Cognitive impairment varies widely in bipolar disorder. Identifying cognitive subgroups and their biological correlates may improve understanding of the disorder. Brain-derived neurotrophic factor (BDNF) and C-reactive protein (CRP) are key candidates due to their roles in neuroplasticity and inflammation.

The aim was to investigate cognitive subgroups in patients with bipolar disorder and their association with serum levels of BDNF and CRP.

A cross-sectional study was conducted on 149 bipolar disorder patients and 48 healthy controls. Cognitive performance was assessed using a comprehensive battery of neuropsychological tests. Cluster analysis was performed to identify cognitive subgroups, followed by discriminant function analysis to validate the classification. Serum levels of BDNF and CRP were measured and compared across cognitive subgroups.

Cluster analysis identified three cognitive subgroups: intact cognition, selectively impaired cognition (SIC) and globally impaired cognition (GIC). SIC exhibited the highest BDNF levels, while GIC demonstrated the highest CRP levels. CRP levels were negatively associated with performance across all cognitive domains. BDNF showed a negative correlation with verbal fluency, short-term memory and working memory. CRP levels exceeding 4.3 mg/L predicted global cognitive impairment with a sensitivity of 72.41% and specificity of 73.63%.

Cognitive impairments in bipolar disorder patients can be classified into distinct subgroups, which are associated with serum levels of BDNF and CRP. These findings suggest that inflammation and neuroplasticity play key roles in the pathophysiology of cognitive decline in bipolar disorder, providing potential biomarkers for identifying patients at risk for severe cognitive impairments.

In schizophrenia, relative stability in the magnitude of cognitive deficits across age and illness duration is inconsistent with the 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 buffer against brain pathology and minimize its impact on cognitive or clinical indicators of illness.

Age-related change 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.

Patients showed exaggerated age-related decline in brain structure, but not fluid reasoning 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.

In schizophrenia-spectrum illness, CR may negate ageing effects on fluid reasoning by buffering 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 in the extant literature.