Journal of Geriatric Psychiatry and Neurology

Psychosis in elderly patients is a growing clinical concern because psychotic symptoms most frequently occur as noncognitive manifestations of Alzheimer’s disease, as side effects of drug therapy for Parkinson’s disease, or as the primary abnormalities in schizophrenia, and the clinical characteristics of psychosis are distinct for each. In planning antipsychotic pharmacotherapy for elderly patients, age-related pharmacokinetic changes, polypharmacy for comorbid diseases, and concerns about the underlying conditions responsible for the psychotic symptoms must be considered. Traditional antipsychotic agents bind to dopamine receptors and effectively relieve positive schizophrenic symptoms but frequently cause tardive dyskinesia and other extrapyramidal symptoms, a problem for elderly patients, particularly for those with Parkinson’s disease. Atypical antipsychotics bind to dopamine and serotonin receptors, relieving both positive and negative symptoms, and are less likely to cause extrapyramidal symptoms. The authors review common diagnostics associated with psychosis in the elderly and clinical guidelines to selecting antipsychotic pharmacotherapy.

The nosology, classification, and biological basis of psychosis in the elderly have been much debated. Psychotic features are seen in schizophrenia, affective illness, and dementia in the elderly. This article reviews evidence for the biological basis of psychosis in older people. In schizophrenia, there is evidence of gender differences in brain volume loss and dopamine receptor numbers, possibly linked to estrogen loss in women. Neuroimaging evidence of ventricular brain changes and more dopamine receptors have also been documented. In Alzheimer’s disease, genetic factors such as PS1 and ApoE4 have been associated with psychotic symptoms, and histopathological studies have revealed differences in neuronal pathology. Radiological studies have shown right and left hemisphere differences in size, blood flow, and glucose metabolism between psychotic and nonpsychotic patients. In affective illnesses, there is evidence of structural brain changes in psychotic depression. Ample evidence suggests that biological substrates underlie many psychotic symptoms. More research will identify causal links between brain changes, symptom appearance, and the effects of psychosocial factors in their genesis.

Objective.Psychotic symptoms are seen in numerous psychiatric illnesses afflicting the elderly. This article reviews the efficacy of the pharmacologic management of psychotic symptoms in primary psychotic disorders, affective disorders, and neurodegenerative disorders. Method.A comprehensive literature review. Results.Evidence to support the use of pharmacologic interventions to manage psychotic symptoms in elderly patients afflicted with primary psychotic disorders and affective disorders is limited by the absence of randomized, placebo-controlled trials (RCTs). The use of low-dose clozapine is supported by RCTs in Parkinson’s disease. The efficacy of risperidone and olanzapine for the treatment of psychotic symptoms has been demonstrated by large RCTs in Alzheimer’s disease. Conclusion.There is evidence of the efficacy of antipsychotic medications to manage psychotic symptoms in elderly patients. However, the absence of published evidence from RCTs in primary psychotic and affective disorders, and the limited evidence in the neurodegenerative illnesses, is notable.

This article proposes an initial nomenclature and systematic approach for the nonpharmacologic understanding and treatment of psychotic symptoms in dementia. An analysis of delusions and hallucinations must examine alternative etiologies, including misdiagnosis and misunderstanding, the misinterpretation of reality because of cognitive losses, sensory deprivation and vision loss, ambiguous sensations, and delirium and medical causes. Nonpharmacologic treatments frequently follow directly from etiology, such as improving sensory function via hearing aids or eyeglasses, providing stimulation, changing antecedents prone to misinterpretation (eg, reflections in windows), or circumventing misinterpretations (eg, ensuring that an equivalent object is available so there is no sense of loss or theft). Given the differences between psychotic symptoms in Alzheimer’s disease and those in other diseases, the term psychosisshould be abandoned for most dementia patients, and assessments of etiology should be developed. Future research should clarify what proportion of symptoms currently identified as psychotic are attributable to related etiologies.

The elderly population is rapidly growing and increasing in diversity. Furthermore, mental disorders are common in this population. Elderly patients are at increased risk for developing psychotic symptoms. Consequently, clinicians must increase their awareness of culture and its effect on psychosis in the elderly. This article briefly reviews the components of cultural assessments, cultural issues pertaining to diagnosis and treatment, and culture-bound syndromes. Some studies have demonstrated ethnic differences in the presention, assessment, diagnosis, and treatment of psychotic disorders in the elderly. These differences may be explained by factors including clinicians’ bias, cultural distance between patients and clinicians, culturally biased diagnostic instruments, stereotypes of psychopathology, and biological and other environmental factors. However, some studies have not documented ethnic differences in diagnosing and treating psychotic disorders. Appropriate assessments and diagnoses include patients’ and clinicians’ ethnic and cultural contexts. Rigorous methodological research is needed to further evaluate the prevalence and treatment of psychotic disorders in ethnic minority elders.

Erotomania is a delusional syndrome in which an affected individual is convinced that another person loves him or her. Erotomania usually occurs in middle-aged female patients. Only 3 cases have been described in dementia so far. The authors report 2 cases, in Alzheimer’s disease and vascular dementia, in which erotomania emerged in the early stage of the underlying disorder. In both cases, erotomania partially responded to antipsychotic treatment. Erotomania may be understood in evolutionary terms as a pathologic deviation of an evolved psychological mechanism relating to mate selection and may therefore account for the typical sex distribution of the syndrome in favor of women and the onset of the disorder, usually during the late reproductive phase. The association of erotomania with dementing disorders may tentatively be interpreted to suggest that such complex psychological mechanisms and behaviors as involved here in “organic” delusions may have distinct, “hard-wired” representations in the human brain.

Serum •1-acid glycoprotein (AAG) concentrations were examined in relationship to age, medical burden, depression, and mental status in elderly control (n = 19, mean age = 72.1 ± 6.8 years) and depressed (n = 58, mean age = 71.9 ± 7.1 years) subjects. DNA was analyzed for allelic variants of the AGP1 (ORM1) gene in both groups. Depressed subjects’ AAG serum levels were measured at baseline and after 6 weeks of antidepressant treatment. Before treatment, depressed subjects had significantly higher serum AAG concentrations than nondepressed controls (t49.2 = –3.48, P= .0011). Pretreatment AAG levels also correlated with degree of medical burden, measured by the Cumulative Illness Rating Scale–Geriatrics (r= 0.28, P= .0303), but not with age, depression severity, or cognitive scores. There was no significant difference between responders and nonresponders on changes in AAG levels from baseline to week 6. Frequency differences in ORM1 allelic variants apparently did not influence increased AAG concentrations in depressed patients.

The authors previously reported that subcortical hyperintensity (SH) and whole-brain volume (WBV) each covary with different subscale scores of the Mattis Dementia Rating Scale (MDRS) among vascular dementia (VaD) patients. The present longitudinal analysis examined these relationships for change. The authors found that SH volume increased and WBV decreased significantly over 12 months. At baseline, SH volume accounted for significant variance in MDRS total score and every subscale score, except Memory. WBV was unrelated to any MDRS measure. After 12 months, SH volume was related only to the Construction subscale score, whereas WBV accounted for the majority of variance in Attention and Memory subscale performance. These findings indicate that although SH volume increases with disease progression, the relative impact of SH volume on cognitive status decreases among patients with advanced VaD.

To determine if Alzheimer’s disease (AD), its Lewy body (LB) variant (LBV), and diffuse LB disease (DLBD) are distinguishable at initial clinical evaluation, data from autopsy-confirmed AD, LBV, and DLBD were examined. No significant differences were found in age at onset, age at death, total duration of illness, duration of illness before initial visit, duration of illness from initial visit to death, or severity of illness at initial evaluation. Hallucinations and delusions were significantly more frequent for LBV and DLBD, respectively, than for AD, and falls were more frequent for DLBD than for AD. Extrapyramidal symptoms (EPS) were less frequent in neuroleptic-free AD subjects than in LB subjects; the percentage of AD patients with EPS after neuroleptic exposure was less than that among LB patients. Seizures were significantly more common for DLBD than for AD or LBV. LB dementias differed from AD at initial evaluation, with more frequent hallucinations and delusions, EPSs, and seizures, and longitudinally in neuroleptic sensitivity, but the data did not distinguish LBV from DLBD.