bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dementia awareness in Southern Switzerland among older adults
Authors: Fadda Marta , Fiordelli Maddalena , Ibnidris Aliaa , Franscella Giovanni , Albanese Emiliano 
Published: December 2020

AbstractBackgroundPublic awareness of dementia is at the core of the WHO global action plan on the public health response to dementia. Evidence on dementia awareness in cognitively healthy older adults is limited. We measured dementia awareness, acceptance and understanding in a large sample of elders living in the Italian‐speaking part of Switzerland.MethodBetween September and December 2019, 1,364 older adults (65 years or more) living in Ticino were invited to participate in an online survey. We collaborated with a large local association of older adults (Associazione Ticinese Terza Età, ATTE) to recruit participants, and to translate and adapt the Dementia Knowledge Assessment Scale (DKAS), a 25 items Likert scale designed to measure knowledge of dementia from a biomedical perspective. The DKAS was previously validated, its score ranges between 0 and 50.Result628 men and women aged 65 to 97 (Mean: 73.3; Standard Deviation: 5.6) participated in the survey. Of these, 61.7% were women, 85.6% were highly educated (baccalaureate and above), and 75.4% retired. 42% of respondents believed that dementia is part of the normal ageing. DKAS scores varied markedly (Mean: 17.7; Standard Deviation: 6.9; range=1‐40), were higher for women (p<0.001), younger (p=0.031) and more educated (p=0.042) participants.ConclusionThe misconception that dementia is an ineluctable part of ageing was common, and level of dementia awareness markedly varied and was generally low in a large sample of elderly people living in the Italian‐speaking Canton of Switzerland. Our results have important implications for future actions and campaigns to raise awareness about dementia and to assess its effects.
Association between microbiota dysbiosis and endothelial dysfunction in Alzheimer’s disease: An in vivo cross‐sectional study
Authors: Cattaneo Annamaria , Marizzoni Moira , Mirabelli Peppino , Mazzelli Monica , Luongo Delia , Salvatore Marco , Frisoni Giovanni B. 
Published: December 2020

AbstractBackgroundIncreasing evidence shows that the gut microbiota (GMB) may be involved in the pathogenesis of several brain disorders. Metagenomic data support an association between certain bacterial genera and Alzheimer’s Disease (AD), but the functional dynamics of the gut microbiota remains elusive. This study aimed at evaluating whether inflammatory mediators and bacterial products represent a potential pathogenic link between specific gut bacteria and amyloid pathology in AD.MethodSeventy‐two older persons with cognitive performance from normal to dementia with brain amyloid status were recruited and stool and blood samples were collected. Bacterial composition of fecal samples was inferred using 16S sequencing, analyzed with QIIME 2 (Quantitative Insights into Microbial Ecology, https://qiime2.org/). Blood lipopolysaccharide (LPS), short chain fatty acids (SCFAs) acetate, propionate, valerate and butyrate by gas chromatography with flame ionization detector (GC‐FID) and circulating adhesion molecules by flow cytometry bead‐based immunoassay panel. We compared HC, amyloid negative (Amy‐) and positive (Amy+) patients with respect to GMB‐specific variables and endothelial biomarkers.ResultMetagenomic differences were mainly related to the HC rather than Amy+ or Amy‐. Despite a similar GMB, Amy+ and Amy‐ reported differences in the levels of several blood GMB‐related products: Amy+ had increased valerate (p<.001 vs both HC and Amy‐) and LPS (p=.011 vs Amy‐; p=.031 vs HC) levels while Amy‐ decreased acetate (p<.001 vs Amy+; p=.003 vs HC) and increased butyrate (p<.001 vs Amy+; p=.002 vs HC) levels. Endothelial dysfunction, as indicated by the upregulation of adhesion molecules (NCAM, PECAM‐1, ICAM‐2, PSGL‐1), was observed in Amy+ only (p<.030 vs Amy‐; p<.010 vs HC). High levels of these adhesion molecules were associated with elevated levels of acetate and valerate and low levels of butyrate (0.26<|rho|<0.51, p<.024).ConclusionThe mechanisms linking GMB dysbiosis and cognitive impairment in the presence or absence of brain amyloid deposition are different. Reduction of butyrate together with increased acetate, valerate and LPS levels may compromise the tissue‐blood barrier integrity, facilitating the AD pathological cascade. Microbiota functional dynamics, more than its composition, may be a potential biomarker of AD and provide new leads for treatments aimed at preventing or delaying neurodegeneration.
Quantifying the synaptic vesicle‐associated protein, VAMP2, to verify changes in cerebrospinal fluid in preclinical stages of Alzheimer’s disease
Authors: Goossens Julie , Dewit Nele , Belbin Olivia , Lleó Alberto , Vanmechelen Eugeen 
Published: December 2020

AbstractBackgroundSynapse loss, a pathological hallmark of Alzheimer’s disease (AD), is quantified in the brain using synaptophysin in western blot and immunohistochemistry, while the in vivo imaging compound 11C‐UCB‐J targets synaptic vesicle glycoprotein 2A (SV2A). Both proteins are characteristic of synaptic vesicles (SVs) and are found in the majority of synapses. Since synaptophysin is not stable in CSF or serum, it is not a suitable marker to monitor synaptic integrity in fluids (Schlaf et al., 1998). Vesicle‐associated membrane protein 2 (VAMP2), another SV component critical for vesicular trafficking, was identified as potential fluid surrogate for synapse loss using relative quantification (Lleo et al., 2019). Here, we have developed a new digital immunoassay for VAMP2 and evaluated its CSF profile in 226 samples from the AD continuum. For comparison the more established post‐synaptic marker Neurogranin (Ng) was included, which is expressed in dendrites of excitatory glutaminergic neurons.MethodThe immunoassay (Simoa) for VAMP2 was established using a commercial rabbit mAb and a novel high‐affinity mouse mAb 15E4. CSF was measured in duplicate on the HD‐1 analyzer across cognitively normal controls (n=68), preclinical AD stage 1 (Amyloidosis +, n=31), preclinical AD stage 2 (Amyloidosis +, neurodegeneration +, n=8), prodromal AD (n=80) and AD dementia (n=39). Ng was quantified with ELISA (EUROIMMUN).ResultThe assay was able to quantify VAMP2 in all CSF samples with an average CV below 10%. Three quality control samples had an inter‐/intra‐assay variability below 10%. VAMP2 levels correlated strongly with Ng in all AD stages (r=0.78‐0.96, p<0.0001). VAMP2 (p<0.0001) and Ng (p<0.0001) were decreased by 40% in preclinical AD stage 1. They were both elevated in the prodromal (VAMP2 25%, p=0.0009; Ng 70%, p<0.0001) and dementia group (VAMP2 25%, p=0.014; Ng 50%, p<0.0001).ConclusionA novel immunoassay for VAMP2 is capable of detecting changes in different AD stages. CSF changes in VAMP2 and Ng precede clinical symptoms and CSF neurodegeneration markers in the AD continuum. In line with observations that CSF‐tau and CSF‐Aβ abnormality precede plaque and tangle load via PET imaging, future longitudinal studies relating synaptic fluid markers with synaptic PET ligands (i.e. 11C‐UCB‐J) could extend these findings.
Increased Aβ pathology associated with increasing fractional anisotropy in the nucleus basalis of Meynert: A postmortem MRI and histopathology study
Authors: Jonkman Laura E. , Lin Chen‐Pei , Frigerio Irene , Boon Baayla D.C. , Zhou Zihan , Steenwijk Martijn D. , Rozemuller Annemieke J.M. , Schoonheim Menno M. , Bouwman Femke , Van de Berg Wilma D.J. 
Published: December 2020

AbstractBackgroundCholinergic deficiency is an early and key feature of Alzheimer’s disease (AD). Post‐mortem studies have shown accumulation of pathology and cholinergic cell loss in the nucleus basalis of Meynert (NbM). In‐vivo MRI studies have shown decreased NbM volume and microstructural diffusion changes. We aim to connect the two and assess the direct within‐subject association between local Aβ and (p‐)tau burden with MRI volume and diffusion measures of the NbM, using a post‐mortem MRI‐pathology pipeline.MethodEleven clinical and pathological confirmed AD (6F, 66y±12) and 11 age‐matched non‐neurological donors (6F, 70y±7) underwent post‐mortem in‐situ 3T MRI. T1‐w for anatomical labelling and DTI for quantification of microstructural integrity by measuring fractional anisotropy (FA) and mean diffusivity (MD). Upon subsequent autopsy, the basal forebrain was selected for paraffin embedding and ChAT, Aβ, and (p‐)tau immunohistochemistry. The NbM was identified on MRI and histology based on strict anatomical boundaries. Study outcome measures were NbM MRI T1 volume, FA and MD, as well as ImageJ analyzed ChAT neuron count, Aβ and (p‐)tau area %‐load. Group comparisons were made using non‐parametric tests. MRI‐histology measures were correlated using Spearman’s rho.ResultNbM MRI volume was smaller in AD cases than controls (189mm3 ± 36 vs 229mm3 ± 49, p=0.03), but no regional difference in FA or MD was found. Compared to controls, AD cases showed higher Aβ (p=0.015) and (p‐)tau (p=0.003) load in the NbM, but no significant difference in ChAT neurons. All cases taken together, correlations between MRI measures and histology showed a negative association between NbM volume and Aβ (rho=‐0.56, p=0.045) and NbM volume and (p‐)tau (rho=‐0.57, p=0.042). Furthermore, a positive association was found between NbM FA and Aβ load (rho=67, p=0.013).ConclusionCompared to controls, an increase in NbM pathology in AD is associated with a decrease in volume without a significant difference in ChAT cell count, leading to compaction of tissue and hence an increase in fractional anisotropy. Further inclusion of cases should shed light on more subtle associations between NbM pathology and MRI measures, such as microstructural changes in cortical projections.
Incidence of dementia and major subtypes in a population‐based cohort of older people in São Paulo
Authors: Lopes Marcos A , Nassar Silvia M , Litvoc Julio , Folquitto Jefferson C , Barcelos‐Ferreira Ricardo , Filho Geraldo Busatto 
Published: December 2020

AbstractBackgroundEfforts have been done in order to assess changes over time in dementia occurrence around the world. In developing countries, the scarcity of incidence studies and follow‐up of prevalence studies make the perspective of trends much more imprecise and turn the focus to the primary epidemiological objectives. This study aimed to estimate the incidence of dementia in a community‐dwelling elderly population from São Paulo and its distribution in relation to socio‐demographic and clinical variables and habits.MethodA two‐phase design was conducted to a representative cluster sample of individuals aged 60 years old and over from three different socioeconomic levels. The screening‐phase consisted of a tested combination of cognitive and functional tests, applied to the subjects and informants in the community. In the hospital phase, Cambridge Examination, imaging and blood exams were performed; the diagnosis of dementia and dementia subtypes was made according to DSM IV criteria. Incidence rates were calculated dividing the number the dementia cases by the amount of time between the prevalence and incidence studies. Incidence rates were expressed in persons‐year, multiplied by 1000, for dementia and subtypes of dementia. The risk of developing dementia was calculated using Cox regression.ResultFrom 1370 electable subjects, 678 were accessed to evaluation. Forty‐two subjects were diagnosed with dementia. The incidence rate of dementia was 11.22 persons‐years (95%CI: 8.09 – 15.17). The most incident subtype of dementia was Alzheimer’s Disease: 8.90persons‐year (95%CI: 6.13 ‐ 12.51). Multivariate analysis observed that higher ages, presence of diabetes and presence of MCI amnestic increased the risk of developing dementia; age‐adjusted risk was higher in low frequency of playing games and reading books. The risk of developing Alzheimer’s Disease, exclusively, for women compared to men, was nearly three times higher.ConclusionThe incidence rate was very close to the other Brazilian study and European, Western and Asian studies. The predominance of Alzheimer’s Disease corroborated the Western studies and probably had a contribution to the higher risk of MCI amnestic in developing dementia. The findings about intellectual habits and female sex should be seen cautiously considering their complexity and the limitations of the present study.
Internet‐based supportive interventions for family caregivers of people with dementia: A systematic review and meta‐analysis
Authors: Leng Minmin , Wang Zhiwen 
Published: December 2020

AbstractBackgroundFamily caregivers of people with dementia always experience high levels of psychological burden and physical strain, so effective and practical support is essential. Internet‐based interventions can provide convenient and efficient support and education to potentially reduce the physical and psychological burden associated with providing care. This review aimed to (1) assess the efficacy of internet‐based supportive interventions in ameliorating health outcomes for family caregivers of people with dementia, and (2) evaluate potential effects of internet‐based supportive interventions access by caregivers on their care recipients.MethodAn electronic literature search was conducted in the PubMed, Embase, Web of Science, CINAHL, Cochrane Library, and PsycINFO databases to identify relevant studies that were published up to November 2019. The two reviewers worked independently to identify randomized controlled trials (RCTs) that met the inclusion criteria and extracted data independently. The quality of the included RCTs was evaluated using the approach recommended by the Cochrane Handbook for systematic reviews of interventions. Standardized mean difference (SMD) with 95% CI was applied to calculate the pooled effect sizes.ResultIn total, fifteen RCTs met the eligibility criteria and were included in this systematic review. The meta‐analysis showed that internet‐based supportive interventions significantly ameliorated depressive symptoms (SMD = ‐0.20; 95% CI ‐0.31 to ‐0.10; p = 0.0002), perceived stress (SMD = ‐0.36; 95% CI ‐0.53 to ‐0.19; p < 0.0001), anxiety (SMD = ‐0.33; 95% CI ‐0.51 to ‐0.16; p = 0.0002), and self‐efficacy (SMD = 0.19; 95% CI 0.05 to 0.33; p = 0.007) in dementia caregivers. No significant improvements were found in caregiver burden or coping ability. Three studies assessed the unintended effects of internet‐based supportive interventions access by caregivers on their care recipients. The results showed that internet‐based supportive interventions had potential benefits on the quality of life and neuropsychiatric symptoms in care recipients.ConclusionInternet‐based supportive interventions were generally effective at ameliorating depressive symptoms, perceived stress, anxiety, and self‐efficacy in dementia caregivers, although negative results were found in some RCTs. Future researchers are encouraged to adopt personalized internet‐based supportive interventions to improve the health of family caregivers and their care recipients.
Distribution of pathological hallmarks and association with post‐mortem MRI cortical thickness in typical and atypical Alzheimer’s disease
Authors: Jonkman Laura E. , Boon Baayla D.C. , Frigerio Irene , Steenwijk Martijn D. , Preziosa Paolo , Hoozemans Jeroen J.M. , Bouwman Femke , Rozemuller Annemieke J.M. , Van de Berg Wilma D.J. 
Published: December 2020

AbstractBackgroundAlzheimer’s disease (AD) may present with typical amnestic symptoms (70%) as well as atypical non‐amnestic symptoms such as spatial disorientation, aphasia, or behavioural change. This heterogeneity in clinical symptoms is reflected by pathology and neuroimaging, showing different patterns of protein aggregation, inflammation and atrophy. In this study we aimed to assess the within‐subject regional pathological abnormalities and association with MRI cortical atrophy in clinical phenotypes, using a post‐mortem MRI‐pathology pipeline.Method16 clinically confirmed AD donors, eight typical (4F, 73y ± 9) and eight atypical (3F, 63y ± 11), and 11 non‐neurological donors (6F, 70y ± 7) underwent post‐mortem in‐situ 3T MRI. Upon subsequent autopsy, eight cortical regions were selected for paraffin embedding and Aβ, (p‐)tau and CD68 (clone KP1) immunohistochemistry, which was quantitatively analysed as area %‐load with ImageJ. Freesurfer was used on T1 images to calculate regional cortical thickness. Outcome measures were compared across groups using non‐parametric tests. In a linear mixed model we related regional pathology with cortical thickness, adjusting for age and post‐mortem delay.ResultAcross all regions, Aβ, (p‐)tau and CD68 load differed between groups; more pathology in (a)typical AD than controls (all p< 0.001), and more (p‐)tau and CD68 in atypical versus typical AD (p<0.001 and p<0.01). Cortical thickness differed between atypical AD and controls (p<0.001), and between atypical and typical AD (p<0.01).Within regions, only comparing clinical phenotypes, no difference in Aβ load or cortical thickness was found, but there was more (p‐)tau in the precuneus (p = 0.04) and more CD68 in the middle (p = 0.03) and superior frontal cortex (p = 0.028) in atypical AD.Across all groups and regions, there was a negative association between cortical thickness and Aβ (p<0.05), (p‐)tau (p<0.001) and CD68 load (p<0.001). Within AD groups, cortical thickness showed a negative association with Aβ for atypical AD, with (p‐)tau for both phenotypes. Within regions, associations with (p‐)tau and CD68 were found for frontal and parietal thickness in (a)typical AD, but none survived Bonferroni correction.ConclusionOur results show regional differences in (p‐)tau, CD68 and cortical thickness between typical and atypical AD, indicating different patterns of pathology and influence on MRI cortical thickness between phenotypes.
Suitability of dementia risk scores as surrogate outcomes for lifestyle‐based multidomain prevention trials
Authors: Hoevenaar‐Blom Marieke P , Coley Nicola , van Dalen Jan Willem , van Charante Eric P Moll , Kivipelto Miia , Soininen Hilkka , Andrieu Sandrine , Richard Edo ,   PRODEMOS Consortium, preDIVA Study Group, MAPT/DSA Group, HATICE Consortium
Published: December 2020

AbstractBackgroundAlthough not designed as such, dementia risk scores, such as the CAIDE or LIBRA, might be useful as surrogate outcome measures for dementia prevention trials conducted from midlife onwards. In the risk scores’ original categorical scoring systems, changes in risk factors are only taken into account when crossing cut‐off values, which may limit responsiveness and ability to detect intervention effects. We hypothesized that scoring systems based on continuous z‐score measures of risk factors may improve the performance of risk scores in this respect.MethodIn three large multidomain dementia prevention trials (MAPT, preDIVA and HATICE) with 1.5‐2 years of follow up, we assessed of the original and z‐score versions of the CAIDE and LIBRA scores: 1) responsiveness and 2) actual and simulated intervention effects.ResultAcross the three trials, 48 to 58% of intervention group participants underwent change on the CAIDE score between baseline and follow‐up. The LIBRA index was more responsive: 61 to 79% of participants changed over time. The z‐score versions registered changes in risk factors that were not detected by the original scores: subjects with no change over time in the original score showed great variability in their change in z‐scores, ranging from as much as ‐1.25 to 1.25 for the CAIDE. Conversely, for very small changes in z‐score, the change in original CAIDE or LIBRA scores was as much as ‐5 to 5 points, indicating multiple small changes in risk factors just across the cut‐off values for the original scoring system. Original scores and z‐scores were equally able to detect modest but significant intervention effects. When simulating very large intervention effects, mean between‐group differences of ‐0.50 points (23% of potential for improvement) could be attained for original CAIDE score and ‐0.52 points for original LIBRA index (15% of potential for improvement). Their z‐score versions could attain a maximum of ‐0.24 standard deviations for CAIDE and ‐0.15 standard deviations for the LIBRA index.ConclusionDementia risk scores as well as their z‐score versions show potential as surrogate outcomes. How changes in risk scores affect long‐term dementia incidence rates remains to be determined.
Genetic markers for brain plasticity
Authors: Brouwer Rachel M. , Klein Marieke , Grasby Katrina L , Schnack Hugo G. , Jahanshad Neda , Teeuw Jalmar , Medland Sarah E. , Franke Barbara , Thompson Paul , Pol Hilleke E. Hulshoff ,   ENIGMA Plasticity Working Group
Published: December 2020

AbstractBackgroundUnder the influence of genes and a varying environment, human brain structure changes continuously throughout the lifespan. The quest to identify genetic variants that affect the speed of brain aging is of crucial importance for public health and to guide drug development. As structural brain changes vary considerably across individuals, longitudinal studies are crucial to identify genetic and environmental factors that influence development and aging. Brain changes have been shown to be a heritable phenotype (Brouwer et al., 2017). Yet, we still completely lack information on specific genetic variants that influence brain changes throughout life.MethodsThrough the ENIGMA plasticity working group as part of the ENIGMA consortium (Thompson et al., 2019), we recruited 10,163 subjects [age 4 – 99 year] from 37 cohorts worldwide who had longitudinal structural MRI and whole‐genome genotyping data available in a prospective meta‐analysis design. Longitudinal image processing (Reuter et al., 2012), genomic imputation (Das et al., 2016), quality control and genome‐wide association procedures (Feng et al., 2014)followed a harmonized protocol in each cohort separately. Meta‐analysis and genome‐wide meta‐regressions accounting for age‐dependent effects of genetic variants were performed for global and subcortical structures.ResultsChange rates of global brain measures showed different patterns with age. We identified 5 genome‐wide significant loci and 15 genome‐wide significant genes, associated with longitudinal brain changes, including an age‐dependent effect of Apolipoprotein E (APOE) in the hippocampus and amygdala. Our results suggest a role for metabolic and immune related processes‐shaping brain change throughout our lives.ConclusionWe discovered novel genetic effects that influence the speed of both development and aging of brain structures. Our findings are consistent with the changing expression of genes during development and aging (Kang et al., 2011). In conclusion, our study implicates a specific genetic background for inter‐individual differences in human brain plasticity throughout life.