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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.
Method:
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).
Results:
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).
Conclusions:
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.
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).
Design:
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.
Setting:
Participants were recruited from Memory Services in the North East of England.
Participants:
Thirty-eight probable MCI-LB, 33 MCI-AD, 19 possible MCI-LB, and 32HC.
Measurements:
Olfaction was assessed using SS-16 and a questionnaire.
Results:
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.
Conclusions:
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.
Initiatives to optimise preconception health are emerging following growing recognition that this may improve the health and well-being of women and men of reproductive age and optimise health in their children. To inform and evaluate such initiatives, guidance is required on indicators that describe and monitor population-level preconception health. We searched relevant databases and websites (March 2021) to identify national and international preconception guidelines, recommendations and policy reports. These were reviewed to identify preconception indicators. Indicators were aligned with a measure describing the prevalence of the indicator as recorded in national population-based data sources in England. From 22 documents reviewed, we identified 66 indicators across 12 domains. Domains included wider (social/economic) determinants of health; health care; reproductive health and family planning; health behaviours; environmental exposures; cervical screening; immunisation and infections; mental health, physical health; medication and genetic risk. Sixty-five of the 66 indicators were reported in at least one national routine health data set, survey or cohort study. A measure of preconception health assessment and care was not identified in any current national data source. Perspectives from three (healthcare) professionals described how indicator assessment and monitoring may influence patient care and inform awareness campaign development. This review forms the foundation for developing a national surveillance system for preconception health in England. The identified indicators can be assessed using national data sources to determine the population’s preconception needs, improve patient care, inform and evaluate new campaigns and interventions and enhance accountability from responsible agencies to improve preconception health.
Dopaminergic imaging is an established biomarker for dementia with Lewy bodies, but its diagnostic accuracy at the mild cognitive impairment (MCI) stage remains uncertain.
Aims
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.
Method
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.
Results
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.
Conclusions
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.
Recently published diagnostic criteria for mild cognitive impairment with Lewy bodies (MCI-LB) include five neuropsychiatric supportive features (non-visual hallucinations, systematised delusions, apathy, anxiety and depression). We have previously demonstrated that the presence of two or more of these symptoms differentiates MCI-LB from MCI due to Alzheimer's disease (MCI-AD) with a likelihood ratio >4. The aim of this study was to replicate the findings in an independent cohort.
Methods
Participants ⩾60 years old with MCI were recruited. Each participant had a detailed clinical, cognitive and imaging assessment including FP-CIT SPECT and cardiac MIBG. The presence of neuropsychiatric supportive symptoms was determined using the Neuropsychiatric Inventory (NPI). Participants were classified as MCI-AD, possible MCI-LB and probable MCI-LB based on current diagnostic criteria. Participants with possible MCI-LB were excluded from further analysis.
Results
Probable MCI-LB (n = 28) had higher NPI total and distress scores than MCI-AD (n = 30). In total, 59% of MCI-LB had two or more neuropsychiatric supportive symptoms compared with 9% of MCI-AD (likelihood ratio 6.5, p < 0.001). MCI-LB participants also had a significantly greater delayed recall and a lower Trails A:Trails B ratio than MCI-AD.
Conclusions
MCI-LB is associated with significantly greater neuropsychiatric symptoms than MCI-AD. The presence of two or more neuropsychiatric supportive symptoms as defined by MCI-LB diagnostic criteria is highly specific and moderately sensitive for a diagnosis of MCI-LB. The cognitive profile of MCI-LB differs from MCI-AD, with greater executive and lesser memory impairment, but these differences are not sufficient to differentiate MCI-LB from MCI-AD.
Lewy body dementia, consisting of both dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is considerably under-recognised clinically compared with its frequency in autopsy series.
Aims
This study investigated the clinical diagnostic pathways of patients with Lewy body dementia to assess if difficulties in diagnosis may be contributing to these differences.
Method
We reviewed the medical notes of 74 people with DLB and 72 with non-DLB dementia matched for age, gender and cognitive performance, together with 38 people with PDD and 35 with Parkinson's disease, matched for age and gender, from two geographically distinct UK regions.
Results
The cases of individuals with DLB took longer to reach a final diagnosis (1.2 v. 0.6 years, P = 0.017), underwent more scans (1.7 v. 1.2, P = 0.002) and had more alternative prior diagnoses (0.8 v. 0.4, P = 0.002), than the cases of those with non-DLB dementia. Individuals diagnosed in one region of the UK had significantly more core features (2.1 v. 1.5, P = 0.007) than those in the other region, and were less likely to have dopamine transporter imaging (P < 0.001). For patients with PDD, more than 1.4 years prior to receiving a dementia diagnosis: 46% (12 of 26) had documented impaired activities of daily living because of cognitive impairment, 57% (16 of 28) had cognitive impairment in multiple domains, with 38% (6 of 16) having both, and 39% (9 of 23) already receiving anti-dementia drugs.
Conclusions
Our results show the pathway to diagnosis of DLB is longer and more complex than for non-DLB dementia. There were also marked differences between regions in the thresholds clinicians adopt for diagnosing DLB and also in the use of dopamine transporter imaging. For PDD, a diagnosis of dementia was delayed well beyond symptom onset and even treatment.
Human movement constitutes a fundamental part of the archaeological process, and of any interpretation of a site's usage; yet there has to date been little or no consideration of how movement observed (in contemporary situations) and inferred (in archaeological reconstruction) can be documented. This paper reports on the Motion in Place Platform project, which seeks to use motion capture hardware and data to test human responses to Virtual Reality (VR) environments and their real-world equivalents using round houses of the Southern British Iron Age which have been both modelled in 3D and reconstructed in the present day as a case study. This allows us to frame questions about the assumptions which are implicitly hardwired into VR presentations of archaeology and cultural heritage in new ways. In the future, this will lead to new insights into how VR models can be constructed, used and transmitted.
Experimental archaeology is often cited as an important asset in the study of human interaction with material culture, especially in remote periods of history where there are few other sources of data on the human interventions which constitute the archaeological record. This has found many expressions in the discourse of archaeological theory, including the so-called chaîne opératoire, or ‘operational sequence’ theory (see e.g. Bar-Yosef and Van Peer 2009). However, due to an understandable desire to adhere to empirical evidence, means of inferring the human movement behind those interventions are rarely considered in the computational reconstruction of archaeological environments. The most obvious reason for this is that buildings, features and artefacts can be understood and reconstructed (whether digitally or not) from empirical archaeological remains, whereas there is little or no direct evidence for how people might have looked and moved through the spaces they created. Approaches which seek to go beyond this are methodologically fraught, resulting in a limitation of the scope of 3D reconstruction, both as a tool for archaeological research and as means of presenting cultural heritage to the public. The impact on the user's experience of those reconstructions is also limited. In a review of 3D visualization in archaeology, Gillings states: ‘[I]t is worth noting that one of the most striking things about archaeological Virtualmodels is the lack of people in them.
Relative quantitative RT-PCR and western blotting were used to investigate the expression of three genes with potentially regulatory functions from the arbuscular mycorrhizal fungus Glomus intraradices in symbiosis with tomato and barley. Standardisation of total RNA per sample and determination of different ratios of plant and fungal RNA in roots as colonisation proceeded were achieved by relative quantitative RT-PCR using universal (NS1/NS21) and organism-specific rRNA primers. In addition, generic primers were designed for amplification of plant or fungal β-tubulin genes and for plant glyceraldehyde-3-phosphate dehydrogenase (GAPDH) genes as these have been suggested as useful controls in symbiotic systems. The fungal genes Ginmyc1 and Ginhb1 were expressed only in the external mycelium and not in colonised roots at both mRNA and protein levels, with the proteins detected almost exclusively in the insoluble fractions. In contrast, mRNA of Ginmyc2 was identified in both external and intraradical mycelium. In mycorrhizal roots, Ginmyc2 and fungal β-tubulin mRNAs increased in proportion to fungal rRNA as colonisation proceeded, suggesting that accumulation reflected intraradical fungal growth. Fungal α-tubulin protein and β-tubulin mRNA both appeared to be more abundantly accumulated in AM hyphae within heavily colonised roots than in external hyphae, relative to fungal rRNA. Tomato GAPDH mRNA accumulation was proportional to tomato rRNA, but accumulation of tomato β-tubulin mRNA was reduced in colonised roots compared to non-mycorrhizal roots. These results provide novel evidence of differential spatial and temporal regulation of AM fungal genes, indicate that the expression of tubulin genes of both plant and fungus may be regulated during colonisation and validate the use of multiple ‘control’ genes in analysis of mycorrhizal gene expression.
A molecular study of the mycorrhizal symbiosis between barley and Glomus intraradices used differential display PCR and a
synchronous colonization method to identify genes that are differentially expressed in symbiosis. Several PCR products were
consistently differentially amplified. PCR amplification of genomic DNA from either G. intraradices or barley as templates showed
that three such products were encoded by G. intraradices. Sequence analysis of the deduced amino acid sequences of the fungal
fragments, following extension by 3′-RACE, revealed similarities to proteins from higher eukaryotes. One (GINMYC1) shows
similarity to TRIP15, a human protein that interacts in a hormone-dependent manner with the thyroid receptor. A second
(GINMYC2) is similar to O-linked N-acetylglucosamine transferases from vertebrates, and the third (GINHB1) contains a putative
leucine zipper and a homeodomain which indicates that it binds DNA and may act as a transcriptional regulator. Fragments of the
expected sizes were amplified by RT–PCR from mRNA of mycorrhizal barley roots for all three fungal cDNAs, which indicates that
the corresponding genes are expressed during intraradical growth of G. intraradices. The results provide a promising insight to fungal
gene expression early in formation of this compatible and mutualistic symbiosis.
In vesicular–arbuscular mycorrhizal symbioses, specialized fungal structures (the arbuscules) are formed which
are in intimate contact with plant root cortical cells. It is assumed that these arbuscules are the major sites of solute
transfer between the plant and fungus, but there have been no studies that definitively show the extent or types
of transfer processes that occur in this structure. Phosphate is one of the major nutrients that is acquired by
mycorrhizal fungi and transferred to plants. In this study a single Lycopersicon esculentum cDNA was cloned and
shown to be identical to LePT1, a previously cloned inorganic-phosphate transporter. Expression studies revealed
that LePT1 transcript levels remained constant in mycorrhizal plants, but increased in phosphate-starved, non-mycorrhizal plants. Localization of the LePT1 transcript by in situ hybridization showed that this gene is highly
expressed in arbuscule-containing cortical cells in mycorrhizal plants. In non-mycorrhizal plants LePT1
expression was localized to the stele and cortex. The expression studies suggest that this transporter is involved
in phosphate nutrition of L. esculentum and its localization in cells that contain arbuscules indicate that it may be
the mechanism used by the plant to take up phosphate that is effluxed across the fungal plasma membrane of the
arbuscule. Based on our findings and those of others, an integrated model of inorganic phosphate uptake and
transfer in mycorrhizal and non-mycorrhizal plants is presented.
A diet low in fat and rich in fibre has been recommended to optimize general health and in particular cardiovascular health. Health attitudes to fat and fibre were studied in relation to food and nutrient intake and sociocultural and lifestyle factors amongst the general population of Northern Ireland. The study population comprised 592 adults aged 16–64 years; health attitudes to fat and fibre were assessed by questionnaire (based on a social psychological model, which adjusted for taste and convenience factors). Dietary intake was estimated using the weighed inventory technique. Fat-phobic and fibre-philic attitudes were more prevalent in women than men. Fat-phobic attitudes in women were inversely related to intake of fat through a reduced intake of chips, butter and sausages. In contrast, men's fat-phobic attitudes were not strongly correlated with fat intake; consumption of chips and sausages was negatively associated with fat-phobic attitudes, but cake/biscuit, buns/pastries and milk consumption was positively associated with fat-phobic attitudes. Fibre-philic attitudes were positively associated with dietary fibre intake; intakes of potatoes, vegetables, wholemeal bread and breakfast cereal were positively associated with fibre-philic attitudes. There were clear sociocultural and lifestyle differences in relation to dietary attitude. These findings have implications for campaigns designed to effect population dietary change.
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