bluuebunny/crossref_metadata_2025_split huggingface dataset:
Higher dietary intake of advanced glycation end products is associated with faster cognitive decline in community dwelling older adults
Authors: Beeri Michal Schnaider , Lotan Roni , Uribarri Jaime , Leurgans Sue E. , Bennett David A , Buchman Aron S 
Published: December 2022

AbstractBackgroundDietary‐derived advanced glycation end products (AGEs) may contribute to chronic diseases. The goal of this study was to investigate the associations of dietary AGEs (dAGEs) with cognitive decline in older adults.MethodNon‐demented older adults (N = 684) underwent annual testing with 19 cognitive tests summarized as a global cognitive score based on five cognitive domains. We modified a previously validated food frequency questionnaire designed to assess dAGE. The modified questionnaire assessed portion size and frequency of consumption of six food groups (meat, poultry, fish, cheese, spreads and processed foods), as well as the method of their preparation (e.g. grilling, boiling). dAGE was the sum of the scores of the six food groups. Linear mixed‐effect models were used to examine the association of baseline dAGE with cognitive decline. All models controlled for age, sex, education, race and BMI.ResultAverage follow‐up was 3.0 years. Higher baseline dAGEs was associated with a faster rate of global cognitive decline (Estimate = ‐0.003 (standard error = 0.001, p‐value = 0.015). This association was driven by declines in the episodic memory (‐0.004 (0.002, 0.013) and perceptual speed (‐0.003 (0.001, 0.049) but not by semantic memory, working memory and visuospatial domains. These associations were not attenuated by controlling for cardiovascular risk factors and diseases, including diabetes. Levels of dAGE of the specific food groups were not associated with cognitive decline.ConclusionHigher levels of dietary AGE levels in older adults are associated with faster cognitive decline. These data lend further support for the importance of diet and that its modification may slow or prevent late‐life cognitive impairment. Further clinical studies will be needed and the molecular mechanisms underlying these associations will need to be identified.
Changes in modifiable risk factors for Alzheimer´s disease and dementia during the COVID‐19 pandemic in Swedish older adults: a population‐based digital survey
Authors: Rocha Ana Sabsil Lopez , Mangialasche Francesca , Thunborg Charlotta , Levak Nicholas , Aspö Malin , Rydström Anders , Lehtisalo Jenni , de Jager Celeste A , Price Geraint J , Hall Anette , Solomon Alina , Ngandu Tiia , Kivipelto Miia 
Published: December 2022

AbstractBackgroundOlder adults have a higher risk of Alzheimer´s disease (AD) and dementia. In terms of morbidity and mortality, they also represent the group most severely affected by the SARS‐CoV‐2 (COVID‐19) pandemic. Since February 2020, the Swedish government recommended different general measures limiting mobility and social contact, to contain the spread of infection. Pandemic‐related changes in lifestyle and access to healthcare could have a negative impact on modifiable factors for AD and dementia.MethodsA digital survey was distributed to the general population (multiple distribution channels, voluntary participation) during the last waves of the COVID‐19 pandemic in Sweden (May/2021 – December/2021). Participants were people aged 60+ years, free of dementia, and living in Sweden. The survey aimed to measure changes in lifestyle (e.g., diet, physical activity), care of vascular/metabolic risk factors (e.g., diabetes, hypertension), as well as psychosocial factors (e.g., depressive symptoms, sleep quality, social isolation) relevant for AD and dementia. The survey is part of the World‐Wide‐FINGERS‐SARS‐CoV‐2 initiative.Results6,918 participants completed the survey, mean age was 67.9 (5.11 SD), 58% were female, 71.6% were from urban areas. Preliminary results showed that, during the pandemic, 27% of participants decreased their physical activity, 26.3% increased intake of unhealthy snacks, 25.7% experienced increased sleep problems. Also, 58.7% had less contact with family, 40.4% experienced loneliness, 24.7% experienced worsening of memory, and 26.8% rated their health worse than before the pandemic. On the other hand, the reported increase in consumption of vegetables and fruits was 14.1% and 15.7%, respectively, and 65.2% of people had increased the use of digital services to keep in contact with family and friends. Also, 2.6% of participants decreased smoking, and 11.2% reduced their alcohol consumption. The occurrence of chronic vascular and metabolic diseases and related disruption in access to healthcare is presented in Table 1.ConclusionThe COVID‐19 pandemic has had an effect on modifiable factors for AD and dementia in Swedish older adults. These changes can affect future AD/dementia occurrence and should be addressed in forthcoming interventions for AD/dementia risk reduction and prevention. The survey can also be used for pre‐screening participants for prevention trials.
LatAm Fingers Initiative: Challenges and opportunities of launching a multicultural trial in pandemic times
Authors: Calandri Ismael Luis , Crivelli Lucia , Caramelli Paulo , Lopera Francisco , Nitrini Ricardo , Ortiz Ana Luisa Sosa , Suemoto Claudia Kimie , Salinas‐Contreras Rosa Maria , Velilla Lina M , Yassuda Monica Sanches , Sevlever Gustavo , Allegri Ricardo Francisco , Initiative LatAm FINGERS 
Published: December 2022

AbstractBackgroundThe Latin American FINGERS initiative gathers 12 countries, including Spanish and Portuguese‐speaking populations. We aim to describe challenges and opportunities related to launching a multi‐country trial during the Covid‐19 pandemic. Identified challenges included. a) To train personnel from the different teams in trial procedures b) To assess the training results c) To provide support regarding the trial set‐up on the different sites.MethodThe challenges were approached with multiple online networking strategies. a) Training was provided online in workgroup meetings led by specialists from the different interventions. Furthermore, because our project includes English, Spanish and Portuguese speakers, the training sessions were recorded, and subtitles in the alternate language were provided. b) To assess training, a web‐based campus with educational sessions and questionnaires with different educational paths for each role in the intervention was set up. Additionally, we created different certifications, and a medal system to reward the training completion was included. c) Two innovative platforms provided support. We created a WhatsApp Chatbot to assist investigators 24/7, automatically answering questions, sending resources required for visits, and reporting difficulties. The Chatbot includes a database system to register adverse events reports and report them immediately to the clinical core. Finally, a LatAm FINGERS Consulting Room was built to provide weekly online sessions led by the executive committee. Members can connect without a prior appointment and discuss any questions.ResultHitherto, 16 in‐vivo online sessions were provided to 203 trainees, 15 multilingual videos summarizing essential aspects of intervention, and six tutorials solving frequent problems were uploaded in the web‐based campus with multiple language subtitles. A total of 93 participants received certification for the trial. 9 meetings have been carried out so far regarding the Consulting Room, and more than 30 conflicts have been solved. Chatbot has answered a mean of 12 daily questions since its implementation.ConclusionWe present successful tools to implement an intervention in multicultural centers separate by more than 10000 km and 5 time zones where travel was banned. Finally, this trial also brought up the opportunity to increase the spirit of the scientific community and strengthen the network ties.
Maintain Your Brain: a 3‐year online randomized controlled trial to reduce cognitive decline in 55‐77 year olds
Authors: Brodaty Henry , Heffernan Megan , Singh Maria A. Fiatarone , Valenzuela Michael , Lautenschlager Nicola T , Anstey Kaarin J. , Sachdev Perminder S. , Jorm Louisa , McNeil John , Maeder Anthony , Ginige Jeewani Anupama , Chau Tiffany , Jose Juan Carlo San , Millard Michael , Welberry Heidi ,   Maintain Your Brain Research Group
Published: December 2022

AbstractBackgroundTechnology and web‐based approaches potentially provide scalable population‐based interventions to reduce modifiable risk factors for dementia such as physical inactivity, suboptimal nutrition and low cognitive activity. Our aim was to reduce cognitive decline with ageing using an online package of interventions delivered intensively for 12 months followed by monthly boosters for 24 months. The trial was completed in November 2021.MethodInvitations were sent to people aged 55‐77 years from the 45 and Up study, a population‐based cohort study of one in ten people aged 45 years and older in New South Wales, Australia (n = 267,000). Participants were required to be eligible for at least two of four modules. The modules addressed physical inactivity and health risks associated with inactivity (Physical Activity), adherence to a Mediterranean‐type diet and health risks associated with poor nutrition (Nutrition), cognitive activity (Brain Training) and mental well‐being (Peace of Mind). All participants received modules based on their risks, with randomized allocation to active personalised coaching modules (intervention) or static information‐based modules (control). The primary outcome was change in an online combined multi‐domain cognitive score measured using COGSTATE and Cambridge Brain Sciences tests. Secondary outcomes included ANU‐ADRI risk score, specific cognitive domain scores and diagnoses of dementia.ResultFrom 96,418 invitations, 14,064 (14%) consented; 12,281 (13%) were eligible. Of these, 6,236 (6%) completed all 10 baseline assessments and were enrolled in the trial. Nearly 70% or 4,365 participants provided follow‐up data. At final 36‐months’ follow‐up, 3,482 (55.8%) completed the primary outcome and 2594 (41.6%) had returned informant‐rated Amsterdam‐Instrumental Activities of Daily Living Scale questionnaires.ConclusionOnline strategies to prevent cognitive decline in 55‐77 year olds are feasible and appear acceptable for more than half of participants. Analysis of group*time effects will be presented.
The effects of locus coeruleus stimulation on the BOLD global signal in TgF344‐AD rats
Authors: Anumba Nmachi , Kelberman Michael , Smith Corrie , Pan Wen Ju , Clavijo Perrin G , Marriott Alexia , Kim Ellen , Weinshenker David , Keilholz Shella 
Published: December 2022

AbstractBackgroundFunctional connectivity of the brain as measured by the blood oxygen level dependent (BOLD) signal in fMRI is altered during Alzheimer’s disease (AD) progression. Common practice during preprocessing of fMRI data is removal of the global signal, defined as the averaged brain signal, by regression, removing major sources of noise while risking loss of neural activity. The locus coeruleus (LC), one of the first brain regions to accumulate hyperphosphorylated tau, contributes to brainwide neuromodulatory regulation. Therefore, we combined optogenetics and fMRI to study how LC activity affects the global signal in the TgF344‐AD rat model of AD, which overexpresses mutant human amyloid precursor protein and presenilin‐1.MethodsAt 2 months of age, TgF344‐AD rats and WT littermates received intra‐LC infusions of a ChR2‐mCherry virus under the noradrenergic specific PRSx8 promoter. 2‐4 weeks prior to fMRI, rats were implanted with an optic ferrule targeting the LC. Functional ChR2 expression and LC activation were confirmed by pupil dilation following optogenetic LC stimulation. At ∼6 months of age, rats underwent 10‐minute fMRI scans at baseline and during 2 Hz optogenetic stimulation. During scanning, rats were anesthetized with 1.3% isoflurane, intubated, and administered pancuronium (1.5 mg/kg*hr, s.c.). fMRI scans were gradient echo EPI (TR = 1.25 s) and obtained using a 9.4T Bruker Animal MRI scanner. Data were preprocessed using a customized pipeline. The voxel‐wise analysis was performed by correlating each voxel timecourse with the global signal via Pearson’s linear correlation.ResultsIn general, there were levels of slightly higher correlation to the global signal in the anterior medial region of the brain and bilaterally in the posterior region of the brain (Figure 1). The highest levels of correlation to the global signal were observed in the WT rats at baseline, but differences between groups were negligible.ConclusionNeither genotype nor optogenetic simulation profoundly affected global signal. These negative results may be explained by (1) the lack of profound forebrain AD‐like neuropathology in 6‐month TgF344‐AD rats, and (2) the 2 Hz optogenetic stimulation being insufficient to drive changes in global signal above the 1‐2 Hz baseline activity of LC neurons.
Differences in the measurement of cognition for the assessment of dementia across geographic contexts: Recommendations for cross‐national research
Authors: Nichols Emma , Deal Jennifer A , Langa Kenneth M , Ng Derek , Gross Alden L 
Published: December 2022

AbstractBackgroundAlthough 71% of individuals with dementia are projected to live and low‐ and middle‐income countries by 2050, most dementia research to‐date has been conducted in high‐income countries. Cross‐national studies are needed to understand how the causes and consequences of dementia may differ by country. However, factors such as urbanicity, language of administration or race/ethnicity, which vary across countries, affect the measurement of cognition. A better understanding of which cognitive items perform well across countries or within specific countries will allow researchers to optimize dementia measurement in future cross‐national and international studies.MethodWe used data from the Harmonized Cognitive Assessment Protocol surveys in the US, Mexico, India, England, and South Africa (combined N = 11,364). To define cognitive impairment consistently across countries, we compared participants’ cognitive performance with robust neuropsychological norms within each country. For each HCAP country, we assessed item performance by estimating associations between each cognitive item and cognitive impairment using logistic regression models, controlling for age and gender. We avoided circularity in the analysis by using an iterative quasi‐leave‐one‐out approach. We compared patterns of associations across countries using median odds ratios, and visually, using heatmaps.ResultThe associations between cognitive items and cognitive impairment were stronger in the US (Median Odds Ratio [OR] = 0.17) and England (Median OR = 0.19), in comparison to South Africa (Median OR = 0.23), India (Median OR = 0.29), and Mexico (Median OR = 0.28). Memory items, notably delayed recall tasks, had the most consistent associations of the largest magnitudes across countries. In comparison, there was variability in performance between settings for many language items (e.g. naming a hammer). Items requiring numeracy, including the Trail‐making test, did not perform well in countries with low educational attainment.ConclusionThe performance of cognitive items for the classification of cognitive impairment was not consistent across countries. Although items performing well in a single country could be used to improve measurement precision in specific settings, transporting items between countries without prior validation warrants caution. However, we did identify items that performed well across a range of countries (i.e. delayed recall, animal naming); these items may be of particular utility in future cross‐national research.
The SYNERGIC Trial: A Randomized Controlled Trial Assessing Multimodal Interventions to Improve Cognition in Mild Cognitive Impairment in Older Adults
Authors: Montero‐Odasso Manuel , Almeida Quincy J , Burhan Amer M. , Camicioli Richard , Li Karen , Liu‐Ambrose Teresa , Middleton Laura E , Doyon Julien , Fraser Sarah , Hunter Susan W , McIlroy Bill , Morais José A , Pieruccini‐Faria Frederico , Shoemaker Kevin , Speechley Mark R. , Vasudev Akshya , Zou G Y , Berryman Nicolas , Lussier Maxime , Vanderhaeghe Leanne , Bherer Louis 
Published: December 2022

AbstractBackgroundOlder adults with Mild Cognitive Impairment (MCI) have increased risk of dementia. Physical exercise, cognitive training, and vitamin D supplementation are emerging interventions for improving cognition. However, the potential synergism of combining them to improve cognition in MCI has not been yet tested.MethodsThe SYNERGIC trial (SYNnchronizing Exercises, Remedies in Gait and Cognition)— a multi‐site, double‐blinded, controlled, quasi‐factorial trial—assessed the efficacy and synergistic effect of combining bi‐modal exercises (aerobic + progressive resistance training = E), cognitive training (CT) and, vitamin D supplementation (D = 10000IU 3xweekly) to improve cognition in MCI. Personalized interventions were delivered for 20 weeks in 5 arms: Arm 1 received 3 active interventions (E+CT+D), Arm 2 received E+CT+placebo D, Arm 3 received E+ sham CT+ D, Arm 4 received E+ sham CT and placebo D, and Arm 5 received all control interventions (Control E‐balance and toning‐, sham CT and placebo D). Change in ADAS‐Cog‐13 was the primary outcome assessed with linear mixed effects models adjusting for age, sex, education, and number of comorbidities.Results170 MCI participants were randomized. As compared to the control group (Arm 5), multimodal intervention (Arm 1) had significant improvements in ADAS‐Cog‐13 scores (difference = ‐2.3 ADAS‐Cog‐13 points; 95% CI: ‐1.06 ‐3.54). Following analyses guidelines for factorial trials, interactions of intervention across arms were analyzed and no significant interactions were found for vitamin D supplementation. Therefore, we collapsed Arms 1 and 2 (combined E + CT), and we collapsed Arms 3 and 4 (E), and compared them to Arm 5 (control). Relative to the control group (Arm 5), the combined exercise and cognitive intervention (Arms 1+2) had significantly improved cognitive function (difference = ‐2.2 ADAS‐Cog‐13 points; 95% CI: ‐0.70, ‐3.72). In contrast, the exercise only intervention (Arms 3+4) did not have significantly improved cognition as compared to the control group (difference = ‐1.24 ADAS‐Cog‐13 points; 95% CI: ‐0.21, 2.69).ConclusionA synergistic effect of combined bi‐modal exercise with sequential computerized cognitive training was found to improve cognition in older adults with MCI with a large effect size = 0.62. Addition of vitamin D supplementation did not improve the effect.
Pandemic‐Related Stress, Coping, and Wellbeing in an International and Multi‐Ethnic Cohort of Older Adults
Authors: Medina Luis D , Franco Idalid , Thumala Daniela , Miranda‐Castillo Claudia , Acosta Daisy M , Aguero Cinthya , Aguilar‐Navarro Sara Gloria , Baena Ana Y. , Brucki Sonia , Bustin Julian , Duque Lissette , Velazquez Ivonne Z. Jimenez , Marquine Maria J. , Slachevsky Andrea , Soto‐Añari Marcio , Quiroz Yakeel T. 
Published: December 2022

AbstractBackgroundThe COVID‐19 pandemic has impacted the wellbeing of older adults. Pandemic‐related stress has implications on cognitive status, including decline due to Alzheimer’s disease and related dementias. Yet, evidence suggests that COVID‐19 has impacted culturally and linguistically diverse communities differently. We sought to examine the role of COVID‐19 on coping and wellbeing in an international, multi‐ethnic sample of older adults.MethodData from 955 older adults (age = 66.7±7.9 years; education = 15.2±5.9 years; 71% female; 41% Hispanic/Latino) were pulled from a larger, international sample examining the response of older adults to COVID‐19. All participants completed demographic questionnaires, measures of psychological distress, the Brief‐COPE – a 28‐item self‐report questionnaire used to measure respondent’s efforts to minimize distress from a stressful life event – and the Epidemic‐Pandemic Impacts Inventory (EPII) – a 92‐item inventory of pandemic related experiences across several life domains. Using linear regression, we examined relationships between Brief‐COPE scores, ethnicity, and select EPII items controlling for several covariates (age, sex, education, marital status, number of children, employment status, household income, and history of COVID‐19 symptoms) in all analyses.ResultHispanic/Latino (H/L) ethnicity was associated with slightly higher scores on the approach‐focused coping subscale compared to the non‐Hispanic White (NHW) group (Approach: 27.3±6.6 vs 26.1±6.1; B = 1.205, p = 0.015, CI: 0.238, 2.172). There was no effect of ethnicity on Brief‐COPE Total or Avoidance subscale scores (both ps>0.050). Notably, review of covariates suggested increased age was associated with lower scores on Approach (B = ‐0.065, p = 0.041, CI: ‐0.128, ‐0.003), Avoidance (B = ‐0.054, p = 0.034, CI: ‐0.104, ‐0.004), and Total scores (B = ‐0.136, p = 0.028, CI: ‐0.257, ‐0.015). Higher Approach scores were associated with greater endorsement of Positive Life Changes in both ethnic groups (NHW: partial r = 0.298, p<0.001; H/L: partial r = 0.249, p<0.036), but with endorsement of Mental Health Problems in NHWs only (NHW: partial r = 0.144; p = 0.001; H/L: partial r = ‐0.019, p>0.050).ConclusionFindings suggest cross‐cultural differences in the stress coping response of older adults during the pandemic, even after controlling for symptomatic history and other relevant covariates. Moreover, coping may be differentially related to positive and negative outcomes across cultural groups. These results support the need to consider cultural background when considering coping and wellbeing in older adults.
The Functional Role of Amyloid Precursor Protein at Mitochondria
Authors: Strope Taylor A. , Troutwine Benjamin R , Lysaker Colton R , Wilkins Heather M 
Published: December 2022

AbstractBackgroundAβ is generated from amyloid precursor protein (APP) via sequential proteolytic processing. While APP processing and its localization are well understood, the functional role of APP is largely unknown. APP is expressed almost ubiquitously but is concentrated in neuronal synapses and localizes to mitochondria. The functional consequence of mitochondrial APP localization is not well understood. We leveraged a mutant APP construct which does not localize to mitochondria to interrogate the functional role of APP at mitochondria.MethodsWe used a mutant form of APP (3M APP) which harbors mutations at amino acids +41, +44, and +52 (His to Asp). SH‐SY5Y cells were transfected for 24‐48 hours with either WT or 3M APP plasmids. Following transfection, mitochondrial function was analyzed using Seahorse Technology or Vmax spectrophotometric assays of electron transport chain (ETC) function. Mitophagy was examined by qPCR against mitochondrial DNA content. A co‐localization assay using an adenovirus expressing EGFP‐Cox8 was used as a separate measure of mitophagy. To activate mitophagy, cells were either treated with deferiprone (DFP), starvation (glucose and amino acid deprivation), or PINK1 was overexpression. Mitochondrial biogenesis and turnover were measured using an adenoviral vector (MitoTimer). We further assessed the ability of APP to interact with known mitophagy proteins using immunoprecipitation.ResultsCompared to WT APP, cells expressing 3M APP showed a decrease in mitochondrial localization as expected. 3M APP led to a significant decrease in complex II and IV flux of the ETC with decreased in complex IV Vmax. 3M APP showed significantly lower mitochondrial mass and biogenesis. Finally, 3M APP expressing cells appeared to have reduced mitophagy when compared to WT APP. We further found that APP interacts with PINK1 and p62 under conditions of enhanced mitophagy.ConclusionsAPP localization to mitochondria alters ETC function, mitochondrial mass, and mitophagy. Further studies are in progress to elucidate the mechanisms of APP localization at mitochondria, bioenergetic changes, and mitophagy.