.
- Genetic and biochemical factors like dopamine imbalance are implicated in schizophrenia. Brain structures like the prefrontal cortex and hippocampus also show abnormalities.
- Multiple neurotransmitter systems may be involved including dopamine, serotonin, glutamate, GABA, acetylcholine, and norepinephrine.
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3) First line treatments include dopamine agonists, MAO inhibitors and pyridoxine to supplement the deficient enzyme. Additional medications may be used for symptoms like anticholinergics, melatonin, benzodiazepines and alpha blockers
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2. Schizophrenia is a type of psychosis characterized by severe personality changes and thought disorders. It has an onset in late teens to early twenties and has both genetic and environmental risk factors.
3. Antipsychotic drugs treat psychosis by blocking dopamine D2 receptors in the brain. Older "typical" antipsychotics are more likely to cause extrapyramidal side effects while newer "atypical" antipsychotics have fewer neurological side effects.
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There are three main points covered in the document:
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2. Schizophrenia is a type of psychosis characterized by severe personality changes and thought disorders. It has an onset in late teens to early twenties and has both genetic and environmental risk factors.
3. Antipsychotic drugs treat psychosis by blocking dopamine D2 receptors in the brain. Older "typical" antipsychotics are more likely to cause extrapyramidal side effects while newer "atypical" antipsychotics have fewer neurological side effects.
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I would do the following:
1. Assess for delirium by checking vital signs, mental status, and reviewing the medication list for any recent changes.
2. Taper and discontinue the ropinirole and alprazolam which can worsen hallucinations.
3. Consider reducing the levodopa dose gradually if hallucinations persist after stopping the other medications.
4. Initiate a trial of quetiapine or clozapine which are less likely to worsen parkinsonism compared to other antipsychotics. Start low and titrate slowly.
5. Reassure the patient and family that the hallucinations are likely due to Parkinson's disease progression and
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- Schizophrenia is a disruptive psychopathology involving cognition, emotion, perception and behavior that typically emerges before age 25.
- Positive symptoms include delusions and hallucinations, while negative symptoms include anhedonia and avolition.
- Genetic and biochemical factors like dopamine imbalance are implicated in schizophrenia. Brain structures like the prefrontal cortex and hippocampus also show abnormalities.
- Multiple neurotransmitter systems may be involved including dopamine, serotonin, glutamate, GABA, acetylcholine, and norepinephrine.
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Dopamine and Alzheimer's Disease
- 1. DOPAMINE & ALZHEIMER’S AmirHussein Abdolalizadeh Interdisciplinary Neuroscience Research Program (INRP), March 2018
- 2. OVERALL VEIW OVER DOPAMINE
- 3. BRAIN PATHWAYS • A major neurotransmitter with modulatory effects • Involved in many brain systems • Nigrostriatal pathway: Movement • Mesolimbic pathway: Reward • Mesocortical: Executive Function • Tuberoinfundibular: Endocrine • Receptors: D1 to D5
- 4. Metabolism Degradation: • MAO (mostly B) • Monoamine Oxidase • Oxidative Deamination • Produces H2O2 & DOPAL • COMT • Catechol-O-Methyl Transferase • Methyl from S-Adenosyl Methionone to Dopamine • In glial cells (mostly microglia) • Produces Homovanilic Acid (HVA)
- 6. GENERAL MRI MEASURES • Atrophy • “Brain Shrinkage” • T1 MRI • Diffusion MRI • Physical basis • Information Provides • Tractography • Tissue Properties • Functional MRI • BOLD Signal • Activity dependent
- 7. PET • PET basis • Dopamine Imaging • Dopamine Transporters • Dopamine Release
- 8. ARTICLES
- 9. • An overview of the amyloid hypothesis • Ascending dopamine (DA) pathways and synapses with neocortex • Progressive degeneration of DA nuclei in brainstem modulation • Different sensitivity to A toxicity: DAergics are intermediate • Normal aging have effects on DAergic system • Decreased Release • Reduced D2 expression • Reduced DA transporter (DAT) expression • Apathy and Executive function decline: “Unsuccessful aging” • The earlier the DA deficit occurs Faster the cognitive decline • DA agonists improve several domains of cognition in AD patients • Apathy is the most common DA deficit sign, Extrapyramidals next • Cluster of AD patients with apathy and CSF tau: limited response to Choline Esterase Inhibitors,
- 10. • DAT rs6347: severe dementia and minor allele (C) • Subjects from ADNI, only non-Hispanics included • Volume expansion ~ age + sex + diagnosis + APOE + subjects (random factor) + timepoint (repeated measure) • More strongly associated with atrophy rather than cognitive measurements, why?
- 11. • COMT and Psychosis in Schizophrenia: Haplotypes • AD+P: more severe phenotype of disease • Val158Met associated with modest increase in Psychosis
Editor's Notes
- AD+P in 30-60% of subjects, familial with heritability ~70%