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Attentional impairments are common in dementia with Lewy bodies and its prodromal stage of mild cognitive impairment (MCI) with Lewy bodies (MCI-LB). People with MCI may be capable of compensating for subtle attentional deficits in most circumstances, and so these may present as occasional lapses of attention. We aimed to assess the utility of a continuous performance task (CPT), which requires sustained attention for several minutes, for measuring attentional performance in MCI-LB in comparison to Alzheimer’s disease (MCI-AD), and any performance deficits which emerged with sustained effort.
We included longitudinal data on a CPT sustained attention task for 89 participants with MCI-LB or MCI-AD and 31 healthy controls, estimating ex-Gaussian response time parameters, omission and commission errors. Performance trajectories were estimated both cross-sectionally (intra-task progress from start to end) and longitudinally (change in performance over years).
While response times in successful trials were broadly similar, with slight slowing associated with clinical parkinsonism, those with MCI-LB made considerably more errors. Omission errors were more common throughout the task in MCI-LB than MCI-AD (OR 2.3, 95% CI: 1.1–4.7), while commission errors became more common after several minutes of sustained attention. Within MCI-LB, omission errors were more common in those with clinical parkinsonism (OR 1.9, 95% CI: 1.3–2.9) or cognitive fluctuations (OR 4.3, 95% CI: 2.2–8.8).
Sustained attention deficits in MCI-LB may emerge in the form of attentional lapses leading to omissions, and a breakdown in inhibitory control leading to commission errors.
The aim of this proof-of-concept study was to understand the effect of daily intake of a 14-strain probiotic on mood, reward learning and emotional and cognitive processing in adults with low mood in the absence of prescribed medication. Salivary cortisol was measured as a marker for physiological stress.
In this parallel-group double-blind, placebo-controlled trial, 80 healthy adults with self-identified low mood were randomised to receive either the 14-strain probiotic or placebo for a duration of 4 weeks. Data were collected from participants at baseline (week 0) and post-intervention (week 4).
Probiotic intake significantly reduced depression scores (by 50%) compared to baseline, as measured by the Patient Health Questionnaire-9 (PHQ-9) scale (p < 0.05). Analysis of individual items in the PHQ-9 revealed that participants taking probiotics reported improved concentration relative to baseline (+ 51%, p < 0.05) and felt less tired compared to placebo (−21%, p < 0.01).
Regarding emotional processing, the probiotic group was more accurate at recognising facial expressions compared to those receiving placebo (facial emotion recognition test, +12%, p < 0.05). Furthermore, the probiotic group performed less well at the reward learning task relative to the placebo group (probabilistic instrumental learning task, p < 0.05) and was less vigilant to emotional cues compared neutral cues (dot-probe unmasked test, −8%, P < 0.05). The probiotic group also showed increased susceptibility to emotional interference during a cognitive learning task, relative to placebo (auditory visual learning task, −18% p < 0.05).
The study also revealed a downward trend in salivary cortisol in the probiotic group over 4 weeks.
Together, these results suggest that probiotics may work via a different psychological mechanism to that of conventional antidepressants. In other words, probiotics may work by reducing emotional salience across all emotions whereas conventional antidepressants are thought to work by increasing bias to positive emotional cues and decreasing bias to negative ones.
These data suggest that intake of Bio-Kult® Advanced has an effect on mood and that this is achieved in ways distinct from the effects of pharmacological antidepressants. While more research is needed, these results suggest that certain probiotics could form part of an ‘early intervention’ strategy for people experiencing low mood. A second randomised controlled trial (currently recruiting) will provide data on this intervention in patients with a formal diagnosis of depression undergoing concurrent pharmacological treatment.
Early reporting of atypical symptoms following a mild traumatic brain injury (mTBI) may be an early indicator of poor prognosis. This study aimed to determine the percentage of people reporting atypical symptoms 1-month post-mTBI and explore links to recovery 12 months later in a community-dwelling mTBI sample.
Adult participants (>16 years) who had experienced a mTBI were identified from a longitudinal incidence study (BIONIC). At 1-month post-injury, 260 participants completed the Rivermead Post-Concussion Symptoms Questionnaire (typical symptoms) plus four atypical symptom items (hemiplegia, difficulty swallowing, digestion problems and difficulties with fine motor tasks). At 12 months post-injury, 73.9% (n = 193) rated their overall recovery on a 100-point scale. An ordinal regression explored the association between atypical symptoms at 1 month and recovery at 12 months post-injury (low = 0–80, moderate = 81–99 and complete recovery = 100), whilst controlling for age, sex, rehabilitation received, ethnicity, mental and physical comorbidities and additional injuries sustained at the time of injury.
At 1-month post-injury <1% of participants reported hemiplegia, 5.4% difficulty swallowing, 10% digestion problems and 15.4% difficulties with fine motor tasks. The ordinal regression model revealed atypical symptoms were not significant predictors of self-rated recovery at 12 months. Older age at injury and higher typical symptoms at 1 month were independently associated with poorer recovery at 12 months, p < 0.01.
Atypical symptoms on initial presentation were not linked to global self-reported recovery at 12 months. Age at injury and typical symptoms are stronger early indicators of longer-term prognosis. Further research is needed to determine if atypical symptoms predict other outcomes following mTBI.
Impaired olfaction may be a biomarker for early Lewy body disease, but its value in mild cognitive impairment with Lewy bodies (MCI-LB) is unknown. We compared olfaction in MCI-LB with MCI due to Alzheimer’s disease (MCI-AD) and healthy older adults. We hypothesized that olfactory function would be worse in probable MCI-LB than in both MCI-AD and healthy comparison subjects (HC).
Cross-sectional study assessing olfaction using Sniffin’ Sticks 16 (SS-16) in MCI-LB, MCI-AD, and HC with longitudinal follow-up. Differences were adjusted for age, and receiver operating characteristic (ROC) curves were used for discriminating MCI-LB from MCI-AD and HC.
Participants were recruited from Memory Services in the North East of England.
Thirty-eight probable MCI-LB, 33 MCI-AD, 19 possible MCI-LB, and 32HC.
Olfaction was assessed using SS-16 and a questionnaire.
Participants with probable MCI-LB had worse olfaction than both MCI-AD (age-adjusted mean difference (B) = 2.05, 95% CI: 0.62–3.49, p = 0.005) and HC (B = 3.96, 95% CI: 2.51–5.40, p < 0.001). The previously identified cutoff score for the SS-16 of ≤ 10 had 84% sensitivity for probable MCI-LB (95% CI: 69–94%), but 30% specificity versus MCI-AD. ROC analysis found a lower cutoff of ≤ 7 was better (63% sensitivity for MCI-LB, with 73% specificity vs MCI-AD and 97% vs HC). Asking about olfactory impairments was not useful in identifying them.
MCI-LB had worse olfaction than MCI-AD and normal aging. A lower cutoff score of ≤ 7 is required when using SS-16 in such patients. Olfactory testing may have value in identifying early LB disease in memory services.
Dopaminergic imaging is an established biomarker for dementia with Lewy bodies, but its diagnostic accuracy at the mild cognitive impairment (MCI) stage remains uncertain.
To provide robust prospective evidence of the diagnostic accuracy of dopaminergic imaging at the MCI stage to either support or refute its inclusion as a biomarker for the diagnosis of MCI with Lewy bodies.
We conducted a prospective diagnostic accuracy study of baseline dopaminergic imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computerised tomography (123I-FP-CIT SPECT) in 144 patients with MCI. Images were rated as normal or abnormal by a panel of experts with access to striatal binding ratio results. Follow-up consensus diagnosis based on the presence of core features of Lewy body disease was used as the reference standard.
At latest assessment (mean 2 years) 61 patients had probable MCI with Lewy bodies, 26 possible MCI with Lewy bodies and 57 MCI due to Alzheimer's disease. The sensitivity of baseline FP-CIT visual rating for probable MCI with Lewy bodies was 66% (95% CI 52–77%), specificity 88% (76–95%) and accuracy 76% (68–84%), with positive likelihood ratio 5.3.
It is over five times as likely for an abnormal scan to be found in probable MCI with Lewy bodies than MCI due to Alzheimer's disease. Dopaminergic imaging appears to be useful at the MCI stage in cases where Lewy body disease is suspected clinically.
Adolescents living with HIV (ALHIV) experience a high burden of mental health disorder which is a barrier to antiretroviral therapy adherence. In Zimbabwe, trained, mentored peer supporters living with HIV (Community Adolescent Treatment Supporters – CATS) have been found to improve adherence, viral suppression and psychosocial well-being among ALHIV. The Friendship Bench is the largest integrated mental health programme in Africa. We hypothesise that combining the CATS programme and Friendship Bench will improve mental health and virological suppression among ALHIV compared with the CATS programme alone.
We will conduct a cluster-randomised controlled trial in 60 clinics randomised 1:1 in five provinces. ALHIV attending the control arm clinics will receive standard CATS support and clinic support following the Ministry of Health guidelines. Those attending the intervention arm clinics will receive Friendship Bench problem-solving therapy, delivered by trained CATS. Participants with the signs of psychological distress will be referred to the clinic for further assessment and management. The primary outcome is HIV virological failure (≥1000 copies/ml) or death at 48 weeks. Secondary outcomes include the proportion of adolescents with common mental disorder symptoms (defined as Shona Symptom Questionnaire (SSQ-14) score ≥8), proportion with depression symptoms (defined as Patient Health Questionnaire (PHQ-9) score ≥11), symptom severity (mean SSQ-14 and PHQ-9 scores) and EQ-5D score for health-related quality of life.
This trial evaluates the effectiveness of peer-delivery of mental health care on mental health and HIV viral load among ALHIV. If effective this intervention has the potential to be scaled-up to improve these outcomes.
Trial registration: PACTR201810756862405. 08 October 2018.
Emerging data suggest that recovery from mild traumatic brain injury (mTBI) takes longer than previously thought. This paper examines trajectories for cognitive recovery up to 48 months post-mTBI, presenting these visually using a Sankey diagram and growth curve analysis.
This sample (n = 301) represents adults (≥16 years) from a population-based Brain Injury Outcomes in the New Zealand Community study over a 4-year follow-up on the CNS-Vital Signs neuropsychological test. Data were collected within 2 weeks of injury, and then at 1, 6, 12 and 48 months post-injury.
Significant improvement in cognitive functioning was seen up to 6 months post-injury. Using growth curve modelling, we found significant improvements in overall neurocognition from baseline to 6 months, on average participants improved one point per month (0.9; 95% CI 0.42–1.39) p < 0.001. No change in neurocognition was found within the time periods 6–12 months or 12–48 months. The Sankey highlighted that at each time point, a small proportion of participants remained unchanged or declined. Proportionally, few show any improvement after the first 6 months.
Most individuals remained stable or improved over time to 6 months post-injury. Summary statistics are informative regarding overall trends, but can mask differing trajectories for recovery. The Sankey diagram indicates that not all improve, as well as the potential impact of individuals moving in and out of the study. The Sankey diagram also indicated the level of functioning of those most likely to withdraw, allowing targeting of retention strategies.
The impact of traumatic brain injury (TBI) extends beyond the person who was injured. Family caregivers of adults with moderate to severe TBI frequently report increased burden, stress and depression. Few studies have examined the well-being of family members in the mild TBI population despite the latter representing up to 95% of all TBIs.
Five areas of well-being were examined in 99 family members (including parents, partners, siblings, other relatives, adult children, friends or neighbours) of adults (aged ≥16 years) with mild TBI. At 6- and 12-month post-injury, family members completed the Bakas Caregiver Outcomes Scale, Short Form-36 Health Survey, EQ-5D-3L, Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. Outcomes and change over time and associated factors were examined.
At 6 months, group mean scores for health-related quality of life for mental and physical components and overall health status were similar to the New Zealand (NZ) population. Mean scores for sleep, anxiety and depression were below clinically significant thresholds. From 6 to 12 months, there were significant improvements in Bakas Caregiver Outcomes Scale scores by 2.61 (95% confidence interval: 0.72–4.49), health-related quality of life (mental component) and EQ-5D-3L overall health (P = 0.01). Minimally clinically important differences were observed in overall health, anxiety, health-related quality of life and depression at 12 months. Female family members reported significant improvements in physical health over time, and more positive life changes were reported by those caring for males with TBI.
The findings suggest diminished burden over time for family members of adults with mild TBI.
Objective: To identify the systems available to sub-classify mild traumatic brain injury (TBI) and to determine their utility in predicting 1-year outcome.
Methods: A systematic review to identify mild-TBI sub-classification systems was conducted until March 2016. The identified systems were applied to a cohort of N = 290 adults who had experienced a mild-TBI, and who had been assessed for post-concussion symptoms 1-year post injury. ANOVAs and regression models were used to determine whether each sub-classification system could distinguish between outcomes and to explore their contribution to explaining variance in post-concussion symptoms 1-year post injury.
Results: Nineteen sub-classification systems for mild-TBI met the inclusion criteria for this review. The Saal (1991) classification system significantly differentiated the experience of post-concussion symptoms in our cohort 1-year post injury (F = 2.39, p = 0.05). However, the findings did not remain significant following correction for multiple comparisons and inclusion of socio-demographic and contextual factors in the regression model.
Conclusions: Current sub-classification systems fail to explain much of the variance in post-concussion symptoms 1 year following mild-TBI. Further research is needed to identify the factors (including socio-demographic and contextual factors) to determine, who may be at risk of developing persistent post-concussion symptoms.
Background: Depression and anxiety are the two most frequently studied emotional outcomes of stroke. However, few previous studies have been carried out at a population level or beyond 6 months post stroke. The aim of this study was to describe depression and anxiety across the first year following incident ischemic stroke (IS), and identify predictive factors in a population-based study.
Method: The Hospital Anxiety Depression Scale (HADS) was administered at baseline (within 2 weeks of onset), and again at 1-month, 6-months and 12-months after IS in a sample (N = 365) drawn from a population-based study.
Results: Over 75% of those assessed experienced depression or anxiety symptoms below cut-offs for probable disorder across the year post stroke. Moderate to severe symptoms for anxiety were approximately twice as likely (range 4.1%–10.6%) as compared to depression (range 2.5%–5.0%) at each assessment. The greatest improvement in anxiety occurred within the first month post stroke. In contrast, the greatest reduction in depression occurred between 1- to 6-months post stroke.
Conclusions: Anxiety symptoms in the moderate to severe range were twice as common as depression, and improved over the first month post stroke, whilst depression symptoms persisted for up to 6 months, indicating a need to target these two issues at different points in the recovery process.
Background: Neuropsychological deficits occur in over half of the stroke survivors and are associated with the reduced functioning and a decline in quality of life. However, the trajectory of recovery and predictors of neuropsychological outcomes over the first year post stroke are poorly understood.
Method: Neuropsychological performance, assessed using the CNS-Vital signs, was examined at 1 month, 6 months and 12 months after ischaemic stroke (IS) in a sample drawn from a population-based study (N = 198).
Results: While mean scores across neuropsychological domains at each time-point fell in the average range, one in five individuals produced very low-range scores for verbal memory, attention and psychomotor speed. Significant improvements were seen for executive functioning, psychomotor speed and cognitive flexibility within 6 months post stroke, but no gains were noted from 6 to 12 months. Stroke-related neurological deficits and depression at baseline significantly contributed to the prediction of neuropsychological function at 12 month follow-up.
Conclusions: In a significant minority of IS survivors, focal deficits are evident in psychomotor speed, verbal memory, executive functions and attention. Significant improvements in these domains were only evident in the first 6 months post stroke. Initial stroke-related neurological deficits and concurrent depression may be the best predictors of later cognitive functioning.
This chapter brings together all the previous ones. Based on the detailed presentation and analysis of the MRV requirements of so many different carbon pricing and management mechanisms – hereafter “carbon pricing mechanisms,” it synthesizes and compares how they answered to the five cross-cutting questions identified in the general introduction to the book:
• What are the MRV requirements?
• What are the costs for entities to meet these requirements?
• Is a flexible trade-off between requirements and costs allowed?
• Is requirements stringency adapted to the amount of emissions at stake (materiality)?
• What is the balance between comparability and information relevance?
MRV requirements across schemes
The first cross-cutting question – what are the MRV requirements? – is too large to be answered in a synthetic way. This section thus focuses on two components of this question that have a major impact on MRV costs: requirements pertaining to third-party verification and those pertaining to monitoring uncertainty.
Verification requirements are broadly similar across the board
Most carbon pricing mechanisms impose a verification of the reports by an independent third party. Verification requirements are broadly similar across carbon pricing mechanisms:
• the third party must be accredited by a regulator for GHG emissions audits and this accreditation tends to be sector-specific;
• the third party must assess whether the methods used and the reporting format comply with the relevant guidelines;
• the third party must assess the accuracy, i.e., the absence of bias, of the reported figures;
• the regulator is allowed to question the opinion of the auditor, but seldom does so;• the third party tends to be paid directly by the verified entity. Although this creates a potential conflict of interest, the risk of losing the accreditation is a much stronger incentive and keeps auditors from being complacent with their client (Cormier and Bellassen, 2013).
We must begin with names. ‘Tony Edwards’ is the person to whom this volume is dedicated, but it is not a name that everyone will immediately recognize, particularly those who know him only from his published work, for he has made himself known in public, from the first, as A. S. G. Edwards. When he began his career, this was the manner in which most scholars, most men at least, named themselves. Fashions have changed, and given names, one, two, or more, are now almost universal. But Tony has held on tenaciously to his initials, perhaps because he has three of them. We do not believe that he did so in any spirit of emulation of or desire to align himself with ‘Edwards A. S. G.’, the Edwards Active Strain Gauge well known to Google, an advanced form of technical engineering equipment which guarantees the vacuum conditions needed for the manufacture of certain precision instruments, such as aircraft engine turbine blades. It seems strangely apt as an analogous form of ‘A. S. G.’, whether one thinks of the ‘active strain’ involved as what he exerts upon himself or upon other people. The analogy fails, of course, when one comes to the creation of vacuum, where it works back to front, for Tony's work has essentially been to fill the vacuum that once existed in the study of manuscript history.