Secondary causes for psychosis are more common in older adults (65 years or older) than in younger patients. Here are 6 possible culprits.
(This is the second article in a series discussing psychotic disorders in late life. The first installment appeared in the August issue, pages 16-17. —Ed)
Psychosis in late life may result from any of an array of different illnesses with varied etiologies. Indeed, available evidence indicates that secondary causes for psychosis are more common among older adults (65 years and older) when compared with younger individuals.1 It is also necessary to distinguish between late-onset schizophrenia (LOS), very late–onset schizophrenia-like psychosis (VLOS), and early-onset schizophrenia (EOS). Having an appreciation of these possible etiologies is important, as this information will help with early identification and treatment of these disorders.
Cognitive decline, poor health status, visual impairment, and negative life events have been identified as risk factors for the development of psychotic disorders among older adults.2 Older age of onset for schizophrenia is known to be associated with female gender, a lower family history of schizophrenia, lower rates of substance use, better early psychosocial functioning, higher educational attainment, and a greater number of comorbid physical health problems.3 For LOS and VLOS, female gender appears to be a prominent risk factor.4 Additional risk factors for VLOS are more abnormalities in brain structures, family history of schizophrenia or avoidant personality, paranoid or schizoid personality disorder, hearing loss, being from an immigrant population, or having a lower socioeconomic status.1
A detailed cognitive assessment and thorough physical examinations can help differentiate among the various etiologies for psychotic symptoms in late life. Secondary causes for psychotic disorders in late life can be identified by a complete blood count and complete metabolic panel; further blood work that measures thyroid-stimulating hormone, vitamin B12, folate level, rapid plasma reagin, and erythrocyte sedimentation rate; urine toxicology; and autoimmune panels and HIV panels.5 Additionally, neuroimaging studies like magnetic resonance imaging or computerized tomography can rule out structural brain abnormalities causing psychotic symptoms. In complicated cases, neuropsychological testing can help differentiate among the possible etiologies for psychotic symptoms in late life.6
Schizophrenia. The prevalence of schizophrenia among individuals 65 years or older is approximately 0.1% to 0.5%.7,8 Between 20% and 25% of schizophrenia cases are either LOS or VLOS, and the incidence of schizophrenia among individuals 65 years or older is 7.5 per 100,000.9,10 The incidence rate of VLOS is 37.66 per 100,000 person-years at risk (an estimation based on observation time per participant), and 60% of individuals with VLOS are women.11,12 Often debilitating in its own right, schizophrenia is also a risk factor for developing dementia (relative risk = 2.2).13
Schizoaffective disorder. Among older adults, the prevalence of schizoaffective disorder is approximately 0.14%.14 Older adults have higher severity of illness, more treatment resistance, and higher risk for suicide when compared with younger adults.15 Not all schizoaffective disorders in older adults carry the same risk. Older adults with the depressive type of schizoaffective disorder have a higher history of suicide attempts and are more likely to take antidepressant medications when compared with those with the bipolar-type illness.16
Delusional disorder. The prevalence of delusional disorder is approximately 0.03% in this population.17 Individuals with this condition can have normal cognitive, personal, and occupational functioning, but significant social dysfunction.
Depressive and bipolar disorders (affective psychosis). Among older adults, the incidence of affective psychosis is approximately 30.9 per 100,000 person years.11 Older patients with bipolar disorder have more paranoia when compared to younger adults, and delusions are present in 45% of older adults admitted to hospitals for depression.18,19 Older adults with psychotic depression also have a higher prevalence of comorbid anxiety and somatic symptoms.20
Major neurocognitive disorders. Psychotic symptoms occur in approximately 40% of individuals with major neurocognitive disorders. Psychotic symptoms are seen in approximately 41.1% of individuals with Alzheimer disease.21 Psychosis occurs in 15% of the individuals with vascular neurocognitive disorders.22 Visual and auditory hallucinations and delusions occur in 78% and 25% of individuals with neurocognitive disorders with Lewy bodies.23
Delirium. The prevalence of psychotic symptoms among individuals with delirium is approximately 42.7%.24 Visual hallucinations occur in 27%, delusions in 25.6%, auditory hallucinations in 12.4%, and tactile hallucination in 2.7%.24
Differentiating LOS, VLOS, and EOS
The risk for developing secondary psychosis due to drug use, environmental toxins like lead or mercury and medical illness is greater among older adults due to comorbidities, polypharmacy, and sensitivity to drugs.25
When it comes to patient background and risk factors, there are significant differences between LOS, VLOS, and EOS (Table).1,9-13
It has been noted that LOS is associated with a genetic variant indopamine D2 receptor (DRD2), rs2734839.26 Additionally, individuals with LOS appear to have larger thalamic volumes and abnormalities in white matter integrity when compared with individuals with EOS.27-29 Individuals with LOS also present with reduced cerebral blood flow in both postcentral gyri when compared with individuals with EOS who present with reduced blood flow to the precentral gyrus and inferior frontal gyrus.30 Older adults with delusional disorders appear to have larger lateral ventricular volumes than older adults with schizophrenia and almost twice those of age-matched controls.31
Psychosis in late life is not uncommon, with secondary causes of psychosis being more prevalent than primary psychotic disorders. Among older adults who present with psychotic symptoms, a thorough history, the evaluation of risk factors, and conducting an appropriate work-up that includes neuroimaging studies and neuropsychological testing for complicated cases will result in early identification of the etiologies and prompt treatment of these symptoms.
Dr Tampi is chairman of the Department of Psychiatry & Behavioral Sciences, Cleveland Clinic Akron General, Akron, Ohio; chief, Section for Geriatric Psychiatry, Cleveland Clinic, Ohio; and professor of medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio. The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.
1. Howard R, Rabins PV, Seeman MV, Jeste DV. Late-onset schizophrenia and very-late-onset schizophrenia-like psychosis: an international consensus. The International Late-Onset Schizophrenia Group. Am J Psychiatry. 2000;157(2):172-178.
2. Brunelle S, Cole MG, Elie M. Risk factors for the late-onset psychoses: a systematic review of cohort studies. Int J Geriatr Psychiatry. 2012;27(3):240-252.
3. Chen L, Selvendra A, Stewart A, Castle D. Risk factors in early and late onset schizophrenia. Compr Psychiatry. 2018;80:155-162.
4. Jeste DV, Symonds LL, Harris MJ, et al. Nondementia nonpraecox dementia praecox? late-onset schizophrenia. Am J Geriatr Psychiatry. 1997;5(4):302-317.
5. Reinhardt MM, Cohen CI. Late-life psychosis: diagnosis and treatment. Curr Psychiatry Rep. 2015;17(2):1.
6. Javadpour A, Sehatpour M, Mani A, et al. Assessing diagnosis and symptoms profiles of late-life psychosis. GeroPsych. 2013;26(4):205-209.
7. Castle DJ, Murray RM. The epidemiology of late-onset schizophrenia. Schizophr Bull. 1993;19(4):691-700.
8. Copeland JR, Dewey ME, Scott A, et al. Schizophrenia and delusional disorder in older age: community prevalence, incidence, comorbidity, and outcome. Schizophr Bull. 1998;24(1):153-161.
9. Harris MJ, Jeste DV. Late-onset schizophrenia: an overview. Schizophr Bull. 1988;14(1):39-55.
10. Stafford J, Howard R, Kirkbride JB. The incidence of very late-onset psychotic disorders: a systematic review and meta-analysis, 1960-2016. Psychol Med. 2018;48(11):1775-1786.
11. Stafford J, Howard R, Dalman C, Kirkbride JB. The incidence of nonaffective, nonorganic psychotic disorders in older people: a population-based cohort study of 3 million people in Sweden. Schizophr Bull. 2019;45(5):1152-1160.
12. Riisgaard Ribe A, Munk Laursen T, Charles M, et al. Long-term risk of dementia in persons with schizophrenia: a Danish population-based cohort study. JAMA Psychiatry. 2015;72(11):1095-1101.
13. Cai L, Huang J. Schizophrenia and risk of dementia: a meta-analysis study. Neuropsychiatr Dis Treat. 2018;14:2047-2055.
14. Meesters PD, de Haan L, Comijs HC, et al. Schizophrenia spectrum disorders in later life: prevalence and distribution of age at onset and sex in a Dutch catchment area. Am J Geriatr Psychiatry. 2012;20(1):18-28.
15. Post F. Schizo-affective symptomatology in late life. Br J Psychiatry. 1971;118(545):437-445.
16. Baran XY, Young RC. Bipolar and depressive types of schizoaffective disorder in old age. Am J Geriatr Psychiatry. 2006;14(4):382-383.
17. González-Rodríguez A, Molina-Andreu O, Navarro V, et al. Delusional disorder: no gender differences in age at onset, suicidal ideation, or suicidal behavior. Braz J Psychiatry. 2014;36(2):119-124.
18. Depp CA, Jeste DV. Bipolar disorder in older adults: a critical review. Bipolar Disord. 2004;6(5):343-367.
19. Owoeye O, Kingston T, Scully PJ, et al. Epidemiological and clinical characterization following a first psychotic episode in major depressive disorder: comparisons with schizophrenia and bipolar I disorder in the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS). Schizophr Bull. 2013;39(4):756-765.
20. Gournellis R, Oulis P, Rizos E, et al. Clinical correlates of age of onset in psychotic depression. Arch Gerontol Geriatr. 2011;52(1):94-98.
21. Ropacki SA, Jeste DV. Epidemiology of and risk factors for psychosis of Alzheimer’s disease: a review of 55 studies published from 1990 to 2003. Am J Psychiatry. 2005;162(11):2022-2030.
22. Leroi I, Voulgari A, Breitner JCS, Lyketsos CG. The epidemiology of psychosis in dementia. Am J Geriatr Psychiatry. 2003;11(1):83-91.
23. Nagahama Y, Okina T, Suzuki N, et al. Classification of psychotic symptoms in dementia with Lewy bodies. Am J Geriatr Psychiatry. 2007;15(11):961-967.
24. Gareri P, Segura-García C, Manfredi VGL, et al. Use of atypical antipsychotics in the elderly: a clinical review. Clin Interv Aging. 2014;9:1363-1373.
25. Keshavan MS, Kaneko Y. Secondary psychoses: an update. World Psychiatry. 2013;12(1):4-15.
26. Voisey J, Swagell CD, Hughes IP, et al. A novel DRD2 single-nucleotide polymorphism associated with schizophrenia predicts age of onset: HapMap tag-single-nucleotide polymorphism analysis. Genet Test Mol Biomarkers. 2012;16(2):77-81.
27. Sachdev P, Brodaty H, Rose N, Cathcart S. Schizophrenia with onset after age 50 years. 2: neurological, neuropsychological and MRI investigation. Br J Psychiatry. 1999;175:416-421.
28. Corey-Bloom J, Jernigan T, Archibald S, et al. Quantitative magnetic resonance imaging of the brain in late-life schizophrenia. Am J Psychiatry. 1995;152(3):447-449.
29. Chen L, Chen X, Liu W, et al. White matter microstructural abnormalities in patients with late-onset schizophrenia identified by a voxel-based diffusion tensor imaging. Psychiatry Res. 2013;212(3):201-207.
30. Wake R, Miyaoka T, Araki T, et al. Regional cerebral blood flow in late-onset schizophrenia: a SPECT study using 99mTc-ECD. Eur Arch Psychiatry Clin Neurosci. 2016;266(1):3-12.
31. Howard RJ, Almeida O, Levy R, et al. Quantitative magnetic resonance imaging volumetry distinguishes delusional disorder from late-onset schizophrenia. Br J Psychiatry. 1994;165(4):474-480. ❒