Abstract
BACKGROUND: In schizophrenia, relative stability in the magnitude of fluid cognitive deficits across age and illness duration is inconsistent with evidence of accelerated deterioration in brain regions known to support these functions. These discrepant brain-cognition outcomes may be explained by variability in cognitive reserve (CR), which in neurological disorders has been shown to enable resilience against brain pathology and minimize its impact on cognitive or clinical indicators of illness. METHODS: Age-related changes in fluid reasoning, working memory and frontal brain volume, area and thickness were mapped using regression analysis in 214 individuals with schizophrenia or schizoaffective disorder and 168 healthy controls. In patients, these changes were modelled as a function of CR. RESULTS: Patients showed exaggerated age-related decline in brain structure, but not fluid cognition compared to controls. In the patient group, no moderation of age-related brain structural change by CR was evident. However, age-related cognitive change was moderated by CR, such that only patients with low CR showed evidence of exaggerated fluid reasoning decline that paralleled the exaggerated age-related deterioration of underpinning brain structures seen in all patients. CONCLUSIONS: In schizophrenia-spectrum illness, CR may negate ageing effects on fluid cognition by conferring resilience against pathologically exaggerated structural brain deterioration through some form of compensation. CR may represent an important modifier that could explain inconsistencies in brain structure - cognition outcomes evident in the extant literature.