bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of occupational complexity on cognitive change during a multidomain lifestyle intervention: The FINGER trial
Authors: Rydström Anders , Darin‐Mattsson Alexander , Kåreholt Ingemar , Ngandu Tiia , Solomon Alina , Lehtisalo Jenni , Antikainen Riitta , Bäckman Lars , Hänninen Tuomo , Laatikainen Tiina , Levälahti Esko , Lindstrom Jaana , Paajanen Teemu , Havulinna Satu , Peltonen Markku , Soininen Hilkka , Neely Anna Stigsdotter , Strandberg Timo , Tuomilehto Jaakko , Kivipelto Miia , Mangialsche Francesca 
Published: December 2020

AbstractBackgroundLife‐long mental stimulation through occupational complexity has been associated with late‐life cognition and might affect the rate of cognitive changes in randomized controlled trials (RCTs) testing preventive interventions for dementia. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER, ClinicalTrials.gov NCT01041989) is a landmark RCT that tested a lifestyle‐based multidomain intervention in 1260 community‐dwellers aged 60‐77 years at increased risk of dementia. Participants were randomized to either a group that received general health advice, or a 2‐year multidomain intervention that incorporated dietary counselling, exercise, cognitive training, and vascular/metabolic risk monitoring. The intervention improved global cognition (primary outcome) and cognitive sub‐domains including executive function, processing speed, and memory. This study aimed to test if the cognitive benefits of the 2‐year multimodal intervention were linked to baseline levels of occupational complexity.Method
Study participants: all randomized FINGER participants with at least one cognitive outcome assessment after the baseline visit (modified intention‐to treat population), available data on last held occupation, and who were retired (N: 1026). Occupational complexity was assessed through a validated rating system, identifying three domains: complexity with data; complexity with people; and substantive complexity. Cognition was assessed at baseline, 1‐year and 2‐year with the Neuropsychological Test Battery (NTB). The following cognitive outcomes were considered: global cognition, executive function, processing speed, and memory. Data analysis: Mixed‐model repeated‐measures analyses with maximum likelihood estimation were used to analyse change in cognitive scores as a function of randomization group, time, levels of occupational complexity (standardized Z‐scores), their interaction (randomization group × time × occupational complexity), age, sex, education, study site.ResultSubjects with higher levels of occupational complexity with data (i.e., occupations more mentally demanding) benefitted most in terms of improvement in executive function (interaction coefficient group × time × occupational complexity: ß[SE]: .03 (.01), p= .044) and global cognition (ß[SE]: .02 (.01), p= .060).ConclusionThe cognitive change in a multidomain preventive intervention can be affected by previous occupational complexity. This facet of mental stimulation should be further investigated within RCTs for cognitive impairment.
Association of obesity and diabetes in sex‐related differences in cognitive function: Findings from the Cocoa Supplement and Multivitamin Outcomes Study for the Mind (COSMOS‐Mind)
Authors: Espeland Mark A , Rapp Stephen R , Manson JoAnn E , Gaussoin Sarah A , Hayden Kathleen M , Shumaker Sally A , Sesso Howard D , Banack Hailey R 
Published: December 2020

AbstractBackgroundType 2 diabetes and mid‐life obesity increase the risk for cognitive decline and cognitive impairment in men and women. Studies disagree, however, on whether the associations diabetes and obesity have with cognitive function vary by sex.MethodWe analyzed data from the COSMOS clinical trial and its COSMOS‐Mind ancillary study of cocoa extract (including 600 mg/d cocoa flavanols) and a multivitamin to reduce risks for major cardiovascular events and total invasive cancer (COSMOS), and cognitive decline (COSMOS‐Mind). In COSMOS‐Mind we administered a standardized telephone‐based cognitive battery to assess episodic memory, executive function and global cognition in 2,262 adults, age>65 (mean=73) years, 58% women, 33% obese (body mass index >30 kg/m2), and 10% diabetes. Individuals with histories of myocardial infarction, stroke, or cancer (excluding non‐melanoma skin cancer) were excluded. Sex, obesity, and diabetes were based on self‐report. Multiple regression analyses were used to compare cross‐sectional associations between cognitive function and age for women and men grouped by obesity and diabetes, with adjustments for education and race/ethnicity.ResultWomen averaged better scores than men for memory (mean+standard error difference=0.42+0.04 SDs), executive function (0.26+0.04 SDs), and global cognitive function (0.30+0.4 SDs), all p<0.001. These differences were evident for individuals both with and without obesity or diabetes (all two‐way interactions p>0.20). Obesity, compared with no obesity, was associated with less steep slopes with greater age among women in all domains (all p<0.04), with no differences seen in men for any domain. This held without and with adjustment for diabetes. For composite cognitive function, the slope of the association with greater age was ‐0.064+0.005 SD/year among women without obesity compared with ‐0.030+0.009 SD/year among those with obesity (p=0.001), and the differences between women and men with obesity increased with age. After adjustment for obesity, diabetes was not associated with steeper slopes with age for any domain in either sex.ConclusionIn the COSMOS‐Mind cohort of clinical trial volunteers, the difference in cognitive function between women and men with obesity increased with age. However, in these cross‐sectional analyses we cannot rule out potential biases related to self‐report or differential survival.
Genome‐wide association studies for identifying novel genetic variants providing cognitive resilience against AD pathology
Authors: Hohman Timothy J. 
Published: December 2020

AbstractBackgroundAlzheimer’s disease neuropathology is common among non‐demented older adults, and 30% meet neuropathological criteria for autopsy‐confirmed AD despite showing no clinical symptoms of disease. Yet, the genetic factors that allow these resilient individuals to remain cognitively normal in the face of substantial neuropathology remains poorly understood. We have performed large‐scale multi‐modal data harmonization to enable deep explorations into the genetic architecture of resilience. We will present comprehensive estimates of heritability of AD resilience phenotypes, describe common genetic variants that contribute to resilience, and provide an overview of gene networks and critical genetic pathways that appear to provide putative protection against the downstream consequences of AD neuropathology.MethodWe harmonized neuroimaging (MRI and PET), neuropsychological, fluid biomarker, and genomic data from 8 longitudinal cohort studies as part of the AD sequencing project phenotype harmonization workgroup. Resilience phenotypes were quantified using an established latent variable model based on better‐than‐predicted cognitive performance and brain volume for an individual’s AD neuropathological burden. We quantified estimates of heritability using the Genome‐wide Complex Trait Analysis (GCTA) software package. Next, we performed genome‐wide association study (GWAS) analyses covarying for age, sex, and population principal components. Summary statistics from GWAS were leveraged to characterize genetic pathways enriched for association with resilience phenotypes. Finally, we quantified gene network associations with resilience phenotypes leveraging RNA sequencing data from brain tissue and replicated leveraging predicted gene expression analyses quantified using GWAS data.ResultsResilience phenotypes showed heritability estimates that are on par with complex genetic traits ( 0.19< h2< 0.67, p < 0.005), suggesting that genetic variation explains variance in resilience phenotypes. We observed a number of genome‐wide significant variants associated with resilience that replicate across in vivo biomarker datasets and autopsy datasets implicating acetylcholinesterase genes, bile acid homeostasis, and DNA damage repair. Finally, gene network analyses implicated gene modules involved in RNA binding and transcriptional regulation.ConclusionWe highlight a number of novel genetic variants and genetic pathways that may protect the brain from the downstream consequences of AD neuropathology, highlighting the potential of resilience endophenotypes in the identification of novel therapeutic targets.
A multi‐country, multi‐cohort examination of cortical volume, thickness, and surface area in the motoric cognitive risk (MCR) syndrome
Authors: Blumen Helena M , Schwartz Emily , Allali Gilles , Beauchet Olivier , Callisaya Michele L , Doi Takehiko , Shimada Hiroyuki , Srikanth Velandai K , Verghese Joe 
Published: December 2020

AbstractBackgroundThe motoric cognitive risk (MCR) syndrome is characterized by slow gait and cognitive complaint, and increases the risk for both Alzheimer’s disease and vascular dementia. Our recently established MCR neuroimaging consortium aims to identify the brain substrates and pathologies in MCR – and consists of > 3,000 MRIs from 6 different older adult cohorts and 5 different countries. The current study examined cortical volume, thickness, and surface area in MCR using a subset of 200 older adults from 4 different cohorts/countries, as a function of image processing methods that involved manual intervention and no manual intervention.MethodFifty MRIs from each of the four cohorts were examined (N = 200). FreeSurfer Version 6.0 and general linear statistical models with 1,000 bootstrapped samples (n‐1, with resampling) were used to determine if cortical volume (mm3), thickness (mm) and surface area (mm2) overall and in 34 different cortical regions were associated with MCR – following no manual intervention and manual error correction in the cortical surface. All models were adjusted for age, sex, education, white matter hyperintensities, total intracranial volume, and cohort status.ResultThe mean age was 72.62 years and 33 % met criteria for MCR. Overall cortical thickness – but not cortical volume or surface area – was different in older adults with MCR relative to those without MCR, although a trend in the expected direction was observed in cortical volume (p <.051). Smaller cortical thickness in MCR was pervasive, and included prefrontal (caudal middle frontal, medial orbitofrontal, pars orbitalis, pars opercularis, pars triangularis), insular, cingulate (posterior, isthmus), parietal (inferior parietal, precuneus), temporal (superior temporal, supramarginal) and precentral regions. The relationship between cortical volume, cortical thickness, surface area and MCR did not change following manual interventions (all 95% CIs overlapped).ConclusionThese results suggest that a) cortical thinning in MCR is pervasive and involve regions associated with a number of social, cognitive, affective and motor functions, b) cortical thickness is more sensitive than cortical volume and surface area to the cortical changes observed in MCR, and c) that manual intervention does not influence the relationship between cortical volume, thickness, area and MCR.
Evaluation of patient burden using online social media in mild cognitive impairment
Authors: Monfared Amir Abbas Tahami , Stern Yaakov , Irizarry Michael C , Doogan Stephen , Zhang Quanwu 
Published: December 2020

AbstractBackgroundDetection and diagnosis of Mild Cognitive Impairment due to Alzheimer’s Disease (MCI‐AD) can be challenging due to the subtlety of changes in early stages of disease progression. As a result, opportunities to capture the patient burden in MCI‐AD can be limited.MethodWe used Natural Language Processing (NLP) to analyze challenges and issues that were the most frequently reported online by patients living with MCI‐AD and caregivers. Patients’ self‐reports and caregivers’ reports on patients were identified based on online narratives posted between January 1998 and December 2019 across 84 social media sources. The RLytics NLP platform was used in combination with manual curation to codify verbatim symptoms and impairments against standardized medical taxonomies such as WHO‐ICF and MedDRA, and further into the following categorizations: Social, Physical, Emotional, Cognitive, and Role Activity (SPEC‐R).Result63,933 narratives from 311 patients with MCI‐AD and 1,454 caregivers were qualified into the sample for analysis. The most frequently reported issues varied between patients and caregivers. Cognitive issues (e.g. memory impairments and comprehension‐related) were the most frequently reported by both groups, however, patients reported at a higher rate. This may suggest a deeper concern with losing cognitive ability felt by patients themselves at the disease stage of MCI. This is further supported by a higher reporting rate of anxiety and depressive disorders among patients relative to caregivers. In contrast, certain role activity, physical and social issues (e.g. driving, fatigue, walking and mobility, relationships with spouse or partner) are reported by caregivers at a higher rate than patients, suggesting that these issues may have a greater impact on the daily lives of caregivers or may be more readily recognizable than cognitive issues.ConclusionThe SPEC‐R framework helps identify, understand, and prioritize the most pressing concerns at the symptom and functional level by patients and caregivers. It can uncover areas of disease burden in MCI‐AD that are less frequently associated with MCI, particularly in the non‐cognitive domains, that may not be sufficiently captured by early diagnostic processes in the clinical setting.
High fat diet leads to aberrant protein O‐GlcNAcylation and to the development of Alzheimer disease signatures in mice
Authors: Domenico Fabio Di , Zuliani Ilaria , Lanzillotta Chiara , Barone Eugenio , Fusco Salvatore , Grassi Claudio , Tramutola Antonella , Perluigi Marzia 
Published: December 2020

AbstractBackgroundHigh fat diet (HFD) is the most commonly used experimental model of obesity and insulin resistance, resembling the hallmarks of humans metabolic syndromes. It causes detrimental effects on brain function, but the molecular mechanisms involved are still poorly understood. Recent studies show that HFD may lead to the reduction of glucose uptake, which represent an early step in neuronal damage. In this regard, Alzheimer’s disease (AD) was recently proposed to be a form of CD caused by metabolic dys‐homeostasis. Intriguingly, during AD glucose hypometabolism precedes the appearance of clinical symptoms leading to the downregulation of O‐GlcNAcylation, a reversible glucose‐dependent protein PTM, which competes with phosphorylation for Ser or Thr residues. The enzymes (OGT and OGA) regulating the O‐GlcNAcylation cycle rely on brain nutrients through the hexosamine biosynthesis pathway for substrate availability. Recent studies from our lab observed the reduction of O‐GlcNAcylation in the hippocampus of insulin resistant 3xTG‐AD mice supporting a role for this PTMs in the development of CD.MethodWe employed C57 mice fed for 6 weeks with HFD (60% calories from fat) compared with C57 fed with standard diet. Further, we subjected mouse astrocyte to insulin + palmitic acid (IPA) treatment for 24h. The experimental procedures encompassed the analysis of: total and protein specific O‐GlcNAcylation and phosphorylation on Ser and Thr residues, OGT and OGA levels and activity, Tau and APP PTMs and the alteration of metabolic parameters.ResultWe demonstrate that HFD mice show the reduction of protein O‐GlcNAcylation in the hippocampus but not in the liver. Such reduction lead to unbalanced O‐GlcNAcylation/phosphorylation ratio of total proteins and of tau and APP, suggesting its involvement in the development of pathological tau and Aβ. A reduction of OGT protein levels is reported in hippocampal cells supporting a role for this enzyme as metabolic sensor. Similarly, astrocytes treated with IPA show insulin resistance coupled with reduced O‐GlcNAcylation and the progression of AD markers. Intriguingly, altered O‐GlcNAcylation seems to be associated also with mitochondrial defects.ConclusionOur data support a key role for aberrant O‐GlcNAcylation in promoting the development of AD markers during diet‐driven brain insulin resistance and glucose hypo metabolism.
Concept development of self appraisal of caregiving in family caregivers of older adults with dementia: A convergent parallel mixed methods design
Authors: Karimi Zahra , Farhadi Akram , Foroughan Mahshid , Mohammadi Farahnaz , Rassouli Maryam 
Published: December 2020

AbstractBackgroundThe caregivers‟ assessment of their own caregiving is considered the most important concept in exploring their experiences and has a major role in care outcomes. This study was conducted with the aim to develop the concept of self appraisal of caregiving in family caregivers of older adults with dementia.Methodmixed method with convergent parallel design was used to clarify and determine different dimensions of self appraisal of caregiving among caregivers of dementia patients. The study consisted of two parts: qualitative and quantitative. Confirmatory factor analysis and calculation of goodness of fit indices were performed on the data gathered from 236 family caregivers who were entered the study by convenient method to confirm the 5 factors of the revised caregiving appraisal scale ( RCAS) (caregiving burden, satisfaction, mastery, demand, and impact) in Iranian family caregivers of older adults with dementia. The data were saturated after interviews with 12 primary caregivers .Confirmatory factor analysis was performed in LISREL‐8.8 software in Windows®.ResultIn the quantitative analysis, 5 dimensions of RCAS were confirmed, which were discussed and compared with the obtained qualitative themes in the rest of the study. The content and face validities of the scale were confirmed according to the views of the family caregivers and the panel of experts. The confirmatory factor analysis results reported appropriate values for all the fit indices (RMSEA = 0.046, df / X2 = 2.428, CFI = 0.98, AGFI = 0.84 and GFI = 0.9), and the 5‐factorial model was confirmed with 27 items. The scale‐level Cronbach's alpha was reported as 0.894 and the scalelevel ICC as 0.94. Besides the confirmation of the 5 dimensions of RCAS, in the qualitative phase, other dimensions also emerged including “ caregiving burden”, “caregiving satisfaction”, ”losses and threat”, “ personal growth”, “philosophy of care” and “caregiving gains”.ConclusionAccording to the results, the Persian version of RCAS showed good validity and reliability, with 5‐factor structure that matched the original version. Therefore, I it can be an appropriate tool for assessment of caregiving and the deigned interventions to change it in family caregivers of patients with dementia.
A 48‐year‐old female, with a family history of AD PSEN1 mutation, who developed mild cognitive impairment and tried ketogenic diet‐associated medium‐chain triglyceride as treatment
Authors: de Andrade Lima Gustavo Melo , Corrado Marta , Gregório Marcela Marques de Oliveira , Bertolucci Paulo Henrique Ferreira 
Published: December 2020

AbstractBackground48 years old female, biologist researchers, with a family history of AD PSEN1 mutation, symptoms compatible with Mild Cognitive Impairment (MCI) due to probable Alzheimer's disease. As part of clinical approach Ketogenic Diet and medium‐chain triglyceride was tried combined with conventional treatment.Methodthe patient had a 2 ‐year long history of amnestic symptoms with a slow worsening, when medical help was sought. She underwent neurological and neuropsychological evaluation, magnetic resonance and specific genetic tests. It was observed memory and attention deficit, executive functions impairment; left hippocampal atrophy, ApoE E2/E3 profile and a variant of uncertain significance of PSEN1. At 48, she was classified as Mild Cognitive Impairment and started a treatment with middle‐chain triglycerides and Ketogenic Diet. Before starting the treatment, she underwent another neuropsychological evaluation, PET‐FDG and cerebrospinal fluid biomarkers profile. During the treatment, she will be monitored weekly by a nutritionist expert in ketogenic diet. After three months of treatment, she will repeat tests and exams.ResultCurrently, the patient is being treated, until March 2020, at the end of it she will repeat tests and exams. According to previous studies1, 6 weeks of modified ketogenic diet, is associated with an improvement of the cerebrospinal fluid biomarker profile, cerebral perfusion, and cerebral ketone body uptake, in older adult with risk for Alzheimer Disease.ConclusionThis case is of great importance in describing a woman’s history with the PSEN1 mutation, who underwent a Ketogenic Diet treatment while diagnosed with MCI. Regardless of the outcome, this case is essential to identify the effects of ketogenic diets on the biomarkers and neuropsychological tests on patients with the same profile. References: 1) Neth, B.J., Mintz, A., Whitlow, C., Jung, Y., Sai, K.S., Register, T.C. Kellar, D., Lockhart, S.N., Hoscheidt, S., Maldjian, J., Heslegrave, A.J., Blennow, K., Cunnane, S.C., Castellano, C.‐A., Zetterberg, H., Craft, S., Modified Ketogenic Diet Is Associated With Improved Cerebrospinal Fluid Biomarker Profile, Cerebral Perfusion, And Cerebral Ketone Body Uptake In Older Adults At‐Risk For Alzheimer’s Disease: A Pilot Study, Neurobiology of Aging (2019).