The older patients experienced less severe symptoms overall and were on lower daily doses of neuroleptics than

Although schizophrenia is commonly thought of as an illness of young adulthood, it can both extend into and first appear in later life. Diagnostic criteria for schizophrenia are the same across the life span, and DSM-IV places no restrictions on age of onset for a diagnosis to be made. Symptoms include delusions, hallucinations, disorganized speech, disorganized or catatonic behavior (the so-called “positive” symptoms), as well as affective flattening, alogia, or avolition5 (the so-called “negative” symptoms). Symptoms must cause significant social or occupational dysfunction, must not be accompanied by prominent mood symptoms, and must not be uniquely associated with substance use.

Prevalence and Cost
One-year prevalence of schizophrenia among those 65 years or older is reportedly only around 0.6 percent, about one-half the 1-year prevalence of the 1.3 percent that is estimated for the population aged 18 to 54.

The economic burden of late-life schizophrenia is high. A study using records from a large California county found the mean cost of mental health service for schizophrenia to be significantly higher than that for other mental disorders (Cuffel et al., 1996); the mean expenditure among the oldest patients with schizophrenia (> 74 years old) was comparable to that among the youngest patients (age 18 to 29). While long-term studies have shown that use of nursing homes, state hospitals, and general hospital care by patients with all mental disorder diagnoses has declined in recent decades, the rate of decline is lower for older patients with schizophrenia (Kramer et al., 1973; Redick et al., 1977). The high cost of these settings contributes to the greater economic burden associated with late-life schizophrenia.

Late-Onset Schizophrenia
Studies have compared patients with late onset (age at onset 45 years or older) and similarly aged patients with earlier onset of schizophrenia (Jeste et al., 1997); both were very similar in terms of genetic risk, clinical presentation, treatment response, and course.

Among key differences between the groups, patients with late-onset schizophrenia were more likely to be women in whom paranoia was a predominant feature of the illness. Patients with late-onset schizophrenia had less impairment in the specific neurocognitive areas of learning and abstraction/cognitive flexibility and required lower doses of neuroleptic medications for management of their psychotic symptoms. These and other differences between patients with early- and late-onset illness suggest that there might be neurobiologic differences mediating the onset of symptoms (DeLisi, 1992; Jeste et al., in press).

Course and Recovery
The original conception of “dementia praecox,” the early term for schizophrenia, emphasized progressive decline (Kraepelin, 1971); however, it now appears that Kraepelin’s picture captures the outcome for a small percentage of patients, while one-half to two-thirds significantly improve or recover with treatment and psychosocial rehabilitation (Chapter 4). Although the rates of full remission remain unclear, some patients with schizophrenia demonstrate remarkable recovery after many years of chronic dysfunction (Nasar, 1998). Research suggests that a factor in better long-term outcome is early intervention with antipsychotic medications during a patient’s first psychotic episode (see Chapter 4).

A recent cross-sectional study that compared middle-aged with older patients, all of whom lived in community settings, found some similarities and differences (Eyler-Zorrilla et al., 1999). The older patients experienced less severe symptoms overall and were on lower daily doses of neuroleptics than middle-aged patients who were similar in demographic, clinical, functional, and broad cognitive measures. In addition, positive symptoms were less prominent (or equivalent) in the older group, depending on the measure used. Negative symptoms were more prominent (or equivalent) in the older group, and older patients scored more poorly on severity of dyskinesia. Older patients were impaired relative to middle-aged ones on two measures of global cognitive function. This finding, however, appeared to reflect a normal degree of decline from an impaired baseline, as the degree of change in cognitive function with age in the patient group was equivalent to that seen in the comparison group.

A recent study used the Direct Assessment of Functional Status scale (DAFS) (Loewenstein et al., 1989) to compare the everyday living skills of middle-aged and older adults with schizophrenia with those of people without schizophrenia of similar ages (Klapow et al., 1997). The patients exhibited significantly more functional limitations than the controls did across most DAFS subscales. In another recent study that used a measure of overall disease impact, the Quality of Well-Being Scale, older outpatients with schizophrenia manifested significantly lower quality of well-being than did comparison subjects, and their scores were slightly worse than those of ambulatory AIDS patients (Patterson et al., 1996).

Thus, while schizophrenia may be less universally deteriorating than previously has been assumed, older patients with the disorder continue nonetheless to exhibit functional deficits that warrant research and clinical attention.

Etiology of Late-Onset Schizophrenia
Recent studies support a neurodevelopmental view of late-onset schizophrenia (Jeste et al., 1997). Equivalent degrees of childhood maladjustment have been found in patients with late-onset schizophrenia and early-onset schizophrenia, for example, suggesting that some liability for the disorder exists early in life. Equivalent degrees of minor physical anomalies in patients with late-onset schizophrenia and early-onset schizophrenia suggest the presence of developmental defects in both groups (Lohr et al., 1997). The presence of a genetic contribution to late-onset and early-onset schizophrenia is evident in increased rates of schizophrenia among first-degree relatives (Rokhlina, 1975; Castle & Howard, 1992; Castle et al., 1997).

If late-onset schizophrenia is neurodevelopmental in origin, an explanation for the delayed onset may be that late-onset schizophrenia is a less severe form of the disorder and, as such, is less likely to manifest early in life. Recent research suggests that in several arenas—for example, neuropsychological impairments in learning, retrieval, abstraction, and semantic memory as well as electroencephalogram abnormalities—the deficits of patients with late-onset schizophrenia are less severe (Heaton et al., 1994; Jeste et al., 1995b; Olichney et al., 1995, 1996; Paulsen et al., 1995, 1996). Also, negative symptoms are less pronounced and neuroleptic doses are lower in patients with late-onset schizophrenia (Jeste et al., 1995b). The etiology and onset of schizophrenia in younger adults often are explained by a diathesis-stress model in which there is a genetic vulnerability in combination with an environmental insult (such as obstetric complications), with onset triggered by maturational changes or life events that stress a developmentally damaged brain (Feinberg, 1983; Weinberger, 1987; Wyatt, 1996). Under this multiple insult model, patients with late-onset schizophrenia may have had fewer insults and thus have a delayed onset. An alternative or complementary explanation for the delayed onset in late-onset schizophrenia is the possibility that these patients possess protective features that cushion the blow of any additional insults. The preponderance of women among patients with late-onset schizophrenia has fueled hypotheses that estrogen plays a protective role.

The view of late-onset schizophrenia as a less severe form of schizophrenia, in which the delayed onset results from fewer detrimental insults or the presence of protective factors, suggests a continuous relationship between age at onset and severity of liability. An alternative view is that late-onset schizophrenia is a distinct neurobiological subtype of schizophrenia. The preponderance of women and of paranoid subtype patients seen in late-onset schizophrenia supports this view. These two etiologic theories of late-onset schizophrenia call for further research.

Treatment of Schizophrenia in Late Life
Pharmacological treatment of schizophrenia in late life presents some unique challenges. Conventional neuroleptic agents, such as haloperidol, have proven effective in managing the “positive symptoms” (such as delusions and hallucinations) of many older patients, but these medications have a high risk of potentially disabling and persistent side effects, such as tardive dyskinesia (Jeste et al., in press). The cumulative annual incidence of tardive dyskinesia among older outpatients (29 percent) treated with relatively low daily doses of conventional antipsychotic medications is higher than that reported in younger adults (Jeste et al., in press).

Recent years have witnessed promising advances in the management of schizophrenia. Studies with mostly younger schizophrenia patients suggest that the newer “atypical” antipsychotics, such as clozapine, risperidone, olanzapine, and quetiapine, may be effective in treating those patients previously unresponsive to traditional neuroleptics. They also are associated with a lower risk of extrapyramidal symptoms and tardive dyskinesia (Jeste et al., in press). Moreover, the newer medications may be more effective in treating negative symptoms and may even yield partial improvement in certain neurocognitive deficits associated with this disorder (Green et al., 1997).

The foremost barriers to the widespread use of atypical antipsychotic medications in older adults are (1) the lack of large-scale studies to demonstrate the effectiveness and safety of these medications in older patients with multiple medical conditions, and (2) the higher cost of these medications relative to traditional neuroleptics (Thomas & Lewis, 1998).

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Mental Health: A Report of the Surgeon General
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