Physical comorbidities of older age bipolar disorder (OABD) patients: A global replication analysis of prevalence and sex differences.

OBJECTIVES: To compare the prevalence of physical morbidities between older aged patients with bipolar disorder (OABD) and non-psychiatric comparisons (NC), and to analyze sex differences in prevalence. METHODS: OABD was defined as bipolar disorder among adults aged ≥50 years. Outcomes analyzed were the prevalence of diseases affecting the cardiovascular, respiratory, gastrointestinal, genitourinary, renal, musculoskeletal, and endocrine systems. The analysis used cross-sectional data of OABD participants (n = 878; mean age 60.9 ± 8.0 years, n = 496 (56%) women) from the collaborative Global Aging & Geriatric Experiments in Bipolar Disorder (GAGE-BD) dataset and NC participants recruited at the same sites (n = 355; mean age 64.4 ± 9.7 years, n = 215 (61%) women). RESULTS: After controlling for sex, age, education, and smoking history, the OABD group had more cardiovascular (odds ratio [95% confidence interval]: 2.12 [1.38-3.30]), renal (5.97 [1.31-43.16]), musculoskeletal (2.09 [1.30-3.43]) and endocrine (1.90 [1.20-3.05]) diseases than NC. Women with OABD had more gastrointestinal (1.56 [0.99-2.49]), genitourinary (1.72 [1.02-2.92]), musculoskeletal (2.64 [1.66-4.37]) and endocrine (1.71 [1.08-2.73]) comorbidities than men with OABD, when age, education, smoking history, and study site were controlled. CONCLUSIONS: This replication GAGE-BD study confirms previous findings indicating that OABD present more physical morbidities than matched comparison participants, and that this health burden is significantly greater among women.

Subjective Sleep Quality and Trajectories of Interleukin-6 in Older Adults.

BACKGROUND: We aimed to identify trajectories of inflammation in older adults at elevated risk for syndromal depression and anxiety and to determine whether baseline physical, cognitive, and psychosocial factors could distinguish 15-month longitudinal trajectories. METHODS: Older adults (N = 195, mean age (±SD) = 74.4 years (9.0) participating in three depression and anxiety prevention protocols completed a comprehensive battery of psychosocial assessments and provided blood samples for analysis of interleukin-6 (IL-6) every 3 months over a maximum of 15 months. Group-based trajectory modeling identified trajectories. Adjusted logistic regression examined associations between baseline factors and trajectory groups. RESULTS: Two 15-month trajectories were identified: stable lower IL-6 levels (84%; mean (±SD) = 3.2 (2.1) pg/mL); and consistently higher IL-6 levels (16%; mean = 9.5 (7.4) pg/mL). Poor sleep quality predicted consistently higher levels of IL-6 (OR = 1.9, 95% CI = 1.03-3.55). CONCLUSION: Poor sleep quality may represent a therapeutic target to reduce inflammation.

Inflammation associated with volume reduction in the gray matter and hippocampus of older patients with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) and aging appear to be associated with inflammatory activation. Inflammatory processes might affect hippocampal function, neurogenesis, and gray matter loss. This study investigated the relationship between BD-specific brain regions and the total gray matter volume, peripheral inflammatory markers, and clinical features in older patients with BD. METHODS: We recruited euthymic patients with bipolar I disorder aged ≥50 years to undergo whole-brain magnetic resonance imaging. Each brain region was divided by an individual's total intracranial volume to obtain that brain region's volume in percentage relative to the total intracranial volume. We measured the plasma levels of soluble tumor necrosis factor receptor-1 (sTNF-R1), soluble interleukin (IL)-2 receptor (sIL-2R), sIL-6R, IL-1ß, and IL-1 receptor antagonist when patients were euthymic. Clinical data were obtained by reviewing available medical records and interviewing patients along with their reliable others. RESULTS: There were 32 patients with a mean age of 61.2 ±â€¯8.3 years and a mean age at illness onset of 33.4 ±â€¯13.8 years in this study. Stepwise regression showed that the right hippocampal volume was negatively associated with the levels of sIL-2R and sTNF-R1. The left hippocampal volume were negatively associated with the sIL-2R level and body mass index. The total gray matter volume had an inverse relationship with sTNF-R1 and IL-1ß levels. The duration of bipolar illness, lithium treatment, and antipsychotic use were not associated with hippocampal and total gray matter volumes. CONCLUSIONS: It is suggested that persistent inflammation is associated with reduction of hippocampal and gray matter volumes in older patients with BD. This phenomenon is supported by increases in sTNF-R1, sIL-2R, and IL-1ß levels. Neuroinflammation due to aging, obesity, and BD pathophysiology may play a role in BD neuroprogression across the life span.

The relationship between interleukin-1 receptor antagonist and cognitive function in older adults with bipolar disorder.

OBJECTIVE: Cognitive impairments are a feature of bipolar disorder (BD) and could be worsened by inflammatory cytokines. We determined whether (i) serum interleukin-1 receptor antagonist (IL-1RA) was increased in elderly BD subjects; (ii) whether IL-1RA was associated with worse neurocognitive function; and (iii) whether IL-1RA was associated with white matter integrity. METHODS: Twenty-one euthymic BD patients (65 +/- 9 years) with serum available for IL-1RA measures by enzyme-linked immunoassays were compared with 26 similarly aged control participants. Four factor analysis-derived z-scores and a global z-score were obtained from a battery of 21 neurocognitive tests. Diffusion tensor images were used to obtain fractional anisotropy (FA), and an automated labeling pathway algorithm was used to obtain white matter hyperintensity burden. RESULTS: Interleukin-1 receptor antagonist was elevated in BD subjects compared with controls (439+/-326 pg/mL vs. 269+/-109 pg/mL; p = 0.004). Moreover, IL-1RA was inversely correlated with three cognitive function factors and global cognition (r = -0.37; p = 0.01). IL-1RA continued to correlate with global cognitive function even when covarying for either IL-6 or brain-derived neurotrophic factor. Although FA was lower in BD subjects (0.368 +/- 0.02 vs. 0.381 +/- 0.01; p = 0.02), IL-1RA was not associated with FA or white matter hyperintensity burden. CONCLUSION: Elevated serum levels of IL-1RA in BD subjects, even during euthymic states, were associated with worse cognitive function. This association was not explained by co-occurring increases in IL-6, by decreased brain-derived neurotrophic factor, nor by measures of white matter integrity. These cross-sectional findings support the possibility that the IL-1 family may contribute to cognitive impairments in BD.