bluuebunny/crossref_metadata_2025_split huggingface dataset:
White matter integrity and types of memory complaints in mild cognitive impairment
Authors: Ryu Seon Young , Lee Sang Bong , Lee Taek Jun , Jung Yu Jin 
Published: December 2020

AbstractBackgroundMemory complaints are a frequent phenomenon in individuals with mild cognitive impairment (MCI). However, clinical significance for different types of memory complaints in MCI remains unclear. The aim of this study was to examine whether white matter (WM) integrity would be affected due to different aspects of memory complaints (i.e., prospective memory (PM) versus retrospective memory (RM) complaints) in individuals with MCI.MethodThe study included a total of 73 participants (mean age: 69.37 ± 7.40 years) with MCI. Memory complaints were assessed using the Prospective and Retrospective Memory Questionnaire (PRMQ) consisting of 16 items that describe everyday memory failure of both PM and RM. WM integrity was evaluated by anatomically defined regions of interest analysis using diffusion tensor imaging (DTI). The discrepancies regarding more PM or more RM complaints were assessed by the PM‐RM discrepancy scores (median = 1, range: −9–12) based on the PM and RM subscores of the PRMQ, and participants with more PM complaints (PRMQ‐PM score > PRMQ‐RM score) were compared to those with more RM complaints with regard to DTI‐derived WM fractional anisotropy (FA). The subjects with PM‐RM discrepancy scores of 0 or 1 were excluded from the group analyses.ResultMore PM complaints group (n = 34) had higher FA in the body of corpus callosum (p = 0.03), and a tendency to higher FA in the genu of corpus callosum (p = 0.08) and right entorhinal WM (p = 0.092) than more RM complaints group (n = 20).ConclusionRM complaints among subjective memory complaints might be associated with more alterations in WM integrity. This cross‐sectional study suggests that different types of memory complaints could affect WM microstructural alterations in individuals with MCI. To clarify our results, further investigations in larger samples are required.
Clinical phase I data of the first orally available anti‐aβ‐prionic drug PRI‐002 that reverses behavioral and cognitive deficits, and decelerates neurodegeneration in AD animal models
Authors: Willbold Dieter , Kutzsche Janine , Willuweit Antje , Windisch Manfred , Jürgens Dagmar 
Published: December 2020

AbstractBackgroundMore and more data suggest that the toxic protein assemblies of Aβ and TAU behave prion like. The drug candidate PRI‐002 has been developed to directly disassemble and destroy toxic Aβ oligomer prions. The anti‐prionic compound PRI‐002 (alias “RD2”) is BBB penetrable and has demonstrated target engagement in vitro and in vivo. Treatments in three different transgenic mouse models in three different laboratories yielded improved cognition and deceleration of neurodegeneration. Oral treatment of old‐aged transgenic AD mice with full‐blown pathology reversed cognitive and behavioral deficits to levels of healthy wild‐type littermates. We wanted to demonstrate safety and tolerability of PRI‐002 in healthy volunteers up to doses that are much higher than the expected therapeutic dose.MethodWe carried out a single (4 to 320 mg PRI‐002) and a multiple ascending dose (160 and 320 mg PRI‐002/volunteer) phase I clinical trial in 63 healthy volunteers.ResultNo drug‐related adverse events (AE) have been observed in the SAD study. The few possibly drug‐related AEs in the MAD study were equally distributed across groups. Already in the SAD, PRI‐002 plasma levels were reached (AUC0‐24 104 ng h/mL) that were measured in the highest dosed animals of the successful preclinical PoC studies.ConclusionDaily administered oral doses of PRI‐002 up to 320 mg/subject/day for 28 days have been proven to be safe. PoC studies in humans for anti‐prionic compounds may be based on shorter treatment durations and do not necessarily have to be life‐long.
The differential genetic architecture between posterior cortical atrophy and amnestic Alzheimer's disease
Authors: Scelsi Marzia Antonella , Napolioni Valerio , Mead Simon , Crutch Sebastian J. , Schott Jonathan M. , Greicius Michael D. , Altmann Andre ,   PCA Genetics Consortium and the National Alzheimer's Coordinating Center (NACC)
Published: December 2020

AbstractBackgroundPosterior cortical atrophy (PCA) is a rare early‐onset form of dementia, typically due to Alzheimer’s disease (PCA‐AD) characterised by predominant deficits of higher‐order visual functions, with relatively preserved memory, verbal fluency and insight with respect to typical, amnestic AD (tAD). A prior genetic study by Schott et al. (2016) investigated genetic risk factors for PCA‐AD in comparison to healthy controls; it also compared the magnitude of effect of known tAD risk loci in PCA. However, little is known about whether the difference between PCA‐AD and tAD is modulated by genetic factors outside the established tAD risk loci. Here we present the first large‐scale genetic study directly comparing PCA‐AD and tAD, in order to identify novel genetic variants driving the difference between these two syndromic variants.MethodWe imputed autosomal Single Nucleotide Polymorphism (SNP) data for 287 PCA‐AD cases from Schott et al. (2016) and 1,687 tAD cases from Naj et al. (2011), all unrelated Caucasians. We compared PCA to tAD cases in a genome‐wide association study (GWAS). SNP associations with diagnosis were tested through logistic regression, including sex, age‐at‐onset, and ten principal components of population structure as covariates. A sensitivity analysis was conducted omitting age‐at‐onset from the covariates, after detecting a significant difference in the mean age‐at‐onset of PCA and tAD cases (Table 1).ResultEleven independent genome‐wide significant loci were identified (Figure 1). APOE ε4 almost reached genome‐wide significance (p = 5.11 × 10−8). GWAS‐significant SNPs mapped to the following genes: MORN1, CNTNAP5, SPPL3, MARK3. The sensitivity analysis increased statistical power, with APOE ε4 and 6 additional loci reaching significance.ConclusionWe present the first GWAS of PCA vs tAD and identify five genes. In keeping with previous findings we confirm that APOE ε4 has a weaker effect in PCA than tAD, also showing that CNTNAP5 increases risk not only vs controls (Schott et al. 2016) but also over tAD. Of the new genes identified, SPPL3 is a presenilin‐like protein, and MARK3 is involved in the phosphorylation of tau proteins MAP2 and MAP4. These findings suggest that differential genetic factors may influence the development of AD, but also its phenotypic expression.
Assessing the generalizability of findings from the Alzheimer’s Disease Neuroimaging Initiative to the Atherosclerosis Risk in Communities study cohort
Authors: Power Melinda C , Bennett Erin , Glymour M Maria , Gianattasio Kan Z , Couper David , Mosley Thomas H , Gottesman Rebecca F , Griswold Michael E , Wei Jingkai , Mehrotra Megha , Stuart Elizabeth A 
Published: December 2020

AbstractBackgroundThe Alzheimer’s Disease Neuroimaging Initiative (ADNI) collects and shares high quality imaging, biomarker, genetic, and clinical data. Whether findings from ADNI generalize broadly is unclear, given its highly‐selected, predominantly white and well‐educated participants. We compared associations estimated in ADNI to those estimated in the Atherosclerosis Risk in Communities (ARIC) study, which initially recruited participants randomly from four US communities, to examine the potential generalizability of ADNI findings.MethodWe identified common risk factor, cognitive, and imaging variables at the ADNI screening/baseline visits and ARIC Visit 5. Data were pooled to estimate associations between risk factors and cognitive or imaging data, and between cognitive and imaging data, using adjusted linear and logistic regression models. Models included a term for cohort and its interaction with the variable of interest, allowing for cohort‐specific estimates and statistical evaluation of cohort differences. We repeated analyses on data subsets defined by race and cognition. Sensitivity analyses accounted for cohort differences in the impact of confounders by including cohort by covariate interactions.ResultThe proportion of estimated associations that differed significantly by cohort (interaction p‐value<.05) in primary analyses was 42% (range 25‐42% across subset and sensitivity analyses). Many differences were substantively meaningful (e.g. OR for APOE‐4 on amyloid positivity in ARIC: OR=2.75; in ADNI: OR=8.44; OR for any functional limitations on MMSE score < 25: OR = 5.05 (2.87 ‐ 8.90) in ADNI, OR = 1.34 (0.99 ‐ 1.81) in ARIC).ConclusionThe proportion of associations that differed significantly between ADNI and ARIC was substantially higher than would be expected by chance. Differences may stem from inherent differences in the populations from which participants were recruited. This has implications for the generalizability of highly selected samples, including deeply phenotyped samples typically used for biomarker research.
Amyloid angiopathy may contribute to white‐matter hyperintensities in Alzheimer’s disease
Authors: Xia Ying , Fazlollahi Amir , Yates Paul A. , Yassi Nawaf , Desmond Patricia M. , Salvado Olivier , Villemagne Victor L.L. , Rowe Christopher C. , Fripp Jurgen , Masters Colin L. , Raniga Parnesh 
Published: December 2020

AbstractBackgroundCerebral amyloid angiopathy (CAA) is characterised by the accumulation of amyloid‐b (Aβ) in cerebral vessels and is often coexistent with Alzheimer’s disease (AD). However, the overlap between CAA and AD and the contribution of CAA pathology to cerebrovascular lesions are not well understood. We hypothesize that in subjects with high Aβ load, the presence of imaging markers of CAA would be associated with greater white matter hyperintensities (WMH) burden.MethodData used in the preparation of this article was obtained from the Australian Imaging Biomarkers and Lifestyle flagship study of ageing (AIBL). See www.aibl.csiro.au. We analysed MRI (SWI and FLAIR) and 11C‐PiB‐PET data from 98 cognitively normal (CN), 34 mild‐cognitive impairment (MCI) and 38 AD participants. Subjects were classified as being Aβ+ if their Aβ load was above 20 centiloid.SWI images were manually read for lobar microbleeds (LMB) and superficial siderosis. Subjects were classified as probable‐CAA (PCAA, 2 or more LMB or siderosis), possible‐CAA (SCAA, single LMB or siderosis) or non‐CAA (NCAA) based on the modified Boston criteria. Subjects classified as SCAA (n = 24) were excluded from further analysis since literature shows this group to be heterogenous and having low incidence of CAA pathology. WMH were automatically quantified on FLAIR. Group comparisons of WMH load were made using Kruskal Wallis rank test. A GLM was performed comparing WMH (log10 transformed) and CAA/ Aβ+ classification with age, intracranial volume, gender, APOE‐ε4 genotype and use of anti‐platelet or anticoagulant medication modelled as covariates.ResultSignificantly higher WMH volume was observed in PCAA (n = 17) than NCAA (n = 129) (p‐value = 0.021, d = 0.36). When amyloid status was considered, PCAA/Aβ+ (n = 15) subjects had a significantly higher WMH load than NCAA/Aβ+ (n = 57) subjects (p‐value = 0.012, d = 0.57) and NCAA/Aβ‐ (n = 72) subjects (p‐value = 0.0006, d = 0.76) (Figure 1). PCAA/Aβ‐ (n = 2) were removed from further analysis. GLM results showed a significant association of WMH with PCAA/Aβ+ as compared to NCAA/Aβ+ (p‐value = 0.02, beta = 0.322 [0.056,0.588]).ConclusionOur findings suggest that CAA may contribute to WMH burden in subjects with high Aβ load. Further studies are required to validate our observations and characterise the contributions of CAA compared to small vessel disease associated with traditional risk factors towards the phenotype of AD.
A pilot randomized controlled trial on iSupport in India: Results on the use of the online program and its effectiveness
Authors: Baruah Upasana , Varghese Mathew , Loganathan Santosh , Mehta Kala , Gallagher‐Thompson Dolores , Zandi Diana , Dua Tarun , Pot Anne Margriet 
Published: December 2020

AbstractBackgroundThe World Health Organization’s online program ‘iSupport’ for family caregivers of people with dementia was adapted and pilot‐tested in India. Although there are promising outcomes of Internet‐based interventions in Western countries, there has hardly been any research on the use and effectiveness of such interventions in developing countries.MethodsCaregivers were recruited from multiple sources including physician referrals, advertisement and word‐of‐mouth. 338 caregivers were assessed for eligibility of which 187 were excluded in the trial. 151 caregivers were randomized to either the intervention group (iSupport; n=74) or the comparison group (web‐based education only; n=77). Of these, 29 caregivers in the iSupport group and 26 in the control condition completed the 3‐month follow‐up assessment. Linear regression analysis was carried out to analyze the data.ResultsOf the 151 randomized caregivers, 81 (54%) were male and 144 (95%) had a Bachelor’s degree or higher. In terms of caregiver relationship, the majority (60%) were adult children, followed by spouses (21%). No significant differences could be shown in the intervention and control conditions at 3‐month follow‐up on the primary outcomes depressive symptoms and feelings of burden. However, we did find a significant improvement in caregivers’ person‐centred attitude towards persons with dementia in the iSupport group.ConclusionAlthough no significant differences were found on the primary outcome measures, the significant improvement on person‐centredness of caregivers in the iSupport group is encouraging, since the number of participants and hence the power to find changes, was small. The difficulty in recruiting and retaining participants require closer attention and indicates need for further adaptations of the online iSupport programme. From this pilot study important lessons have been learned that will be discussed during the presentation and will guide further development of caregiver support in India.
Preparing the ground for the adaptation of iSupport in Switzerland
Authors: Fiordelli Maddalena , Albanese Emiliano 
Published: December 2020

AbstractBackgroundIn 2013, Switzerland developed a national dementia strategy, which entails the implementation of interventions for caregivers of people with dementia. iSupport, an online knowledge and skills training program purposely developed by the WHO holds the promise to respond to the complex and largely unmet needs of caregivers. There is evidence that online interventions can contribute to improve quality of care and caregivers’ wellbeing, but evidence to inform the implementation and scalability of iSupport is still extremely limited, We planned to seek funds, collaborate with local authorities, institutions, and stakeholders (including people with dementia and their informal caregivers) to locally adapt, pilot, test, and scale iSupport in selected Swiss cantons, and to pave the way to a formal monitoring of its implementation and effectiveness.MethodWe combined quantitative and qualitative methods in two preparatory studies: a pilot study aimed at testing the feasibility, acceptability, and accuracy of an innovative data capturing system to profile caregivers’ strain and needs, and care needs of people with dementia; a survey to assess the level of dementia knowledge, awareness and acceptance, and the willingness to participate in implementation research in a large sample of older adults.ResultData collection was feasible, well received, and efficient in a sample of caregivers of people with dementia (N=52). Strain was marked in all caregivers, who confirmed their interest in receiving a structured training to improve their understanding of dementia, and acquire competences and skills for care provision, and coping strategies. Of the 628 respondents to the survey, 47% considered dementia a normal part of aging, 95% considered research on support to family caregivers important or greatly important, and 45% declared their willingness to participate in a future study on this matter. Local authorities agreed (and committed) to mobilize resources and funds to support the implementation of iSupport, of its integration in existing health and social care services, and of appropriate indicators to monitor its use and impact.ConclusionEngaging local stakeholders, including local institutions and potential funders since the beginning of implementation research is feasible, and can contribute to address unmet needs of informal caregivers of people with dementia.
Hearing aid use and cognition in older adults: Can we delay decline or even improve cognitive function?
Authors: Sarant Julia , Harris David , Busby Peter , Maruff Paul T , Schembri Adrian , Phillips Jocelyn , Nixon Grace , Lemke Ulrike , Launer Stefan , Tomlin Dani , Dowell Richard 
Published: December 2020

AbstractBackgroundHearing loss is associated with accelerated cognitive decline in older adults, and has been identified as a modifiable risk factor for dementia. Although hearing aids are a successful treatment for hearing loss, it is unknown whether hearing aid use can delay the onset of cognitive decline or improve cognitive function in older adults with hearing loss. This prospective longitudinal study is investigating the effect of hearing aid use on cognitive decline and addresses many of the methodological limitations of previous studies.MethodPatients are recruited from the University of Melbourne Academic Hearing Aids Audiology Clinic and assessed before and every 18 months after hearing aid fitting. When numbers are sufficient, results will be compared with those of a control group of approximately 400 participants of a cohort study of ageing in older adults. Assessments include cognitive function (visually presented computerised assessment battery), hearing, speech perception, quality of life, activity, diet, loneliness and isolation, anxiety, depression, medical health and genetic risk.ResultAt baseline, multiple linear regression for 98 participants (62‐82 years), controlling for age, gender, cardiovascular conditions, education, and working/retired, with mean better ear PTA 31dB showed hearing loss and age predicted significantly poorer executive function, while tertiary education predicted significantly better executive function and visual learning. At 18‐month follow up, results for a subset of participants showed significant improvements in speech perception, listening disability and quality of life. Group mean scores across the cognitive assessment battery showed no significant decline and executive function was significantly improved. There was either clinically significant improvement or stability for executive function for over 97% of the subset, and for females for working memory, visual learning and visual attention, despite significantly greater hearing loss over this period.ConclusionDespite a small initial sample size, hearing loss, age and education significantly predicted baseline cognitive function. At 18‐month follow up, the majority of participants had either remained stable or demonstrated a meaningful clinical improvement in cognitive function, with significant group mean improvements for executive function and working memory. Treatment of hearing loss with hearing aids may delay cognitive decline. These are initial results, and further follow up is required.
Minocycline treatment effects on cognition, sleep, breathing and body temperature in a model for sporadic Alzheimer's disease
Authors: Vicente Mariane Cristine , Carrettiero Daniel , Almeida Maria Camila , Bícego Kênia Cardoso , Paneghini Julia de Lima , Batalhão Luciane Helena Gargaglioni 
Published: December 2020

AbstractBackgroundChronic inflammation plays an important role in the cascade of molecular events in the brain of patients with Alzheimer's disease (AD). Preclinical studies have shown that minocycline has a potent anti‐inflammatory effect exerted by its neuroprotective action in various neurodegenerative diseases, such as AD. Thus, we tested the hypothesis that minocycline treatment could reverse / minimize the cognitive and respiratory and sleep deficits of our sporadic AD model.MethodWe used as an animal model for sporadic Alzheimer’s disease (AD) induced by icv injection of streptozotocin (STZ) (2 mg/kg). After five consecutive days of daily dosing with minocycline (30 mg / kg, i.p) the animals were submitted to the experiments. We evaluated memory and learning by Barnes' maze (n = 12), ventilatory parameters during sleep and wakefulness by the whole body plethysmography method and sleep time by electroencephalography method. We evaluate body temperature also during all experiments.ResultThe minocycline treatment improved learning and memory of the STZ‐AD model (n = 12, p < 0.05). But it did not decrease the sensitivity of STZ‐AD model to CO2 ventilatory response during wakefulness Placebo (VE mean ± standard deviation: STZ‐AD = 2477.5 ± 514.8 mL. Kg−1. min−1 vs VE Placebo‐Vehicle = 2005.1 ± 364.2 mL. Kg−1. min−1) vs Minocycline (VE Minocycline‐STZ‐AD = 2535.0 ± 246.7 vs VE Minocycline‐Vehicle = 1936.0 ± 226.4 mL. Kg−1. min−1) (P >0.05 test Two‐Way ANOVA). Similarly, minocycline treatment had no effect on reversal of wakefulness increase in STZ‐AD model (% Time spent in awake state mean ± standard deviation: Placebo‐STZ = 66.4 ± 17.7 vs Placebo‐Vehicle = 53.0 ± 9.9 % ) (Minocycline‐STZ = 66.6 ± 8.2 vs Minocycline‐Vehicle = 44.8 ± 11.7 %). No difference was observed in the body temperature of the animals during the experiments, but the hypoxia promoted a regulated fall in body temperature.ConclusionIn summary, our data suggest that minocycline is a promising drug to minimize cognitive dysfunctions in the AD model without changing the respiratory and sleep‐wake cycle parameters.