Long-term course of cognitive impairment in schizophrenia

The aim of this study was to examine the long-term course ofcognitive impairment in people with schizophrenia. Forty-threepeople with schizophrenia were followed up over an averageof 33 years along with a control group of 12 matched individualsfree from psychosis. Cognitive function was assessed at baselineand follow-up. The participants with schizophrenia were foundto show impairment in verbal and non-verbal intelligence atbaseline compared with estimated premorbid scores, this wasnot found in the control group. At follow-up there was a significantdecline in non-verbal intelligence over time in participantswith schizophrenia compared with controls (P=0.007). This differentialchange over time was not seen in verbal intelligence (P= 0.318).

INTRODUCTION

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INTRODUCTION

Cognitive impairment can be found in the majority of patientswith schizophrenia (Kelly et al, 2000) and is a strong predictorof eventual social and functional outcome (Green, 1996). The published research examining the long-term course of impairmentis inconsistent. Cross-sectional studies have provided evidenceboth for (Stratta et al, 2004) and against (Hyde et al, 1994)progressive deterioration but are vulnerable to cohort effectsproducing differences not due to within-individual changes.More recently, well-designed longitudinal studies have againproduced conflicting results with some supporting the notionof progressive decline (Stirling et al, 2003) and others refutingit (Gold et al, 1999; Hoff et al, 1999). Here we report astudy examining the course of schizophrenic cognitive impairmentover a period of, on average, 33 years.

METHOD

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METHOD

Until 1977 routine neuropsychological testing was performedon all patients admitted for the first time to Crichton RoyalHospital, Dumfries. Since 1981, repeated censuses have identifiedall known people in Nithsdale, south-west Scotland, with adiagnosis of schizophrenia for a number of published studies. Of the 182 people with ICD–10 schizophrenia (World Health Organization, 1992)identified in the 1998 census, 48 had their first admission to Crichton Royal Hospital before 1978 and thus had undergoneroutine neuropsychological testing. Patients with a historyof other possible causes of cognitive impairment were excluded.Three potential participants were excluded for this reasonand another two declined to participate, thus 43 people withschizophrenia took part: 18 men and 25 women, mean age 61.2years (s.d.=11.3), mean number of years of education 10 (s.d.=2.2)and mean follow-up interval 32.9 years (s.d.=8). For each participantwith schizophrenia three potential controls matched for yearof testing, gender and age were identified from hospital psychologyrecords. The current address of only 16 potential controlscould be identified, two potential controls had developed apsychotic disorder during the intervening period and were thus excluded and two declined to take part in the study, leaving12 participating individuals (2 men and 10 women). The diagnosesin the control group were personality disorder (n=5), admittedafter overdose (n=4), dissociative motor disorder (n=1) andmoderate depressive episode (n=2); the group’s mean agewas 55.8 years (s.d.=7.9), the mean number of years of educationwas 10.7 (s.d.=1) and the mean follow-up interval was 30.3years (s.d.=5.4). Baseline neuropsychological testing was performed by members of the clinical psychology department: for manyyears this was under the direct supervision of the psychologist(John Raven) who designed the tests. At followup, testing wasperformed by a trained psychiatrist and testing was not time-limited.Raven’s Standard Progressive Matrices (RSPM; Raven, 1958a) test was administered at baseline and follow-up. This testmeasures non-verbal abstract reasoning and visuospatial problem-solvingabilities; it is a valid measure of general and nonverbal intelligence (Lezak, 1995). The Mill Hill Vocabulary Scale (MHVS; Raven, 1958b)was administered at baseline and follow-up; this has been usedin studies of people with schizophrenia and provides a validand reliable measure of verbal intelligence (Lezak, 1995).At follow-up the National Adult Reading Test (Nelson, 1982)was administered as an estimate of premorbid ability, and depressivesymptoms were rated using the Zung Depression Rating Scale (ZDRS; Zung, 1965). Independent t-test analysis was used to comparethe groups on potential confounding variables and Fisher’sexact test was used to test for differences in gender ratio.Repeated-measure analyses of covariance (ANCOVAs) were performedon cognitive test scores (patients v. controls) from baselineand follow-up assessments with test–retest interval andZDRS scores as covariates. Post hoc two-tailed paired t-tests were used to assess intra-individual changes in cognitive testscores.

RESULTS

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RESULTS

There was no significant difference between the control andschizophrenia groups on general characteristics. At follow-uptesting everyone in the schizophrenia group was receiving antipsychoticmedication (typical antipsychotics, n=27; atypical antipsychotics,n=16; 36 were living in the community and 7 were long-stayin-patients. None of the control group was receiving psychotropicmedication; all were resident in the community. In the schizophreniagroup there was a highly significant difference between estimatedpremorbid and baseline RSPM (P=0.0004, t=3.86, d.f.=42) andMHVS (P<0.0001, t=7.48, d.f.=42) scores. This differencewas not found in the control group.

Repeated-measure ANCOVAs of cognitive test scores at baselineand follow-up with test–retest interval and Zung depressionscores as covariates showed a highly significant groupxtimeinteraction in RSPM performance over time in participants withschizophrenia compared with controls: F(1,59)=7.895, P=0.007.This differential change over time was not observed for theMHVS scores: F(1,59)=1.017, P=0.318. Changes over time expressedin change per year of follow-up are shown in Fig. 1 (full detailsof all results available on request).

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Fig. 1 Change in scores per year of follow-up on Raven’s Standard Progressive Matrices (; P=0.007) and on the Mill Hill Vocabulary Scale ( ${blacksquare}$ ; P=0.318).

DISCUSSION

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DISCUSSION

This study offers a view of the long-term course of schizophreniccognitive impairment over an average of 33 years, some 23 yearslonger than any recent studies. Despite weaknesses inherentin its opportunistic design and difficulties in recruitingcontrols, we believe it offers interesting results. Participantswith schizophrenia showed broad-based cognitive impairment early in their illness, as demonstrated by the significant differencebetween estimated premorbid scores and actual first-test scoreson both the MHVS and RSPM. This difference was not seen inthe control groups. Subsequently there was no further significantdecline in verbal intelligence as measured by MHVS in the schizophreniagroup even over an extended follow-up period, and even thoughthis group arguably might have been particularly severely affected given their continued contact with services and need for antipsychotic medication.

In contrast, there was a significant decline in RSPM scoresover time in the schizophrenia group compared with the controlgroup. This could represent a genuine decline, but a numberof alternative explanations require consideration. Conditionslikely to cause cognitive impairment were specifically excludedin the recruitment process; it is nevertheless possible thatsome participants had developed a dementia such as Alzheimer’s disease. However, the prevalence of Alzheimer’s diseasein the normal population at this age (mean of the study groupwas age 61 years) is low and people with schizophrenia do notappear to have a higher incidence of dementia (Purohit et al, 1998). Adverse medication effects might impair cognition; however,there is variability in the reported effects of antipsychoticdrugs on cognition (Sharma, 1999). Could the observed declinebe due to normal cognitive ageing? Importantly, there was no significant decline in RSPM scores over 30 years in our matchedcontrol group. Although to our knowledge there are no longitudinalnorms for RSPM over extended periods, a recent re-analysisof sets of RSPM norms collected at different times suggeststhat little, if any, decline occurs in the normal populationbetween the ages of 20 and 70 years (Raven, 2000). Lastly,testing was not time-limited, thus minimising the effect ofslowed psychomotor speed with ageing. These arguments supportour belief that the decline in cognitive functions measuredby the RSPM in people with schizophrenia (but not observed inour control group) is probably genuine. This is in direct contradistinction to the 5-year longitudinal studies of Gold et al (1999) andHoff et al (1999) but is in keeping with a more recent 10-yearstudy showing progressive visuospatial impairment (Stirling et al, 2003),suggesting cognitive decline in schizophrenia occurs over a longer period than 5 years. Our results also suggest that cognitivedecline is not global, that is it does not resemble a truedementia, but instead affects specific areas of cognition andmay thus reflect ongoing pathological changes in certain areasof the brain or brain systems involved in visuospatial problemsolvingand the fluid components of intelligence.

REFERENCES

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