Functioning In Late-life Depression Research Articles

A mediation analysis of the role of total free fatty acids on pertinence of gut microbiota composition and cognitive function in late life depression

BackgroundExtensive evidence demonstrates correlations among gut microbiota, lipid metabolism and cognitive function. However, there is still a lack of researches in the field of late-life depression (LLD). This research targeted at investigating the relationship among gut microbiota, lipid metabolism indexes, such as total free fatty acids (FFAs), and cognitive functions in LLD.MethodsTwenty-nine LLD patients from the Cognitive Outcome Cohort Study of Depression in Elderly were included. Cognitive functions were estimated through the Chinese version of Montreal Cognitive Assessment (MoCA). Blood samples were collected to evaluate serum lipid metabolism parameters. Fecal samples were evaluated for gut microbiota determination via 16S rRNA sequencing. Spearman correlation, linear regression and mediation analysis were utilized to explore relationship among gut microbiota, lipid metabolism and cognitive function in LLD patients.ResultsSpearman correlation analysis revealed significant correlations among Akkermansia abundance, total Free Fatty Acids (FFAs) and MoCA scores (P < 0.05). Multiple regression indicated Akkermansia and total FFAs significantly predicted MoCA scores (P < 0.05). Mediation analysis demonstrated that the correlation between decreased Akkermansia relative abundance and cognitive decline in LLD patients was partially mediated by total FFAs (Bootstrap 95%CI: 0.023–0.557), accounting for 43.0% of the relative effect.ConclusionThese findings suggested a significant relationship between cognitive functions in LLD and Akkermansia, as well as total FFAs. Total FFAs partially mediated the relationship between Akkermansia and cognitive functions. These results contributed to understanding the gut microbial-host lipid metabolism axis in the cognitive function of LLD.

23 Cognitive Reserve Moderates Cognitive Functioning in Late-Life Depression

Objective:The concept of cognitive reserve (CR) explains why individuals with higher education, intelligence, or occupational attainment exhibit less severe cognitive changes in the presence of age-related or neurodegenerative pathology. CR may be a useful construct in understanding the cognitive performance of patients with late life depression (LLD), a cohort who are twice as likely to later receive a clinical diagnosis of dementia. It follows that depressed older adults with low CR may be at greater risk of cognitive decline compared to non-depressed older adults matched for CR. However, the literature on CR and LLD is limited to cross-sectional studies with mixed findings as to whether proxies of CR moderate cognitive outcomes in LLD. For example, both higher and lower education levels in LLD are associated with greater cognitive impairment in LLD compared to similarly educated non-depressed older adults. Longitudinal studies may help disentangle the association between CR and cognitive outcomes in LLD. The current study investigated the interaction between proxies of CR (e.g., education) and depression status on cognitive functioning over three years. We hypothesized that depressed older adults with low CR would demonstrate greater cognitive impairment and decline compared to depressed elders with high CR and non-depressed older adults with comparable CR.Participants and Methods:Older adults with LLD and non-depressed older adults age 59+ participated. All participants were free of dementia at baseline. We divided both patients and non-depressed participants into low (&lt;16) and high (&gt;=16) education groups based upon the median years of education (16) of the entire sample. All participants underwent detailed neuropsychological testing. Composite measures of episodic memory (CERAD Wordlist and recall, LM I and LM II, BVRT), processing speed-executive functioning (SDMT and Trail Making Part B), working memory (forward, reverse, ascending Digit Span), and verbal fluency (Animal Naming and COWA) were calculated based on the non-depressed older adults.Results:The baseline sample included 210 non-depressed older adults and 465 older adults with major depression (LLD). 150 non-depressed older adults and 235 LLD patients provided three-year follow-up data. Separate ANOVAs revealed a statistically significant interaction between education and depression status at baseline on the composite score of executive functioning F (1, 668) = 8.74, p &lt;.003. Consistent with our hypothesis, LLD with low education performed significantly worse compared to non-depressed with low education (z-score difference -1.35) and this effect was significantly greater than the difference between LLD patients and non-depressed with high education (z-score difference -0.36). No other interactions were found at baseline. Longitudinal analyses also revealed significant interactions between education and depression on memory over time, although sensitivity analyses did not suggest findings consistent with our hypothesis.Conclusions:Cognitive reserve contribute to group differences between LLD and non-depressed older adults in cognitive performance but may not alter cognitive trajectories over time. Future studies should further explore structural and functional brain changes associated with CR in LLD.

Cerebrospinal fluid markers for synaptic function and Alzheimer type changes in late life depression

To explore markers for synaptic function and Alzheimer disease (AD) pathology in late life depression (LLD), predementia AD and normal controls (NC). A cross-sectional study to compare cerebrospinal fluid (CSF) levels of neurogranin (Ng), Beta-site amyloid-precursor-protein cleaving enzyme1 (BACE1), Ng/BACE1 ratio and Amyloid-β 42/40 ratio, phosphorylated-tau and total-tau in LLD with (LLD AD) or without (LLD NoAD) AD pathology, predementia AD and normal controls (NC). We included 145 participants (NC = 41; predementia AD = 66 and LLD = 38). LLD comprised LLD AD (n = 16), LLD NoAD (n = 19), LLD with non-AD typical changes (n = 3, excluded). LLD AD (pADJ < 0.05) and predementia AD (pADJ < 0.0001) showed significantly higher Ng than NC. BACE1 and Ng/BACE1 ratio were altered similarly. Compared to LLD NoAD, LLD AD showed significantly higher Ng (pADJ < 0.001), BACE1 (pADJ < 0.05) and Ng/BACE1 ratio (pADJ < 0.01). All groups had significantly lower Aβ 42/40 ratio than NC (predementia AD and LLD AD, p < 0.0001; LLD NoAD, p < 0.05). Both LLD groups performed similarly on tests of memory and executive function, but significantly poorer than NC. Synaptic function in LLD depended on AD pathology. LLD showed an association to Amyloid dysmetabolism. The LLD groups performed poorer cognitively than NC. LLD AD may be conceptualized as “predementia AD with depression”.

Exploring Language Learning as a Potential Tool against Cognitive Impairment in Late-Life Depression: Two Meta-Analyses and Suggestions for Future Research.

Late-life depression (LLD) affects about an eighth of community-dwelling seniors. LLD impacts well-being, with loneliness and small social networks being typical. It has also been linked to cognitive dysfunction and an increased risk of developing dementia. Safety and efficacy of pharmacological treatments for LLD have been debated, and cognitive dysfunction often persists even after remission. Various cognitive interventions have been proposed for LLD. Among these, one has received special attention: foreign language learning could serve as a social intervention that simultaneously targets brain structures affected in LLD. Lifelong bilingualism may significantly delay the onset of cognitive impairment symptoms by boosting cognitive reserve. Even late-life foreign language learning without lifelong bilingualism can train cognitive flexibility. It is then counterintuitive that the effects of language learning on LLD have never been examined. In order to create a theoretical basis for further interdisciplinary research, this paper presents a status quo of current work through two meta-analyses investigating cognitive functioning in LLD on the one hand and in senior bilinguals or seniors following a language course on the other hand. While LLD was consistently associated with cognitive dysfunction, inconsistent results were found for bilingualism and language learners. Possible reasons for this and suggestions for future research are subsequently discussed.

Cognitive Reserve Moderates Effects of White Matter Hyperintensity on Depressive Symptoms and Cognitive Function in Late-Life Depression.

IntroductionWhite matter hyperintensity (WMH) has been regarded as one of the major contributor of the vascular hypothesis of late-life depression (LLD) and cognitive decline in the elderly. On the other hand, cognitive reserve (CR) has long been hypothesized to provide resilience and adaptability against age- and disease-related insults. This study examined the role of CR, using proxy of education, in moderating the association between WMH and clinical LLD expression.MethodsA total of 54 elderly diagnosed with major depressive disorder and 38 matched healthy controls participated in this study. They received MRI scanning and a battery of neuropsychological tests. WMH was quantified by an automated segmentation algorithm. Linear regression analyses were conducted separately in the LLD and control groups to examine the effects of WMH, education and their interaction in depression severity and various cognitive domains.ResultsWMH was significantly and negatively associated with executive function only in the healthy controls. In patients with LLD, we observed a significant interactive effect in education on the association between WMH and depression severity and language domain (category fluency task). Specifically, those with high education showed less depressive symptoms and cognitive decline as WMH increased.ConclusionWMH is associated with lower cognitive function. However, in patients with LLD, high education attenuates the deleterious effect of WMH on mood and cognition. Therefore, CR appears to exert a protective effect on neurocognitive functioning in people with LLD.

Deep learning-based automated speech detection as a marker of social functioning in late-life depression.

Late-life depression (LLD) is associated with poor social functioning. However, previous research uses bias-prone self-report scales to measure social functioning and a more objective measure is lacking. We tested a novel wearable device to measure speech that participants encounter as an indicator of social interaction. Twenty nine participants with LLD and 29 age-matched controls wore a wrist-worn device continuously for seven days, which recorded their acoustic environment. Acoustic data were automatically analysed using deep learning models that had been developed and validated on an independent speech dataset. Total speech activity and the proportion of speech produced by the device wearer were both detected whilst maintaining participants' privacy. Participants underwent a neuropsychological test battery and clinical and self-report scales to measure severity of depression, general and social functioning. Compared to controls, participants with LLD showed poorer self-reported social and general functioning. Total speech activity was much lower for participants with LLD than controls, with no overlap between groups. The proportion of speech produced by the participants was smaller for LLD than controls. In LLD, both speech measures correlated with attention and psychomotor speed performance but not with depression severity or self-reported social functioning. Using this device, LLD was associated with lower levels of speech than controls and speech activity was related to psychomotor retardation. We have demonstrated that speech activity measured by wearable technology differentiated LLD from controls with high precision and, in this study, provided an objective measure of an aspect of real-world social functioning in LLD.

An inverse relationship between cortical plasticity and cognitive inhibition in late-life depression.

Executive dysfunction is a common and disabling component of late-life depression (LLD), yet its neural mechanisms remain unclear. In particular, it is not yet known how executive functioning in LLD relates to measures of cortical physiology that may change with age and illness, namely cortical inhibition/excitation and plasticity. Here, we used transcranial magnetic stimulation (TMS) to measure cortical inhibition/excitation (n = 51), and the potentiation of cortical activity following paired associative stimulation, which is thought to reflect long-term potentiation (LTP)-like cortical plasticity (n = 32). We assessed the correlation between these measures of cortical physiology and two measures of executive functioning: cognitive inhibition, assessed using the Delis-Kaplan Executive Function System Color-Word Interference ["Stroop"] Test, and cognitive flexibility, assessed using the Trail Making Test. Correlations with recall memory and processing speed were also performed to assess the specificity of any associations to executive functioning. A significant correlation was found between greater LTP-like cortical plasticity and poorer cognitive inhibition, a core executive function (rp = -0.56, p < 0.001). We did not observe significant associations between cortical inhibition/excitation and executive functioning, or between any neurophysiological measure and cognitive flexibility, memory, or processing speed. Our finding that elevated cortical plasticity is associated with diminished cognitive inhibition emphasizes the importance of balanced synaptic strengthening to healthy cognition. More specifically, our findings suggest that hyper-excitability of cortical circuits following repeated cortical activation may promote inappropriate prepotent responses in LLD. LTP-like cortical plasticity might therefore represent a neural mechanism underlying an inhibitory control cognitive endophenotype of LLD.

Cognitive Functioning in Late-life Depression: A Critical Review of Sociodemographic, Neurobiological, and Treatment Correlates

Both clinical and subthreshold depression in older adults are associated with cognitive dysfunction. This review summarizes the latest literature on patterns of cognitive functioning in late-life depression (LLD), including moderators of the relationship between depression and cognitive functioning and underlying neurobiological mechanisms. LLD is associated with cognitive dysfunction across multiple domains, particularly processing speed and executive functions. This relationship is moderated by demographic and clinical variables such as sex, race, age of onset, and severity of different symptom dimensions of depression. The impact of depression treatment on cognitive deficits in LLD differs across treatment approaches, but overall LLD is associated with persistent cognitive deficits after depression remission. Clarifying treatments with dual mood and cognitive benefits is an important area for future research. Our understanding of and treatment for cognitive deficits in LLD will also benefit from additional work that examines clinical and demographic contributions.

Neurocognitive Correlates of Resilience in Late-Life Depression

Increasing understanding of the neurocognitive correlates of resilience in late-life depression (LLD) could inform interventions to promote more sustained remission. We investigated cross-sectional relations between baseline resilience and domains of neurocognitive functioning in depressed older adults enrolled in one of four trials. Participants (N = 288) completed neurocognitive tests of memory, language performance, and executive functioning as well as measures of subjective memory performance and components of resilience (grit, active coping self-efficacy, accommodative coping self-efficacy, and spirituality). Medium-sized associations were observed between greater resilience (overall resilience, accommodative coping) and lower frequency of self-reported forgetting. Small positive associations were observed between language performance and total resilience, active coping self-efficacy, and accommodative coping self-efficacy. Small negative associations were observed between spirituality and each objective measure of cognitive performance. Future longitudinal studies will help elucidate the complex relation between resilience and cognitive functioning in LLD. In addition, randomized controlled trials targeting coping self-efficacy may inform the development of more effective and personalized interventions.

The impact and measurement of social dysfunction in late-life depression: an evaluation of current methods with a focus on wearable technology.

Depression is known to negatively impact social functioning, with patients commonly reporting difficulties maintaining social relationships. Moreover, a large body of evidence suggests poor social functioning is not only present in depression but that social functioning is an important factor in illness course and outcome. In addition, good social relationships can play a protective role against the onset of depressive symptoms, particularly in late-life depression. However, the majority of research in this area has employed self-report measures of social function. This approach is problematic, as due to their reliance on memory, such measures are prone to error from the neurocognitive impairments of depression, as well as mood-congruent biases. Narrative review based on searches of the Web of Science and PubMed database(s) from the start of the databases, until the end of 2015. The present review provides an overview of the literature on social functioning in (late-life) depression and discusses the potential for new technologies to improve the measurement of social function in depressed older adults. In particular, the use of wearable technology to collect direct, objective measures of social activity, such as physical activity and speech, is considered. In order to develop a greater understanding of social functioning in late-life depression, future research should include the development and validation of more direct, objective measures in conjunction with subjective self-report measures. Copyright © 2016 John Wiley & Sons, Ltd.

Vascular burden and cognitive function in late-life depression.

To evaluate the relation of vascular risk factors, subclinical, and manifest vascular disease with four domains of cognitive functioning in a large sample of clinically depressed older persons. A cross-sectional analysis was used, and depressed patients were recruited from general practices and mental healthcare institutes. Presence of a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, depressive episode was established with the Composite International Diagnostic Interview. Framingham Risk Score (FRS) was used as a measure for vascular risk profile, ankle-brachial index for subclinical vascular disease, and history of a cardiovascular event as a measure for manifest vascular disease. Three neurocognitive tasks evaluated processing speed, working memory, verbal memory, and interference control. In 378 participants, linear regression analysis showed that FRS was related to poorer interference control (t = -2.353; df = 377; p <0.05) but to no other cognitive domain after adjustment for age, sex, education level, and depressive symptom severity. Lower ankle-brachial index and history of cardiovascular event were related to slower processing speed (t = 2.659; df = 377; p <0.05 and t = -3.328; df = 377; p <0.01, respectively) but to no other cognitive domain. In 267 participants without manifest vascular disease, higher FRS was related to slower processing speed (t = -2.425; df = 266; p <0.05) and poorer interference control (t = -2.423; df = 266; p <0.05), and lower ankle brachial index was related to slower processing speed (t = 2.171; df = 266; p <0.05). In depressed older persons, vascular burden is related to slower processing speed also in the absence of manifest vascular disease. Poorer interference control was only related to vascular risk factors but not to subclinical or manifest vascular disease.

Cognitive Functioning and Late-Life Depression

This brief report provides an introduction to the topic of cognitive functioning in late-life depression (LLD). In addition to providing a review of the literature, we present a framework for understanding the heterogeneity of cognitive outcomes in this highly prevalent disorder. In addition, we discuss the relationship between LLD and dementia, and highlight the importance of regularly assessing cognitive functioning in older adults who present with depressive symptoms. If cognitive deficits are discovered during a neuropsychological assessment, we recommend referral to a geriatric psychiatrist or cognitive neurologist, for evaluation and treatment of the patient's symptoms.

Executive Functioning in Late-Life Depression

Executive functions are control mechanisms that regulate aspects of cognition and emotion. Impairments in executive functioning are prominent following disruption to frontolimbic connections involved in mood regulation. Executive dysfunction is common in older adults with major depression and is associated with poor course of illness and worse clinical outcome. Thus, elderly depressed patients with executive functioning impairment require careful treatment planning and close follow-up. This review aims to provide the clinician with a practical understanding of executive dysfunction in older adults with major depression. To this end, it provides an introduction to the neurobiology and clinical manifestations of executive dysfunction in late-life depression. Special attention is given to current assessment practices that can be used to enhance clinical evaluation and treatment planning.

Neuropsychological functioning in late-life depression

Background: The literature describing neurocognitive function in patients with late-life depression (LLD) show inconsistent findings in regard to incidence and main deficits. Reduced information processing speed is in some studies found to explain deficits in higher order cognitive function, while other studies report specific deficits in memory and executive function. Our aim was to determine the characteristics of neuropsychological functioning in non-demented LLD patients.Methods: A comprehensive neuropsychological battery was administered to a group of hospitalized LLD patients and healthy control (HC) subjects. Thirty-nine patients without dementia, 60 years or older meeting DSM-IV criteria for current episode of major depression, and 18 non-depressed control subjects were included. The patient group was characterized by having a long lasting current depressive episode of late-onset depression and by being non-responders to treatment with antidepressants. Neurocognitive scores were calculated for the domains of information processing speed, verbal memory, visuospatial memory, executive function, and language. Number of impairments (performance below the 10th percentile of the control group per domain) for each participant was calculated.Results: Nearly half of the patients had a clinically significant cognitive impairment in at least one neurocognitive domain. Relative to HC subjects, LLD patients performed significantly poorer in the domains of information processing speed and executive function. Executive abilities were most frequently impaired in the patient group (39% of the patients). Even when controlling for differences in processing speed, patients showed more executive deficits than controls.Conclusions: Controlling for processing speed, patients still showed impaired executive function compared to HCs. Reduced executive function thus appears to be the core neurocognitive deficit in LLD. Executive function seems to be an umbrella concept for several connected but distinct cognitive functions. Further studies of neuropsychological functioning in LLD patients are needed to characterize more specific what kinds of executive impairments patients have. Additional studies of remitted LLD patients are needed to separate episode-related and persistent impairments.

Sleep disturbance relates to neuropsychological functioning in late-life depression

Sleep-wake disturbance in older people is a risk factor for depression onset and recurrence. The aim of this study was to determine if objective sleep-wake disturbance in late-life depression relates to neuropsychological functioning. Forty-four older patients with a lifetime history of major depression and 22 control participants underwent psychiatric, medical and neuropsychological assessments. Participants completed self-report sleep measures, sleep diaries and wore wrist actigraphy for two weeks. Outcome measures included sleep latency, the number and duration of nocturnal awakenings and the overall sleep efficiency. Patients with depression had a greater duration of nocturnal awakenings and poorer sleep efficiency, in comparison to control participants. Sleep disturbance in patients was associated with greater depression severity and later ages of depression onset. It also related to poorer psychomotor speed, poorer verbal and visual learning, poorer semantic fluency as well as poorer performance on tests of executive functioning. These relationships largely remained significant after controlling for depression and estimated apnoea severity. This sample had only mild levels of depression severity and results require replication in patients with moderate to severe depression. The inclusion of polysomnography and circadian markers would be useful to delineate the specific features of sleep-wake disturbance that are critical to cognitive performance. Sleep-wake disturbance in older patients with depression is related to neuropsychological functioning and to later ages of illness onset. This study suggests that common neurobiological changes may underpin these disease features, which may, in turn, warrant early identification and management.

Cognitive Function in Late Life Depression: Relationships to Depression Severity, Cerebrovascular Risk Factors and Processing Speed

A number of studies have examined clinical factors linked to worse neuropsychological performance in late life depression (LLD). To understand the influence of LLD on cognition, it is important to determine if deficits in a number of cognitive domains are relatively independent, or mediated by depression- related deficits in a basic domain such as processing speed. Patients who met DSM-IV criteria for major depression (n = 155) were administered a comprehensive neuropsychological battery of tasks grouped into episodic memory, language, working memory, executive function, and processing speed domains. Multiple regression analyses were conducted to determine contributions of predictor variables to cognitive domains. Age, depression severity, education, race and vascular risk factors all made significant and independent contributions to one or more domains of cognitive function, with all five making independent contributions to processing speed. Age of onset made no independent contribution, after accounting for age and vascular risk factors. Of the five cognitive domains investigated, changes in processing speed were found to most fully mediate the influence of predictor variables on all other cognitive domains. While slowed processing speed appears to be the most core cognitive deficit in LLD, it was closely followed by executive function as a core cognitive deficit. Future research is needed to help clarify mechanisms leading to LLD- related changes in processing speed, including the potential role of white matter abnormalities.