Late-life Depression Patients Research Articles

Crosstalk between Depression and Dementia with Resting-State fMRI Studies and Its Relationship with Cognitive Functioning

Alzheimer’s disease (AD) is the most common type of dementia, and depression is a risk factor for developing AD. Epidemiological studies provide a clinical correlation between late-life depression (LLD) and AD. Depression patients generally remit with no residual symptoms, but LLD patients demonstrate residual cognitive impairment. Due to the lack of effective treatments, understanding how risk factors affect the course of AD is essential to manage AD. Advances in neuroimaging, including resting-state functional MRI (fMRI), have been used to address neural systems that contribute to clinical symptoms and functional changes across various psychiatric disorders. Resting-state fMRI studies have contributed to understanding each of the two diseases, but the link between LLD and AD has not been fully elucidated. This review focuses on three crucial and well-established networks in AD and LLD and discusses the impacts on cognitive decline, clinical symptoms, and prognosis. Three networks are the (1) default mode network, (2) executive control network, and (3) salience network. The multiple properties emphasized here, relevant for the hypothesis of the linkage between LLD and AD, will be further developed by ongoing future studies.

Molecular imaging of beta-amyloid deposition in late-life depression

Late-life depression (LLD) is associated with an increased risk of all-cause dementia and may involve Alzheimer's disease pathology. Twenty-one LLD patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for a current major depressive episode and 21 healthy controls underwent clinical and neuropsychological assessments, magnetic resonance imaging to measure gray matter volumes, and high-resolution positron emission tomography to measure beta-amyloid (Aβ) deposition. Clinical and neuropsychological assessments were repeated after 10–12 weeks of Citalopram or Sertraline treatment (LLD patients only). LLD patients did not differ from healthy controls in baseline neuropsychological function, although patients improved in both depressive symptoms and visual-spatial memory during treatment. Greater Aβ in the left parietal cortex was observed in LLD patients compared with controls. Greater Aβ was correlated with greater depressive symptoms and poorer visual-spatial memory, but not with improvement with treatment. The study of LLD patients with prospective measurements of mood and cognitive responses to antidepressant treatment is an opportunity to understand early neurobiological mechanisms underlying the association between depression and subsequent cognitive decline.

Molecular imaging of the serotonin transporter availability and occupancy by antidepressant treatment in late-life depression

Patients with late-life depression (LLD) have a more variable response to pharmacotherapy relative to patients with mid-life depression. Degeneration of the serotonergic system and lower occupancy of the initial target for antidepressant medications, the serotonin transporter (5-HTT), may contribute to variability in treatment response. The focus of this study was to test the hypotheses that lower cortical and limbic serotonin transporter (5-HTT) availability in LLD patients relative to controls and less 5-HTT occupancy by antidepressant medications would be associated with less improvement in mood and cognition with treatment in LLD patients. Twenty LLD patients meeting DSM-IV criteria for a current major depressive episode and 20 non-depressed controls underwent clinical and neuropsychological assessments, magnetic resonance imaging to measure gray matter volumes and high-resolution positron emission tomography (PET) scanning to measure 5-HTT before and after 10–12 weeks of treatment with Citalopram or Sertraline (patients only). Prior to treatment, 5-HTT was lower in LLD patients relative to controls in mainly temporal cortical and limbic (amygdala and hippocampus) regions. Gray matter volumes were not significantly different between groups. 5-HTT occupancy was detected throughout cortical, striatal, thalamic and limbic regions. The magnitude of regional 5-HTT occupancy by antidepressants was 70% or greater across cortical and sub-cortical regions, consistent with the magnitude of 5-HTT occupancy observed in mid-life depressed patients. Greater regional 5-HTT occupancy correlated with greater improvement in depressive symptoms and visual-spatial memory performance. These data support the hypothesis that serotonin degeneration and variability in 5-HTT occupancy may contribute to heterogeneity in treatment response in LLD patients.

Comparison of cognitive functioning of elders with late-life depression and patients with and without a history of depressive episodes: a cross-sectional study

ABSTRACT Nowadays there are numerous studies on the occurrence of cognitive dysfunction in late-life depression (LLD). The role of executive dysfunctions in the psychopathology of depression is particularly emphasized and needs further examination. The aim was to assess cognitive functions and their relation to depressive symptoms in elders with LLD, previously depressed, and patients without the history of depressive episodes. The study consisted of 824 older adults who underwent a neuropsychological evaluation (97 currently depressed, 114 previously depressed and 613 patients without the history of depressive episodes). LLD patients performed poorer in ACE-III and AVLT and poorer in TMT-B than those previously depressed and never depressed. The LLD group also performed significantly poorer than the previously depressed on Digit Span Forward. Results of a multiple regression analysis indicated that performance on measures of executive functioning was associated with depression severity in LLD (β =.227, P =.024). The results of this study suggest that executive functions are the most impaired in the elderly with LLD. Furthermore, there is a relationship between executive dysfunction and the severity of depression in LLD. Executive dysfunction appears to be the core neurocognitive deficit in LLD.

Neurotransmitters and Neurometabolites in Late-Life Depression: A Preliminary Magnetic Resonance Spectroscopy Study at 7T

BackgroundMagnetic resonance spectroscopy (MRS) methods have quantified changes in levels of neurotransmitters and neurometabolites in patients with major depression across the lifespan. The application of 7T field strengths and greater have not been a major focus of study in patients with late-life depression (LLD). MethodsNine LLD patients who met DSM-IV criteria for a current major depressive episode and nine non-depressed, healthy, age-matched controls underwent clinical and neuropsychological assessment and single-voxel 7T 1H-MRS at baseline and after 10-12 weeks of antidepressant treatment (Citalopram; patients only). Spectra were acquired from two brain regions implicated in both depressive symptoms and neuropsychological deficits in LLD, the anterior (ACC) and posterior cingulate (PCC). Levels of γ-aminobutyric acid (GABA), glutamate (Glu), glutathione (GSH), N-acetylaspartylglutamate (NAAG), N-acetylaspartate (NAA), and myo-inositol (mI) were quantified relative to total creatine (tCr) using linear-combination modeling. ResultsBaseline Glu/tCr levels were not significantly different between groups. Decreased Glu/tCr levels after Citalopram treatment were observed in a subset of LLD patients. Exploratory analyses showed that LLD patients had lower NAA levels in the PCC relative to controls. Higher levels of ml in the LLD patients relative to the controls and decreases after Citalopram treatment had large effect sizes but were not statistically significant. Further, decreases in PCC Glu/tCr and increases in ACC GSH/tCr were associated with improvement in depressive symptoms. LimitationsSample size. ConclusionsThese preliminary results suggest a role of neurochemicals and neurometabolites in the neurobiology of LLD and antidepressant treatment response.

442 - Neurocognitive markers of passive suicidal ideation in late life depression

Aims:Late life suicide is an international public health crisis, yet the mechanisms underlying late life suicide risk are far less understood compared to younger age groups. Executive dysfunction is widely documented in late life depression (LLD), and cognitive flexibility and inhibition are specifically hypothesized as vulnerabilities for suicide risk. There is some evidence that LLD patients with suicidal ideation or attempt suicide have worse executive dysfunction than LLD patients that do not; however, it is unknown whether these differences exist in Passive Suicidal Ideation (PSI), which may be an important early stage of suicide risk. Delineating the mechanisms of risk for PSI in LLD is a crucial direction for late life suicide research. The purpose of our study was to examine whether cognitive flexibility and inhibitory ability are neurocognitive markers of PSI. The secondary purpose of our study was to determine if neurocognitive differences due to PSI are mediated by volumetric differences in the prefrontal cortex.Methods:Forty community-dwelling middle- and older-aged adults with LLD (18 with PSI, 22 without) completed a neurocognitive battery that assessed cognitive flexibility, inhibitory ability, as well as other neurocognitive domains, and underwent structural neuroimaging.Results:The PSI group performed significantly worse on cognitive flexibility and inhibitory ability, but not on other neurocognitive tasks which included other measures of executive function. The PSI group had a larger left mid-frontal gyrus (LMFG) than those without PSI, but there was no association between LMFG and cognitive flexibility or inhibitory ability, nor was there statistical evidence of mediation.Conclusions:Our findings implicate a unique neurocognitive signature in LLD with PSI: poorer cognitive flexibility and poorer inhibitory ability not better accounted for by other domains of cognitive dysfunction and not mediated by volumetric differences in the prefrontal cortex. Volumetric brain differences in the LMFG appear unrelated to differences in cognitive flexibility and inhibitory ability, which suggests two specific but independent risk factors for PSI in middle- and older-aged adults.

Correlation between suicidal ideation and polysomnography parameters in late-life depression patients

To investigate the relationship between sleep parameters and suicidal ideation in patients with late-life depression (LLD). Seventy-seven LLD patients over 60 years old from Sir Run Run Shaw Hospital of Zhejiang University during July 2017 and July 2018 were included in the study. All patients were assessed with Hamilton Depression Rating Scale (HAMD) and polysomnography (PSG) overnight. The suicidal score of item 3 in HAMD (HAM-D3)was used to define whether there was a suicidal ideation. Participants were subsequently grouped according to endorsement of presence (HAM-D3 score ≥1, n=46) versus absence (HAM-D3 score=0, n=31) of suicidal ideation symptoms. The sleep efficiency, total sleep time, wakefulness after sleep onset, rapid eye movement percent/latency, and non-rapid eye movement sleep stages 1-3 (N1-N3) were assessed. ANOVA analyses were conducted to explore the correlation of sleep parameters with suicidal ideation between the groups with and without suicidal ideation. In model 1, the HAM-D3 constituted the independent variable in separate ANOVA tests; in model 2 the impact of depressive symptoms were assessed as a covariate with sleep parameters. There was less stage N3 [(55±41)min, t=-4.731, P<0.05] and the reduced percentage of N3 [(15±11)%, t=-4.194, P<0.05] in LLD patients with suicidal ideation, compared with the LLD patients without suicidal ideation [(104±49) min, (26±11)%]. Correlation analyses revealed that there was a significant correlation between the suicidal ideation and the percentage of stage N3 and sleep time of stage N3 (both P<0.05). Suicidal ideation is associated with less N3 sleep in LLD patients.

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

BackgroundDepressive 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.ObjectiveWe 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.MethodsThirty-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.ResultsThe 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.ConclusionsKYN metabolism played an important role in altruistic behavior in LLD.

Research on Supportive Psychosocial, Drug Treatment, and Health Education Intervention and Health Management Model of Community-Residing Elderly Adults With Late Life Depression in Liaoning Province: A Protocol.

BackgroundLate life depression (LLD), a common mental disorder, has become an increasingly acute public health concern with a quickly expanding geriatric population worldwide. To our knowledge, however, the incidence of LLD in northern cities in China has not been empirically investigated, and many elderly people with depressive moods and mild depressive symptoms have not been given sufficient attention.Methods/DesignThis is a multi-stage and prospective study. The first stage is a cross-sectional study, investigating the epidemiological characteristics of LLD in northern China and exploring the biological, psychological, and social risk factors for developing LLD based on a set of questionnaires from 6,800 community-residing elderly adults. The second stage involves statistical analysis, by constructing a risk factor model for LLD and analyzing their direct and indirect functional routes on the basis of structural equation modeling. The third stage is an experimental study a total of 60 elderly patients with LLD and their principle caregivers will be randomly assigned to control and trial groups. The trial group patients and caregivers will undergo supportive psychosocial, drug treatment, and health education (PDH) intervention, whereas the control group patients and caregivers will be treated routinely (treatment as routine, TAR, which includes drug treatment and health education). At the end of the intervention, depressive symptoms, quality of life, and the social and cognitive functioning of the patients in the two groups will be respectively assessed at a baseline and after 6, 9, and 12 months post-intervention by employing scales and questionnaires to analyze the effectiveness of the supportive PDH intervention measures in comparison with TAR. Ultimately, a supportive PDH intervention and health management model will be obtained by combining PDH intervention with mental health institutions, community health services, and aging families as the main line.DiscussionThis study will provide strong and suitable evidence for enhancing the integrated supportive PDH intervention and health management model of LLD patients among community-dwelling residents.EthicsThis study has been approved by the Ethics and Research Committee of the First Affiliated Hospital of China Medical University (approval No. [2019] 2019-312-2).

NON-PHARMACOLOGICAL INTERVENTIONS IN LATE-LIFE DEPRESSION AND LATE-LIFE ANXIETY

Mindfulness, Mindfulness Based Cognitive Therapy MBCT and based Problem-solving therapy (PST) techniques have emerging research supporting them as positive additions to treatment as usual/standard care for mood, anxiety and/or cognitive disorders among older adults. This session will highlight this recent research and evidence of the benefits of these interventions in the context of late-life depression (LLD) and late-life anxiety (LLA). In the spirit of the 2020 American Association of Geriatric Psychiatry (AAGP) conference's theme of partnership, these results are presented by a team of researchers located at McGill University, Montreal, Quebec, Canada and the University of Western Ontario, London, Ontario, Canada, working with a variety of interdisciplinary stakeholders and contexts. The aim of this session is to present findings of non-pharmacological, meditation-based intervention clinical trials for, LLD and LLA, as well as potential effects on cognition. The session will be chaired by Soham Rej MD. Emily Ionson M.Sc. will present research findings that examined the feasibility and efficacy of implementing case manager-delivered group-based Problem-solving therapy for LLD in a real-world community setting. Marouane Nassim, M.Sc., will be presenting an RCT examining the efficacy of a chair-side mindfulness intervention compared to an active control condition, the Health Enhancement Program (HEP), in the treatment of depression and anxiety for older patients on hemodialysis. Elena Dikaios, B.A., will present findings of a study examining whether continuation groups are helpful to maintain sustained therapeutic effects of MBCT for late-life depression and anxiety patients in primary care. Following the presentations, there will be an interactive discussion, led by Dr. Akshya Vasudev (discussant) and Dr. Rej, concerning the clinical applications of these interventions and directions for future research.

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.

Neuroanatomical predictors of L-DOPA response in older adults with psychomotor slowing and depression: A pilot study

Declining function in dopamine circuits is implicated in normal aging and late-life depression (LLD). Dopamine augmentation recently has shown therapeutic promise, but predictors of response are unknown. Depressed elders with slowed gait underwent baseline magnetic resonance imaging (MRI) and [11C]raclopride positron emission tomography (PET). Subjects then received open treatment with carbidopa/levodopa (L-DOPA) for three weeks. Linear regressions examined relationships between baseline MRI measures, [11C]raclopride binding, and behavioral outcomes. Among N=16 participants aged 72.5±6.8 years, higher left superior temporal gyrus volume was associated with higher processing speed at baseline, while cortical thinning in a processing speed network was associated with greater improvement following L-DOPA. Greater volume and cortical thickness in brain regions associated with mobility were associated with higher baseline gait speed. Higher baseline white matter hyperintensity volume predicted less post-L-DOPA improvement on dual task gait speed and IDS-SR scores. Higher [11C]raclopride binding in the associative striatum was associated with cortical thickness in some, but not all, processing speed brain regions, while higher binding in sensorimotor striatum was significantly associated with left caudate volume. Limiting the conclusions drawn from this pilot study are the small sample size and open administration of L-DOPA. Greater baseline brain volumes and cortical thickness in regions supporting cognition and gait were associated with higher behavioral performance, while lower structural integrity was associated with increased responsivity to L-DOPA. If substantiated in larger studies, these findings could facilitate the targeting of dopaminergic treatments to those LLD patients most likely to respond.

Disruption of the structural and functional connectivity of the frontoparietal network underlies symptomatic anxiety in late-life depression

The present study investigated functional connectivity and white matter integrity of the fronto-parietal network (FPN) to reveal the neural mechanisms that underlie late-life depression (LLD). Fifty patients with LLD and 40 non-depressed controls were included in the study. A multi-parametric approach was used by applying independent component analysis (ICA) to estimate functional connectivity of the FPN and by applying tract­based spatial statistics to examine white-matter integrity in tracts to the FPN. Patients with LLD exhibited functional abnormalities in the right inferior frontal gyrus, middle frontal gyrus, and inferior parietal gyrus and lower white matter fractional anisotropy in the right inferior fronto-occipital fasciculus, anterior thalamic radiation, and uncinate fasciculus. Alterations of functional connectivity and white matter fractional anisotropy in these regions were negatively correlated with the severity of symptomatic anxiety in LLD patients. The right inferior frontal gyrus might be a crucial hub in transferring information between these abnormal regions. Significant correlations were found between anxiety symptoms and brain alterations, suggesting that impairments in the FPN network might be involved in symptomatic anxiety in elderly individuals with depression.

DETERMINANTS OF SUICIDAL IDEATION IN OLDER ADULTS WITH MAJOR DEPRESSION – ASSOCIATIONS WITH PERCEIVED STRESS

Introduction Depression has been strongly linked to suicide ideation in older adults. However, the role of other factors is less clear. Perceived stress is a factor that is emerging as a potential contributing factor in suicide ideation in older adults. We hypothesized higher levels of perceived stress would be associated with increased self-reported suicidal ideation independent of depressive symptom severity in older adults with LLD. Methods This study used data from community-dwelling older adults aged 65 with current diagnosis of major depression. Eligible participants completed measures of depression symptom severity (Hamilton Depression Rating Scale-17 item), current suicidal ideation (Geriatric Suicide Ideation Scale; GSIS), and perceived stress (Perceived Stress Scale; PSS). Statistical analyses were conducted using SPSS version 20. Descriptive statistics, including demographic and clinical characteristics of the participants were obtained. A linear regression analysis was then conducted, assessing the relationship of perceived stress to suicidal ideation, controlling for the effects of age, education, gender, and depression symptom severity. R2 were then calculated based on standardized beta values in the final model. Results Participants were 225 older adults with a mean age of 71.4 (SD = 5.6), who were 64.9% female. Sixteen percent of the variance in suicidality (GSIS total score) was accounted for by the variables assessed. In particular, lower education (B = −.13, p = .04), male gender (B = −.13, p = .04), greater depression severity (B = .15, p = .02) and higher current perceived stress (B = .32, p Conclusions Our findings suggest that increased perceived stress might be a particularly important factor of those more likely to think about suicide. Perceive stress may thus be a useful factor that could improve early identification and intervention of suicide ideation among late life depression patients at a high risk for suicidal behaviors. Mechanisms and coping strategies to reduce perceived stress could be directly implemented in depressed patients with suicidal ideation. Further research is warranted on perceived stress in relation to suicidal ideation. This research was funded by This work was supported by R01 MH0977669: (PI:Mackin), R01 MH101472 (PI:Mackin); UCSF Epstein Endowment Fund

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

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. 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. 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. 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.

Reduced GABAergic cortical inhibition in aging and depression.

The neurobiology underlying depression in older adults is less extensively evaluated than in younger adults, despite the putative influence of aging on depression neuropathology. Studies using transcranial magnetic stimulation (TMS), a neurophysiological tool capable of probing inhibitory and excitatory cortical neurotransmission, have identified dysfunctional GABAergic inhibitory activity in younger adults with depression. However, GABAergic and glutamatergic cortical neurotransmission have not yet been studied in late-life depression (LLD). Here, we used single- and paired-pulse TMS to measure cortical inhibition and excitation in 92 LLD patients and 41 age-matched healthy controls. To differentiate the influence of age and depression, we also compared these TMS indices to those of 30 younger depressed adults and 30 age- and sex-matched younger healthy adults. LLD patients, older healthy adults, and younger depressed adults demonstrated significantly lower GABAA receptor-mediated cortical inhibition than younger healthy controls. By contrast, no significant differences in cortical inhibition were observed between older adults with and without depression. No significant differences in GABAB receptor-mediated inhibition or cortical excitation were found between the groups. Altogether, these findings suggest that reduced cortical inhibition may be associated with both advancing age and depression, which (i) supports the model of depression as a disease of accelerated aging, and (ii) prompts future investigation into diminished GABAergic neurotransmission in late-life as a biological predisposing factor to the development of depression. Given that cortical neurophysiology was similar in depressed and healthy older adults, future prospective studies need to establish the relative influence of age and depression on cortical inhibition deficits.

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.

Cognitive Impairment and Structural Abnormalities in Late Life Depression with Olfactory Identification Impairment: an Alzheimer's Disease-Like Pattern.

BackgroundLate-life depression patients are at a high risk of developing Alzheimer’s disease, and diminished olfactory identification is an indicator in early screening for Alzheimer’s disease in the elderly. However, whether diminished olfactory identification is associated with risk of developing Alzheimer’s disease in late-life depression patients remains unclear.MethodsOne hundred and twenty-five late-life depression patients, 50 Alzheimer’s disease patients, and 60 normal controls were continuously recruited. The participants underwent a clinical evaluation, olfactory test, neuropsychological assessment, and neuroimaging assessment.ResultsThe olfactory identification impairment in late-life depression patients was milder than that in Alzheimer’s disease patients. Diminished olfactory identification was significantly correlated with worse cognitive performance (global function, memory language, executive function, and attention) and reduced grey matter volume (olfactory bulb and hippocampus) in the late-life depression patients. According to a multiple linear regression analysis, olfactory identification was significantly associated with the memory scores in late-life depression group (B=1.623, P<.001). The late-life depression with olfactory identification impairment group had worse cognitive performance (global, memory, language, and executive function) and more structural abnormalities in Alzheimer’s disease-related regions than the late-life depression without olfactory identification impairment group, and global cognitive function and logical memory in the late-life depression without olfactory identification impairment group was intact. Reduced volume observed in many areas (hippocampus, precuneus, etc.) in the Alzheimer’s disease group was also observed in late-life depression with olfactory identification impairment group but not in the late-life depression without olfactory identification impairment group.ConclusionThe patterns of cognitive impairment and structural abnormalities in late-life depression with olfactory identification impairment patients were similar to those in Alzheimer’s disease; olfactory identification may help identify late-life depression patients who are at a high risk of developing Alzheimer’s disease.

When Cognitive Decline and Depression Coexist in the Elderly: CSF Biomarkers Analysis Can Differentiate Alzheimer's Disease from Late-Life Depression

Late-life depression (LLD) and Alzheimer's Disease (AD) are the two most frequent neuropsychiatric disorders affecting elderly. LLD and AD may clinically present with depressive and cognitive symptoms. Therefore, when cognitive decline is coupled with depression in the elderly, the differential diagnosis between LLD and AD could be challenging. The aim of the present study was to evaluate in a population of elderly patients affected by depression and dementia the usefulness of CSF AD biomarkers (tau proteins and β-amyloid42–Aβ42) and 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography (18FFDG-PET) in early differentiating LLD from AD. Two hundred and fifty-six depressed and demented patients, after performing CSF AD biomarkers and 18FFDG-PET, were distributed in two groups on the basis of the current diagnostic guidelines for AD (n = 201) and LLD (n = 55). Patients were then observed for 2 years to verify the early diagnosis. After the 2 year follow-up we compared AD and LLD patients' CSF and 18FFDG-PET data obtained at baseline to a group of age- and sex-matched controls. We found CSF Aβ42 levels significantly higher in LLD compared to AD patients. Remarkably, CSF Aβ42 levels of LLD patients (range between 550 and 1204 pg/mL) did not overlap with those of AD patients (range between 82 and 528 pg/mL). Moreover, we documented no differences in CSF AD biomarkers (Aβ42 and tau proteins) when comparing LLD patients to controls. In addition, AD patients showed the significant reduction of 18FFDG-PET uptake in temporo-parietal regions compared to both controls and LLD. Conversely, LLD and control groups did not differ at 18FFDG-PET analysis, although LLD patients showed heterogeneous patterns of glucose hypometabolism involving cortical and subcortical brain areas. It is noteworthy that at the end of the clinical follow-up, patients owing to AD group showed the expected significant decline of cognitive performances, whereas patients assigned to LLD group improved cognition as depressive symptoms recovered. Hence, in case of co-existence of cognitive impairment and depression in the elderly, we propose CSF AD biomarkers analysis to early differentiate LLD from AD and properly target the patient's therapeutic strategy and clinical follow-up.

Multiple cortical thickness sub-networks and cognitive impairments in first episode, drug naïve patients with late life depression: A graph theory analysis

BackgroundCoordinated and pattern-wise changes in large scale gray matter structural networks reflect neural circuitry dysfunction in late life depression (LLD), which in turn is associated with emotional dysregulation and cognitive impairments. However, due to methodological limitations, there have been few attempts made to identify individual-level structural network properties or sub-networks that are involved in important brain functions in LLD. MethodsIn this study, we sought to construct individual-level gray matter structural networks using average cortical thicknesses of several brain areas to investigate the characteristics of the gray matter structural networks in normal controls and LLD patients. Additionally, we investigated the structural sub-networks correlated with several clinical measurements including cognitive impairment and depression severity. ResultsWe observed that small worldness, clustering coefficients, global and local efficiency, and hub structures in the brains of LLD patients were significantly different from healthy controls. We further found that a sub-network including the anterior cingulate, dorsolateral prefrontal cortex and superior prefrontal cortex is significantly associated with attention control and executive function. The severity of depression was associated with the sub-networks comprising the salience network, including the anterior cingulate and insula. LimitationsWe investigated cortico-cortical connectivity, but omitted the subcortical structures such as the striatum and thalamus. ConclusionWe report differences in patterns between several clinical measurements and sub-networks from large-scale and individual-level cortical thickness networks in LLD.