Increasing variance of rich-club nodes distribution in early onset depression according to dynamic network.

Early onset depression (EOD) and late onset depression (LOD) are thought to have different pathogeneses, but lack of pathological evidence. In the current study we describe the dynamic rich-club properties of patients with EOD and LOD to address this question indirectly. We recruited 82 patients with late life depression (EOD 40, LOD 42) and 90 healthy controls. Memory, executive function and processing speed were measured, and resting-stage functional MRI was performed with all participants. We constructed a dynamic functional connectivity network and carried out rich-club and modularity analyses. Normalized mutual information (NMI) was applied to describe the variance in rich-club nodes distribution and partitioning. The NMI coefficient of rich club nodes distribution among the three groups was the lowest in the EOD patients (F = 4.298; P = 0.0151, FDR = 0.0231), which was positively correlated with rich-club connectivity (R = 0.886, P < 0.001) and negatively correlated with memory (R = -0.347, P = 0.038) in the EOD group. In the LOD patients, non-rich-club connectivity was positively correlated with memory (R = 0.353, P = 0.030 and R = 0.420, P = 0.009). Furthermore, local connectivity was positively correlated with processing speed in the LOD patients (R = 0.374, P = 0.021). The modular partition was different between the EOD patients and the HCs (P = 0.0013 < 0.05/3). The temporal instability of rich-club nodes was found in the EOD patients, but not the LOD patients, supporting the hypothesis that EOD and LOD result from different pathogenesis, and showing that the instability of the rich-club nodes across time might disrupt rich-club connectivity.

Relationships Among Short Self-Reported Sleep Duration, Cognitive Impairment, and Insular Functional Connectivity in Late-Life Depression.

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.

Static and dynamic functional connectivity variability of the anterior-posterior hippocampus with subjective cognitive decline.

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.

Elevated homocysteine levels, white matter abnormalities and cognitive impairment in patients with late-life depression.

Background: Cognitive impairment in late-life depression (LLD) is considered to be caused by neurodegenerative changes. Elevated homocysteine (Hcy) levels may be linked to cognitive abnormalities associated with LLD. The important role of white matter (WM) damage in cognitive impairment and pathogenesis in patients with LLD has been widely reported. However, no research has explored the interrelationships of these features in patients with LLD. Objective: The goal of the study was to examine the interrelationship between Hcy levels, cognition, and variations in WM microstructure detected by diffusion tensor imaging (DTI) in patients with LLD. Methods: We recruited 89 healthy controls (HCs) and 113 patients with LLD; then, we measured the plasma Hcy levels of participants in both groups. All individuals performed a battery of neuropsychological tests to measure cognitive ability. Seventy-four patients with LLD and 68 HCs experienced a DTI magnetic resonance imaging (MRI) scan. Results: Patients with LLD showed significantly lower fractional anisotropy (FA) values in the bilateral inferior longitudinal fasciculus than those of healthy participants. Only in LLD patients was Hcy concentration inversely associated to FA values in the forceps minor. Finally, multiple regression analyses showed that an interaction between Hcy levels and FA values in the right cingulum of the cingulate cortex and right inferior longitudinal fasciculus were independent contributors to the executive function of patients with LLD. Conclusion: Our results highlight the complex interplay between elevated homocysteine levels and WM abnormalities in the pathophysiology of LLD-related cognitive impairment, consistent with the neurodegeneration hypothesis.

Disrupted olfactory functional connectivity in patients with late-life depression.

BACKGROUND: Odor identification (OI) impairment increases the risk of Alzheimer's disease and brain abnormalities in patients with late-life depression (LLD). However, it remains unclear whether abnormal functional connectivity (FC) of olfactory regions is involved in the relationship between OI impairment and dementia risk in LLD patients. The current study aims to explore the olfactory FC patterns of LLD patients and how olfactory FCs mediate the relationship between OI and cognition. METHODS: A total of 150 participants underwent resting-state functional magnetic resonance imaging and psychometric and olfactory assessments. The primary and secondary olfactory regions were selected as regions of interest to investigate olfactory FC patterns and their association with OI and cognitive performance in LLD patients. RESULTS: Compared with LLD patients without OI impairment and normal controls, LLD patients with OI impairment exhibited increased FC between the left orbital frontal cortex (OFC) and left calcarine gyrus, between the left OFC and right lingual gyrus, between the right OFC and right rectus gyrus, and decreased FC between the right piriform cortex and right superior parietal lobule. Additionally, these abnormal FCs were associated with scores of OI, global cognition and language function. Finally, the FC between the right piriform cortex and right superior parietal lobule exhibited a partially mediated effect on the relationship between OI and MMSE scores. LIMITATIONS: The present study did not exclude the possible effect of drugs. CONCLUSION: LLD patients with OI impairment exhibited more disrupted olfactory FC (a decrease in the primary olfactory cortex and an increase in the secondary olfactory cortex) than LLD patients with intact OI, and these abnormal FCs may serve as potential targets for neuromodulation in LLD patients to prevent them from developing dementia.

Structural and Functional Abnormalities of Olfactory-Related Regions in Subjective Cognitive Decline, Mild Cognitive Impairment, and Alzheimer's Disease.

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.

Neuropsychiatric Symptoms Exacerbate the Cognitive Impairments in Patients With Late-Life Depression.

Background: Neuropsychiatric symptoms (NPS) and cognitive impairments are both common in patients with late-life depression (LLD). However, the relationship between NPS and cognitive functions in LLD patients remains unclear. The current study aims to explore the effects of NPS on cognitive impairments in LLD patients. Methods: Two hundred and sixty-two LLD patients and 141 normal controls (NC) were recruited. Exploratory factor analysis was used to extract factors from the Neuropsychiatric Inventory (NPI). Correlation, mediation, and moderation analyses were used to explore whether NPS exacerbated the cognitive impairments in LLD and whether NPS exhibited different effects on cognitive impairments in acute-state LLD (aLLD) and recovery-state LLD (rLLD). Results: Three main factors were extracted from the NPI, including emotional, behavioral, and psychotic factors. The patients with LLD exhibited worse cognition and higher NPI scores, and the scores of NPI-total and three extracted factors were negatively associated with cognitive scores. The mediation analyses exhibited that NPI-total and behavioral factor scores increase the difference in cognition scores between LLD and NC groups. The mediation analyses exhibited that behavioral factor score played a greater effect on impairing MMSE in the rLLD group than in the aLLD group. Additionally, behavioral factor score was in a trend to be negatively associated with Mini-Mental State Examination (MMSE) score changes at a one-year follow-up (p = 0.051). Conclusions: NPS, especially behavioral symptoms, exacerbate cognitive impairments in LLD and may contribute to residual cognitive impairment in rLLD patients. Early intervention for behavioral symptoms in LLD patients may be beneficial to their long-term clinical prognosis.

Longitudinal Association Between Cognition and Depression in Patients With Late-Life Depression: A Cross-Lagged Design Study.

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 (ß = 0.864, p = 0.049) but not vice versa. Moreover, depressive symptoms were predicted by a decline in scores of working memory test (ß = -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.

The additive effect of late-life depression and olfactory dysfunction on the risk of dementia was mediated by hypersynchronization of the hippocampus/fusiform gyrus.

Early detection of patients with late-life depression (LLD) with a high risk of developing dementia contributes to early intervention. Odor identification (OI) dysfunction serves as a marker for predicting dementia, but whether OI dysfunction increases the risk of dementia in LLD patients remains unclear. The present study aimed to explore the interactive effect of LLD and OI dysfunction on the risk of dementia and its underlying neuroimaging changes. One hundred and fifty-seven LLD patients and 101 normal controls were recruited, and data on their OI, cognition, activity of daily living (ADL), and resting-state functional magnetic resonance imaging were collected. Two × two factorial analyses were used to analyze the interactive effects of LLD and OI dysfunction on neuropsychological and neuroimaging abnormalities. Mediation analyses were used to explore whether abnormalities detected by neuroimaging mediated the the associations between OI and cognition/ADL. The results suggested that LLD and OI dysfunction exhibited additive effects on reduced ADL, global cognition and memory scores, as well as neuroimaging variables including (i) increased fractional amplitude of low-frequency fluctuation (fALFF) in the right orbitofrontal cortex and right precentral cortex, and (ii) increased regional homogeneity (ReHo) in the left hippocampus/fusiform gyrus, etc. In addition, these increased fALFF and ReHo values were associated with reduced neuropsychological scores (ADL, global cognition, memory, and language). Moreover, ReHo of the left hippocampus/fusiform gyrus completely mediated the relationship between OI and ADL, and partially mediated the relationship between OI and global cognition. Overall, mediated by the hypersynchronization of the left hippocampus/fusiform gyrus, OI dysfunction may increase the risk of dementia in LLD patients.

Different Modular Organization Between Early Onset and Late Onset Depression: A Study Base on Granger Causality Analysis.

Background: Modular organization reflects the activity patterns of our brain. Different disease states may lead to different activity patterns and clinical features. Early onset depression (EOD) and late onset depression (LOD) share the same clinical symptoms, but have different treatment strategies and prognosis. Thus, explored the modular organization of EOD and LOD might help us understand their pathogenesis. Method: The study included 82 patients with late life depression (EOD 40, LOD 42) and 90 healthy controls. We evaluated the memory, executive function and processing speed and performed resting-stage functional MRI for all participants. We constructed a functional network based on Granger causality analysis and carried out modularity, normalized mutual information (NMI), Phi coefficient, within module degree z-score, and participation coefficient analyses for all the participants. Result: The Granger function network analysis suggested that the functional modularity was different among the three groups (P auc = 0.0300), and NMI analysis confirmed that the partition of EOD was different from that of LOD (P auc = 0.0190). Rh.10d.ROI (polar frontal cortex) and Rh.IPS1.ROI (dorsal stream visual cortex) were shown to be the potential specific nodes in the modular assignment according to the Phi coefficient (P = 0.0002, P fdr = 0.0744 & P = 0.0004, P fdr = 0.0744). Conclusion: This study reveal that the functional modularity and partition were different between EOD and LOD in Granger function network. These findings support the hypothesis that different pathological changes might exist in EOD and LOD.

Olfactory Dysfunction Is Already Present with Subjective Cognitive Decline and Deepens with Disease Severity in the Alzheimer's Disease Spectrum.

BACKGROUND: Odor identification dysfunction occurs early in Alzheimer's disease (AD) and is considered a preclinical symptom along with subjective cognitive decline (SCD). Nevertheless, whether subjects with SCD are co-symptomatic with odor identification dysfunction remains unclear. OBJECTIVE: To compare the degree of odor identification dysfunction and assess the relation between odor identification and cognitive performance in the AD spectrum (including SCD, mild cognitive impairment (MCI), and AD). METHODS: Patients (84 SCD, 129 MCI, 52 AD) and 35 controls underwent the Sniffin' Sticks Screen 16 test and comprehensive neuropsychological examination. RESULTS: Odor identification scores were progressively lower moving from normal older adult to SCD, MCI, and AD. Additionally,the proportion of odor identification dysfunction were increasingly higher in the AD spectrum (p for trend <0.001), but no significant difference was found in the proportion of subjective olfactory dysfunction. No significant correlation was found between odor identification and cognition in the normal older adults and SCD subjects, but odor identification correlated with global cognition in the MCI (r = 0.199, p = 0.033) and in the AD (r = 0.300, p = 0.036) patients. Multiple linear regression showed that odor identification dysfunction was most strongly associated with memory among different cognitive subdomains and was most strongly associated with immediate verbal recall among different memory subdomains. CONCLUSION: Odor identification dysfunction is already present with SCD and deepens with disease severity in the AD spectrum, and it may contribute to predicting cognitive decline and identifying SCD subjects who are at risk of developing AD.

Neuropsychiatric Symptoms Mediated the Relationship Between Odor Identification and Cognition in Alzheimer's Disease Spectrum: A Structural Equation Model Analysis.

Background: Odor identification dysfunction is an early predictor of the development of Alzheimer's disease (AD), but neuropsychiatric symptoms (NPS), which are common in AD and mild cognitive impairment (MCI), are also associated with odor identification dysfunction. Whether NPS affect the specificity of using odor identification dysfunction to predict cognitive decline in AD and MCI remains unclear. Methods: Patients (233 with MCI and 45 with AD) and 45 healthy controls (HCs) underwent assessments of odor identification (Sniffin' Sticks), NPS (Neuropsychiatric Inventory-12), and cognitive function (global cognition, memory, language, executive function, visual-spatial skill, and attention). Structural equation modeling (SEM) with bootstrapping estimation was conducted to explore the relationships between odor identification, NPS, and cognition. Results: Patients with NPS showed significantly worse performance in odor identification and cognition than patients without NPS and HCs. The SEM showed odor identification to be positively associated with cognition, and cognition had special indirect effects on odor identification through affective and psychosis symptoms (two factors extracted from Neuropsychiatric Inventory-12). Additionally, affective and psychosis symptoms partially mediated the effect of cognition on odor identification. Conclusion: Neuropsychiatric symptoms are associated with odor identification dysfunction in patients with AD and MCI. Studies exploring the relationship between odor identification dysfunction and cognitive decline in patients with AD and MCI should include an assessment of affective and psychosis symptoms, and adjust their confounding effects.

Abnormal Serum Bilirubin/Albumin Concentrations in Dementia Patients With Aß Deposition and the Benefit of Intravenous Albumin Infusion for Alzheimer's Disease Treatment.

BACKGROUND: Our previous study in animal models revealed that bilirubin could induce Aß formation and deposition. Bilirubin may be important in neurodegenerative dementia with Aß deposition. Hence, lowering the concentration of the free bilirubin capable of crossing the blood brain-barrier may benefit the treatment of Alzheimer's disease (AD). OBJECTIVES: The objectives of this study were to examine the change in the serum bilirubin and albumin concentrations of dementia patients with Aß deposition, and to determine the effects of intravenous administration of albumin in the treatment of AD. METHODS: Bilirubin and albumin concentrations in dementia patients with Aß deposition were examined. Cell viability and apoptosis were determined in dopaminergic neuron-like cells MN9D treated with bilirubin in the presence of diverse concentrations of serum. Human albumin at a dose of 10 g every 2 weeks for 24 weeks was administered intravenously to AD patients to examine the effect of albumin on AD symptoms. RESULTS: Significantly higher indirect bilirubin (IBIL) concentrations, lower albumin concentrations, and higher ratio of IBIL to albumin (IBIL/ALB) were observed in dementia patients with Aß deposition, including AD, dementia with Lewy bodies, and general paresis of insane. In vitro assays showed that bilirubin-induced injury in cultured dopaminergic neuron-like cells negatively depends on the concentration of serum in the culture medium. General linear model with repeated measures analysis indicated a main effect of group on the change in albumin concentrations and Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory scale (ADCS-ADL) scores, and the main effect of time and group, and group-by-time interaction on the change of Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) scores. Analysis of the combined data of the entire 28 weeks of assessment period using the area under curve convincingly showed significantly improvements in the change of albumin concentrations, ADCS-ADL scores, and CDR-SB scores. CONCLUSION: IBIL and the IBIL/ALB ratio are significantly higher in dementia patients with Aß deposition, and intravenous administration of albumin is beneficial to AD treatment. TRIAL REGISTRATION: The intervention study was registered at http://www.chictr.org.cn (ChiCTR-IOR-17011539). Date of registration: June 1, 2017.

BACE1 and Other Alzheimer's-Related Biomarkers in Cerebrospinal Fluid and Plasma Distinguish Alzheimer's Disease Patients from Cognitively-Impaired Neurosyphilis Patients.

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 ß-amyloid precursor protein cleaving enzyme (BACE1) in cerebrospinal fluid (CSF)/plasma, together with amyloid-ß 1-40 (Aß40), Aß42, 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.

Interactive effects of elevated homocysteine and late-life depression on cognitive impairment.

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.

Changes of Altruistic Behavior and Kynurenine Pathway in Late-Life Depression.

BACKGROUND: Depressive patients show less altruistic behavior. While, older adults present higher tendencies for altruism than younger adults. Depression and age are two of the influencing factors of altruism, kynurenine (KYN), and its metabolites. However, the characteristics of altruism in late-life depression (LLD) and its possible underlying mechanism have not been studied. OBJECTIVE: We aimed to explore the characteristics of altruism in LLD patients and its neurobiological mechanism and structural brain network. We investigated whether the levels of metabolites in kynurenine pathway (KP) and white matter (WM) network topological features would influence the altruistic behavior in LLD patients. METHODS: Thirty-four LLD patients and 36 heathy controls (HCs) were included. Altruism was evaluated by the Dictator Game (DG) paradigm. Serum concentrations of KP metabolites were detected by the liquid chromatography-tandem mass spectrometry method. The topological features of the WM network were calculated from diffusion tensor imaging data in conjunction with graph-theoretical analysis. RESULTS: The LLD participants exhibited a higher level of altruism and WM global network properties than the HCs. Kynurenic acid to kynurenine (KYNA/KYN) ratio was associated with the DG performance in LLD group. KYNA/KYN ratio was associated with the WM network properties in HC group. CONCLUSIONS: KYN metabolism played an important role in altruistic behavior in LLD.

Determining the effects of LLD and MCI on brain decline according to machine learning and a structural covariance network analysis.

BACKGROUND: Late-life depression (LLD) and mild cognitive impairment (MCI) are risk factors for Alzheimer disease (AD). However, the interactive effect between LLD and MCI in the progression to AD remains unknown. The purpose of this research is to clarify whether this interaction exists and determined the characteristics of the structural change patterns in LLD and MCI. METHOD: To address this question, a total 225 participants (91 with intact cognitive function (IC), 34 with MCI, 35 with LLD-IC, 47 with LLD-MCI and 18 with AD) were recruited for the current study and their T1 scanning were acquired. Machine learning was applied to estimate the brain's age gap according to grey matter information (thickness and volume was calculated based on the Human Connectome Project Multi-Modal Parcellation version 1.0 and the Desikan atlas). A structural covariance network (SCN) was constructed based on grey matter volume. Rich-club analysis, global network properties and the Jaccard distance were utilized to describe the topological features in each cohort. Their cognitive functions (executive function, processing speed and memory) were evaluated by a full-scale battery of neuropsychological tests. RESULT: The interactive effect between LLD and MCI was detected through the brain age gap. The estimated age was positively correlated with processing speed and memory in LLD and non-LLD subjects. In the SCN analysis, the rich-club coefficient and global network properties were disrupted in the MCI group, but remained normal in the LLD-IC, LLD-MCI and AD groups. There was a significant discrepancy in brain structural change patterns between the AD and other cohorts by the Jaccard distance. CONCLUSION: The application of machine learning reflects that synergies between LLD and MCI could increase the risk of developing AD. According to the SCN, the structural coordination was disrupted in MCI and was kept normal in the other cohorts, while the discrepancies in brain structural change patterns appeared in AD. Overall, the brain age gap could be a potential predictor of AD, and the Jaccard distance has the potential to be a new type of SCN analysis indicator.

Cardiovascular diseases and related risk factors accelerated cognitive deterioration in patients with late-life depression: a one-year prospective study.

OBJECTIVES: Cognitive impairment in late-life depression is common and associated with a higher risk of all-cause dementia. Late-life depression patients with comorbid cardiovascular diseases (CVDs) or related risk factors may experience higher risks of cognitive deterioration in the short term. We aim to investigate the effect of CVDs and their related risk factors on the cognitive function of patients with late-life depression. METHODS: A total of 148 participants were recruited (67 individuals with late-life depression and 81 normal controls). The presence of hypertension, coronary heart disease, diabetes mellitus, or hyperlipidemia was defined as the presence of comorbid CVDs or related risk factors. Global cognitive functions were assessed at baseline and after a one-year follow-up by the Mini-Mental State Examination (MMSE). Global cognitive deterioration was defined by the reliable change index (RCI) of the MMSE. RESULTS: Late-life depression patients with CVDs or related risk factors were associated with 6.8 times higher risk of global cognitive deterioration than those without any of these comorbidities at a one-year follow-up. This result remained robust after adjusting for age, gender, and changes in the Hamilton Depression Rating Scale (HAMD) scores. CONCLUSIONS: This study suggests that late-life depression patients with comorbid CVDs or their related risk factors showed a higher risk of cognitive deterioration in the short-term (one-year follow up). Given that CVDs and their related risk factors are currently modifiable, active treatment of these comorbidities may delay rapid cognitive deterioration in patients with late-life depression.

Interactive Effect of Depression and Cognitive Impairment on Olfactory Identification in Elderly People.

Olfactory identification (OI) deficits have been regarded as an indicator of cognitive impairment in the elderly, but few studies have analyzed the mixed effect of depression on OI. Since depression is common in the elderly and strongly associated with OI, we aimed to explore whether the comorbidity of depression and cognitive impairment may be associated with worse outcomes. In total, 153 elderly patients with depression and 154 normal elderly were recruited. Subjects underwent assessments of depression, cognitive function, and OI. Information on the factors that may affect OI performance was collected (age, sex, smoking history, diabetes, etc.). Correlation analysis showed that several factors had a significant influence on OI performance in the elderly, including severity of depression, cognitive scores, age, sex, and years of education (p < 0.05). Among the different cognitive domains, OI was positively associated with global cognition, memory, language, executive function, and attention performance (p < 0.05). The multiple linear regression analysis indicated that memory scores, age, HAMD scores, and sex were the most relevant factors to OI scores across all elderly participants. The factorial analysis suggested that elderly with comorbidity of depression and cognitive impairment (memory deficits or language deficits) had worse OI impairment, and there was an interactive effect of depression and memory deficits on OI in elderly people. The present study suggested that the coexistence of depressive symptoms and cognitive impairment was associated with worse OI in the elderly. Studies exploring the association between OI and cognitive function should include an assessment of depression and adjust the interactive effects of depression.

A reliable global cognitive decline and cortisol as an associated risk factor for patients with late-life depression in the short term: A 1-year prospective study.

BACKGROUND: Late-life depression is a risk factor of dementia. It may increase the risk of reliable cognitive decline in the short term, and its associated risk factors remain unclear. Cortisol level may be one of the important predictors. OBJECTIVES: To estimate whether patients with late-life depression are at an increased risk for reliable global cognitive declines in 1 year, and explore associated risk factors predicting cognitive declines. METHODS: This prospective 1-year follow-up study involved 148 participants (67 with late-life depression and 81 normal elderly). Global cognitive function was assessed by the Mini-Mental State Examination (MMSE). The reliable global cognitive decline was defined by the reliable change index (RCI) of the MMSE. Factors related to cognitive function (e.g., age, gender, education, duration of depression and severity of depression) were obtained. Serum cortisol levels were measured at baseline. RESULTS: At the 1-year follow-up assessment, 19 patients with late-life depression (28.4%) showed reliable global cognitive declines, a risk that was 6.4 times (95% CIs = 1.3-31.1, p = 0.021) higher than that of normal elderly. Elevated serum cortisol levels and older age were associated with the risk of cognitive decline that was 1.6- and 1.2-times higher (95% CIs = 1.07-2.5, p = 0.02, and 95% CIs = 1.04-1.4, p = 0.01 respectively). LIMITATIONS: Serum cortisol levels were measured only in the morning. CONCLUSIONS: Late-life depression is associated with a greatly increased risk of reliable cognitive decline in short term. Cortisol dysregulation may contribute to the pathology of cognitive decline.