Lifetime antipsychotic medication and cognitive performance in schizophrenia at age 43 years in a general population birth cohort.

This naturalistic study analysed the association between cumulative lifetime antipsychotic dose and cognition in schizophrenia after an average of 16.5 years of illness. Sixty participants with schizophrenia and 191 controls from the Northern Finland Birth Cohort 1966 were assessed at age 43 years with a neurocognitive test battery. Cumulative lifetime antipsychotic dose-years were collected from medical records and interviews. The association between antipsychotic dose-years and a cognitive composite score based on principal component analysis was analysed using linear regression. Higher lifetime antipsychotic dose-years were significantly associated with poorer cognitive composite score, when adjusted for gender, onset age and lifetime hospital treatment days. The effects of typical and atypical antipsychotics did not differ. This is the first report of an association between cumulative lifetime antipsychotic dose and global cognition in midlife schizophrenia. Based on these data, higher lifetime antipsychotic dose-years may be associated with poorer cognitive performance at age 43 years. Potential biases related to the naturalistic design may partly explain the results; nonetheless, it is possible that large antipsychotic doses harm cognition in schizophrenia in the long-term.

Predictors of Long-Term Change in Adult Cognitive Performance: Systematic Review and Data from the Northern Finland Birth Cohort 1966.

OBJECTIVE: Several social life events and challenges have an impact on cognitive development. Our goal was to analyze the predictors of change in cognitive performance in early midlife in a general population sample. Additionally, systematic literature review was performed. METHOD: The study sample was drawn from the Northern Finland Birth Cohort 1966 at the ages of 34 and 43 years. Primary school performance, sociodemographic factors and body mass index (BMI) were used to predict change in cognitive performance measured by the California Verbal Learning Test, Visual Object Learning Test, and Abstraction Inhibition and Working Memory task. Analyses were weighted by gender and education, and p-values were corrected for multiple comparisons using Benjamini-Hochberg procedure (B-H). RESULTS: Male gender predicted decrease in episodic memory. Poor school marks of practical subjects, having no children, and increase in BMI were associated with decrease in episodic memory, though non-significantly after B-H. Better school marks, and higher occupational class were associated with preserved performance in visual object learning. Higher vocational education predicted preserved performance in visual object learning test, though non-significantly after B-H. Likewise, having children predicted decreased performance in executive functioning but non-significantly after B-H. CONCLUSIONS: Adolescent cognitive ability, change in BMI and several sociodemographic factors appear to predict cognitive changes in early midlife. The key advantage of present study is the exploration of possible predictors of change in cognitive performance among general population in the early midlife, a developmental period that has been earlier overlooked.

Changes in verbal learning and memory in schizophrenia and non-psychotic controls in midlife: A nine-year follow-up in the Northern Finland Birth Cohort study 1966.

Findings on longitudinal change of cognitive performance in schizophrenia are extremely variable in the case of verbal learning and memory, and it is still unclear which dimensions of verbal learning and memory exhibit possible deterioration over the long-term. Our aim was to compare the change in verbal learning and memory in individuals with schizophrenia 10-20 years after the illness onset and healthy controls during a nine-year follow-up in a general population sample. Our sample included 41 schizophrenia spectrum subjects and 73 controls from the Northern Finland Birth Cohort study 1966. The California Verbal Learning Test (CVLT) was used to estimate the degree of change in verbal learning and memory during a nine-year follow-up from age 34-years to 43- years. Both cases and controls deteriorated. There was statistically significant decline in two out of 20 CVLT items among cases and in 13 out of 20 CVLT items among controls. With the exception of two variables, the decline in verbal learning and memory over nine years was not significantly larger in cases. We conclude that during midlife verbal learning and memory in schizophrenia mostly declines in a normative fashion with aging at the same rate as the general population.

Twenty Years of Schizophrenia Research in the Northern Finland Birth Cohort 1966: A Systematic Review.

Birth cohort designs are useful in studying adult disease trajectories and outcomes, such as schizophrenia. We review the schizophrenia research performed in the Northern Finland Birth Cohort 1966 (NFBC 1966), which includes 10,934 individuals living in Finland at 16 years of age who have been monitored since each mother's mid-pregnancy. By the age of 44, 150 (1.4%) had developed schizophrenia. There are 77 original papers on schizophrenia published from the NFBC 1966. The early studies have found various risk factors for schizophrenia, especially related to pregnancy and perinatal phase. Psychiatric and somatic outcomes were heterogeneous, but relatively poor. Mortality in schizophrenia is high, especially due to suicides. Several early predictors of outcomes have also been found. Individuals with schizophrenia have alterations in brain morphometry and neurocognition, and our latest studies have found that the use of high lifetime doses of antipsychotics associated with these changes. The schizophrenia research in the NFBC 1966 has been especially active for 20 years, the prospective study design and long follow-up enabling several clinically and epidemiologically important findings. When compared to other birth cohorts, the research in the NFBC 1966 has offered also unique findings on course and outcome of schizophrenia.

Poor premorbid school performance, but not severity of illness, predicts cognitive decline in schizophrenia in midlife.

Neurocognitive dysfunction is common in schizophrenia but its course and determinants remain uncertain. Our aim was to analyse if premorbid school performance and the severity of illness and functioning predict change in cognition in schizophrenia in a general population sample. The sample included cases with schizophrenia spectrum disorder from the Northern Finland Birth Cohort 1966. Data on school marks at the age of 16 years, educational level at the age of 34 years, severity of symptoms and occupational functioning around first episode and after years of illness were gained from national registers, hospital notes and interviews. Change of verbal and visual learning and memory and executive functioning were examined between ages 34 and 43 years. The number of cases varied in analyses from 29 to 41, depending on missing data in particular cognitive tests. Lower school marks at age 16 years and lower education at age 34 years predicted more decline of cognition. Measures of severity of illness or functioning were not associated statistically significantly with change of cognition. Premorbid school performance, but not later course of schizophrenia, related to change of cognition in midlife. Poor premorbid scholastic performance and post-onset cognitive decline may represent related processes as part of an endophenotype of schizophrenia.

Lifetime use of antipsychotic medication and its relation to change of verbal learning and memory in midlife schizophrenia - An observational 9-year follow-up study.

BACKGROUND: The association between the course of cognition and long-term antipsychotic medication in schizophrenia remains unclear. We analysed the association between cumulative lifetime antipsychotic medication dose and change of verbal learning and memory during a 9-year follow-up. METHOD: Forty schizophrenia subjects and 73 controls from the Northern Finland Birth Cohort 1966 were assessed by California Verbal Learning Test (CVLT) at the ages of 34 and 43 years. Data on the lifetime antipsychotic doses in chlorpromazine equivalents were collected. The association between antipsychotic dose-years and baseline performance and change in CVLT was analysed, controlling for baseline performance, gender, age of onset and severity of illness. RESULTS: Higher antipsychotic dose-years by baseline were significantly associated with poorer baseline performance in several dimensions of verbal learning and memory, and with a larger decrease in short-delay free recall during the follow-up (p=0.031). Higher antipsychotic dose-years during the follow-up were associated with a larger decrease of immediate free recall of trials 1-5 during the follow-up (p=0.039). Compared to controls, decline was greater in some CVLT variables among those using high-doses, but not among those using low-doses. CONCLUSION: This is the first report of an association between cumulative lifetime antipsychotic use and change in cognition in a long-term naturalistic follow-up. The use of high doses of antipsychotics may be associated with a decrease in verbal learning and memory in schizophrenia years after illness onset. The results do not support the view that antipsychotics in general prevent cognitive decline or promote cognitive recovery in schizophrenia.