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Background: Treatment-resistant depression (TRD) is a growing clinical challenge. Electroconvulsive therapy (ECT) is an effective tool for TRD treatment. However, there remains a subset of patients who do not respond to this treatment with common anesthetic agent. Ketamine, a noteworthy anesthetic agent, has emerged as an augmentation to enhance the antidepressant efficacy of ECT. Trials of i.v. ketamine in TRD indicated dose-related mood enhancing efficacy. We aimed to explore anesthetic and subanesthetic concentrations of ketamine in ECT for TRD with respect to their impact on mood and neuropsychological effects., Methods: Ninety TRD patients (36 males, 54 females; average age, 30.6 years old) were randomly assigned to receive either ketamine (0.8mg/kg) (n=30), subanesthetic ketamine (0.5mg/kg) plus propofol (0.5mg/kg) (n=30) or propofol (0.8mg/kg) (n=30) as an anesthetic and underwent 8 ECT sessions. The primary outcome measures were the 17-item Hamilton Depression Rating Scale (HDRS-17), cognitive assessments and seizure parameters., Results: The ketamine group had an earlier improvement in HDRS-17, longer seizure duration, lower electric quantity, a higher remission rate, and a lower degree of executive cognitive impairment compared to the ketamine+propofol and propofol groups. The ketamine+propofol group showed earlier improvement in the HDRS-17, a longer seizure duration and a different seizure energy index when compared to the propofol group., Limitations: The postoperative dissociative side effect was not assessed., Conclusions: Both anesthetic and subanesthetic concentrations of ketamine have rapid mood enhancing actions in ECT for TRD, while anesthetic concentrations results in larger magnitudes of antidepression and cognitive protection. ECT with ketamine anesthesia might be an optimized therapy for patients with TRD., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Elevated homocysteine levels and late‐life depression are risk factors for cognitive decline: a comparative study highlighted the association of late‐onset depression (LOD) with more significant cognitive deficits and brain pathology than early‐onset depression (EOD). Limited research has explored the possible interaction between homocysteine levels and their correlation with cognitive performance in patients with EOD and LOD. Methods: Fifty‐seven individuals with EOD, 56 with LOD, and 89 matched healthy controls (HC) were recruited. Global cognition, memory, execution, language, attention, visuospatial skills, and plasma homocysteine levels were examined. Results: Compared with HC and patients with EOD, patients with LOD had higher plasma homocysteine levels (p < 0.05), with no significant difference between HC and patients with EOD (p > 0.05). Furthermore, homocysteine levels and diagnosis groups showed significant main effects on depression and cognition, with no significant interaction effects being observed. Additionally, plasma homocysteine levels were negatively correlated with global cognition, attention, visuospatial skills, and executive function in patients with LOD (p < 0.05). Conclusions: Compared with HC and patients with EOD, elevated homocysteine levels in patients with LOD were independently associated with cognitive performance. The potential therapeutic efficacy of homocysteine‐lowering B‐vitamin supplementation could be explored as a viable intervention to mitigate the documented debilitating effects of cognitive deficits in this population. [ABSTRACT FROM AUTHOR]

Background: Functional abnormalities of the habenula in patients with depression have been demonstrated in an increasing number of studies, and the habenula is involved in cognitive processing. However, whether patients with late‐life depression (LLD) exhibit disrupted habenular functional connectivity (FC) and whether habenular FC mediates the relationship between depressive symptoms and cognitive impairment remain unclear. Methods: Overall, 127 patients with LLD and 75 healthy controls were recruited. The static and dynamic FC between the habenula and the whole brain was compared between LLD patients and healthy controls, and the relationships of habenular FC with depressive symptoms and cognitive impairment were explored by correlation and mediation analyses. Results: Compared with the controls, patients with LLD exhibited decreased static FC between the right habenula and bilateral inferior frontal gyrus (IFG); there was no significant difference in dynamic FC of the habenula between the two groups. Additionally, the decreased static FC between the right habenula and IFG was associated with more severe depressive symptoms (especially psychomotor retardation) and cognitive impairment (language, memory, and visuospatial skills). Last, static FC between the right habenula and left IFG partially mediated the relationship between depressive symptoms (especially psychomotor retardation) and cognitive impairment (verbal fluency and working memory). Conclusions: Patients with LLD exhibited decreased static FC between the habenula and IFG but intact dynamic FC of the habenula. This decreased static FC mediated the relationship between depressive symptoms and cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: Both late-life depression (LLD) and short sleep duration increase the risk of cognitive impairment. Increased insular resting-state functional connectivity (FC) has been reported in individuals with short sleep duration and dementia. Objective: This study aimed to investigate whether short sleep duration is associated with impaired cognition and higher insular FC in patients with LLD. Methods: This case– control study recruited 186 patients with LLD and 83 normal controls (NC), and comprehensive psychometric assessments, sleep duration reports and resting-state functional MRI scans (81 LLD patients and 54 NC) were conducted. Results: Patients with LLD and short sleep duration (LLD-SS patients) exhibited more severe depressive symptoms and worse cognitive function than those with normal sleep duration (LLD-NS patients) and NC. LLD-SS patients exhibited higher FC between the bilateral insula and inferior frontal gyrus (IFG) pars triangularis than LLD-NS patients and NC, while LLD-NS patients exhibited lower FC than NC. Increased insular FC was correlated with short sleep duration, severe depressive symptoms, and slower information processing speeds. Furthermore, an additive effect was found between sleep duration and LLD on global cognition and insular FC. Conclusion: LLD-SS patients exhibited impaired cognition and increased insular FC. Abnormal FC in LLD-SS patients may be a therapeutic target for neuromodulation to improve sleep and cognitive performance and thus decrease the risk of dementia. [ABSTRACT FROM AUTHOR]

Background: Subjective cognitive decline (SCD) is a putative Alzheimer's disease (AD) precursor without objective neuropsychological deficits. The hippocampus plays an important role in cognitive function and emotional responses and is generally aberrant in SCD. However, previous studies have mainly focused on static functional connectivity (sFC) by resting-state functional magnetic resonance imaging (fMRI) in SCD individuals, and it remains unclear whether hippocampal dynamic functional connectivity (dFC) changes exist in SCD and whether those changes are associated with subtle changes in cognitive function or affect. Methods: Seventy SCD patients and 65 healthy controls were recruited. Demographic data, comprehensive neuropsychology assessments, and resting-state fMRI data were collected. The bilateral anterior and posterior hippocampi were selected as seeds to investigate the static and dynamic functional connectivity alterations in SCD. Results: Compared to healthy controls, subjects with SCD exhibited: (1) decreased sFC between the left caudal hippocampus and left precuneus; (2) decreased dFC variability between the bilateral caudal hippocampus and precuneus; (3) increased dFC variability between the bilateral rostral hippocampus and caudate nucleus; and (4) increased dFC variability between the left rostral hippocampus and left olfactory cortex. Additionally, the attention scores were positively correlated with dFC variability between the left posterior hippocampus and left precuneus, and the dFC variability between the bilateral anterior hippocampus and caudate nucleus was positively correlated with depression scores and negatively correlated with global cognition scores. Conclusion: SCD individuals exhibited abnormal sFC and dFC in the anterior-posterior hippocampus, and abnormal dFC was more widespread than abnormal sFC. A combination of sFC and dFC provides a new perspective for exploring the brain pathophysiological mechanisms in SCD and offers potential neuroimaging biomarkers for the early diagnosis and intervention of AD. [ABSTRACT FROM AUTHOR]

Background Odor identification (OI) dysfunction is an early marker of Alzheimer's disease (AD), but it remains unclear how olfactory-related regions change from stages of subjective cognitive decline (SCD) and mild cognitive impairment (MCI) to AD dementia. Methods Two hundred and sixty-nine individuals were recruited in the present study. The olfactory-related regions were defined as the regions of interest, and the grey matter volume (GMV), low-frequency fluctuation, regional homogeneity (ReHo), and functional connectivity (FC) were compared for exploring the changing pattern of structural and functional abnormalities across AD, MCI, SCD, and normal controls. Results From the SCD, MCI to AD groups, the reduced GMV, increased low-frequency fluctuation, increased ReHo, and reduced FC of olfactory-related regions became increasingly severe, and only the degree of reduced GMV of hippocampus and caudate nucleus clearly distinguished the 3 groups. SCD participants exhibited reduced GMV (hippocampus, etc.), increased ReHo (caudate nucleus), and reduced FC (hippocampus-hippocampus and hippocampus-parahippocampus) in olfactory-related regions compared with normal controls. Additionally, reduced GMV of the bilateral hippocampus and increased ReHo of the right caudate nucleus were associated with OI dysfunction and global cognitive impairment, and they exhibited partially mediated effects on the relationships between OI and global cognition across all participants. Conclusion Structural and functional abnormalities of olfactory-related regions present early with SCD and deepen with disease severity in the AD spectrum. The hippocampus and caudate nucleus may be the hub joining OI and cognitive function in the AD spectrum. [ABSTRACT FROM AUTHOR]

Background: Late-life depression (LLD) is a risk factor for cognitive decline in older adults, and odor identification (OI) deficits are an early indicator of cognitive decline with LLD. However, neuropsychiatric symptoms (NPSs) are common in LLD and are associated with OI deficits. In subjects with LLD, when OI deficits forecast cognitive decline, whether and how NPS affects the relationship between OI and cognition still must be further explored. Objective: To comprehensively explore the potential effects of various NPSs on the relationship between OI and cognition in participants with LLD. Methods: There were 167 patients with LLD and 105 normal elderly (NE) participants. The odor identification test (Sniffin' Sticks), cognitive function assessments (global cognition, memory, executive function, attention, language, visual space), and an NPS assessment (the neuropsychiatric inventory questionnaire) were performed on the subjects. In patients with LLD, the relationship among OI, cognition and NPSs was examined using correlation analysis and moderation analysis. Results: In patients with LLD, OI was positively correlated with cognition (global cognition, memory, executive function, attention, language) and negatively associated with NPSs (agitation and aberrant motor behavior). In NE group, OI was correlated with executive function. Moderation analysis showed that there was an interactive effect of agitation and cognitive impairment (language deficit or attention deficit) on OI in patients with LLD. Conclusion: The coexistence of agitation and language or attention deficit was associated with worse OI in subjects with LLD. Agitation should be considered since OI predicts cognitive decline in patients with LLD. [ABSTRACT FROM AUTHOR]

Objectives: Although previous studies have extensively confirmed the cross-sectional relationship between cognitive impairment and depression in depressed elderly patients, the findings of their longitudinal associations are still mixed. The purpose of this study was to explore the two-way causal relationship between depression symptoms and cognition in patients with late-life depression (LLD). Methods: A total of 90 patients with LLD were assessed across two time points (baseline and 1-year follow up) on measures of 3 aspects of cognition and depressive symptoms. The data were then fitted to a structural equation model to examine two cross-lagged effects. Results: Depressive symptoms predicted a decline in executive function (β = 0.864, p = 0.049) but not vice versa. Moreover, depressive symptoms were predicted by a decline in scores of working memory test (β = −0.406, p = 0.023), respectively. None of the relationships between the two factors was bidirectional. Conclusion: These results provide robust evidence that the relationship between cognition and depressive symptoms is unidirectional. Depressive symptoms may be a risk factor for cognitive decline. The decrease of information processing speed predicts depressive symptoms. [ABSTRACT FROM AUTHOR]

Background: Both an elevated homocysteine (Hcy) level and depression are risk factors for cognitive impairment in the general population, but no study has analyzed whether the coexistence of an elevated Hcy level and late-life depression (LLD) is associated with worse cognitive performance.Objective: We aimed to investigate the relationship between Hcy levels and cognitive function in individuals with LLD and whether the coexistence of an elevated Hcy level and LLD is associated with worse cognitive performance.Methods: A total of 113 LLD patients and 89 normal controls underwent a standardized clinical interview and comprehensive neuropsychological assessment battery. Plasma concentrations of Hcy were detected. Factorial analyses were performed to examine the impact of the coexistence of an elevated Hcy level and LLD on cognitive performance.Results: Plasma Hcy levels in patients with LLD were significantly higher than that in normal controls. Only for LLD patients, Hcy level was negatively correlated with global cognition, executive function, attention, and visual space. The factorial analysis showed that there was a significant interactive effect of Hcy level (normal and elevated levels) and LLD (with and without LLD) on global cognition. In post hoc comparisons, the elderly individuals with both elevated Hcy levels and LLD tended to have the worst global cognitive function compared with those with LLD or elevated Hcy levels alone.Conclusions: The coexistence of an elevated Hcy level and LLD was associated with worse cognitive performance. Early intervention should be initiated to protect cognition in LLD patients with elevated Hcy levels. [ABSTRACT FROM AUTHOR]

Background: Patients with spirochetal infection, which causes neurosyphilis (NS) and at a later stage general paresis of the insane (GPI), present with brain pathology features of Alzheimer's disease (AD). However, the relationships among these illnesses regarding biomarker levels are still unclear.Objective: To explore biomarker levels in NS and GPI compared with those in AD and the relationship between biomarker levels and cognitive function in NS and GPI.Methods: Levels of neurogranin (NGRN) and β-amyloid precursor protein cleaving enzyme (BACE1) in cerebrospinal fluid (CSF)/plasma, together with amyloid-β 1-40 (Aβ40), Aβ42, and total tau in the CSF of 23 AD patients, 55 GPI patients, and 13 NS patients were measured. Patients were classified into none-to-mild, moderate, and severe stages of cognitive impairment.Results: Levels of CSF NGRN, BACE1, and tau as well as plasma BACE1 levels were significantly different among groups. In the none-to-mild stage, plasma BACE1 levels correlated with the protein levels in CSF and were significantly increased in AD patients versus GPI patients. The CSF tau levels in AD patients were significantly increased versus GPI patients in the moderate and severe stages. Pooling data from GPI and NS patients, both CSF tau and plasma NGRN levels correlated with cognitive scale scores.Conclusion: GPI and NS patients might have different biomarker level patterns compared to AD patients. While plasma BACE1 could be a promising early biomarker for distinguishing AD from GPI, CSF tau and plasma NGRN levels might be valuable in indications of cognitive function in pooled NS populations. [ABSTRACT FROM AUTHOR]

Background: The pattern of neuropsychiatric features of patients with neurosyphilis and the impact of the severity of cognitive impairment on neuropsychiatric syndromes are unknown. Objective: We aim to assess the neuropsychiatric features of patients with neurosyphilis, and compare the impact of the severity of cognitive impairment on the neuropsychiatric syndromes between neurosyphilis and Alzheimer disease (AD). Methods: Neuropsychiatric symptoms and the degree of cognitive impairment were assessed in a case-control study of 91 neurosyphilis, 162 AD, 157 mild cognitive impairment, and 139 normal controls by the Neuropsychiatric Inventory (NPI) scale and Clinical Dementia Rating scale, respectively. Factor analysis was performed on the 12 NPI items. Results: Factor analysis showed that patients with neurosyphilis showed more severe neuropsychiatric syndromes at the dementia stage than those neurosyphilis patients at the mild cognitive impairment stage, while neuropsychiatric manifestations were equally common among the different stages of dementia (all p < 0.05). Frontal lobe syndrome was more severe in patients with neurosyphilis than in patients with AD from the early mild cognitive impairment stage to the moderate dementia stage (all p < 0.01). Conclusions: Patients with neurosyphilis show different patterns of neuropsychiatric syndromes at the mild cognitive impairment and dementia stages, and differ from patients with AD. [ABSTRACT FROM AUTHOR]

Suicide is one of the most lethal complications of late-life depression (LLD), and habenular dysfunction may be involved in depression-related suicidality and may serve as a potential target for alleviating suicidal ideation. This study aimed to investigate abnormal functional connectivity of the habenula in LLD patients with suicidal ideation. One hundred twenty-seven patients with LLD (51 with suicidal ideation (LLD-S) and 76 without suicidal ideation (LLD-NS)) and 75 healthy controls (HCs) were recruited. The static functional connectivity (sFC) and dynamic functional connectivity (dFC) between the habenula and the whole brain were compared among the three groups, and correlation and moderation analyses were applied to investigate whether suicidal ideation moderated the relationships of habenular FC with depressive symptoms and cognitive impairment. The dFC between the right habenula and the left orbitofrontal cortex (OFC) increased in the following order: LLD-S > LLD-NS > control. No significant difference in the habenular sFC was found among the LLD-S, LLD-NS and control groups. The dFC between the right habenula and the left OFC was positively associated with global cognitive function and visuospatial skills, and the association between this dFC and visuospatial skills was moderated by suicidal ideation in patients with LLD. The increased variability in dFC between the right habenula and left OFC was more pronounced in the LLD-S group than in the LLD-NS group, and the association between habenular-OFC dFC and visuospatial skills was moderated by suicidal ideation in patients with LLD. • LLD-S exhibited increased dFC between habenula and OFC than LLD-NSl The association between dFC and cognition was moderated by suicidal ideation [ABSTRACT FROM AUTHOR]

Cognitive impairments are prevalent in late-life depression (LLD). However, it remains unclear whether there are concurrent brain oscillation alterations in resting condition across varying level of depression severity. This cross-sectional study aims to investigate the characteristics of altered resting-state oscillations, including power spectrum and functional connectivity, and their association with the cognitive impairments in LLD with different depression severity. A total of 65 patients with LLD and 40 elder participants without depression were recruited. Global cognition and subtle cognitive domains were evaluated. A five-minute resting-state electroencephalography (EEG) was conducted under eyes-closed conditions. Measurements included the ln-transformed absolute power for power spectrum analysis and the weighted phase lag index (wPLI) for functional connectivity analysis. Attentional and executive dysfunction were exhibited in Moderate-Severe LLD group. Enhanced posterior upper gamma power was observed in both LLD groups. Additionally, enhanced parietal and fronto-parietal/occipital theta connectivity were observed in Moderate-Severe LLD group, which were associated with the attentional impairment. Limitations include a small sample size, concomitant medication use, and a relatively higher proportion of females. Current study observed aberrant brain activity patterns in LLD across different levels of depression severity, which were linked to cognitive impairments. The altered posterior brain oscillations may be trait marker of LLD. Moreover, cognitive impairments and associated connectivity alterations were exhibited in moderate-severe group, which may be a state-like marker of moderate-to severe LLD. The study deepens understanding of cognitive impairments with the associated oscillation changes, carrying implications for neuromodulation targets in LLD. • Firstly explored altered brain oscillations in late-life depression (LLD) across severity, linking them to cognitive impairments. • Elevated posterior gamma power in LLD may be a trait marker. • Theta connectivity increased in LLD, serving as state-like marker linked to attentional impairments. • Highlights link between cognitive deficits and altered brain ocsillation in LLD, suggesting neuromodulation targets and interventions. [ABSTRACT FROM AUTHOR]