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Improvement and decline of cognitive function in schizophrenia over one year: a longitudinal investigation using latent growth modelling.

ABSTRACT: Long-term follow-up studies of people with schizophrenia report stability of cognitive performance; less is known about any shorter-term changes in cognitive function.This longitudinal study aimed to establish whether there was stability, improvement or decline in memory and executive functions over four assessments undertaken prospectively in one year. Cognitive performance was assessed during randomized controlled trials of first- and second-generation antipsychotic medication. Analyses used a latent growth modeling approach, so that individuals who missed some testing occasions could be included and trajectories of cognitive change explored despite missing data.Over the year there was significant decline in spatial recognition but no change in pattern recognition or motor speed. Improvement was seen in planning and spatial working memory tasks; this may reflect improved strategy use with practice. There were significant individual differences in the initial level of performance on all tasks but not in rate of change; the latter may have been due to sample size limitations. Age, sex, premorbid IQ and drug class allocation explained significant variation in level of performance but could not predict change. Patients randomized to first-generation drugs improved more quickly than other groups on the planning task.We conclude that cognitive change is present in schizophrenia but the magnitude of change is small when compared with the large differences in cognitive function that exist between patients. Analyses that retain patients who drop out of longitudinal studies, as well as those who complete testing protocols, are important to our understanding of cognition in schizophrenia.

SUBMITTER: Barnett JH

PROVIDER: S-EPMC1885799 | biostudies-other | 2007 May

REPOSITORIES: biostudies-other

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Improvement and decline of cognitive function in schizophrenia over one year: a longitudinal investigation using latent growth modelling.

Barnett Jennifer H JH Croudace Tim J TJ Jaycock Sue S Blackwell Candice C Hynes Fiona F Sahakian Barbara J BJ Joyce Eileen M EM Jones Peter B PB

BMC psychiatry 20070509

<h4>Background</h4>Long-term follow-up studies of people with schizophrenia report stability of cognitive performance; less is known about any shorter-term changes in cognitive function.<h4>Methods</h4>This longitudinal study aimed to establish whether there was stability, improvement or decline in memory and executive functions over four assessments undertaken prospectively in one year. Cognitive performance was assessed during randomized controlled trials of first- and second-generation antips ...[more]

PMID: 17490472

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Project description:BackgroundHere, we address a pivotal factor in Alzheimer's prevention-identifying those at risk early, when dementia can still be avoided. Recent research highlights an accelerated forgetting phenotype as a risk factor for Alzheimer's disease. We hypothesized that delayed recall over 4?weeks would predict cognitive decline over 1 year better than 30-min delayed recall, the current gold standard for detecting episodic memory problems which could be an early clinical manifestation of incipient Alzheimer's disease. We also expected hippocampal subfield volumes to improve predictive accuracy.MethodsForty-six cognitively healthy older people (mean age 70.7?±?7.97, 21/46 female), recruited from databases such as Join Dementia Research, or a local database of volunteers, performed 3 memory tasks on which delayed recall was tested after 30?min and 4?weeks, as well as Addenbrooke's Cognitive Examination III (ACE-III) and CANTAB Paired Associates Learning. Medial temporal lobe subregion volumes were automatically measured using high-resolution 3T MRI. The ACE-III was repeated after 12?months to assess the change in cognitive ability. We used univariate linear regressions and ROC curves to assess the ability of tests of delayed recall to predict cognitive decline on ACE-III over the 12?months.ResultsFifteen of the 46 participants declined over the year (??3 points lost on ACE-III). Four-week verbal memory predicted cognitive decline in healthy older people better than clinical gold standard memory tests and hippocampal MRI. The best single-test predictor of cognitive decline was the 4-week delayed recall on the world list (R2?=?.123, p?=?.018, ??=?.418). Combined with hippocampal subfield volumetry, 4-week verbal recall identifies those at risk of cognitive decline with 93% sensitivity and 86% specificity (AUC?=?.918, p?<?.0001).ConclusionsWe show that a test of accelerated long-term forgetting over 4 weeks can predict cognitive decline in healthy older people where traditional tests of delayed recall cannot. Accelerated long-term forgetting is a sensitive, easy-to-test predictor of cognitive decline in healthy older people. Used alone or with hippocampal MRI, accelerated forgetting probes functionally relevant Alzheimer's-related change. Accelerated forgetting will identify early-stage impairment, helping to target more invasive and expensive molecular biomarker testing.

Project description:ObjectiveTo delineate the trajectories of Aβ42 level in cerebrospinal fluid (CSF), fludeoxyglucose F18 (FDG) uptake using positron emission tomography, and hippocampal volume using magnetic resonance imaging and their relative associations with cognitive change at different stages in aging and Alzheimer disease (AD).DesignCohort study.SettingThe 59 study sites for the Alzheimer's Disease Neuroimaging Initiative.ParticipantsA total of 819 participants 55 to 90 years of age with normal cognition, mild cognitive impairment, and AD who were followed up during the period from 2005 to 2007.Main outcome measuresRates of change in level of Aβ42 in CSF, FDG uptake, hippocampal volume, and the Alzheimer Disease's Assessment Scale-cognitive subscale score during up to 36 months of follow-up by diagnostic group as well as prediction of cognitive change by each biomarker.ResultsReductions in the level of Aβ42 in CSF were numerically greater in participants with normal cognition than in participants with mild cognitive impairment or AD; whereas both glucose metabolic decline and hippocampal atrophy were significantly slower in participants with normal cognition than in participants with mild cognitive impairment or AD. Positive APOE4 status accelerated hippocampal atrophic changes in participants with mild cognitive impairment or AD, but did not modify rates of change in level of Aβ42 in CSF or FDG uptake. The Alzheimer Disease's Assessment Scale-cognitive subscale scores were related only to the baseline level of Aβ42 in CSF and the baseline FDG uptake in participants with normal cognition, which were about equally associated with change in FDG uptake and hippocampal volume in participants with mild cognitive impairment and best modeled by change in FDG uptake in participants with AD.ConclusionTrajectories of Aβ42 level in CSF, FDG uptake, and hippocampal volume vary across different cognitive stages. The longitudinal patterns support a hypothetical sequence of AD pathology in which amyloid deposition is an early event before hypometabolism or hippocampal atrophy, suggesting that biomarker prediction for cognitive change is stage dependent.

Dataset Information

Improvement and decline of cognitive function in schizophrenia over one year: a longitudinal investigation using latent growth modelling.

Publications

Improvement and decline of cognitive function in schizophrenia over one year: a longitudinal investigation using latent growth modelling.

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