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Alzheimer’s Disease Psychosis (ADP)

Alzheimer’s disease psychosis symptoms may include hallucinations and delusions experienced by as many as 30% of Alzheimer’s patients.

About Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common form of dementia. Approximately 6 million people in the United States have AD, with this number projected to rise as the elderly population grows.1,2 

AD is a neurocognitive disorder, with diagnosis requiring a combination of clinical assessments.1,3 Criteria like the National Institute on Aging and Alzheimer’s Association guidelines may be used to guide clinical diagnosis,4 that can then only be confirmed through autopsy.5

About ADP

Some patients with AD may experience symptoms of psychosis, such as hallucinations and delusions.3 

The overall prevalence of these symptoms of psychosis in AD is approximately 30%. While the literature varies based on study setting, the median prevalence of symptoms is 36% for delusions and 18% for hallucinations.6 

Typically, delusions in patients with AD occur earlier than hallucinations and are of the paranoid type, and hallucinations are more often visual than auditory.3,7

The Impact of ADP on Patients

The prevalence of psychosis has been shown to increase as cognitive impairment becomes more severe.6 In addition, the presence of delusions and hallucinations predicts a greater likelihood of progression to severe dementia and death in people with incident AD.8

Diagnosis

In 2020, the International Psychogeriatric Association (IPA) published Criteria for Psychosis in Major and Mild Neurocognitive Disorder: hallucinations or delusions occurring after the onset of cognitive decline, present (at least intermittently) for 1 month or longer, and not better explained by delirium, other medical conditions with psychotic features, or other medical conditions known to cause hallucinations (e.g., epilepsy, stroke, migraine).3 

Serotonin Dysfunction in ADP

Serotonin is thought to play a role in CNS disorders by modulating networks that impact a variety of other neurotransmitters (e.g., glutamate and dopamine).17-21 Dysfunction in the neural networks involving serotonin receptors has been linked to hallucinations and delusions associated with ADP.17,22,23

There is evidence that suggests symptoms of psychosis in AD dementia are associated with polymorphisms in the serotonergic pathway genes, in particular the 5-HTTLPR polymorphism in SLA6A4, which codes for the serotonin transporter.8-10 A recent meta-analysis has also found evidence for an association between polymorphisms of a 5-HT2A receptor gene and psychosis in AD.11

5-HT2A Receptors in ADP

Activation of the 5-HT2A receptors has been associated with altered visual perceptions and altered cortical activity in visuospatial cortices.20 On a cellular level, 5-HT2A receptor modulation of cortical pyramidal glutamate neurons could correspond with excess glutamate signaling to subcortical structures,17,20,24 such as the ventral tegmental area.25,26 

Delusions and auditory hallucinations are thought to stem from sustained hyperactive cortical glutamate neurons projecting to the ventral tegmental area and hyperactivating the dopamine mesolimbic pathway.24,26-28 Visual hallucinations are thought to stem from excess signaling via 5-HT2A receptors in the visual cortex with different hyperactive glutamate neurons in the occipital cortex.20,29 These dysfunctional neural networks involving serotonin receptors are thought to be responsive to the modulation of 5-HT2A receptors on cortical glutamate neurons.17-20,25 

Explore other Areas of Focus

Parkinson’s Disease Psychosis (PDP)
Rett Syndrome
References
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  3. Cummings J, Pinto LC, Cruz M, et al. Criteria for psychosis in major and mild neurocognitive disorders: International Psychogeriatric Association (IPA) consensus clinical and research definition. Am J Geriatr Psychiatry. Dec 2020;28(12):1256-1269.  
  4. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology. Jul 1984;34(7):939-44.  
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