Elsevier

Schizophrenia Research

Volume 196, June 2018, Pages 14-21
Schizophrenia Research

Cognitive and functional deficits in people with schizophrenia: Evidence for accelerated or exaggerated aging?

https://doi.org/10.1016/j.schres.2017.05.009Get rights and content

Abstract

Cognitive and functional deficits are commonly seen in people with schizophrenia. The profile of these impairments has a resemblance to the cognitive changes seen in healthy aging. In specific, many of the cognitive ability domains that change the most with aging in healthy people are the most salient of these deficits seen in people with schizophrenia, including prominent deficits in processing speed, working memory, and episodic memory. Functional deficits seen in schizophrenia are also similar to those seen in healthy aging. There is a relationship between multiple psychotic relapses and treatment resistance and longitudinal cognitive and functional changes in schizophrenia, with this relationship starting early in the course of illness. Cognitive performance in people with schizophrenia may be consistent with accelerated or premature aging. People with schizophrenia perform similarly to healthy people who are 3 or more decades older on indices of both cognition and their everyday functional skills. Some people with schizophrenia show exaggerated cognitive changes as well. Cognitive and functional performance worsens at the outset of the illness in schizophrenia compared to premorbid functioning, meaning that these deficits are not due to development disabilities. There are multiple medical and substance abuse comorbidities in schizophrenia and although these comorbidities affect cognitive functioning, they are not completely responsible for age-related changes.

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.

References (99)

  • C.M. Coulston et al.

    The neuropsychological correlates of cannabis use in schizophrenia: lifetime abuse/dependence, frequency of use, and recency of use

    Schizophr. Res.

    (2007)
  • S.J. Czaja et al.

    Assessing functional performance using computer-based simulations of everyday activities

    Schizophr. Res.

    (2017)
  • K.L. Davis et al.

    Ventricular enlargement in poor-outcome schizophrenia

    Biol. Psychiatry

    (1998)
  • L. Delisi et al.

    Schizophrenia as a chronic active brain process: A study of progressive brain structural change subsequent to the onset of psychosis

    Psychiatry Research Brain Imaging

    (1997)
  • R.E. Featherstone et al.

    The role of nicotine in schizophrenia

    Int. Rev. Neurobiol.

    (2015)
  • R. Fucetola et al.

    Age and neuropsychologic function in schizophrenia: a decline in executive abilities beyond that observed in healthy volunteers

    Biol. Psychiatry

    (2000)
  • A. Georgiades et al.

    Psychometric characteristics of the MATRICS Consensus Cognitive Battery in a large pooled cohort of stable schizophrenia patients

    Schizophr. Res.

    (2017)
  • Jm M. Gold et al.

    Cognitive deficits in schizophrenia

    Psychiatr. Clin. N. Am.

    (1993)
  • F. Gould et al.

    Self-assessment of functional ability in schizophrenia: milestone achievement and its relationship to accuracy of self-evaluation

    Psychiatry Res.

    (2013)
  • P.D. Harvey et al.

    Cognitive decline in late-life schizophrenia: a longitudinal study of geriatric chronically hospitalized patients

    Biol. Psychiatry

    (1999)
  • P.D. Harvey et al.

    The course of neuropsychological performance and functional capacity in older patients with schizophrenia: influences of previous history of long-term institutional stay

    Biol. Psychiatry

    (2010)
  • P.D. Harvey et al.

    Functional milestones and clinician ratings of everyday functioning in people with schizophrenia: overlap between milestones and specificity of ratings

    J. Psychiatr. Res.

    (2012)
  • M.C. Jockers-Scherübl et al.

    Cannabis induces different cognitive changes in schizophrenic patients and in healthy controls

    Prog. Neuro-Psychopharmacol. Biol. Psychiatry

    (2007)
  • S. Kumra et al.

    Correlates of substance abuse in adolescents with treatment-refractory schizophrenia and schizoaffective disorder

    Schizophr. Res.

    (2005)
  • J.P. Lindenmayer et al.

    Relationship between metabolic syndrome and cognition in patients with schizophrenia

    Schizophr Res.

    (2012 Dec)
  • D.A. Loewenstein et al.

    Age-associated differences in cognitive performance in older patients with schizophrenia: a comparison with healthy older adults

    Am. J. Geriatr. Psychiatry

    (2012)
  • T. Lundqvist

    Cognitive consequences of cannabis use: comparison with abuse of stimulants and heroin with regard to attention, memory and executive functions

    Pharmacol. Biochem. Behav.

    (2005)
  • V. Manning et al.

    Cognitive impairment in dual diagnosis in patients with schizophrenia and alcohol use disorder

    Schizophr. Res.

    (2009)
  • J.M. Meyer et al.

    The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia Trial: clinical comparison of subgroups with and without the metabolic syndrome

    Schizophr. Res.

    (2005)
  • S. Potvin et al.

    CANTAB explicit memory is less impaired in addicted schizophrenia patients

    Brain Cogn.

    (2005)
  • B.D. Power et al.

    No additive effect of cannabis on cognition in schizophrenia

    Schizophr. Res.

    (2015)
  • R.A. Rabin et al.

    The effects of cannabis use on neurocognition in schizophrenia: a meta-analysis

    Schizophr. Res.

    (2011)
  • M.R. Serper et al.

    Learning and memory impairment in cocaine dependent and comorbid schizophrenic patients

    Psychiatry Res.

    (2000)
  • M.R. Serper et al.

    Neurocognitive functioning in recently abstinent, cocaine abusing schizophrenic patients

    J. Subst. Abus.

    (2000)
  • S. Sevy et al.

    Iowa gambling task in schizophrenia: a review and new data in patients with schizophrenia and co-occurring cannabis use disorders

    Schizophr. Res.

    (2007)
  • D.A. Smelson et al.

    Cognitive disparity in schizophrenics with and without cocaine dependency

    J. Subst. Abus. Treat.

    (2003)
  • J. Stirling et al.

    Cannabis use prior to first onset psychosis predicts spared neurocognition at 10-year follow-up

    Schizophr. Res.

    (2005)
  • M. Strassnig et al.

    Physical performance and disability in schizophrenia

    Schizophr. Res. Cogn.

    (2014)
  • R.J. Wyatt et al.

    The effects of early and sustained intervention on the long-term morbidity of schizophrenia

    J. Psychiatr. Res.

    (1998)
  • M.S. Albert et al.

    Geriatric Neuropsychology

    (1988)
  • N.C. Andreasen et al.

    Relapse duration, treatment intensity, and brain tissue loss in schizophrenia: a prospective longitudinal MRI study

    Am. J. Psychiatry

    (2013)
  • C.R. Bowie et al.

    Cognitive and functional changes associated with alcohol abuse in older patients with schizophrenia

    Schizophr. Bull.

    (2005)
  • C.R. Bowie et al.

    Determinants of real-world functional performance inschizophrenia subjects: correlations with cognition, functional capacity, and symptoms

    Am. J. Psychiatry

    (2006)
  • C.R. Bowie et al.

    Combined cognitive remediation and functional skills training for schizophrenia: effects on cognition, functional competence, and real-world behavior

    Am. J. Psychiatry

    (2012)
  • A. Breier et al.

    National Institute of Mental Health longitudinal study of schizophrenia: prognosis and predictors of outcome

    Arch. Gen. Psychiatry

    (1991)
  • W. Cahn et al.

    Brain volume changes in the first year of illness and 5-year outcome of schizophrenia

    Br. J. Psychiatry

    (2006)
  • L. Cooper et al.

    Neurocognitive deficits in the dually diagnosed with schizophrenia and cocaine abuse

    Psychiatr. Rehabil. Skills

    (1999)
  • C.M. Coulston et al.

    The neuropsychology of cannabis and other substance use in schizophrenia: a review of the literature and critical evaluation of methodological issues

    Aust. N. Z. J. Psychiatry

    (2007)
  • M. Davidson et al.

    Cognitive impairment in old-age schizophrenia: a comparative study of schizophrenia and Alzheimer's disease

    Am. J. Psychiatry

    (1996)
  • Cited by (57)

    • Schizophrenia in Older Adults

      2022, Comprehensive Clinical Psychology, Second Edition
    View all citing articles on Scopus
    View full text