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The criteria for objective memory impairment in mild cognitive impairment (MCI) are vaguely defined. Aggregating the number of abnormal memory scores (NAMS) is one way to operationalise memory impairment, which we hypothesised would predict progression to Alzheimer’s disease (AD) dementia.
As part of the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing, 896 older adults who did not have dementia were administered a psychometric battery including three neuropsychological tests of memory, yielding 10 indices of memory. We calculated the number of memory scores corresponding to z ≤ −1.5 (i.e., NAMS) for each participant. Incident diagnosis of AD dementia was established by consensus of an expert panel after 3 years.
Of the 722 (80.6%) participants who were followed up, 54 (7.5%) developed AD dementia. There was a strong correlation between NAMS and probability of developing AD dementia (r = .91, p = .0003). Each abnormal memory score conferred an additional 9.8% risk of progressing to AD dementia. The area under the receiver operating characteristic curve for NAMS was 0.87 [95% confidence interval (CI) .81–.93, p < .01]. The odds ratio for NAMS was 1.67 (95% CI 1.40–2.01, p < .01) after correcting for age, sex, education, estimated intelligence quotient, subjective memory complaint, Mini-Mental State Exam (MMSE) score and apolipoprotein E ϵ4 status.
Aggregation of abnormal memory scores may be a useful way of operationalising objective memory impairment, predicting incident AD dementia and providing prognostic stratification for individuals with MCI.
Early detection of Alzheimer's disease is vital for developing novel treatments. Attempts to identify the intermediate state between normal cognition and dementia have evolved over the past 50 years. Current taxonomies of mild cognitive impairment (MCI) may be criticised for their imprecise operationalisation. With the advent of biomarkers such as amyloid-beta positron emission tomography imaging in established Alzheimer's disease, much research has focused on establishing which factors predict progression from MCI to Alzheimer's disease dementia. In this review, we discuss the historical context of MCI before reviewing the literature of MCI subtypes and their risk of progression to Alzheimer's disease dementia. Finally, we summarise the literature and discuss limitations and weaknesses of how the construct is operationalised and implemented, before offering suggestions for development of the concept of MCI. We conclude that MCI must be empirically defined for the sake of its predictive validity to identify Alzheimer's disease before dementia develops.
To describe trends of childhood stunting among under-5s in Uganda and to assess the impact of maternal education, wealth and residence on stunting.
Serial and pooled cross-sectional analyses of data from Uganda Demographic and Health Surveys (UDHS) of 1995, 2001, 2006 and 2011. Prevalence of stunting and mean height-for-age Z-score were computed by maternal education, wealth index, region and other sociodemographic characteristics. Multivariable logistic and linear regression models were fitted to survey-specific and pooled data to estimate independent associations between covariates and stunting or Z-score. Sampling weights were applied in all analyses.
Children aged <5 years.
Weighted sample size was 14 747 children. Stunting prevalence decreased from 44·8% in 1995 to 33·2% in 2011. UDHS reported stunting as 38% in 1995, underestimating the decline because of transitioning from National Center for Health Statistics/Centers for Disease Control and Prevention standards to WHO standards. Nevertheless, one in three Ugandan children was still stunted by 2011. South Western, Mid Western, Kampala and East Central regions had highest odds of stunting. Being born in a poor or middle-income household, of a teen mother, without secondary education were associated with stunting. Other persistent stunting predictors included small birth size, male gender and age 2–3 years.
Sustained decrease in stunting suggests that child nutrition interventions have been successful; however, current prevalence does not meet Millennium Development Goals. Stunting remains a public health concern and must be addressed. Customizing established measures such as female education and wealth creation while targeting the most vulnerable groups may further reduce childhood stunting.
The causative agent of urogenital schistosomiasis, Schistosoma haematobium, was thought to be the only schistosome species transmitted through Bulinus snails on Unguja and Pemba Island (Zanzibar, United Republic of Tanzania). For insights into the environmental risk of S. haematobium transmission on Pemba Island, malacological surveys collecting Bulinus globosus and B. nasutus, two closely related potential intermediate hosts of S. haematobium were conducted across the island in November 2016. Of 1317 B. globosus/B. nasutus collected, seven B. globosus, identified through sequencing a DNA region of the mitochondrial cytochrome oxidase subunit 1 (cox1), were observed with patent infections assumed to be S. haematobium. However, when the collected cercariae were identified through sequencing a region of the cox1 and the nuclear internal transcribed spacer (ITS1 + 2), schistosomes from five of these B. globosus collected from a single locality were in fact S. bovis. The identified presence of S. bovis raises concerns for animal health on Pemba, and complicates future transmission monitoring of S. haematobium. These results show the pertinence for not only sensitive, but also species-specific markers to be used when identifying cercariae during transmission monitoring, and also provide the first molecular confirmation for B. globosus transmitting S. bovis in East Africa.
The Richtmyer–Meshkov instability (RMI) is experimentally investigated in a vertical shock tube using a broadband initial condition imposed on an interface between a helium–acetone mixture and argon (Atwood number
). In the present work, a shear layer is introduced at the interface to serve as a statistically repeatable, broadband initial condition to the RMI, and the density interface is accelerated by either an
planar shock wave. The development of the ensuing mixing layer is investigated using simultaneous planar laser-induced fluorescence (PLIF) and particle image velocimetry (PIV). PLIF images are processed to reveal the light-gas mole fraction, while PIV particle image pairs yield corresponding two-component planar velocity results. Field structure and distribution are explored through probability density functions (PDFs), and a decomposition is performed on concentration and velocity results to obtain a mean flow field and define fluctuations. Simultaneous concentration and velocity field measurements allow – for the first time in this regime – experimentally determined turbulence quantities such as Reynolds stresses, turbulent mass-flux velocities and turbulent kinetic energy to be obtained. We show that by the latest times the mixing layer has passed the turbulent threshold, and there is evidence of turbulent mixing occurring sooner for the higher Mach number case. Interface measurements show nonlinear growth with a power-law fit to the thickness data, and that integral measurements of mixing layer thickness are proportional to threshold measurements. Spectral analysis demonstrates the emergence of an inertial range with a slope
when considering both density and velocity effects in planar turbulent kinetic energy (TKE) measurements.
Adult schistosomes live in the blood vessels and cannot easily be sampled from humans, so archived miracidia larvae hatched from eggs expelled in feces or urine are commonly used for population genetic studies. Large collections of archived miracidia on FTA cards are now available through the Schistosomiasis Collection at the Natural History Museum (SCAN). Here we describe protocols for whole genome amplification of Schistosoma mansoni and Schistosome haematobium miracidia from these cards, as well as real time PCR quantification of amplified schistosome DNA. We used microgram quantities of DNA obtained for exome capture and sequencing of single miracidia, generating dense polymorphism data across the exome. These methods will facilitate the transition from population genetics, using limited numbers of markers to population genomics using genome-wide marker information, maximising the value of collections such as SCAN.
Recent evidence suggests that exercise plays a role in cognition and that the posterior cingulate cortex (PCC) can be divided into dorsal and ventral subregions based on distinct connectivity patterns.
To examine the effect of physical activity and division of the PCC on brain functional connectivity measures in subjective memory complainers (SMC) carrying the epsilon 4 allele of apolipoprotein E (APOE 4) allele.
Participants were 22 SMC carrying the APOE ɛ4 allele (ɛ4+; mean age 72.18 years) and 58 SMC non-carriers (ɛ4–; mean age 72.79 years). Connectivity of four dorsal and ventral seeds was examined. Relationships between PCC connectivity and physical activity measures were explored.
ɛ4+ individuals showed increased connectivity between the dorsal PCC and dorsolateral prefrontal cortex, and the ventral PCC and supplementary motor area (SMA). Greater levels of physical activity correlated with the magnitude of ventral PCC–SMA connectivity.
The results provide the first evidence that ɛ4+ individuals at increased risk of cognitive decline show distinct alterations in dorsal and ventral PCC functional connectivity.
The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism Met allele exacerbates amyloid (Aβ) related decline in episodic memory (EM) and hippocampal volume (HV) over 36–54 months in preclinical Alzheimer's disease (AD). However, the extent to which Aβ+ and BDNF Val66Met is related to circulating markers of BDNF (e.g. serum) is unknown. We aimed to determine the effect of Aβ and the BDNF Val66Met polymorphism on levels of serum mBDNF, EM, and HV at baseline and over 18-months.
Non-demented older adults (n = 446) underwent Aβ neuroimaging and BDNF Val66Met genotyping. EM and HV were assessed at baseline and 18 months later. Fasted blood samples were obtained from each participant at baseline and at 18-month follow-up. Aβ PET neuroimaging was used to classify participants as Aβ– or Aβ+.
At baseline, Aβ+ adults showed worse EM impairment and lower serum mBDNF levels relative to Aβ- adults. BDNF Val66Met polymorphism did not affect serum mBDNF, EM, or HV at baseline. When considered over 18-months, compared to Aβ– Val homozygotes, Aβ+ Val homozygotes showed significant decline in EM and HV but not serum mBDNF. Similarly, compared to Aβ+ Val homozygotes, Aβ+ Met carriers showed significant decline in EM and HV over 18-months but showed no change in serum mBDNF.
While allelic variation in BDNF Val66Met may influence Aβ+ related neurodegeneration and memory loss over the short term, this is not related to serum mBDNF. Longer follow-up intervals may be required to further determine any relationships between serum mBDNF, EM, and HV in preclinical AD.
The paper on predictors of repeat self-harm and suicide by Cheung et al. (2017), which has been chosen by the editorial team as paper of the month for this issue of International Psychogeriatrics, makes a very useful contribution to the study of self-harm and suicide in late life. Of 339 individuals presenting with an index episode of self-harm to one of seven Emergency Departments (EDs) in New Zealand, close to 15% harmed themselves again within one year and for nearly one in six of these 50 people, the repeat episode was fatal. Having alcohol in the blood and already being engaged with mental health services at the time of the index episode both had some utility in predicting the occurrence of a further self-harm episode. While it is encouraging that mental health services look to have been focusing on those who turned out to be at highest risk, clinicians may need to be particularly vigilant when following up individuals who had been drinking alcohol at the time of an initial self-harm presentation. This study also emphasizes the high risk of recurrent self-harm and completed suicide in those older adults who harm themselves and survive the initial episode. It deserves to be widely cited and gives some direction for future research on interventions designed to diminish the recurrence of self-harm in those of our patients who have presented to an ED with an initial self-harm episode.
Fronto-temporal dementia (FTD) associated with Fused in Sarcoma (FUS) protein accumulation is an uncommon cause of FTD with a distinct syndrome of young age onset behavioral variant FTD, without a family history of FTD and caudate atrophy. We present a sporadic case of a 61-year-old patient with mixed features of both behavioral variant FTD with later semantic language dissolution associated with pathologically proven FUS. He was older than usual for FUS pathology, his course was rapidly progressive, and he had atypical language features. This case broadens the clinical spectrum caused by FUS-protein-related FTD.
Most people who work in aged care have a fair idea of what is meant by cognitive impairment or decline, and we have some moderately robust instruments for detecting it and measuring change over time. Frailty is much more difficult to define, but like hard core pornography (Stewart, 1964), many of us “know it when we see it.”
Over 20 years ago, the Australian Liberal/National Party Federal Opposition had a set of policies with which it hoped to persuade the Australian people to return it to government in the election due in 1996. This particular collection of proposed initiatives was called “The things that matter”. When the then leader of the opposition, Alexander Downer (later Australia's Foreign Minister 1996–2007 and now Australian High Commissioner in London), launched the Opposition's policy on family violence (the Coalition parties, like their Labor opponents, were and are against it in principle), his introductory line was: “From the things that matter to the things that batter”. Not long afterwards he lost his job as Opposition Leader, his engagement with what was and is a serious and troubling issue having been deemed too glib by half by the shapers of public opinion.