EEG as a Functional Marker of Nicotine Activity: Evidence From a Pilot Study of Adults With Late-Life Depression.
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ABSTRACT:
SUBMITTER: Conley AC
PROVIDER: S-EPMC8732868 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesTelomeres are structures at the extremity of chromosomes that prevents genomic instability, and its shortening seems to be a hallmark of cellular aging. Past studies have shown contradictory results of telomere length (TL) in major depression, and are a few studies in late-life depression (LLD). This explores the association between TL as a molecular marker of aging and diagnosis of LLD, the severity of depressive symptoms, and cognitive performance in older adults.Methods/designWe included 78 older adults (45 with LLD and 33 nondepressed controls, according to DSM-V criteria), aged 60-90 years. TL was measured in leukocytes by a quantitative polymerase chain reaction, determining the relative ratio (T/S) between the telomere region copy number (T) and a single copy gene (S), using a relative standard curve.ResultsTL was significantly shorter in the LLD compared with control participants (p = .039). Comparing groups through the severity of depressive symptoms, we found a negative correlation with the severity of depressive symptoms (Hamilton Depression Rating Scale-21, r = -0.325, p = .004) and medical burden (r = -0.271, p = .038). There was no significant correlation between TL and cognitive performance (Mattis Dementia Rating Scale, r = 0.152, p = .21).ConclusionsWe found that older adults with LLD have shorter telomere than healthy controls, especially those with a more severe depressive episode. Our findings suggest that shorter TL can be a marker of the severity of depressive episodes in older adults and indicate that these individuals may be at higher risk of age-associated adverse outcomes linked to depression.
| S-EPMC8413729 | biostudies-literature
Project description:ObjectivesThe study purpose is to estimate the correlation between depression and competing models of frailty, and to determine to what degree the comorbidity of these syndromes is determined by shared symptomology.MethodsData come from the 2010 Health and Retirement Study. Analysis was limited to community-dwelling participants 65 and older (N = 3,453). Depressive symptoms were indexed by the 8-item Centers for Epidemiologic Studies Depression (CESD) scale. Frailty was indexed by 3 alternative conceptual models: (a) biological syndrome, (b) frailty index, and (c) functional domains. Confirmatory factor analysis (CFA) was used to estimate the correlation between depression and each model of frailty.ResultsEach of the 3 frailty latent factors was significantly correlated with depression: biological syndrome (? = .68, p < .01), functional domains (? = .70, p < .01), and frailty index (? = .61, p < .01). Substantial correlation remained when accounting for shared symptoms between depression and the biological syndrome (? = .45) and frailty index (? = .56) models.DiscussionResults indicate that the correlation of frailty and depression in late life is substantial. The association between the two constructs cannot be fully explained by symptom overlap, suggesting that psychological vulnerability may be an important component of frailty.
| S-EPMC4903031 | biostudies-literature
Project description:BackgroundLate-life depression (LLD) is considered as a prodrome to dementia and plays a major role in the development of long-term cognitive disabilities. We aimed to estimate the prevalence and correlates of LLD and cognitive impairment and to explore their associations among older adults in India.MethodsData for this study was derived from the Longitudinal Ageing Study in India (LASI) Wave 1 (2017-18). The total sample included 31,464 (15,098 male and 16,366 female) older individuals aged 60 years and above. Cognitive impairment measured from various domains derived from the cognitive module of the Health and Retirement Study (HRS), and major depression measured by the CIDI-SF (Composite International Diagnostic Interview- Short Form) were the outcome variables. Descriptive, bivariate, and multivariable analyses were performed to fulfill the objectives of the study.ResultsThe overall prevalence of LLD and cognitive impairment for the current sample was 8.7% and 13.7 % respectively. Among older individuals who have rated their health status as poor were 2.59 times more likely to suffer from LLD [OR: 2.59, CI: 2.24-2.99] as compared to their counterparts. The older adults who had difficulty in activities of daily living (ADL) and instrumental activities of daily living (IADL) were 74% and 69 % more likely to suffer from LLD. Similarly, older adults who were depressed had higher odds of cognitive impairment [OR: 1.22, CI: 1.01-1.48] compared to their counterparts. Also, older adults who were depressed and belonged to rural areas were 2.58 times [AOR: 2.58, CI: 1.95-3.41] more likely to be cognitively impaired than those who were not depressed and resided in urban areas.ConclusionsDepression is linked to an increased risk of cognitive decline and dementia; therefore, failing to diagnose and treat LLD in later life may have significant health implications. Moreover, treatment under the care of a cognitive neurologist or geriatric psychiatrist is recommended for people with LLD and cognitive disability due to both the disorders' complex existence.
| S-EPMC8204463 | biostudies-literature
Project description:Indices of functional connectivity in the default mode network (DMN) are promising neural markers of treatment response in late-life depression. We examined the differences in DMN functional connectivity between treatment-responsive and treatment-resistant depressed older adults. Forty-seven depressed older adults underwent MRI scanning pre- and post-pharmacotherapy. Forty-six never depressed older adults underwent MR scanning as comparison subjects. Treatment response was defined as achieving a Hamilton Depression Rating Scale of 10 or less post-treatment. We analyzed resting state functional connectivity using the posterior cingulate cortex as the seed region-of-interest. The resulting correlation maps were employed to investigate between-group differences. Additionally we examined the association between white matter hyperintensity burden and functional connectivity results. Comparison of pre- and post-treatment scans of depressed participants revealed greater post-treatment functional connectivity in the frontal precentral gyrus. Relative to treatment-responsive participants, treatment-resistant participants had increased functional connectivity in the left striatum. When adjusting for white matter hyperintensity burden, the observed differences lost significance for the PCC-prefrontal functional connectivity, but not for the PCC-striatum functional connectivity. The post-treatment "frontalization" of the DMN connectivity suggests a normalizing effect of antidepressant treatment. Moreover, our study confirms the central role of white matter lesions in disrupting brain functional connectivity.
| S-EPMC3865521 | biostudies-literature
Project description:Late-life depression (LLD) and amnestic mild cognitive impairment (aMCI) are associated with medial temporal lobe structural abnormalities. However, the hippocampal functional connectivity (HFC) similarities and differences related to these syndromes when they occur alone or coexist are unclear. Resting-state functional connectivity MRI (R-fMRI) technique was used to measure left and right HFC in 72 elderly participants (LLD [n = 18], aMCI [n = 17], LLD with comorbid aMCI [n = 12], and healthy controls [n = 25]). The main and interactive relationships of LLD and aMCI on the HFC networks were determined, after controlling for age, gender, education and gray matter volumes. The effects of depressive symptoms and episodic memory deficits on the hippocampal functional connections also were assessed. While increased and decreased left and right HFC with several cortical and subcortical structures involved in mood regulation were related to LLD, aMCI was associated with globally diminished connectivity. Significant LLD-aMCI interactions on the right HFC networks were seen in the brain regions critical for emotion processing and higher-order cognitive functions. In the interactive brain regions, LLD and aMCI were associated with diminished hippocampal functional connections, whereas the comorbid group demonstrated enhanced connectivity. Main and interactive effects of depressive symptoms and episodic memory performance were also associated with bilateral HFC network abnormalities. In conclusion, these findings indicate that discrete hippocampal functional network abnormalities are associated with LLD and aMCI when they occur alone. However, when these conditions coexist, more pronounced vulnerabilities of the hippocampal networks occur, which may be a marker of disease severity and impending cognitive decline. By utilizing R-fMRI technique, this study provides novel insights into the neural mechanisms underlying LLD and aMCI in the functional network level.
| S-EPMC3814948 | biostudies-literature
Project description:OBJECTIVE:Late-life depression (LLD) is characterized by poor antidepressant response and cognitive dysfunction. This study examined whether transdermal nicotine benefits mood symptoms and cognitive performance in LLD. METHODS:In a 12-week open-label outpatient study conducted between November 2016 and August 2017, transdermal nicotine was given to 15 nonsmoking older adults (? 60 years of age). Eligible participants met DSM-IV-TR criteria for major depressive disorder with ? 15 on the Montgomery-Asberg Depression Rating scale (MADRS) and endorsed subjective cognitive impairment. Transdermal nicotine patches were applied daily and titrated in a rigid dose escalation strategy to a maximum dose of 21.0 mg/d, allowing dose reductions for tolerability. The primary mood outcome was MADRS change measured every 3 weeks, with response defined as ? 50% improvement from baseline and remission as MADRS score ? 8. The primary cognitive outcome was the Conners Continuous Performance Test (CPT), a test of attention. RESULTS:Robust rates of response (86.7%; 13/15 subjects) and remission (53.3%; 8/15 subjects) were observed. There was a significant decrease in MADRS scores over the study (? = -1.51, P < .001), with improvement seen as early as 3 weeks (Bonferroni-adjusted P value = .004). We also observed improvement in apathy and rumination. We did not observe improvement on the CPT but did observe improvement in subjective cognitive performance and signals of potential drug effects on secondary cognitive measures of working memory, episodic memory, and self-referential emotional processing. Overall, transdermal nicotine was well tolerated, although 6 participants could not reach the maximum targeted dose. CONCLUSIONS:Nicotine may be a promising therapy for depressed mood and cognitive performance in LLD. A definitive placebo-controlled trial and establishment of longer-term safety are necessary before clinical usage. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT02816138?.
| S-EPMC6129985 | biostudies-literature
Project description:Neuroimaging features of small vessel disease (SVD) are highly prevalent in older adulthood and associated with significant variability in clinical symptoms, yet the factors predicting these symptom disparities are poorly understood. We employed a novel metric of SVD, peak width of skeletonized mean diffusivity (PSMD), to elucidate the relationship of late-life depression (LLD) to the cognitive presentation of vascular pathology. A total of 109 older adults without a diagnosis of a neurocognitive disorder were enrolled in the study; 44 with major depressive disorder and 65 age-matched controls. Subjects completed neuropsychological testing and magnetic resonance imaging including FLAIR and diffusion tensor imaging sequences, from which white matter hyperintensity volume and diffusion metrics (fractional anisotropy, mean diffusivity, PSMD) were quantified. In hierarchical models, the relationship between vascular burden and cognitive performance varied as a function of diagnostic status, such that the negative association between PSMD and processing speed was significantly stronger in participants with LLD compared to controls. Greater PSMD also predicted poorer performance on delayed memory and executive function tasks specifically among those with LLD, while there were no associations between PSMD and task performance among controls. PSMD outperformed conventional SVD and diffusion markers in predicting cognitive performance and dysexecutive behaviors in participants with LLD. These data suggest that LLD may confer a vulnerability to the cognitive manifestations of white matter abnormalities in older adulthood. PSMD, a novel biomarker of diffuse microstructural changes in SVD, may be a more sensitive marker of subtle cognitive deficits stemming from vascular pathology in LLD.
| S-EPMC8674355 | biostudies-literature
Project description:BackgroundLate-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.MethodsTwenty 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.ResultsCompared 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.ConclusionsUsing 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.
| S-EPMC8311821 | biostudies-literature
Project description:Depression is a debilitating mental disorder that frequently occurs in older adults, especially in those with vascular diseases. Nutritional factors have the potential to decrease the occurrence of late-life depression but have not been adequately studied. Low folate levels, disturbed omega-3 fatty acid metabolism and obesity have been associated with depression, and may be causal factors. Longitudinal studies are urgently needed in order to examine the potential of dietary factors to prevent late-life depression.
| S-EPMC2841351 | biostudies-other
Project description:Late-life depression (LLD), compared to depression at a young age, is more likely to have poor prognosis and high risk of progression to dementia. A recent systemic review and meta-analysis of the present antidepressants for LLD showed that the treatment response rate was 48% and the remission rate was only 33.7%, thus implying the need to improve the treatment with other approaches in the future. Recently, agents modulating the glutamatergic system have been tested for mental disorders such as schizophrenia, dementia, and depressive disorder. Ketamine, a noncompetitive NMDA receptor (NMDAR) antagonist, requires more evidence from randomized clinical trials (RCTs) to prove its efficacy and safety in treating LLD. The metabotropic receptors (mGluRs) of the glutamatergic system are family G-protein-coupled receptors, and inhibition of the Group II mGluRs subtypes (mGlu2 and mGlu3) was found to be as effective as ketamine in exerting rapid antidepressant activity in some animal studies. Inflammation has been thought to contribute to depression for a long time. The cytokine levels not only increase with age but also decrease serotonin. Regarding LLD, interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) released in vivo are likely to contribute to the reduced serotonin level. Brain-derived neurotrophic factor (BDNF), a growth factor and a modulator in the tropomyosin receptor kinase (Trk) family of tyrosine kinase receptors, probably declines quantitatively with age. Recent studies suggest that BDNF/TrkB decrement may contribute to learning deficits and memory impairment. In the process of aging, physiological changes in combination with geriatric diseases such as vascular diseases result in poorer prognosis of LLD in comparison with that of young-age depression. Treatments with present antidepressants have been generally unsatisfactory. Novel treatments such as anti-inflammatory agents or NMDAR agonists/antagonists require more studies in LLD. Last but not least, LLD and dementia, which share common pathways and interrelate reciprocally, are a great concern. If it is possible to enhance the treatment of LDD, dementia can be prevented or delated.
| S-EPMC8303929 | biostudies-literature