Combination of white matter hyperintensities and Aß burden is related to cognitive composites domain scores in subjective cognitive decline: the FACEHBI cohort.

BACKGROUND: To explore whether the combination of white matter hyperintensities (WMHs) and amyloid-beta (Aß) deposition is associated with worse cognitive performance on cognitive composites (CCs) domain scores in individuals with subjective cognitive decline (SCD). METHODS: Two hundred participants from the FACEHBI cohort underwent structural magnetic resonance imaging (MRI), 18F-florbetaben positron emission tomography (FBB-PET), and neuropsychological assessment. WMHs were addressed through the Fazekas scale, the Age-Related White Matter Changes (ARWMC) scale, and the FreeSurfer pipeline. Eight CCs domain scores were created using the principal component analysis (PCA). Age, sex, education, and apolipoprotein E (APOE) were used as adjusting variables. RESULTS: Adjusted multiple linear regression models showed that FreeSurfer (B - .245; 95% CI - .1.676, - .393, p = .016) and ß burden (SUVR) (B - .180; 95% CI - 2.140, - .292; p = .070) were associated with face-name associative memory CCs domain score, although the latest one was not statistically significant after correction for multiple testing (p = .070). There was non-significant interaction of these two factors on this same CCs domain score (p = .54). However, its cumulative effects on face-name associative performance indicated that those individuals with either higher WMH load or higher Aß burden showed the worst performance on the face-name associative memory CCs domain score. CONCLUSIONS: Our results suggest that increased WMH load and increased Aß are independently associated with poorer episodic memory performance in SCD individuals, indicating a cumulative effect of the combination of these two pathological conditions in promoting lower cognitive performance, an aspect that could help in terms of treatment and prevention.

Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group.

Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 × 10-21), left fusiform gyrus (d=-0.288; P=8.25 × 10-21) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10-19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.

Correlatos estructurales y funcionales del deterioro cognitivo en pacientes eutímicos con trastorno bipolar / Structural and functional brain correlates of cognitive impairment in euthymic patients with bipolar disorder

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Brain functional changes in first-degree relatives of patients with bipolar disorder: evidence for default mode network dysfunction.

BACKGROUND: Relatively few studies have investigated whether relatives of patients with bipolar disorder show brain functional changes, and these have focused on activation changes. Failure of de-activation during cognitive task performance is also seen in the disorder and may have trait-like characteristics since it has been found in euthymia. METHOD: A total of 20 euthymic patients with bipolar disorder, 20 of their unaffected siblings and 40 healthy controls underwent functional magnetic resonance imaging during performance of the n-back working memory task. An analysis of variance (ANOVA) was fitted to individual whole-brain maps from each set of patient-relative-matched pair of controls. Clusters of significant difference among the groups were used as regions of interest to compare mean activations/de-activations between them. RESULTS: A single cluster of significant difference among the three groups was found in the whole-brain ANOVA. This was located in the medial prefrontal cortex, a region of task-related de-activation in the healthy controls. Both the patients and their siblings showed significantly reduced de-activation compared with the healthy controls in this region, but the failure was less marked in the relatives. CONCLUSIONS: Failure to de-activate the medial prefrontal cortex in both euthymic bipolar patients and their unaffected siblings adds to evidence for default mode network dysfunction in the disorder, and suggests that it may act as a trait marker.

Brain structural changes in schizoaffective disorder compared to schizophrenia and bipolar disorder.

OBJECTIVE: Brain structural changes in schizoaffective disorder, and how far they resemble those seen in schizophrenia and bipolar disorder, have only been studied to a limited extent. METHOD: Forty-five patients meeting DSM-IV and RDC criteria for schizoaffective disorder, groups of patients with 45 matched schizophrenia and bipolar disorder, and 45 matched healthy controls were examined using voxel-based morphometry (VBM). RESULTS: Analyses comparing each patient group with the healthy control subjects found that the patients with schizoaffective disorder and the patients with schizophrenia showed widespread and overlapping areas of significant volume reduction, but the patients with bipolar disorder did not. A subsequent analysis compared the combined group of patients with the controls followed by extraction of clusters. In regions where the patients differed significantly from the controls, no significant differences in mean volume between patients with schizoaffective disorder and patients with schizophrenia in any of five regions of volume reduction were found, but mean volumes in the patients with bipolar disorder were significantly smaller in three of five. CONCLUSION: The findings provide evidence that, in terms of structural gray matter brain abnormality, schizoaffective disorder resembles schizophrenia more than bipolar disorder.