first conceptualized schizophrenia as a disorder of progressive cognitive decline, and the cognitive changes with aging in schizophrenia are also consistent with the hypothesis that schizophrenia is associated with accelerated aging.
Cognitive functioning in schizophrenia presents an intriguing picture where the most substantial deficits seen in the illness across the life span are in processing speed, episodic verbal memory (learning and recall), and high-load information processing, the exact ability domains with the most substantial changes with aging in healthy individuals.27
In contrast, people with schizophrenia show much more limited deficits compared with healthy people at any point in the life span on tests of crystallized intelligence (the ability to use previously acquired knowledge and experience), such as word recognition reading performance. Cognitive ability domains that are relatively spared in schizophrenia include long-term verbal memory (eg, reading), recognition memory, and verbal abilities that do not require rapid processing, such as naming. These are domains that are also spared from major aging effects in healthy individuals. In fact, some of these ability areas are affected so little in schizophrenia that they are often used to infer premorbid levels of functioning.
Patients with schizophrenia who do show cognitive decline with aging manifest a markedly increased risk for these changes during the period in life (age 65 years and older) when the ability areas described above start to show the greatest change in healthy individuals as well.28
Thus, the profile of cognitive impairment in schizophrenia at any point in their life could be compared with that of an older healthy individual, one whose brain and subsequent cognitive performance has already experienced the effects of aging. It is clear that in people with schizophrenia, there is little evidence of change in performance associated with aging during the ages of 20–50 years.28,29
Healthy individuals also show the least decline in cognitive abilities during this same period.
There is considerable evidence that cognitive functioning in schizophrenia changes for the worse during the period of time from the premorbid through prodromal periods, resulting in notable deterioration in performance that occurs over an abbreviated period of time.30,31
This deterioration, because it occurs in ability areas that are vulnerable to decline with normal aging, could be characterized as a period of “compressed aging.” Thus, the decline that occurs within a period of a few months to years affects the same ability areas as normal aging does.
, based on previously unpublished data collected by Drs C.R.B. and P.D.H., shows the resemblance between the pattern of cognitive performance in people with schizophrenia and that of older healthy individuals. We selected a subset of the types of tests that are differentially sensitive to the effects of aging in healthy individuals. These include processing speed and episodic memory as examples of abilities that are sensitive to aging in healthy individuals and visual confrontation naming as a test of crystallized intelligence that is not markedly vulnerable to aging influences in healthy individuals.
Fig. 1. Performance of Younger and Older Healthy Controls (HCs) and Patients with Schizophrenia on Tests that are Differentially Sensitive to Aging in Healthy Individuals. Specific cognitive decline in schizophrenia and HCs. Schizophrenia patients, n = 113; HC (more ...)
Healthy individuals 70–80 years of age show performance on tests of processing speed (measured by Wechsler Adult Intelligence Scale-III digit symbol) and episodic verbal memory (measured by Rey Auditory Verbal Learning Test [RAVLT] delayed recall) that are consistent with the performance of 50- to 60-year-old people with schizophrenia, while 50- to 60-year-old healthy individuals perform markedly better on these 2 tests than do similar aged people with schizophrenia. However, when the performance of all 3 of these groups is compared on a test of verbal confrontation naming, there is remarkably little difference among the groups. Thus, the age-associated burden in cognitive performance on the part of people with schizophrenia appears most prominent on tests where healthy individuals show evidence of reduced performance with aging.
In short, the cognitive changes seen in schizophrenia, even at the time of the first episode, have a strong overlap with those abilities that are vulnerable to the most substantial changes seen in normal aging. People with schizophrenia consistently perform more poorly in aging-vulnerable ability areas than healthy individuals of the same age. Cognitive change in schizophrenia may occur over a shorter time period than normal aging-related changes, with detectable deterioration occurring over abbreviated periods at the time of onset of the illness and in some cases in late life. While the similarly in profile of cognitive abilities affected by schizophrenia and healthy aging does not prove similarity in underlying mechanisms of the change, the possibility of a vulnerable circuit, prone to deterioration with aging and schizophrenia, could be a topic for future investigation.
A major limitation of this line of argument is the small number of studies that compares the cognitive performance in older people with schizophrenia with that of comparison groups. Moreover, many such studies have been cross-sectional, rather than longitudinal, leaving the results vulnerable to bias.
The findings of stable performance
after the first episode are not necessarily suggestive of stable cognitive abilities
throughout the rest of the course as measured in previous studies. Most research has found severe cognitive deficits by the time of the first episode as measured by traditional neuropsychological tests, but when patients exhibit this degree of impairment, they are manifesting performance at a level that reduces the sensitivity for detection of further decline because of floor effects for some tests. The more that baseline performance deviates from the average performance of the healthy population, the more difficult it is to both measure and make meaningful sense of performance on these tests. The Wechsler IQ Scale subtests, eg, have a mean of 10 and an SD of 3, so once a patient is 2.5 SD or 3 SD below the mean, a level consistent with the severity seen in people with schizophrenia on many measures by the time of first episode of psychosis, there is limited validity of attempts to measure further decline on these tests due to floor effects. In such a case, attempts to measure declines in cognition will fail not necessarily because of cognitive ability but because of the ability of the instruments employed to measure changes in performance. We32
found that traditional neuropsychological tests were insensitive to progressive impairments in late-life schizophrenia due to floor effects. However, when we used a scale designed for measuring truly profound cognitive impairment, the Alzheimer Disease Assessment Scale (ADAS)—Late Stage, we found sensitivity to cognitive impairments in patients with Mini-Mental State Examination (MMSE) scores less than 10—in fact, we could differentiate those with MMSE of 1 from those with MMSE of 0. Further, when using tests that are more sensitive to complex information processing demands, we33,34
found that older schizophrenia outpatients show age-associated impairments into late life. Thus, the supposed stability of cognitive impairment after first episode may have more to do with test selection (relying on neuropsychological tests that were originally designed to distinguish impairment from normal performance, rather than tracking the progression of impairment as is done by scales such as the ADAS-Late Stage) than on what is actually happening to the aging person with schizophrenia.
Thus, what appears to be, from neuropsychological performance on standard clinical measures, nonlinear pattern that entails early decline, followed by stability through much of the course and decline in only a subset of patients and/or on a subset of measures, might simply be the result of our inability to finely measure performance. This issue may be resolved with newer imaging techniques and the development of complex information processing tasks that are sensitive to a wider range of performance than traditional neuropsychological measures.