Cognitive and functional deficits in people with schizophrenia: Evidence for accelerated or exaggerated aging?
Introduction
Schizophrenia is a condition with functional changes in many of the same areas where there are commonly detected changes with aging. For instance, schizophrenia is marked by impairments in cognition and the ability to perform everyday functional skills. Cognitive changes with aging are normative, and elderly individuals often require some incremental assistance in performing these everyday activities as they age. Aging-related changes in cognition and everyday functioning have a differential impact across cognitive domains and functional skills areas, with some cognitive domains being largely unaffected and others being performed at levels that are half that seen earlier in life. In people with schizophrenia, there is also a profile of impairments in cognitive abilities; the similarity of this profile to that seen in aging is also quite interesting and potentially informative.
Functional skills challenges with aging also include the constant demand to learn new functional skills. As technology is ever-changing and older individuals have to use technology much like younger people, the challenge in learning new technology is constant. Similar to older people, technology challenges also confront people with schizophrenia. Much like elderly individuals, people with schizophrenia are often forced to use technology to manage medication, handle finances, and plan travel. Comparison of the relative ability to adopt new technology (internet usage, banking, and on-line and telephone based menu usage) and other everyday living skills can provide information as to whether people with schizophrenia manifest similar challenges related to everyday functioning as seen in older individuals.
So, there are several issues involved in a comparison of older healthy people and individuals with schizophrenia in terms of whether cognitive and everyday functional skills support the idea of accelerated or exaggerated aging. First is whether profiles of cognitive impairment in schizophrenia are consistent with the types of cognitive abilities that change with aging. Impairments earlier in life in people with schizophrenia would suggest accelerated aging. Second is whether changes in cognition and functioning occur in people with schizophrenia to a greater extent than they do in healthy controls. This would implicated exaggerated aging effects on cognition and everyday functioning. The fact that cognitive performance seems stable over the lifetime in many people with schizophrenia suggests that the changes that would substantiate accelerated aging may occur very early in the illness. The third issue is whether alternative explanations for changes in cognitive functioning are plausible. These include substance abuse and metabolic syndrome, factors which affect as many as half of all people with schizophrenia and disproportionately more people with schizophrenia compared to healthy controls. Finally, the question must be addressed as to whether cognitive and functional changes with aging are caused by the same processes in schizophrenia and healthy aging. It is entirely possible that processes could look very similar even if they have different causes. The data suggesting that multiple extended periods of psychosis early in the course of illness leads to cognitive and brain changes would implicate a different etiology with a similar phenotypic manifestation.
Section snippets
Profiles of cognitive impairment in schizophrenia
Cognitive impairments in schizophrenia impact a large number of cognitive ability domains. These include working and episodic memory, processing speed and executive functioning, and certain language skills (Bowie and Harvey, 2005). Abilities that seem less affected appear to be crystalized abilities such as vocabulary and information skills, as well as word recognition reading (Harvey et al., 2006). In terms of the performance-based abilities that seem less affected, people with schizophrenia
Changes in cognitive performance with healthy aging
Like schizophrenia, there is a very systematic hierarchy of cognitive abilities that change in older people compared to their early-life experience. Interestingly, this hierarchy is surprisingly similar to the changes that are seen in people with schizophrenia. Processing speed, episodic memory, and working memory decline with aging (Albert and Moss, 1988). These changes are relatively substantial on an individual basis, on average, with performance declining about 50% for processing speed
What is the relative burden of schizophrenia on age-related cognitive decline?
There are several estimates of the level of overall cognitive impairments in schizophrenia. Reviews examining cognitive impairments of healthy controls and schizophrenia patients across studies often conclude that the magnitude of deficit is about 1.0 to 1.5 SD across different domains (Gold and Harvey, 1993). However a very recent study of 2416 schizophrenia patients assessed with the same systematic cognitive assessment (Georgiades et al., 2017) found an average performance deficit of over
What is the nature of functional deficit in schizophrenia compared to healthy people?
The critical functional activities of daily living are classified into the Basic Activities of Daily Living (ADLs) and the Instrumental Activities of Daily Living (IADLs), with these constructs defined for nearly 50 years. The first include the six main activities necessary for self-care: bathing, dressing, toileting, transferring, continence, and feeding (Katz et al., 1963). The latter involve more complex tasks, including using transportation, preparing food, and handling finances (Lawton and
Performance-based assessments of functional capacity
One of the main areas of current research on schizophrenia is the ability to perform everyday functional skills, referred to as functional capacity. Performance-based measurement has been shown to have considerable reliability and concurrent validity (Green et al., 2008) and these measures have been used in treatment studies aimed at cognitive enhancement (Harvey et al., 2007; Bowie et al., 2012). If the early onset reductions in everyday functioning in people with schizophrenia are due to
When do these cognitive changes start and what is associated with their onset?
Cognitive impairment is present in individuals who are destined to develop schizophrenia and can be detected, on a group-wise basis, in both childhood and adolescence. However, these impairments are not substantial (Woodberry et al., 2008, Reichenberg et al., 2002; d = 0.5) and are consequently not useful for screening of individuals who are at risk because as much as a third of the overall population falls below this criterion. Further, changes in cognitive performance prior to the onset of the
A neurotoxic origin of cognitive decline in early illness?
One of the long-term controversies in the treatment and study of schizophrenia has been whether psychosis exerts a toxic effect on the brain. This idea partially originated from the observation that the global outcome of schizophrenia has appeared to improve following the availability of antipsychotic medication and the standard of care evolving into the early treatment of psychosis (Wyatt, 1991). This paper summarized data regarding outcomes of schizophrenia from the “pre-neuroleptic” era and
Progression of cognitive and functional deterioration in treatment resistant patients
Although the majority of patients with schizophrenia experience a beneficial effect from treatment with antipsychotic medications and sustain the benefit as long as they are adherent, there exists a substantial minority who does not experience a good clinical response. The common term for this subgroup of patients is “treatment-resistant”, despite the fact that patients who are adherent to their treatments are not “resisting” the interventions offered. There are several important issues in the
What about confounding factors?
There are multiple possible alternative contributions to poor cognitive and functional performance, including comorbidities such as substance use and metabolic syndrome, and the possibility that cognitive and functional capacity measures are always performed at very poor levels instead of showing some type of decline over time. We will address these two possibilities below.
Some comorbidities highly associated with schizophrenia, such as metabolic syndrome and substance abuse, have been shown to
The timing of onset of cognitive and functional capacity limitations
Skills that were never learned cannot be lost and cognitive functions that were never achieved cannot be seen to have deteriorated. One possible explanation for very poor performance at the time of the first episode in schizophrenia patients is that patients have been like this on a lifetime basis, with long term impairments resembling developmental disabilities. The data, both in domains of cognition and functional capacity, suggest that this explanation is not particularly viable.
Implications
These data suggest that cognitive and functional capacity performance in schizophrenia, the primary predictors of the substantial everyday disability seen in most patients, have a developmental course that is understandable. The cognitive impairments seen in schizophrenia patients have a cross-sectional profile that includes the major domains of cognitive functioning that are vulnerable to decline in healthy people and excludes the cognitive processes that seen invulnerable to decline with
Contributions of the authors
Dr. Harvey and Ms. Rosenthal wrote this commentary jointly.
Role of funding source
The data collected by Dr. Harvey in the studies described in this paper was funded by grants from the National Institute of Mental Health (MH 63116). The NIMH had no role in the preparation of this paper.
Conflict of interest statement
Dr. Harvey has received consulting fees or travel reimbursements from Allergan, Boehringer Ingelheim, Lundbeck Pharma, Minerva Pharma, Otsuka Digital Health, Sanofi Pharma, Sunovion Pharma, and Takeda Pharma during the past year. He has a research grant from Takeda and from the Stanley Medical Research Foundation.
Acknowledgments
Both authors who contributed to this paper are listed as authors. No professional medical writer was involved in any portion of the preparation of the manuscript.
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