Inflammation in older subjects with early- and late-onset depression in the NESDO study: a cross-sectional and longitudinal case-only design.

OBJECTIVE: Different biological mechanisms may underlie depression beginning in early life (early-onset) and depression beginning later in life (late-onset). Although the relation between inflammation and depression has been studied extensively, the distinct role of inflammation in early and late-onset depression in older patients has not been addressed before. In the cross-sectional part of this study, we explored differences in levels of circulating inflammatory markers and cytokine levels in lipopolysaccharide (LPS) stimulated whole blood between older subjects with a late-life onset depression (≥60 years) and older subjects with an early-onset depression (<60 years). Secondly, in a 2-year follow-up study, we examined if circulating and stimulated inflammatory markers influenced the change in Inventory of Depressive Symptomatology (IDS) scores, and if this relation was different for early- and late-onset depression. METHODS: The study was part of the Netherlands Study of Depression in Older Persons (NESDO). We included 350 patients, all aged 60 and older, with a depressive episode in the previous 6 months: 119 with a late-onset depression and 231 with an early-onset depression. Blood samples were collected and CRP, IL-6, NGAL, GDF15, and, LPS plasma levels were determined and whole blood was LPS stimulated and cytokine levels IL-1ß, IL-6, TNFα, IFNγ, IL-10, and IL-1 receptor antagonist (IL-1ra) were determined. RESULTS: After adjustment for demographics, health indicators, and medication use, increased plasma CRP levels were more strongly associated with late-onset depression than early-onset depression (OR [95% CI]: 1.43 [1.05-1.94]). In the longitudinal analyses, higher circulating IL-6 levels were associated with a significantly slower decline in IDS scores in the crude and the adjusted models (p ≤ 0.027). This relation was not different between late- and early-onset depression. Other circulating and stimulated inflammatory markers were not associated with late- and/or early-onset depression. CONCLUSIONS: This study provides preliminary evidence that low-grade inflammation is more strongly associated with late-onset than early-onset depression in older adults, suggesting a distinct inflammatory etiology for late-onset depression. Cytokine production capacity did not distinguish between early- and late-onset depression.

Emotion Reactivity and Cerebrovascular Burden in Late-Life GAD: A Neuroimaging Study.

OBJECTIVE: Generalized anxiety disorder (GAD) in older adults is associated with persistent deficits in emotion reactivity (ER) and regulation, yet the neural basis of these deficits has not been explored. This study focuses on the neural basis of ER deficits in late-life GAD and the association with cerebrovascular burden. METHODS: Twenty elderly nonanxious participants and 17 late-life GAD participants were included. The faces-shapes functional magnetic resonance imaging task was used to assess ER; the Hamilton Anxiety Rating Scale and the Penn State Worry Questionnaire to measure global anxiety and worry, respectively; linear regression models to examine the association between ER and global anxiety severity and between ER and worry severity; and mediation analysis to explore the effect of ER on the relationship between global anxiety/worry severity and cerebrovascular burden. RESULTS: A positive association was found between ER and global anxiety in the left parahippocampus, left and right precuneus, and right superior occipital gyrus. A negative association was found between ER and worry severity in the left and right precuneus. The association between cerebrovascular burden and anxiety/worry severity was indirectly mediated by increased ER in limbic and paralimbic areas and by decreased ER in prefrontal regulatory regions. CONCLUSION: These results indicate that ER is associated with different neural activation patterns for worry and global anxiety and that ER-related functional connectivity indirectly mediates the relationship between cerebrovascular burden and late-life GAD. This latter result supports a yet-unexplored cerebrovascular pathway involved in the pathophysiology of late-life anxiety.

Altered Functional Magnetic Resonance Imaging Markers of Affective Processing During Treatment of Late-Life Depression.

OBJECTIVE: This study investigated neural substrate changes in affective processing among late-life depression (LLD) patients undergoing antidepressant treatment and determined if these changes correlated with remission status. METHODS: Thirty-three LLD patients were enrolled in a 12-week venlafaxine treatment course. During treatment functional magnetic resonance imaging (fMRI) scans, paired with an affective task that assessed emotional reactivity and regulation, were performed on days 1, 2, 3, and 7 and at week 12. Following treatment patients were classified as remitters or non-remitters. A voxel-wise two-way repeated-measures ANOVA was performed to assess the fMRI data at a significance level of α = 0.05, corrected. RESULTS: The emotional reactivity contrast demonstrated a significant interaction between remission status and scan time in the right middle temporal gyrus (MTG) (F = 24.1, df = 1,112, k = 102). Further analysis showed increased emotional reactivity-induced activity among non-remitters, and decreased activity among remitters, which significantly differed from baseline at day 7 (95% CI: 0.027, 0.540; Cohen's d = -1.35) and week 12 (95% CI: -0.171, -0.052; Cohen's d = 0.68), respectively. No significant interaction was observed with the emotional regulation contrast, but multiple regions had significant main effects of scan time, including the cuneus, occipital lobe, insula, lingual gyrus, posterior cingulate cortex, and MTG. CONCLUSIONS: During treatment of LLD patients, affective processing-induced activity in the right MTG shows changes based on remission status. This alteration becomes evident early during the course of treatment, suggesting that antidepressant pharmacotherapy may acutely affect the neural basis of emotional reactivity in a differential manner that is relevant to illness remission.

Blunted Hypercapnic Respiratory Drive Response in Subjects With Late-Onset Pompe Disease.

BACKGROUND: Patients with late-onset Pompe disease develop progressive hypercapnic respiratory failure that can be disproportionate to the respiratory muscle compromise and/or thoracic restriction. Although recent studies have reported the presence of a blunted hypercapnic respiratory response in some subjects with neuromuscular disorders and chronic hypercapnia, no study has evaluated the integrity of the respiratory drive in subjects with late-onset Pompe disease. Thus, we endeavor to determine the CO2 rebreathing response in subjects with late-onset Pompe disease. METHODS: Respiratory muscle strength was assessed by measuring the maximum inspiratory pressure, and the maximum expiratory pressure. The maximum inspiratory pressure reflects the strength of the diaphragm and other inspiratory muscles, whereas the maximum expiratory pressure reflects the strength of the abdominal muscles and other expiratory muscles. We studied the hypercapnic drive response (measured as the ratio of the change in airway-occlusion pressure 0.1 s after the start of inspiration and end-tidal PCO2 in 13 subjects with late-onset Pompe disease and 51 healthy controls. RESULTS: Overall inspiratory muscle strength was within normal limits or slightly diminished in the late-onset Pompe disease group. Five subjects (38.5%) were chronically hypercapnic, and 9 (69.2%) had an increased breath-holding time. Compared with controls, the change in airway-occlusion pressure 0.1 s/change in end-tidal CO2 pressure slope (hypercapnic respiratory drive) was lower in the late-onset Pompe disease group (median 0.050 [interquartile range 0.027-0.118] vs 0.183 [0.153-0.233], P < .001). Nine subjects (69.2%) had a blunted change in airway-occlusion pressure 0.1 s/change in end-tidal carbon dioxide pressure slope. CONCLUSIONS: Subjects with late-onset Pompe disease had an impaired hypercapnic respiratory drive response. The clinical impact of this phenomenon in this subject subset deserves further investigation.

Mild clinical behaviour of Crohn disease in elderly patients in a Latin American country: A case-control study.

BACKGROUND: Crohn disease is characterized by fluctuating clinical behaviour, which is influenced by various factors. There are no data from Latin America that evaluate the clinical behaviour of Crohn disease in elderly patients. OBJECTIVE: To evaluate the clinical course of elderly onset Crohn disease compared with younger onset in the Mexican population. METHODS: The present analysis was a case-control study that included 132 patients with a histopathological diagnosis of Crohn disease between 1983 and 2013 in an inflammatory bowel disease clinic of a tertiary care centre. Statistical analysis was performed using SPSS version 17 (IBM Corporation, USA) and descriptive statistics, χ2 and Fisher's exact test for categorical variables and Student's t test for numerical variables. Univariate and multivariate analysis were performed to identify associated risk factors and OR was calculated. RESULTS: A total of 132 patients (73 men and 59 women) were divided into two groups according to age at diagnosis: 27 cases (>60 years of age) and 105 controls (≤60 years of age). Factors influencing the clinical course of Crohn disease in the elderly were: female sex (OR 2.55 [95% CI 1.06 to 6.10]; P=0.02); colonic location (OR 0.22 [95% CI 0.03 to 0.89]; P=0.02); mild clinical behaviour of disease (OR 10.08 [95% CI 3.74 to 27.17]; P=0.0001); response to medical treatment (OR 2.85 [95% CI 1.08 to 7.48]; P=0.02); frequent use of sulfasalazine (OR 4.46 [95% CI 1.22 to 16.28]; P=0.03); less use of azathioprine (OR 0.38 [95% CI 0.13 to 1.03]; P=0.04); and long-term remission (OR 4.96 [95% CI 1.70 to 14.48]; P=0.002). CONLCUSION: Elderly patients with Crohn disease had a mild clinical course characterized by the lack of escalation to immunosuppressive and anti-tumour necrosis factor therapy, as well as long-term remission.