Late-onset Depression Patients Research Articles

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.

Involvement of differential tau pathologies in late‐onset bipolar disorder assessed by PET with 18F‐florzolotau

AbstractBackgroundNeurodegenerative pathologies, including tau depositions, have been implicated in late‐onset depression (LOD), while there is a lack of in‐vivo evidence for the neuropathological basis of late‐onset bipolar disorder (LOBD) despite postmortem findings of cerebral tau accumulations. The current study aimed to assess tau pathologies in LOBD and LOD patients positron emission tomography (PET) with 18F‐florzolotau, a radioligand for Alzheimer’s disease (AD) and non‐AD tau fibrils.MethodsWe studied LOBD and LOD patients who developed the first episode of mania or depression after age 45. Twenty‐one patients with LOBD (68.8 ± 9.6 years old; 11 females), 15 patients with LOD (73.0 ± 5.8 years old; 11 females), and 39 age‐matched healthy controls (HCs) (67.1 ± 9.1 years old; 19 females) underwent tau and amyloid PET scans with 18F‐florzolotau and 11C‐PiB, respectively. Amyloid positivity was determined by a visual read of 11C‐PiB‐PET images, and tau depositions were assessed by calculating standardized uptake value ratios (SUVRs) in 52 regions covering the cerebral grey matter and basal ganglia to the optimized reference tissue. All SUVRs were corrected for age and sex and converted to Z‐score relative to HCs. The positivity and topology of tau pathologies were determined according to the presence of a region with a Z‐score ≥ 2.0.Results 18F‐florzolotau‐PET positivity was observed in 13 LOBD (62%), 7 LOD (47%), and 11 HC (28%) subjects, whereas 4 LOBD, 4 LOD, and no HC individuals were 11C‐PiB‐PET‐positive. A significant difference in the prevalence of tau pathologies was only found between LOBD and HCs (P = 0.043, corrected for multiple comparisons). Tau topologies in the cases with 11C‐PiB‐PET‐positive AD pathologies consisted of predominant frontal (1 LOBD and 3 LODs), lateral temporal (3 LOBDs and 1 LOD), and posterior (1 LOBD) accumulations. Meanwhile, tau pathologies in 11C‐PiB‐negative cases showed predominant frontal (2 LOBDs and 1 LOD), temporal (1 LOBD and 1 LOD), posterior (4 LOBDs and 1 LOD), and basal ganglia (2 LOBDs) localizations.ConclusionOur findings suggest that a significant subset of LOBD patients harbor tau lesions linked to various AD subtypes and non‐AD tauopathies indicative of distinct early‐stage frontotemporal lobar degeneration subcategories.

Differences in olfactory functional connectivity in early-onset depression and late-onset depression.

Late-onset depression (LOD) and early-onset depression (EOD) exhibit different pathological mechanisms and clinical phenotypes, including different extents of olfactory dysfunction. However, the brain abnormalities underlying the differences in olfactory dysfunction between EOD and LOD remain unclear. The aim of this study was to compare the functional connectivity (FC) patterns of olfactory regions between EOD patients and LOD patients and examine their relationship with cognitive function. One hundred and five patients with EOD, 101 patients with LOD and 160 normal controls (NCs) were recruited for the present study. Participants underwent clinical assessment, olfactory testing, cognitive assessments, and magnetic resonance imaging. Eight regions of the primary and secondary olfactory regions were selected to investigate olfactory FC. Patients with LOD exhibited decreased odor identification (OI) compared with patients with EOD and NCs. The LOD group exhibited decreased FC compared with the EOD and NC groups when primary and secondary olfactory regions were selected as the regions of interest (the piriform cortex, lateral entorhinal cortex, and orbital-frontal cortex). Additionally, these abnormal olfactory FCs were associated with decreased cognitive function scores and OI, and the FC between the left orbital-frontal cortex and left amygdala was a partial mediator of the relationship between global cognitive scores and OI. Overall, patients with LOD exhibited decreased FC in both the primary and secondary olfactory cortices compared with patients with EOD, and abnormal olfactory FC was associated with OI dysfunction and cognitive impairment. The FC between the orbital-frontal cortex and amygdala mediated the relationship between global cognitive function and OI.

Differences in Odor Identification in Early-Onset and Late-Onset Depression.

(1) Background: Odor identification (OI) dysfunction is a potential predictor of developing dementia in late life depression (LLD). However, it is not clear whether patients with early onset depression (EOD) and late onset depression (LOD) may exhibit different OI dysfunctions. The aim of this study was to compare OI between EOD patients and LOD patients and its relationship with cognitive function. (2) Methods: A total of 179 patients with LLD and 189 normal controls were recruited. Participants underwent clinical assessment, olfactory testing, and comprehensive neuropsychological assessment. The OI scores of EOD patients and LOD patients were compared, and correlation analyses and mediation analyses were used to explore the relationship between OI and cognition. (3) Result: LOD patients exhibited lower OI scores than EOD patients and normal controls (NCs). Additionally, the LOD patients exhibited a higher percentage of OI dysfunction than the EOD patients. Moreover, OI scores were associated with global cognition, memory, language, and visuospatial ability in the EOD group (p < 0.05) but were not associated with any cognitive score in the LOD patients (p > 0.05). Finally, the scores of the Auditory Verbal Learning Test Immediate recall and Boston Naming Test exhibited a partially mediating effect on the difference in OI scores between the EOD and LOD patients. (4) Conclusions: LOD patients exhibited worse OI than EOD patients, and their difference in OI was mediated by their memory and language function.

Changes in Regional Homogeneity of Medication-Free Major Depressive Disorder Patients With Different Onset Ages.

Background: Neurobiological mechanisms underlying the development of major depressive disorder (MDD) may differ depending on onset ages. Our aim was to determine whether regional homogeneity (ReHo) changes in early-onset depression (EOD) and late-onset depression (LOD) are different, which could also delineate EOD and LOD.Methods: Ninety-one MDD patients and 115 healthy controls (HCs) were recruited, and resting-state functional magnetic resonance imaging data were collected. The ReHo comparison was conducted using analysis of variance.Results: Compared with HCs, MDD patients showed decreased ReHo in the left precentral gyrus and the left middle cingulum area, and increased ReHo in the left middle orbital frontal gyrus and superior temporal gyrus. Compared with LOD patients, young HC separately, EOD patients had significantly increased ReHo in the right inferior frontal triangular gyrus and the left postcentral gyrus. However, compared with young HC, EOD patients showed decreased ReHo in the right superior frontal gyrus/supplementary motor area and the right medial frontal gyrus. ReHo in the right inferior frontal triangular gyrus was negatively correlated with the severity of cognitive disturbance in LOD patients (r = −0.47, p = 0.002), but not in EOD patients (r = 0.21, p = 0.178).Conclusion: MDD patients with different onset ages may have different pathophysiological mechanisms; the EOD patients had more abnormal ReHo than LOD patients in the prefrontal lobe, especially the right inferior frontal triangular gyrus.

Study of neuropsychological deficits in late onset depression.

Older adults with depression often have cognitive deficits contributing to higher morbidity and increased risk for conversion to dementia. Research on this area is limited from India. The objective of the current study is to examine the neuropsychological measures in older adults with Late-onset depression (LOD) compared to healthy controls (HC). Sample included older adults with depression as per DSM-IV TR criteria seeking treatment from Geriatric Clinic and Services, National Institute of Mental Health and Neurosciences (NIMHANS). Geriatric depression scale, Montgomery Asberg depression rating scale and Hamilton anxiety rating scale were applied to screen and measure the severity of depression. Comprehensive assessment of neurocognitive function was done using NIMAHNS Neuropsychological Battery for Elderly (NNBE, 2013). Sample included 76 LOD patients and 76 healthy controls (HC) who were matched for age, gender and education. The mean age of onset of illness was 63.17(SD-6.54) years and median duration of total illness was 29.5 months. In the standard assessments, the mean score on GDS was 9.28 (SD-3.32) and MADRS was 18.88 (SD-6.07). The LOD group had lower Hindi Mental Status Examination (HMSE) score compared to HC (28.64 ± 2.09 vs 30.05 ± 1.26, p < 0.001). Compared to HC, LOD group performed poorly on tasks of attention, executive function, verbal and visual memory, verbal fluency and visuo-spatial skills. Recognition memory and logical memory were relatively preserved in LOD compared to HC. Cognitive deficits were seen predominantly in attention and executive function, visuo-spatial skills and memory similar to previous studies. It is advisable to routinely assess cognitive symptoms in older adults presenting with depression.

Abnormal Voxel-Wise Degree Centrality in Patients With Late-Life Depression: A Resting-State Functional Magnetic Resonance Imaging Study.

ObjectivesLate-life depression (LLD) has negative impacts on somatic, emotional and cognitive domains of the lives of patients. Elucidating the abnormality in the brain networks of LLD patients could help to strengthen the understanding of LLD pathophysiology, however, the studies exploring the spontaneous brain activity in LLD during the resting state remain limited. This study aimed at identifying the voxel-level whole-brain functional connectivity changes in LLD patients.MethodsFifty patients with late-life depression (LLD) and 33 healthy controls were recruited. All participants underwent a resting-state functional magnetic resonance imaging scan to assess the voxel-wise degree centrality (DC) changes in the patients. Furthermore, DC was compared between two patient subgroups, the late-onset depression (LOD) and the early-onset depression (EOD).ResultsCompared with the healthy controls, LLD patients showed increased DC in the inferior parietal lobule, parahippocampal gyrus, brainstem and cerebellum (p < 0.05, AlphaSim-corrected). LLD patients also showed decreased DC in the somatosensory and motor cortices and cerebellum (p < 0.05, AlphaSim-corrected). Compared with EOD patients, LOD patients showed increased centrality in the superior and middle temporal gyrus and decreased centrality in the occipital region (p < 0.05, AlphaSim-corrected). No significant correlation was found between the DC value and the symptom severity or disease duration in the patients after the correction for multiple comparisons.ConclusionsThese findings indicate that the intrinsic abnormality of network centrality exists in a wide range of brain areas in LLD patients. LOD patients differ with EOD patients in cortical network centrality. Our study might help to strengthen the understanding of the pathophysiology of LLD and the potential neural substrates underlie related emotional and cognitive impairments observed in the patients.

Aspirin and Risk of Dementia in Patients with Late-Onset Depression: A Population-Based Cohort Study.

Background Late onset depression (LOD) often occurs in the context of vascular disease and may be associated with risk of dementia. Aspirin is widely used to reduce the risk of cardiovascular disease and stroke. However, its role in patients with LOD and risk of dementia remains inconclusive. Materials and Methods. A population-based study was conducted using data from National Health Insurance of Taiwan during 1996–2009. Patients fulfil diagnostic criteria for LOD with or without subsequent dementia (incident dementia) and among whom users of aspirin (75 mg daily for at least 6 months) were identified. The time-dependent Cox proportional hazards model was applied for multivariate analyses. Propensity scores with the one-to-one nearest-neighbor matching model were used to select matching patients. Cumulative incidence of incident dementia after diagnosis of LOD was calculated by Kaplan–Meier Method. Results A total of 6028 (13.4%) and 40,411 (86.6%) patients were defined as, with and without diagnosis of LOD, among whom 2,424 (41.9%) were aspirin users. Patients with LOD had more comorbidities such as cardiovascular diseases, diabetes, and hypertension comparing to those without LOD. Among patients with LOD, aspirin users had lower incidence of subsequent incident dementia than non-users (Hazard Ratio = 0.734, 95% CI 0.641–0.841, p < 0.001). After matching aspirin users with non-users by propensity scores-matching method, the cumulative incidence of incident dementia was significantly lower in aspirin users of LOD patients (p < 0.001). After matching aspirin users with non-users by propensity scores-matching method, the cumulative incidence of incident dementia was significantly lower in aspirin users of LOD patients (Conclusions Aspirin may be associated with a lower risk of incident dementia in patients with LOD. This beneficial effect of aspirin in LOD patients needs validation in prospective clinical trials and our results should be interpreted with caution.

Disrupted structural brain connectome underlying the cognitive deficits in remitted late-onset depression.

Cognitive deficit is a key feature of late-onset depression (LOD) and remains after clinical recovery. LOD has been associated with widespread neurobiological difficulties, including atrophy in gray and white matter (WM) tissue in areas distributed throughout the brain. However, little is known about the topological pattern changes of WM structural networks in LOD in the remitted state and its relationship to cognitive deficits. We acquired diffusion tensor images in 37 remitted LOD (rLOD) patients and 30 healthy controls. The tract-based spatial statistics method was employed to investigate WM tract integrity in rLOD. Graph-theory based network models were further used to characterize the topological organization of WM structural networks between the two groups. Compared with controls, rLOD patients showed decreased fractional anisotropy values in the left posterior cingulate bundle, right inferior fronto-occipital fasciculus and superior longitudinal fasciculus. Moreover, rLOD patients showed abnormal small-world architecture (i.e., increased path length and decreased network efficiency) in the WM structural networks. rLOD patients also showed reduced nodal efficiencies predominantly in the frontal-striatal-occipital and posterior default-mode regions. Importantly, these structural connectomic changes significantly correlated with cognitive deficits in the rLOD patients. Finally, rLOD networks showed more vulnerable to targeted attacks compared with healthy controls. These findings provide structural evidence to support the concept of rLOD that the core aspects of the pathophysiology of this disease are associated with disruptive alterations in the coordination of large-scale brain networks and advance our understanding of the neurobiological mechanism underlying cognitive deficits in the rLOD patients.

Aortic Pulsatility Propagates Intracranially and Correlates with Dilated Perivascular Spaces and Small Vessel Compliance

Introduction: To test the hypotheses that changes in the aortic pulse-wave produced by arterial stiffening are (1) propagated into cerebral small vessels, (2) associated with reduced compliance of small cerebral arterial vessels, and (3) associated with the presence of dilated perivascular spaces (PVS). Methods: Fifteen volunteers and 19 patients with late-onset depression (LOD) were prospectively recruited, of which 6 fulfilled the criteria for treatment-resistant depression (TRD). Aortic pulse-wave velocity (PWV) was determined using Carotid-Femoral Doppler. Pulse-wave analysis (PWA) was performed using a SphygmoCor system. White-matter lesion load and PVS were scored on established MRI scales. Cerebral arterial and aqueductal cerebrospinal fluid (CSF) flow patterns were studied using quantitative phase-contrast angiography. Results: Depressed patients had more PVS (P < .05) and prolongation of the width of the arterial systolic pulse-wave in the carotid arteries (P < .01). There was no significant group difference for any PWV or PWA measurement. TRD patients showed more PVS than other LOD patients (P < .05). The fractional width of the arterial systolic peak correlated significantly with augmentation index (AIx) and heart rate-corrected augmentation index (AIx75; R2 = 0.302, P < .01and R2 = 0.363, P < .01 respectively). Arterial–aqueductal delay showed a negative correlation with estimated aortic systolic pressure (PWVsys; R2 = 0.293; P < .01), AIx (R2 = −0.491; P < .01) and AIx75 (R2 = −0.310; P < .01). PVS scores correlated with AIx (R2 = 0.485; P < .01) and AIx75 (R2 = −0.292; P < .01). Conclusion: Our findings support the hypothesis that increased arterial pulsatility resulting from central arterial stiffness propagates directly into cerebral vessels and is associated with the development of microvascular angiopathy, characterized by dilated PVS and decreased compliance of small arterial vessels.

Aberrant Default Mode Network Underlying the Cognitive Deficits in the Patients With Late-Onset Depression.

Late-onset depression (LOD) is regarded as a risk factor or a prodrome of Alzheimer’s disease (AD). Moreover, LOD patients with cognitive deficits have the higher risk of subsequent AD. Thus, it is necessary to understand the neural underpinnings of cognitive deficits and its pathological implications in LOD. Consistent findings show that the default mode network (DMN) is an important and potentially useful brain network for the cognitive deficits in LOD patients. In recent years, genetics has been actively researched as a possible risk factor in the pathogenesis of LOD. So, in this review, we discuss the current research progress on the cognitive deficits and DMN in LOD through a combined view of brain network and genetics. We find that different structural and functional impairments of the DMN might be involved in the etiological mechanisms of different cognitive impairments in LOD patients.

Risk factors associated with cognitions for late-onset depression based on anterior and posterior default mode sub-networks

BackgroundAbnormal functional connectivity (FC) in the default mode network (DMN) plays an important role in late-onset depression (LOD) patients. In this study, the risk predictors of LOD based on anterior and posterior DMN are explored. MethodsA total of 27 LOD patients and 40 healthy controls (HC) underwent resting-state functional magnetic resonance imaging and cognitive assessments. Firstly, FCs within DMN sub-networks were determined by placing seeds in the ventral medial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC). Secondly, multivariable logistic regression was used to identify risk factors for LOD patients. Finally, correlation analysis was performed to investigate the relationship between risk factors and the cognitive value. ResultsMultivariable logistic regression showed that the FCs between the vmPFC and right middle temporal gyrus (MTG) (vmPFC–MTG_R), FCs between the vmPFC and left precuneus (PCu), and FCs between the PCC and left PCu (PCC–PCu_L) were the risk factors for LOD. Furthermore, FCs of the vmPFC-MTG_R and PCC-PCu_L correlated with processing speed (R = 0.35, P = 0.002; R = 0.32, P = 0.009), and FCs of the vmPFC-MTG_R correlated with semantic memory (R = 0.41, P = 0.001). LimitationsThe study was a cross-sectional study. The results may be potentially biased because of a small sample. ConclusionsIn this study, we confirmed that LOD patients mainly present cognitive deficits in processing speed and semantic memory. Moreover, our findings further suggested that FCs within DMN sub-networks associated with cognitions were risk factors, which may be used for the prediction of LOD.

Kynurenine pathway changes in late-life depression

BackgroundKynurenine pathway (KP) activation is associated with several neuropsychiatric diseases, including major depression disorder (MDD). Although several investigations have been conducted on MDD, these have seldom shed light on KP changes in late-life depression (LLD). ObjectiveWe aimed to investigate whether tryptophan (TRP) metabolism and kynurenine (KYN) metabolism are imbalanced in LLD patients and to explore the differences in KP characteristics between early onset depression (EOD) and late onset depression (LOD) patients. MethodsWe investigated 170 LLD patients (EOD 90, LOD 80) and 135 normal controls. Serum concentrations of TRP, KYN and kynurenic acid (KYNA) were detected by the liquid chromatography-tandem mass spectrometry method. Depressive symptoms were assessed by the 17-item Hamilton Depression Scale (HAMD-17). ResultsLLD patients exhibited lower levels of TRP, KYN, KYNA and KYNA/KYN ratio and a higher level of KYN/TRY ratio than normal controls. The decrease in TRP and the increase in KYN/TRP ratio were found in LOD patients. A low TRP level without increased KYN/TRP ratio was found in EOD patients. The “Depression” factor, which was extracted from HAMD-17 by the principal component factor analysis, was correlated with the TRP level and KYNA/KYN ratio in the EOD group, but no such correlation was found in the LOD group. ConclusionsKP changes were observed in LLD patients; LOD patients showed profound shifts in TRP metabolism, while EOD patients showed low TRP level and a shift in KYN metabolism.

The Study of White Matter Hyperintensity (WMH) and Factors Related to Geriatric Late-Onset Depression.

BackgroundGeriatric depression is one of the most common and harmful mental illnesses seen in the elderly. However, there are few studies focusing on the relationship between late-onset depression (LOD) and social and psychological factors, as well as brain structure.AimsTo explore factors related to late-onset depression (LOD) in elderly patients.Methods24 first onset LOD patients over 60 years old (meeting ICD-10 diagnostic criteria for depression) and 23 non-depressed elders were selected for inclusion into this study. Scale assessments, including Fazelasscale for white matter hyperintensity (WMH) high signal level and the MTA-scale for medial temporal lobe atrophy levels, were combined with general demography and sociology data to find factors related to LOD.ResultsThere was no significant difference in age (t=0.419, p=0.678), gender (X2=1.705, p=0.244), or years of education (t=1.478, p=0.146) between the two groups. However, statistical differences were shown on scores on the WMH, (X2=7.817, p=0.008), periventricular white matter hyperintensity (PWMH)(Fisher exact test: p=0.031), having or not having religious beliefs (Fisher exact test: p=0.265) and family harmony (yes or no) (Fisher exact test: p=0.253) between the LOD group and control group. The results of linear regression analysis showed that the total score for WMH, religious beliefs (with or without) and family harmony (yes or no) were associated with depressive symptomology.ConclusionScores on the WMH, religious beliefs and family harmony are all potentially related to LOD in elderly patients.

Cerebral blood flow changes in remitted early- and late-onset depression patients.

Abnormal cerebral blood flow (CBF) is reportedly associated with major depressive disorder (MDD). We have investigated CBF changes in early-onset depression (EOD) and late-onset depression (LOD), and their impact on cognitive function. Thirty-two remitted EOD patients, 32 remitted LOD patients, and 43 age-matched healthy controls were recruited, and the pulsed arterial spin labeling data were scanned under 3.0T MRI and processed through voxel-by-voxel statistical analysis. Compared to healthy controls, LOD patients had decreased normalized CBF in the bilateral precuneus, cuneus, right fronto-cingulate-striatal areas, and right temporal, occipital and parietal lobes, but increased normalized CBF in the left frontal and temporal cortices and the cingulate gyrus. EOD patients had decreased normalized CBF in the left cerebellum and right calcarine/lingual/fusiform gyrus, and increased normalized CBF in right angular gyrus. LOD patients displayed hemispheric asymmetry in CBF, and had more regions with abnormal CBF than EOD patients. A significant correlation between abnormal CBF and impaired cognitive function was detected in LOD patients, but not EOD patients. These results demonstrate greater CBF abnormalities in LOD patients than EOD patients, and suggest these CBF changes may be associated with progressive degradation of cognitive function in LOD patients.

Structural and Functional Connectivity of Default Mode Network underlying the Cognitive Impairment in Late-onset Depression.

To identify the association between the functional and structural changes of default mode network (DMN) underlying the cognitive impairment in Late-onset depression (LOD), 32 LOD patients and 39 normal controls were recruited and underwent resting-state fMRI, DTI scans, and cognitive assessments. Seed-based correlation analysis was conducted to explore the functional connectivity (FC) of the DMN. Deterministic tractography between FC-impaired regions was performed to examine the structural connectivity (SC). Partial correlation analyses were employed to evaluate the cognitive association of those altered FC and SC. Compared with controls, LOD patients showed decreased FC between DMN and the cingulo-opercular network (CON), as well as the thalamus. Decreased FA and increased RD of these fiber tracts connecting DMN with CON were found in LOD patient. The DMN-CON FC and the FA, RD of the fiber tracts were both significantly correlated with the cognitive performance. Therefore, the cognitive impairment in LOD might be associated with the decreased FC between the DMN and the CON, which probably resulted from the demyelination of the white matter.

Cerebral vascular burden on hippocampal subfields in first-onset drug-naïve subjects with late-onset depression

BackgroundAlthough there is substantial evidence of associations between frontal-striatal circuits and cerebral vascular burden in late-onset depression (LOD), relationships between vascular burden and hippocampal subfields are not clear. The purpose of this study was to investigate relationships between cerebral vascular burden and hippocampal subfield volume in LOD patients. MethodsFifty subjects with LOD and 50 group-matched healthy control subjects underwent magnetic resonance imaging scanning. Hippocampal subfields volumes were measured and compared between the groups. In addition, association patterns between white matter hyperintensity (WMH) volumes, clinical measures and hippocampal subfield volumes were investigated in the LOD group. ResultsSubjects with LOD exhibited significant hippocampal volume reductions in the total hippocampus, cornu ammonis (CA) 1 and 3 and dentate gyrus (DG) areas compared with healthy subjects. Total WMH volume was negatively correlated with left total hippocampal volume and CA1 in the LOD group. In addition, depression severity was negatively associated with left and right CA3 volumes in the LOD group. LimitationOur findings of distinctive relationships between WMH and hippocampal subfields demonstrate a simple correlation, but do not prove causation ConclusionThis study is the first to elaborate distinctive association patterns between hippocampal subfield volumes and cerebral vascular burden in LOD. These structural changes in the hippocampal CA1, CA3 and DG areas might be at the core of the underlying neurobiological mechanisms of hippocampal dysfunction in LOD. However, longitudinal studies will be needed to identify the mechanisms of these structural changes.

Disrupted Interhemispheric Synchrony in Default Mode Network Underlying the Impairment of Cognitive Flexibility in Late-Onset Depression.

The intuitive association between cognitive impairment and aberrant functional activity in the brain network has prompted interest in exploring the role of functional connectivity in late-onset depression (LOD). The relationship of altered voxel-mirrored homotopic connectivity (VMHC) and cognitive dysfunction in LOD is not yet well understood. This study was designed to examine the implicit relationship between the disruption of interhemispheric functional coordination and cognitive impairment in LOD. LOD patients (N = 31) and matched healthy controls (HCs; N = 37) underwent neuropsychological tests and functional magnetic resonance imaging (fMRI) in this study. The intergroup difference of interhemispheric coordination was determined by calculating VMHC value in the whole brain. The neuro-behavioral relevancy approach was applied to explore the association between disrupted VMHC and cognitive measures. Receiver operating characteristic (ROC) curve analysis was used to determine the capability of disrupted regional VMHC to distinguish LOD. Compared to the HC group, significantly attenuated VMHC in the superior frontal gyrus (SFG), superior temporal gyrus (STG), posterior cerebellar lobe (CePL) and post- and precentral gyri were observed in the bilateral brain of LOD patients. The interhemispheric asynchrony in bilateral CePLs was positively correlated with the performance of trail making test B (TMT-B) in LOD patients (r = 0.367, P = 0.040). ROC analysis revealed that regions with abnormal VMHC could efficiently distinguish LOD from HCs (Area Under Curve [AUC] = 0.90, P < 0.001). Altered linkage patterns of intrinsic homotopic connectivity and impaired cognitive flexibility was first investigated in LOD, and it would provide a novel clue for revealing the neural substrates underlying cognitive impairment in LOD.

Aberrant topographical organization of the default mode network underlying the cognitive impairment of remitted late-onset depression

To investigate the alteration of resting-state functional connectivity (FC) and topological organization of the default mode network (DMN), and their contribution to the cognitive impairment in remitted late-onset depression (rLOD) patients. Thirty-three rLOD patients and thirty-one healthy controls underwent clinical and cognitive evaluations as well as resting-state functional magnetic resonance imaging (R-fMRI) scans. The FC networks were constructed by thresholding Pearson correlation metrics of the DMN regions, and their topological properties were analyzed using graph theory-based approaches. Nonparametric permutation tests were further used for group comparisons of topological metrics. Finally, multiple linear regression analyses were performed to examine the relationships between the network measures and cognitive performances. Patients displayed universally decreased FC of DMN and abnormal global topology of the DMN (i.e., increased characteristic path length Lp and reduced global efficiency Eglob) compared with healthy controls. According to the distance-dependent FC results, the long-distance connections were mainly involved in the connectivity between anterior and posterior hubs, and the short-distance connections were primarily located in the frontal lobe. There were significant correlations between the global topology and the episodic memory performance in rLOD patients. In conclusion, the present study indicated that the disrupted topological organization of the DMN might be considered as a potential biomarker of the episodic memory deficits in rLOD patients.

Structural integrity and functional connectivity of default mode network underlying the cognitive impairment in Late-onset depression

Objective To determine the association between the functional changes and the structural lesions of the DMN underlying the cognitive impairments in Late-onset depression (LOD). Methods Thirty-two LOD patients and thirty-nine normal controls (NCs) were recruited and underwent resting-state fMRI and DTI scans. Cognition was evaluated with MMSE and a battery of neuropsychological measurements. Seed-based correlation analysis was performed to explore the functional connectivity (FC) of the DMN. Then deterministic tractography between FC-impaired regions were calculated to examine structural connectivity (SC). Tracts connecting FC-impaired regions were selected to count fiber number (FN) and to calculate average FA, AD and RD of all voxels along these fibers. Partial correlation analyses were applied to examine cognitive association of these altered FC and SC, controlling the effects of age and education. Results LOD patients showed decreased FC between PCC/Pcu and dACC as well as the thalamus. Decreased FA and increased RD of these fiber tracks connecting PCC/Pcu with dACC were found in LOD patients, without significant difference in AD and FN. The FC between PCC/Pcu and dACC was positively correlated with the FA of fiber tracks connecting them. The PCC/Pcu-dACC FC and the FA of the fiber tracks between them were both positively correlated with Symbol Digit Modalities Test and Verbal Fluency Test scores which conversely displayed negative association with RD. Conclusions The cognitive impairment in LOD, especially executive speed and semantic memory might be associated with the decreased FC in DMN which probably resulted from the demyelination of the white matter.