In summary, Mr. A had no history of psychiatric illness until the age of 60. He presented with paranoid delusions and auditory hallucinations. Limited family psychiatric history was available; his mother had been admitted to an inpatient psychiatric unit at the age of 22, but her diagnosis was unknown. Results of medical examination and history were unremarkable. Neuropsychological performance did not suggest dementia. Moderate central and mild cortical volume loss was noted on the MRI. Although Mr. A had tried several psychotropic medications, he felt he benefited most from haloperidol. He developed tardive dyskinesia within a year of treatment.
Diagnostic Implications
Mr. A presented at the local hospital with psychotic symptoms. His initial symptom presentation was atypical, in that at age 60, he had no history of psychiatric illness, no known history of substance abuse, and no obvious medical illness. A number of evaluations, including history, physical examination, and laboratory tests, were conducted to rule out specific diagnoses. The differential diagnosis included 1) psychotic disorder due to a general medical condition (metabolic or other medical encephalopathy), 2) delirium, 3) psychosis secondary to substance abuse/dependence, 4) dementia with delusions and hallucinations, 5) mood disorder with psychotic features, 6) delusional disorder, 7) psychosis not otherwise specified or schizophreniform disorder, 8) brief reactive psychosis, and 9) schizophrenia with onset before versus after age 45.
1. Psychotic disorder due to a general medical condition (metabolic or other medical encephalopathy). Late age at onset and no past psychiatric history would point in favor of this diagnosis. According to history, physical examination, and laboratory results, however, there was no evidence of medical conditions known to cause psychiatric symptoms. The few neurological abnormalities identified were generally consistent with age. The MRI findings were nonspecific.
2. Delirium. Mr. A’s physical examination yielded largely negative results. He had no fever and no medical conditions associated with delirium.
3. Psychosis secondary to substance abuse/dependence. There was no history of substance abuse. Laboratory results showed no evidence of acute drug or alcohol intoxication or liver disease.
4. Dementia with delusions and hallucinations. Points in favor of this diagnosis would include late age at onset, scattered abnormalities on neurological and neuropsychological examination, and moderate central and mild cortical volume loss with multiple areas of focal hyperintensities on the MRI. There are, however, several points against this diagnosis including an absence of marked memory disturbances, dysphasia, and significant visuoconstructional deficits on neurological examination, no decrement in cognitive performance over the follow-up period, and global neuropsychological performance within normal limits. On clinical mental status examination, Mr. A did not demonstrate any evidence of dementia, such as word-finding difficulties or inability to retain newly learned information over time. Neurological findings did not fit a clear pattern. Although not conclusive, the MRI results, along with history and mental status findings, pointed away from dementia as the cause of Mr. A’s current psychotic symptoms. However, the possibility of a very early dementing process could not be ruled out.
5. Mood disorder with psychotic features. Mr. A never met the criteria for a manic or hypomanic episode; he never had a distinct period of abnormally and persistently elevated, expansive, or irritable mood lasting at least 4 days. He did not have inflated self-esteem or grandiosity, a decreased need for sleep (in fact, on numerous occasions he reported sleep disturbances and the need for more sleep), pressure to keep talking (he was usually quite guarded), flight of ideas, distractibility, increased goal-directed activity, or excessive involvement in pleasurable activities with a high potential for painful consequences. He also did not meet the criteria for major depressive episodes (i.e., for a period of at least 2 weeks, there was either depressed mood or loss of interest or pleasure in nearly all activities). In addition, he did not have psychomotor agitation or retardation, fatigue or loss of energy, feelings of worthlessness or excessive or inappropriate guilt, diminished ability to think or concentrate, or indecisiveness nearly every day or recurrent thoughts of death, suicidal ideation, or expansive or irritable mood. Mr. A’s affect was typically described as flat. There was no history of marked mood fluctuations.
In terms of family history, the reason for Mr. A’s mother’s past psychiatric hospitalization was unknown and therefore was not helpful for evaluating the possibility of a mood disorder.
6. Delusional disorder. Late-onset psychosis with paranoid delusions may seem to favor the diagnosis of delusional disorder. Bizarre delusions, including thought insertion, and prominent auditory hallucinations would, however, rule out this condition.
7. Psychosis not otherwise specified or schizophreniform disorder. Mr. A could have been given a provisional diagnosis of psychosis not otherwise specified or schizophreniform disorder at the initial presentation, but the follow-up showed persistence of some symptoms of schizophrenia.
8. Brief reactive psychosis. When questioned about the onset of his symptoms, Mr. A denied having any recent stressors in his life.
9. Schizophrenia. Mr. A met all DSM-IV criteria for schizophrenia. One issue was whether he might have had onset of illness before age 45. Pointers against this possibility include a lack of prodromal symptoms, functional decline, or history of treatment before the age of 60. Mr. A had had a stable vocational history, and he had been able to function successfully. Although he was always somewhat of a loner, he had been able to sustain some relationships.
At follow-up, Mr. A was comprehensively reevaluated as part of his research participation. Baseline neuropsychological testing (including assessments of learning and memory) did not reveal deficits consistent with dementia, and his isolated cognitive deficits did not fit a pattern characteristic of a known neurological disorder. He did not experience any significant mood changes. Although Mr. A discontinued research participation after 4 years, he continued to be followed clinically. Earlier repeated neuropsychological evaluations were generally in the average range and showed no evidence of a progressive decline. Mr. A’s cognitive strengths and weaknesses did not suggest any common neurological illness but were consistent with the pattern commonly seen in schizophrenia
(4). He continued to take haloperidol, and he experienced a significant improvement in positive symptoms. Given Mr. A’s symptoms and course of illness, his diagnosis would be late-onset schizophrenia.
At the initial presentation, Mr. A’s clinical subtype was paranoid. The clinical picture does change over time, however, especially with neuroleptic treatment. In the present case, the alternative subtype diagnosis at follow-up would have been either undifferentiated or residual.
Late-Onset Schizophrenia
Late-onset schizophrenia is predominantly of the paranoid subtype. According to DSM-III-R, the onset of symptoms, including prodromal symptoms, must be after the age of 45. DSM-IV, however, does not specify the term “late onset,” nor does it set an upper age limit for the diagnosis of schizophrenia. Often, the most notable symptom of late-onset schizophrenia is a bizarre, persecutory delusion. A number of patients experience systematized delusions of physical or mental influence. Auditory hallucinations are the next most prominent psychotic symptom. Schneiderian first-rank symptoms as well as mood symptoms may be seen in patients with late-onset schizophrenia. A review of the literature suggests that 13% of all hospitalized patients with schizophrenia had onset of illness in their 40s, 7% had onset in their 50s, and only 3% first presented after age 60
(5). Most studies report that late-onset schizophrenia is two to 10 times more common in women than in men
(6–
9). The higher prevalence of late-onset schizophrenia among women may result from postmenopausal neuroendocrine changes, psychosocial stressors, or unknown neurobiological factors. Most studies suggest a chronic course for late-onset schizophrenia
(5,
10–
12).
Reported similarities between late-onset schizophrenia and the typical early-onset schizophrenia include severity of positive symptoms, chronicity of course, sensory impairment, family history of schizophrenia, early childhood maladjustment, number of minor physical anomalies, increased mortality, overall pattern of neuropsychological impairment, nonspecific brain imaging abnormalities, and qualitative response to neuroleptics
(13–
16). In comparison to patients with early-onset schizophrenia, those with late-onset schizophrenia have a higher female-to-male ratio, less severe negative symptoms, less severe impairment in learning and abstraction, and a more intact semantic network. In adolescence and early adulthood, patients with late-onset schizophrenia also have had better premorbid functioning. In addition, patients with late-onset schizophrenia may have a larger thalamus, as shown on MRI, and seem to need lower doses of neuroleptics than age-comparable patients with early-onset schizophrenia. In summary, it appears that although there is a similar predisposition and probably similar brain lesions in patients with early-onset and late-onset schizophrenia, patients with late-onset may have a less severe form and a neurobiologically distinct subtype of the illness
(15). Discontinuation of neuroleptics tends to exacerbate psychotic symptoms. Infrequently, spontaneous remissions may occur.
Late-onset schizophrenia is still a controversial entity. Beginning with the Kraepelinian notion of dementia praecox
(17) and recently exemplified by DSM-III, the conventional wisdom limits the age at onset of schizophrenia to adolescence and young adulthood. It is postulated that negative symptoms, personality and cognitive deterioration, and social dysfunction typically associated with schizophrenia are typically lacking in patients with later onset of the illness. For this reason, various terms such as paraphrenia, late paraphrenia, and paranoia have been employed to describe late-onset paranoid psychotic disorders. One problem with such nosology, however, is that these terms have been used by different authors with varying definitions and do not have consistent clinical criteria
(5).
Psychosis at any age can be due to any one of multiple causes, including substance use, specific brain disorders (e.g., tumors), and other general medical conditions. In later life, the likelihood of new-onset psychosis being secondary to identifiable brain disorders increases, and these must first be ruled out. Nonetheless, there is a proportion of patients, as illustrated by Mr. A, whose late-onset psychotic disorder is similar to that of patients with early-onset schizophrenia, particularly the paranoid type, in terms of symptoms, course, and treatment response. Furthermore, neuropsychological and brain imaging findings, as well as follow-up data, do not support alternative diagnoses. It is worth noting that paranoid schizophrenia at any age is characterized by relative paucity of negative symptoms, absence of pronounced deterioration, and better prognosis than other clinical subtypes such as disorganized schizophrenia
(18) We believe that on the basis of the overall clinical picture, the most appropriate diagnosis for individuals such as Mr. A is late-onset schizophrenia. Making a distinct categorization of late-onset schizophrenia and continuing research on this topic are necessary to learn more about the factors associated with delayed onset of schizophrenia.
Treatment Considerations
Pharmacological. Mr. A was treated with an antipsychotic (haloperidol). Because of the potential side effects associated with neuroleptic use, informed consent was obtained and documented in his medical chart. At the time of his first symptoms, the only atypical antipsychotic medication available was clozapine, which, in the elderly, is recommended only for severe, refractory cases
(19). The starting dose of haloperidol was 10 mg b.i.d.; this would generally be considered too high for a person with late-onset schizophrenia. The dose was later reduced to 10 mg/day and subsequently to 6 mg/day. His last maintenance dose was 2 mg at bedtime. Given the sensitivity of older patients to side effects, it is critical to prescribe antipsychotics in doses that are considerably lower than those used in younger adults
(19).
Mr. A had a partial response to haloperidol; his auditory hallucinations remitted and his delusions improved, although mild paranoia persisted, along with some residual symptoms. He also developed parkinsonism, akathisia, and, within a year of treatment, tardive dyskinesia. Older patients are more likely to develop tardive dyskinesia even with lower doses
(20,
21). Vitamin E did not improve his tardive dyskinesia.
Despite recommendations from his treating physician to switch to an atypical antipsychotic medication, Mr. A continued to take haloperidol. He was given information about the risks and benefits associated with typical and atypical antipsychotics, but he was unwilling to change medicines because of fears that his positive psychotic symptoms would return.
Psychosocial. Mr. A did not follow up with recommendations to participate in individual or group therapy that could improve his coping skills. Possible reasons for his refusal include the existence of better than average social supports, along with a lack of awareness of his limitations and of the benefit he might derive from therapy, the fact that he was always a loner, and his continued underlying suspiciousness toward others. It appeared that Mr. A was overly dependent on his older sister in terms of housing, financial, and social support. It would be important to develop alternative resources for him so that he would be prepared if his sister carried through with her plans to live without him.
Prognostic Implications
A comprehensive assessment of Mr. A revealed several good prognostic indicators
(18). These include later onset of schizophrenia, paranoid subtype, relatively good premorbid adjustment with a supportive social network, treatment initiated early in the course of illness, only mildly impaired neuropsychological functioning, stable living situation (at least for the time being), and neuroleptic medication compliance. Negative prognostic indicators that cloud the picture include persistence of some symptoms, male gender, development of tardive dyskinesia, some treatment noncompliance, impaired insight into his needs and deficits, and the undiagnosed prostatic nodule.
Mr. A should continue to receive antipsychotic medication, with careful monitoring of side effects. As he ages, Mr. A’s dose requirement and tolerance are likely to decline, whereas his risk of and sensitivity to side effects may increase.
In terms of suicide risk, Mr. A is now past the phase of the greatest risk (5 to 10 years after diagnosis of schizophrenia). The fact that he does not have command hallucinations further decreases his risk. In addition, he denies suicidal ideation and has never attempted suicide in the past. On the other hand, as a single, elderly white man, Mr. A is in the demographic group with the highest risk of suicide
(22).
Research has shown that outpatients with schizophrenia are not necessarily at greater risk of developing dementia
(23), but, of course, this risk will increase with age, as it does for the population at large. Thus far, however, repeated neuropsychological and clinical assessments have found Mr. A’s cognitive functioning to be stable.
In terms of his psychosocial functioning, it is important to make long-term plans for Mr. A’s future care needs. Previous plans to move Mr. A to a board-and-care facility failed because of a lack of follow-through and support from Mr. A’s sister. It is important to enlist her support and to make plans while his functioning is still stable.