Persistent Intrinsic Functional Network Connectivity Alterations in Middle-Aged and Older Women With Remitted Depression.

BACKGROUND: In younger adults, residual alterations in functional neural networks persist during remitted depression. However, there are fewer data for midlife and older adults at risk of recurrence. Such residual network alterations may contribute to vulnerability to recurrence. This study examined intrinsic network functional connectivity in midlife and older women with remitted depression. METHODS: A total of 69 women (24 with a history of depression, 45 with no psychiatric history) over 50 years of age completed 3T fMRI with resting-state acquisition. Participants with remitted depression met DSM-IV-TR criteria for an episode in the last 10 years but not the prior year. Whole-brain seed-to-voxel resting-state functional connectivity analyses examined the default mode network (DMN), executive control network (ECN), and salience network (SN), plus bilateral hippocampal seeds. All analyses were adjusted for age and used cluster-level correction for multiple comparisons with FDR < 0.05 and a height threshold of p < 0.001, uncorrected. RESULTS: Women with a history of depression exhibited decreased functional connectivity between the SN (right insula seed) and ECN regions, specifically the left superior frontal gyrus. They also exhibited increased functional connectivity between the left hippocampus and the left postcentral gyrus. We did not observe any group differences in functional connectivity for DMN or ECN seeds. CONCLUSIONS: Remitted depression in women is associated with connectivity differences between the SN and ECN and between the hippocampus and the postcentral gyrus, a region involved in interoception. Further work is needed to determine whether these findings are related to functional alterations or are predictive of recurrence.

Medial temporal lobe volumes in late-life depression: effects of age and vascular risk factors.

Substantial work associates late-life depression with hippocampal pathology. However, there is less information about differences in hippocampal subfields and other connected temporal lobe regions and how these regions may be influenced by vascular factors. Individuals aged 60 years or older with and without a DSM-IV diagnosis of Major Depressive Disorder completed clinical assessments and 3 T cranial MRI using a protocol allowing for automated measurement of medial temporal lobe subfield volumes. A subset also completed pseudo-continuous arterial spin labeling, allowing for the measurement of hippocampal cerebral blood flow. In 59 depressed and 21 never-depressed elders (mean age = 66.4 years, SD = 5.8y, range 60-86y), the depressed group did not exhibit statistically significant volumetric differences for the total hippocampus or hippocampal subfields but did exhibit significantly smaller volumes of the perirhinal cortex, specifically in the BA36 region. Additionally, age had a greater effect in the depressed group on volumes of the cornu ammonis, entorhinal cortex, and BA36 region. Finally, both clinical and radiological markers of vascular risk were associated with smaller BA36 volumes, while reduced hippocampal blood flow was associated with smaller hippocampal and cornu ammonis volumes. In conclusion, while we did not observe group differences in hippocampal regions, we observed group differences and an effect of vascular pathology on the BA36 region, part of the perirhinal cortex. This is a critical region exhibiting atrophy in prodromal Alzheimer's disease. Moreover, the observed greater effect of age in the depressed groups is concordant with past longitudinal studies reporting greater hippocampal atrophy in late-life depression.

Intrinsic Functional Network Connectivity Is Associated With Clinical Symptoms and Cognition in Late-Life Depression.

BACKGROUND: Late-life depression (LLD) has been associated with alterations in intrinsic functional networks, best characterized in the default mode network (DMN), cognitive control network (CCN), and salience network. However, these findings often derive from small samples, and it is not well understood how network findings relate to clinical and cognitive symptomatology. METHODS: We studied 100 older adults (n = 79 with LLD, n = 21 nondepressed) and collected resting-state functional magnetic resonance imaging, clinical measures of depression, and performance on cognitive tests. We selected canonical network regions for each intrinsic functional network (DMN, CCN, and salience network) as seeds in seed-to-voxel analysis. We compared connectivity between the depressed and nondepressed groups and correlated connectivity with depression severity among depressed subjects. We then investigated whether the observed connectivity findings were associated with greater severity of common neuropsychiatric symptoms or poorer cognitive performance. RESULTS: LLD was characterized by decreased DMN connectivity to the frontal pole, a CCN region (Wald χ21 = 22.33, p < .001). No significant group differences in connectivity were found for the CCN or salience network. However, in the LLD group, increased CCN connectivity was associated with increased depression severity (Wald χ21 > 20.14, p < .001), greater anhedonia (Wald χ21 = 7.02, p = .008) and fatigue (Wald χ21 = 6.31, p = .012), and poorer performance on tests of episodic memory (Wald χ21 > 4.65, p < .031), executive function (Wald χ21 = 7.18, p = .007), and working memory (Wald χ21 > 4.29, p < .038). CONCLUSIONS: LLD is characterized by differences in DMN connectivity, while CCN connectivity is associated with LLD symptomology, including poorer performance in several cognitive domains.

Transdermal Nicotine for the Treatment of Mood and Cognitive Symptoms in Nonsmokers With Late-Life Depression.

OBJECTIVE: Late-life depression (LLD) is characterized by poor antidepressant response and cognitive dysfunction. This study examined whether transdermal nicotine benefits mood symptoms and cognitive performance in LLD. METHODS: In a 12-week open-label outpatient study conducted between November 2016 and August 2017, transdermal nicotine was given to 15 nonsmoking older adults (≥ 60 years of age). Eligible participants met DSM-IV-TR criteria for major depressive disorder with ≥ 15 on the Montgomery-Asberg Depression Rating scale (MADRS) and endorsed subjective cognitive impairment. Transdermal nicotine patches were applied daily and titrated in a rigid dose escalation strategy to a maximum dose of 21.0 mg/d, allowing dose reductions for tolerability. The primary mood outcome was MADRS change measured every 3 weeks, with response defined as ≥ 50% improvement from baseline and remission as MADRS score ≤ 8. The primary cognitive outcome was the Conners Continuous Performance Test (CPT), a test of attention. RESULTS: Robust rates of response (86.7%; 13/15 subjects) and remission (53.3%; 8/15 subjects) were observed. There was a significant decrease in MADRS scores over the study (ß = -1.51, P < .001), with improvement seen as early as 3 weeks (Bonferroni-adjusted P value = .004). We also observed improvement in apathy and rumination. We did not observe improvement on the CPT but did observe improvement in subjective cognitive performance and signals of potential drug effects on secondary cognitive measures of working memory, episodic memory, and self-referential emotional processing. Overall, transdermal nicotine was well tolerated, although 6 participants could not reach the maximum targeted dose. CONCLUSIONS: Nicotine may be a promising therapy for depressed mood and cognitive performance in LLD. A definitive placebo-controlled trial and establishment of longer-term safety are necessary before clinical usage. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02816138​.

Nicotine and networks: Potential for enhancement of mood and cognition in late-life depression.

Late-life depression is characterized by both lower mood and poor cognitive performance, symptoms that often do not fully respond to current antidepressant medications. Nicotinic acetylcholine receptor (nAChR) agonists such as nicotine may serve as a novel therapeutic approach for this population. Both preclinical and preliminary clinical studies suggest that nAChR agonists can improve depressive behavior in animal models and improve mood in depressed individuals. Substantial literature also supports that nAChR agonists benefit cognitive performance, particularly in older populations. These potential benefits may be mediated by the effects of nAChR stimulation on neural network function and connectivity. Functional neuroimaging studies detail effects of nAChR agonists on the default mode network, central-executive network, and salience network that may oppose or reverse network changes seen in depression. We propose that, given the existent literature and the clinical presentation of late-life depression, nicotine or other nAChR agonists may have unique therapeutic benefits in this population and that clinical trials examining nicotine effects on mood, cognition, and network dynamics in late-life depression are justified.

Retrocaval renal artery bifurcation is not a contraindication to laparoscopic right donor nephrectomy.

BACKGROUND: Laparoscopic donor nephrectomy is preferentially performed on the left side vs the right, even in instances where more complex arterial vasculature is present on the left. This finding is significant given the observation that living donor kidneys with multiple arteries are associated with increased incidence of ureteral complications in the recipient. One common anatomic variant, retrocaval bifurcation of the right renal artery, has potential risks that prompt the decision to procure left-sided kidneys with more complex arterial anatomy. However, these risks may be mitigated by the surgical approaches that can successfully procure right kidneys with this type of arterial variant. STUDY DESIGN: Of 321 total nephrectomies performed, there were 44 right-sided laparoscopic donor nephrectomies. Nineteen of these 44 patients had retrocaval bifurcation and were compared with a cohort of 25 patients without this variant. Standardized parameters were collected including demographics, donor and recipient outcomes, graft function, and renal artery anastomotic velocity. The Mann-Whitney U test and Fisher's exact test were used to show statistical significance. RESULTS: Donor and recipient outcomes and complication rates were not significantly different between the retrocaval bifurcation group and the nonbifurcation group. Notably, graft anastomotic velocity and rates of delayed graft function (DGF) were the same between recipients in the 2 study groups. Comparisons between left-sided nephrectomies and kidneys from the retrocaval bifurcation group showed a slower reduction in immediate creatinine clearance in the retrocaval group; however, both groups had similar outcomes 30 days post-transplantation. CONCLUSIONS: This study provides a detailed, technical laparoscopic methodology for procurement of right-sided kidneys with retrocaval arterial bifurcation, which was associated with outcomes similar to right and left kidneys with single arteries.