Cognitive functioning in chronic fatigue syndrome and the role of depression, anxiety and fatigue

Objective: This study was designed to investigate the role of depression, anxiety, and fatigue in Chronic Fatigue Syndrome (CFS) sufferers' objective and subjective cognitive performance. Methods: Twenty-three CFS sufferers and 23 healthy control participants were compared on objective and subjective assessments of cognitive performance. Depression, anxiety, and fatigue were also evaluated. Results: CFS sufferers did not demonstrate any impairment in objective cognitive functioning compared to the control group, and objective performance was not related to their higher levels of depression or their level of fatigue. Depression scores only accounted for a small amount of the variance in CFS sufferers' lower subjective assessment of their cognitive performance compared to control participants. There were no differences between the groups on anxiety scores. Conclusion: The results are discussed in terms of the heterogeneity of the CFS population and the complex interaction of symptomatological factors that characterise CFS.

Total antioxidant status correlates with cognitive impairment in patients with recurrent depressive disorder

Depressive disorder is a multifactorial diseases, that one of the typical feature are cognitive impairments. The aim of this study was to determine the total antioxidant status (TAS) in patients with recurrent depressive disorder (rDD) and to define relationship between plasma levels of TAS and the cognitive performance. Design and methods: the study comprised 74 subjects: patients with rDD (n = 45) and healthy subjects (n = 29). Cognitive function assessment was based on: Trail Making Test, The Stroop Test, Verbal Fluency Test and Auditory Verbal Learning Test. Statistically significant differences were found in the intensity of depression symptoms, measured by the Hamilton Depression Rating Scale (HDRS) on therapy onset versus the examination results after 8 weeks of treatment (p < 0.001). The level of TAS was substantially higher in patients with rDD (p = 0.01). For rDD patients, elevated TAS levels were associated with worse cognitive test performance. The higher was the concentration of plasma TAS, the greater was the severity of depressive symptoms measured by HDRS before and after pharmacotherapy. (1) Higher concentration of plasma TAS in rDD patients is associated with the severity of depressive symptoms. (2) Elevated levels of plasma TAS are related to impairment of short-term declarative memory, long-term declarative-memory, verbal fluency and working memory.

Effects of N-acetyl cysteine on cognitive function in bipolar disorder

Aims

Bipolar disorder is characterized by progressive changes in cognition with declines in executive functioning, memory and sustained attention. Current pharmacotherapies for bipolar disorder target mood symptoms but have not addressed these cognitive changes resulting in euthymic individuals who still experience cognitive deficits. N-acetyl cysteine (NAC) has been shown to have effects on antioxidant status, glutamate transmission, inflammation and neurogenesis. Adjunctive treatment with NAC improves the symptoms experienced by those with bipolar disorder, particularly depression, and it was hypothesized that cognition may also be improved following NAC treatment.
Methods

As part of a larger randomized, double-blind, placebo-controlled trial, participants in the current report were tested at baseline and 6 months to assess changes in cognitive function following either 2000 mg of NAC daily or placebo.
Results

This study failed to find changes in cognitive function following treatment with NAC compared to placebo.
Conclusions

While an important pilot study, this study had a small sample size and included a limited battery of cognitive tests. Further investigations on the effects of NAC on cognitive performance in bipolar disorder are required.

Cognitive dysfunction in depression - pathophysiology and novel targets

Major depressive disorder (MDD) is associated with cognitive dysfunction encompassing several domains, including memory, executive function, processing speed and attention. Cognitive deficits persist in a significant proportion of patients even in remission, compromising psychosocial functioning and workforce performance. While monoaminergic antidepressants may improve cognitive performance in MDD, most antidepressants have limited clinical efficacy. The overarching aims of this review were: (1) to synthesize extant literature on putative biological pathways related to cognitive dysfunction in MDD and (2) to review novel neurotherapeutic targets for cognitive enhancement in MDD. We found that reciprocal and overlapping biological pathways may contribute to cognitive dysfunction in MDD, including an hyperactive hypothalamic-pituitary-adrenal axis, an increase in oxidative and nitrosative stress, inflammation (eg, enhanced production of pro-inflammatory cytokines), mitochondrial dysfunction, increased apoptosis as well as a diminished neurotrophic support. Several promising neurotherapeutic targets were identified such as minocycline, statins, anti-inflammatory compounds, N-acetylcysteine, omega-3 poliunsaturated fatty acids, erythropoietin, thiazolidinediones, glucagon-like peptide-1 analogues, S-adenosyl-l-methionine (SAMe), cocoa flavonols, creatine monohydrate and lithium. Erythropoietin and SAMe had pro-cognitive effects in randomized controlled trials (RCT) involving MDD patients. Despite having preclinical and/or preliminary evidences from trials suggesting possible efficacy as novel cognitive enhancing agents for MDD, no RCT to date was performed for most of the other therapeutic targets reviewed herein. In conclusion, multiple biological pathways are involved in cognitive dysfunction in MDD. RCTs testing genuinely novel pro-cognitive compounds for MDD are warranted.

Dietary repletion with ω3 fatty acid or with COX inhibition reverses cognitive effects in F3 ω3 fatty-acid-deficient mice

Dietary deficiency of ω3 fatty acid during development leads to impaired cognitive function. However, the effects of multiple generations of ω3 fatty-acid deficiency on cognitive impairment remain unclear. In addition, we sought to test the hypothesis that the cognitive impairments of ω3 fatty-acid-deficient mice are mediated through the arachidonic acid-cyclooxygenase (COX) pathway. To address these issues, C57BL/6J mice were bred for 3 generations and fed diets either deficient (DEF) or sufficient (SUF) in ω3 fatty acids. At postnatal day 21, the F3 offspring remained on the dam's diet or were switched to the opposite diet, creating 4 groups. In addition, 2 groups that remained on the dam's diet were treated with a COX inhibitor. At 19 wk of age, spatial-recognition memory was tested on a Y-maze. Results showed that 16 wk of SUF diet reversed the cognitive impairment of F3 DEF mice. However, 16 wk of ω3 fatty-acid-deficient diet impaired the cognitive performance of the F3 SUF mice, which did not differ from that of the F3 DEF mice. These findings suggest that the cognitive deficits after multigenerational maintenance on ω3 fatty-acid-deficient diet are not any greater than are those after deficiency during a single generation. In addition, treatment with a COX inhibitor prevented spatial-recognition deficits in F3 DEF mice. Therefore, cognitive impairment due to dietary ω3 fatty-acid deficiency appears to be mediated by the arachidonic acid-COX pathway and can be prevented by 16 wk of dietary repletion with ω3 fatty acids or COX inhibition.

Blood pressure and cognitive function: the role of central aortic and brachial pressures

Central (aortic) blood pressures differ from brachial pressures and may be more relevant to the study of cognitive function, given that blood is delivered to the brain through the central large arteries. Pulse-pressure amplification reflects the augmentation of blood pressure between the central and peripheral arteries, which diminishes with aging. We aimed to determine the association between central blood pressure and cognitive function in independently living adults aged 20 to 82 years (N = 493). In adjusted regression models, higher central systolic pressure and higher central pulse pressure were each associated with poorer processing speed, Stroop processing, and recognition memory. Lower amplification was associated with poorer Stroop processing, working memory, and recognition memory. Higher brachial systolic pressure and brachial pulse pressure were both associated with poorer Stroop processing. In summary, central pressures and amplification were sensitive indicators of cognitive aging, predicting aspects of cognitive performance not predicted by brachial blood pressure.

The acute and sub-chronic effects of cocoa flavanols on mood, cognitive and cardiovascular health in young healthy adults: a randomized, controlled trial.

Cocoa supplementation has been associated with benefits to cardiovascular health. However, cocoa's effects on cognition are less clear. A randomized, placebo-controlled, double-blind clinical trial (n = 40, age M = 24.13 years, SD = 4.47 years) was conducted to investigate the effects of both acute (same-day) and sub-chronic (daily for four-weeks) 250 mg cocoa supplementation on mood and mental fatigue, cognitive performance and cardiovascular functioning in young, healthy adults. Assessment involved repeated 10-min cycles of the Cognitive Demand Battery (CDB) encompassing two serial subtraction tasks (Serial Threes and Sevens), a Rapid Visual Information Processing task, and a mental fatigue scale over the course of half an hour. The Swinburne University Computerized Cognitive Assessment Battery (SUCCAB) was also completed to evaluate cognition. Cardiovascular function included measuring both peripheral and central blood pressure and cerebral blood flow. At the acute time point, consumption of cocoa significantly improved self-reported mental fatigue and performance on the Serial Sevens task in cycle one of the CDB. No other significant effects were found. This trial was registered with the Australian and New Zealand Clinical Trial Registry (Trial ID: ACTRN12613000626763). Accessible via http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12613000626763&ddlSearch=Registered.

A single-blind, randomised controlled trial on the effects of lithium and quetiapine monotherapy on the trajectory of cognitive functioning in first episode mania: A 12-month follow-up study

BACKGROUND: Cognitive deficits have been reported during the early stages of bipolar disorder; however, the role of medication on such deficits remains unclear. The aim of this study was to compare the effects of lithium and quetiapine monotherapy on cognitive performance in people following first episode mania. METHODS: The design was a single-blind, randomised controlled trial on a cohort of 61 participants following first episode mania. Participants received either lithium or quetiapine monotherapy as maintenance treatment over a 12-month follow-up period. The groups were compared on performance outcomes using an extensive cognitive assessment battery conducted at baseline, month 3 and month 12 follow-up time-points. RESULTS: There was a significant interaction between group and time in phonemic fluency at the 3-month and 12-month endpoints, reflecting greater improvements in performance in lithium-treated participants relative to quetiapine-treated participants. After controlling for multiple comparisons, there were no other significant interactions between group and time for other measures of cognition. CONCLUSION: Although the effects of lithium and quetiapine treatment were similar for most cognitive domains, the findings imply that early initiation of lithium treatment may benefit the trajectory of cognition, specifically verbal fluency in young people with bipolar disorder. Given that cognition is a major symptomatic domain of bipolar disorder and has substantive effects on general functioning, the ability to influence the trajectory of cognitive change is of considerable clinical importance.

Cognitive and olfactory deficits in Machado-Joseph disease: A dopamine transporter study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Depression severity levels and cognitive functions in institutionalized elderly patients

Depression is a highly prevalent illness among institutionalized aged and assumes peculiar characteristics such as the risk for progressing to dementia. The aims of this study was to assess the cognitive functions of institutionalized elderly with clinical diagnosis of depression and compare the severity of depressive symptoms with cognitive performance. From 120 residents at a nursing home in Rio Claro, Brazil, we study 23 individuals (mean age: 74.3 years; mean schooling: 4.0 years) with diagnosis of depression. At first, a clinical diagnosis of depression and measurement of its symptoms using the Geriatric Depression Scale were performed. The patient then underwent a neuropsychological assessment based on the following tests: Mini-Mental Examination, Verbal Fluency, Visual Perception, Immediate Memory, Recent Memory, Recognition, Clock Drawing Test. The patients were divided into two groups: those with less severe depression symptoms (Group 1: N=9) and more severe symptoms (Group 2: N=14). The significant difference between symptom severity of the two groups was p=0.0001. Patients with more severe symptoms revealed a slightly inferior cognitive performance in most of the tests when compared to those with less severe symptoms (p>0.05). In relation to Verbal Fluency, patients with more severe depression symptoms presented a significantly inferior cognitive performance when compared to those with less severe symptoms (p=0.0082). Verbal Fluency revealed to be a more sensitive test for measuring early cognitive alterations in institutionalized aged with depression, and appears to be a useful resource in monitoring the cognitive functions of patients faced with the risk of dementia. © Copyright Moreira Jr. Editora.

Respiratory training as strategy to prevent cognitive decline in aging: a randomized controlled trial

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Elderly Individuals with Diabetes: Adding Cognitive Training to Psychoeducational Intervention

The present research examined the effects of a cognitive training program combined with psychoeducational intervention for diabetic elderly patients. Specifically, it aimed at assessing the effects of an eight-session cognitive training and educational program in diabetic elderly individuals and investigating changes in their awareness about specific aspects of diabetes. The final sample consisted of 34 individuals-19 in the experimental group (EG) and 15 in the control group (CG), all residing in the eastern region of the city of Sao Paulo. The protocol included clinical and sociodemographic questions; the Diabetes Attitudes Questionnaire (ATT-19); Diabetes Knowledge Scale (DKN-A); Mini Mental State Examination (MMSE); Verbal Fluency-animal category (VF); Geriatric Depression Scale (GDS); Short Cognitive Performance Test (SKT); and the Rivermead Behavioral Memory Test (RBMT). Results pointed to a significant difference between the two groups for the ATT-19, DKN, and SKT-memory and SKT-total, and a marginally significant difference for the RBMT history in the posttest. As for the remaining cognitive variables, no changes were observed. Retest effects were not observed in the CG. We concluded that cognitive training combined with psychoeducational intervention in diabetic elderly individuals may be effective in producing cognitive gains as well as attitude and knowledge improvement concerning diabetes mellitus (DM).

Cognitive function in patients with chronic pain treated with opioids: characteristics and associated factors

Background The paucity of studies regarding cognitive function in patients with chronic pain, and growing evidence regarding the cognitive effects of pain and opioids on cognitive function prompted us to assess cognition via neuropsychological measurement in patients with chronic non-cancer pain treated with opioids. Methods In this cross-sectional study, 49 patients were assessed by Continuous Reaction Time, Finger Tapping, Digit Span, Trail Making Test-B and Mini-mental State Examination tests. Linear regressions were applied. Results Patients scored poorly in the Trail Making Test-B (mean?=?107.6?s, SD?=?61.0, cut-off?=?91?s); and adequately on all other tests. Several associations among independent variables and cognitive tests were observed. In the multiple regression analyses, the variables associated with statistically significant poor cognitive performance were female sex, higher age, lower annual income, lower schooling, anxiety, depression, tiredness, lower opioid dose, and more than 5?h of sleep the night before assessment (P?<?0.05). Conclusions Patients with chronic pain may have cognitive dysfunction related to some reversible factors, which can be optimized by therapeutic interventions.

Cognitive Training and Educational Intervention for Individuals with Hypertension: Effects on Cognition

Objectives: To evaluate the possibility of combining cognitive training to an educational intervention composed by eight sessions about hypertension for a better management of the disease among the elderly. Methods: 64 older adults who reported having hypertension, divided into experimental group (EG, n=35) and control group (CG, n=29) participated in the study. Control participants received training after the post-test. The protocol contained socio-demographic and clinical data, Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Rivermead Behavioral Memory Test (RBMT), Verbal Fluency Animal Category (VF) and Short Cognitive Test (SKT). Results: The EG showed better cognitive performance when compared with the CG, at post-test. Conclusion: Cognitive gains may occur after psychoeducational interventions for older adults with hypertension.

Mini-Mental State Examination performance in frail, pre-frail, and non-frail community dwelling older adults in Ermelino Matarazzo, Sao Paulo, Brazil

Background: Frailty in older adults is a multifactorial syndrome defined by low metabolic reserve, less resistance to stressors, and difficulty in maintaining organic homeostasis due to cumulative decline of multiple physiological systems. The relationship between frailty and cognition remains unclear and studies about Mini-Mental State Examination (MMSE) performance and frailty are scarce. The objective was to examine the association between frailty and cognitive functioning as assessed by the MMSE and its subdomains. Methods: A cross-sectional population-based study (FIBRA) was carried out in Ermelino Matarazzo, a poor subdistrict of the city of Sao Paulo, Brazil. Participants were 384 community dwelling older adults, 65 years and older who completed the MMSE and a protocol to assess frailty criteria as described in the Cardiovascular Health Study (CHS). Results: Frail older adults had significantly worse performance on the MMSE (p < 0.001 for total score). Linear regression analyses showed that the MMSE total score was influenced by age (p < 0.001), education (p < 0.001), family income (p < 0.001), and frailty status (p < 0.036). Being frail was associated more significantly with worse scores in Time Orientation (p < 0.004) and Immediate Memory (p < 0.001). Conclusions: Our data suggest that being frail is associated with worse cognitive performance, as assessed by the MMSE. It is recommended that the assessment of frail older adults should include the investigation of their cognitive status.