Cognitive impairment and vitamin B12 : a review

Background: This review examines the associations between low vitamin B12 levels, neurodegenerative disease, and cognitive impairment. The potential impact of comorbidities and medications associated with vitamin B12 derangements were also investigated. In addition, we reviewed the evidence as to whether vitamin B12 therapy is efficacious for cognitive impairment and dementia.

Methods: A systematic literature search identified 43 studies investigating the association of vitamin B12 and cognitive impairment or dementia. Seventeen studies reported on the efficacy of vitamin B12 therapy for these conditions.

Results: Vitamin B12 levels in the subclinical low-normal range (<250 ρmol/L) are associated with Alzheimer's disease, vascular dementia, and Parkinson's disease. Vegetarianism and metformin use contribute to depressed vitamin B12 levels and may independently increase the risk for cognitive impairment. Vitamin B12 deficiency (<150 ρmol/L) is associated with cognitive impairment. Vitamin B12 supplements administered orally or parenterally at high dose (1 mg daily) were effective in correcting biochemical deficiency, but improved cognition only in patients with pre-existing vitamin B12 deficiency (serum vitamin B12 levels <150 ρmol/L or serum homocysteine levels >19.9 μmol/L).

Conclusion: Low serum vitamin B12 levels are associated with neurodegenerative disease and cognitive impairment. There is a small subset of dementias that are reversible with vitamin B12 therapy and this treatment is inexpensive and safe. Vitamin B12 therapy does not improve cognition in patients without pre-existing deficiency. There is a need for large, well-resourced clinical trials to close the gaps in our current understanding of the nature of the associations of vitamin B12 insufficiency and neurodegenerative disease.

Reducing parental anxiety using a family based intervention for youth mental health : a randomized controlled trial

This paper presents findings on parent anxiety and attachment relationship style from the Deakin Family Options (DFO) pilot study, a randomized controlled pilot study comparing a family-based treatment (BEST Plus), versus a youth only treatment (CBT) versus a group who received both of these treatments (COMBINED). Eligible participants were families with a young person (aged 12 - 25 years) with a high prevalence mental health problem. Youth from participating families scored in the clinical or subclinical range for depression, anxiety and/or substance misuse symptoms on standardized measures during the initial assessment. The collected sample was drawn from regional and urban centers in Victoria, Australia and allocated to treatment condition using a simple randomization procedure (parallel design). It was hypothesized that families receiving the BEST Plus would experience greater reductions in youth and parent mental health symptoms, and improved parent-child relationships, compared with those in the CBT condition. This paper describes and discusses changes in parent anxiety and parent attachment, according to whether the parent participated in a treatment (BEST Plus) or did not (NONBEST Plus). Participants were blind to the study hypotheses. In total 71 parent participants returned pre data and were allocated to a treatment group. In this paper, data from parent participants who completed pre and post measures (n = 48) and pre, post, and 6-month follow-up measures (n = 28) on anxiety and attachment were analyzed by group (BEST Plus versus NONBEST Plus). The results of this study suggest that parent anxiety decreased significantly more following parent involvement in a group treatment, than for parents that did not receive treatment. Unexpectedly, avoidant attachment increased in the no treatment group, but remained relatively stable following the BEST Plus group. There were no significant findings in relation to compulsive traits and anxious attachment. These findings are discussed in light of the study limitations.

Anxiety online - a virtual clinic : preliminary outcomes following completion of five fully automated treatment programs for anxiety disorders and symptoms

Background : The development of e-mental health interventions to treat or prevent mental illness and to enhance wellbeing has risen rapidly over the past decade. This development assists the public in sidestepping some of the obstacles that are often encountered when trying to access traditional face-to-face mental health care services. Objective : The objective of our study was to investigate the posttreatment effectiveness of five fully automated self-help cognitive behavior e-therapy programs for generalized anxiety disorder (GAD), panic disorder with or without agoraphobia (PD/A), obsessive–compulsive disorder (OCD), posttraumatic stress disorder (PTSD), and social anxiety disorder (SAD) offered to the international public via Anxiety Online, an open-access full-service virtual psychology clinic for anxiety disorders. Methods : We used a naturalistic participant choice, quasi-experimental design to evaluate each of the five Anxiety Online fully automated self-help e-therapy programs. Participants were required to have at least subclinical levels of one of the anxiety disorders to be offered the associated disorder-specific fully automated self-help e-therapy program. These programs are offered free of charge via Anxiety Online. Results : A total of 225 people self-selected one of the five e-therapy programs (GAD, n = 88; SAD, n = 50; PD/A, n = 40; PTSD, n = 30; OCD, n = 17) and completed their 12-week posttreatment assessment. Significant improvements were found on 21/25 measures across the five fully automated self-help programs. At postassessment we observed significant reductions on all five anxiety disorder clinical disorder severity ratings (Cohen d range 0.72–1.22), increased confidence in managing one’s own mental health care (Cohen d range 0.70–1.17), and decreases in the total number of clinical diagnoses (except for the PD/A program, where a positive trend was found) (Cohen d range 0.45–1.08). In addition, we found significant improvements in quality of life for the GAD, OCD, PTSD, and SAD e-therapy programs (Cohen d range 0.11–0.96) and significant reductions relating to general psychological distress levels for the GAD, PD/A, and PTSD e-therapy programs (Cohen d range 0.23–1.16). Overall, treatment satisfaction was good across all five e-therapy programs, and posttreatment assessment completers reported using their e-therapy program an average of 395.60 (SD 272.2) minutes over the 12-week treatment period. Conclusions : Overall, all five fully automated self-help e-therapy programs appear to be delivering promising high-quality outcomes; however, the results require replication.

Does Candida and/or Staphylococcus play a role in nipple and breast pain in lactation? A cohort study in Melbourne, Australia

Objective: To investigate Candida species and Staphylococcus aureus and the development of 'nipple and breast thrush' among breastfeeding women. Design: Prospective longitudinal cohort study. Setting: Two hospitals in Melbourne, Australia (one public, one private) with follow-up in the community. Participants: 360 nulliparous women recruited at 36 weeks' gestation from November 2009 to June 2011. Participants were followed up six times: in hospital, at home weekly until 4 weeks postpartum and by telephone at 8 weeks. Main outcome measures: Case definition 'nipple and breast thrush': burning nipple pain and breast pain (not related to mastitis); detection of Candida spp (using culture and PCR) in the mother's vagina, nipple or breast milk or in the baby's mouth; detection of S aureus in the mother' nipple or breast milk. Results: Women with the case definition of nipple/ breast thrush were more likely to have Candida spp in nipple/breast milk/baby oral samples (54%) compared to other women (36%, p=0.014). S aureus was common in nipple/breast milk/baby samples of women with these symptoms as well as women without these symptoms (82% vs 79%) (p=0.597). Time-to-event analysis examined predictors of nipple/breast thrush up to and including the time of data collection. Candida in nipple/breast milk/baby predicted incidence of the case definition (rate ratio (RR) 1.87 (95% CI 1.10 to 3.16, p=0.018). We do not have evidence that S aureus colonisation was a predictor of these symptoms (RR 1.53, 95% CI 0.88 to 2.64, p=0.13). Nipple damage was also a predictor of these symptoms, RR 2.30 (95% CI 1.19 to 4.43, p=0.012). In the multivariate model, with all three predictors, the RRs were very similar to the univariate RRs. This indicates that Candida and nipple damage are independent predictors of our case definition.

The prevalence of vitamin B12 deficiency in a random sample from the Australian population

 Objective: Vitamin B12 deficiency is common in older adults, and may increase the risk of cognitive impairment. The distribution of vitamin B12 insufficiency in younger age groups is less studied. This study aims to assess the prevalence of vitamin B12 deficiency (<156ρmol/L) and subclinical low-normal levels (156-250ρmol/L) in a large, random sample of the Australian population across the adult life span.
Methods: We examined serum vitamin B12 levels in a random sample of 1,085 men and 1,125 women aged 20-97 years between 1994 and 2006; in the Barwon Statistical Division, a regional area in south eastern Australia that is representative of the socioeconomic status of the Australian population.
Results: The age-standardised prevalence of vitamin B12 deficiency in this cohort of men and women was 3.6%. Subclinical low-normal vitamin B12 levels (156-250ρmol/L) were found in 26%. Serum vitamin B12 levels declined with age among men (p-value <0.001) and were lower in men than women (p-value <0.001). Vitamin B12 levels were higher among supplement users (8.0% of the cohort).
Conclusions: Vitamin B12 levels decline with age, and have been associated with neurodegenerative diseases and cognitive decline. Early intervention by diet education or supplement use to address this age-associated decline in vitamin levels may be an effective strategy to prevent decline in a significant segment of the population. Such intervention may need to start in mid-life (from 50-years of age) before the onset age-related decline in vitamin B12 levels.

Context sensitivity in action decreases along the autism spectrum: a predictive processing perspective

Recent predictive processing accounts of perception and action point towards a key challenge for the nervous system in dynamically optimizing the balance between incoming sensory information and existing expectations regarding the state of the environment. Here, we report differences in the influence of the preceding sensory context on motor function, varying with respect to both clinical and subclinical features of autism spectrum disorder (ASD). Reach-to-grasp movements were recorded subsequent to an inactive period in which illusory ownership of a prosthetic limb was induced. We analysed the sub-components of reach trajectories derived using a minimum-jerk fitting procedure. Non-clinical adults low in autistic features showed disrupted movement execution following the illusion compared to a control condition. By contrast, individuals higher in autistic features (both those with ASD and non-clinical individuals high in autistic traits) showed reduced sensitivity to the presence of the illusion in their reaching movements while still exhibiting the typical perceptual effects of the illusion. Clinical individuals were distinct from non-clinical individuals scoring high in autistic features, however, in the early stages of movement. These results suggest that the influence of high-level representations of the environment differs between individuals, contributing to clinical and subclinical differences in motor performance that manifest in a contextual manner. As high-level representations of context help to explain fluctuations in sensory input over relatively longer time scales, more circumscribed sensitivity to prior or contextual information in autistic sensory processing could contribute more generally to reduced social comprehension, sensory impairments and a stronger desire for predictability and routine.

Unmet needs and distress in people with inoperable lung cancer at the commencement of treatment

Purpose : People with lung cancer report a higher burden of unmet needs, specifically psychological and daily living unmet needs. They experience more psychological distress and more physical hardship than other tumour sites. This study examined the levels of unmet need and psychological distress in inoperable lung cancer patients at the start of treatment.

Methods : A cross-section survey methodology was employed using baseline data from a randomised controlled trial designed to evaluate a supportive care intervention. Eligible lung cancer patients were approached to participate at the start of treatment. Consenting patients completed questionnaires prior to or just after the commencement of treatment. Reliable and valid measures included Needs Assessment for Advanced Lung Cancer Patients, Hospital Anxiety and Depression Scale and Brief Distress Thermometer.

Results : Of the 108 patients participating, the top unmet need was ‘Dealing with concerns about your family’s fears and worries’ (62%); with the next four also coming from the psychological/emotional domain, but, on average, most needs related to medical communication. Thirty two percent of patients reported clinical or subclinical anxiety and 19% reported HADS scores suggestive of clinical or subclinical depression. Moreover, 39.8% of the sample reported distress above the cut-off on the distress thermometer and this was associated with higher needs for each need subscale (p < 0.05).

Conclusions : People with lung cancer have high levels of unmet needs especially regarding psychological/emotional or medical communication. People with lung cancer who are classified as distressed have more unmet needs.

Innate immunity in the mammary gland and the role of the milk peptidome

 This research investigated how the mammary gland responds to disease states such as mastitis and how the milk plays a protective role. An in vitro mammary model was developed and shown to replicate the same responses to the breast when challenged with bacterial proteins demonstrating the usefulness of this model for future investigation of therapeutic interventions.

Hot topics in research: preventive neuroradiology in brain aging and cognitive decline

Preventive neuroradiology is a new concept supported by growing literature. The main rationale of preventive neuroradiology is the application of multimodal brain imaging toward early and subclinical detection of brain disease and subsequent preventive actions through identification of modifiable risk factors. An insightful example of this is in the area of age-related cognitive decline, mild cognitive impairment, and dementia with potentially modifiable risk factors such as obesity, diet, sleep, hypertension, diabetes, depression, supplementation, smoking, and physical activity. In studying this link between lifestyle and cognitive decline, brain imaging markers may be instrumental as quantitative measures or even indicators of early disease. The purpose of this article is to provide an overview of the major studies reflecting how lifestyle factors affect the brain and cognition aging. In this hot topics review, we will specifically focus on obesity and physical activity.

The diagnostic validity and reliability of an internet-based clinical assessment program for mental disorders

BACKGROUND: Internet-based assessment has the potential to assist with the diagnosis of mental health disorders and overcome the barriers associated with traditional services (eg, cost, stigma, distance). Further to existing online screening programs available, there is an opportunity to deliver more comprehensive and accurate diagnostic tools to supplement the assessment and treatment of mental health disorders. OBJECTIVE: The aim was to evaluate the diagnostic criterion validity and test-retest reliability of the electronic Psychological Assessment System (e-PASS), an online, self-report, multidisorder, clinical assessment and referral system. METHODS: Participants were 616 adults residing in Australia, recruited online, and representing prospective e-PASS users. Following e-PASS completion, 158 participants underwent a telephone-administered structured clinical interview and 39 participants repeated the e-PASS within 25 days of initial completion. RESULTS: With structured clinical interview results serving as the gold standard, diagnostic agreement with the e-PASS varied considerably from fair (eg, generalized anxiety disorder: κ=.37) to strong (eg, panic disorder: κ=.62). Although the e-PASS' sensitivity also varied (0.43-0.86) the specificity was generally high (0.68-1.00). The e-PASS sensitivity generally improved when reducing the e-PASS threshold to a subclinical result. Test-retest reliability ranged from moderate (eg, specific phobia: κ=.54) to substantial (eg, bulimia nervosa: κ=.87). CONCLUSIONS: The e-PASS produces reliable diagnostic results and performs generally well in excluding mental disorders, although at the expense of sensitivity. For screening purposes, the e-PASS subclinical result generally appears better than a clinical result as a diagnostic indicator. Further development and evaluation is needed to support the use of online diagnostic assessment programs for mental disorders. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN121611000704998; http://www.anzctr.org.au/trial_view.aspx?ID=336143 (Archived by WebCite at http://www.webcitation.org/618r3wvOG).

Analyzing systolic-diastolic interval interaction characteristics in diabetic cardiac autonomic neuropathy progression

Cardiac autonomic neuropathy (CAN), one of the major complications in diabetes, if detected at the subclinical stage allows for effective treatment and avoiding further complication including cardiovascular pathology. Surface ECG (Electrocardiogram)-based diagnosis of CAN is useful to overcome the limitation of existing cardiovascular autonomic reflex tests traditionally used for CAN identification in clinical settings. The aim of this paper is to analyze the changes in the mechanical function of the ventricles in terms of systolic-diastolic interval interaction (SDI) from a surface ECG to assess the severity of CAN progression [no CAN, early CAN (ECAN) or subclinical CAN, and definite CAN (DCAN) or clinical CAN]. ECG signals recorded in supine resting condition from 72 diabetic subjects without CAN (CAN-) and 70 diabetic subjects with CAN were analyzed in this paper. The severity of CAN was determined by Ewing's Cardiovascular autonomic reflex tests. Fifty-five subjects of the CAN group had ECAN and 15 subjects had DCAN. In this paper, we propose an improved version of the SDI parameter (i.e., TQ/RR interval ratio) measured from the electrical diastolic interval (i.e., TQ interval) and the heart rate interval (i.e., RR interval). The performance of the proposed SDI measure was compared with the performance of the existing SDI measure (i.e., QT/TQ interval ratio). The proposed SDI parameter showed significant differences among three groups (no CAN, ECAN, and DCAN). In addition, the proposed SDI parameter was found to be more sensitive in detecting CAN progression than other ECG interval-based features traditionally used for CAN diagnosis. The modified SDI parameter might be used as an alternative measure for the Ewing autonomic reflex tests to identify CAN progression for those subjects who are unable to perform the traditional tests. These findings could also complement the echocardiographic findings of the left ventricular diastolic dysfunction by providing additional information about alteration in systolic and diastolic intervals in heart failure.

Analysis of human breast milk cells: gene expression profiles during pregnancy, lactation, involution, and mastitic infection

The molecular processes underlying human milk production and the effects of mastitic infection are largely unknown because of limitations in obtaining tissue samples. Determination of gene expression in normal lactating women would be a significant step toward understanding why some women display poor lactation outcomes. Here, we demonstrate the utility of RNA obtained directly from human milk cells to detect mammary epithelial cell (MEC)-specific gene expression. Milk cell RNA was collected from five time points (24 h prepartum during the colostrum period, midlactation, two involutions, and during a bout of mastitis) in addition to an involution series comprising three time points. Gene expression profiles were determined by use of human Affymetrix arrays. Milk cells collected during milk production showed that the most highly expressed genes were involved in milk synthesis (e.g., CEL, OLAH, FOLR1, BTN1A1, and ARG2), while milk cells collected during involution showed a significant downregulation of milk synthesis genes and activation of involution associated genes (e.g., STAT3, NF-kB, IRF5, and IRF7). Milk cells collected during mastitic infection revealed regulation of a unique set of genes specific to this disease state, while maintaining regulation of milk synthesis genes. Use of conventional epithelial cell markers was used to determine the population of MECs within each sample. This paper is the first to describe the milk cell transcriptome across the human lactation cycle and during mastitic infection, providing valuable insight into gene expression of the human mammary gland.