bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cortical and substantia nigra 18F‐PI‐2620 tau PET signal in Lewy body disease
Authors: Winer Joseph R. , Vossler Hillary , Young Christina B. , Romero America , Shahid Marian , Abdelnour Carla , Anders David , Shen Bin , Morales Aimara Pacheco , Davidzon Guido , Mormino Elizabeth C. , Poston Kathleen L. 
Published: December 2023

AbstractBackgroundTau PET imaging is a potential tool for measuring comorbid tau pathology in patients with Lewy body disease. Furthermore, tau PET ligands are known to bind to neuromelanin within substantia nigra (SN), with reduced binding in Parkinson’s disease relative to healthy individuals. We sought to characterize 18F‐PI‐2620, a next generation PET tracer, in patients from across the Lewy body disease spectrum.MethodA total of 126 participants from the Stanford Alzheimer’s Disease Center (ADRC) and the Stanford Aging and Memory Study (SAMS) were recruited for PET scanning with 18F‐PI‐2620. We compared 18F‐PI‐2620 uptake within medial temporal (entorhinal cortex, amygdala) and occipital (precuneus, lingual gyrus) regions as well as SN across patients with Parkinson’s disease (PD, n = 26), dementia with Lewy bodies (DLB, n = 6), and Alzheimer’s disease spectrum (AD, n = 21), in addition to cognitively normal older adults (healthy controls, HC, n = 73). Mean bilateral signal was extracted from cortical regions of interest in native space 18F‐PI‐2620 SUVRs (inferior cerebellar gray reference). Amyloid status was determined either by 18F‐florbetaben PET or CSF. To quantify SN, SUVRs were normalized to template space and an anatomical mask was used to extract mean signal. MDS‐UPDRS‐III motor exam scores, collected in an off‐medication state for all patients, were used as a measure of motor impairment.ResultEntorhinal and amygdala SUVR were significantly elevated in the AD group relative to all other groups, and in amyloid‐positive relative to amyloid‐negative HC (Fig 1). Tau burden in all regions was low across PD and DLB groups and did not differ based on amyloid status. SN SUVR was significantly lower in the PD group compared to the HC and AD group (Fig 2A). In patients with Lewy body disease (PD & DLB), MDS‐UPDRS‐III scores were negatively associated with SN SUVR (Fig 2B).ConclusionsThese findings suggest that cortical tau is low in Lewy body disease. Neuromelanin‐related 18F‐PI‐2620 signal within SN carries information about disease severity. Cortical tau and SN binding represent two unique signals in the same tau PET image that may be informative in the context of Lewy body disease.
Delaying Cognitive Decline Through Dietary Approaches and Evidence‐based Practices
Authors: Jackson Yolanda , Roberts Celeste , Glover Rosby , Rhodus Elizabeth K. 
Published: December 2023

AbstractBackgroundAlzheimer’s disease and related dementias (ADRD) disproportionately impact African Americans compared to non‐Hispanic Whites. Lifestyle factors, such as diet and exercise, may contribute toward this difference. Health campaigns tailored to these populations related to healthy lifestyle choices, such as the cognitive benefits seen with the MIND diet (Mediterranean‐dietary approaches to stop hypertension, Intervention for Neurodegenerative Delay) paired with evidence‐based guidelines, may improve self‐efficacy related to healthy behaviors. Utilizing the constructs of the Integrative Model, this study examines behavior change intention after an intervention using a health campaign encouraging MIND diet compliance and evidence‐based healthy aging guidelines.MethodsThis study implemented a culturally tailored health campaign related to healthy brain aging and an educational workshop led by experts in nutrition, Alzheimer’s disease, and behavioral science with older African American adults at a local faith‐based center. Upon completion of the workshop, participants completed select items of the 36‐Item Short Form Survey Instrument (SF‐36) and the Client Satisfaction Questionnaire (CSQ). Analyses of demographic and frequency reports illustrate likelihood to follow through with MIND diet principles.ResultsEighty‐five percent of participants (N = 20) reported little to no knowledge of the health campaign content prior to this study. Following the workshop, all participants reported that they were likely (66.7%) or very likely (33.3%) to incorporate principles learned from the evidence‐based workshop at home. Further, 71.4% reported being confident to follow the diet at home with an additional 28.6% of participants being very confident.ConclusionCulturally tailored health campaigns play an integral role in nutrition education, healthy aging, and lifestyle modification for ADRD reduction in the African American community. This approach enabled communication of evidence‐based practices of dietary modifications, cognition, and brain health as a mechanism to increase knowledge and self‐efficacy to carry out healthier behaviors at home. Community‐based nutrition education utilizing culturally appropriate health messages has potential to improve lifestyle behaviors, health disparities, and reduction of ADRD among African American older adults. Larger pragmatic, and implementation‐based studies using community‐engaged methods are needed to increase evidence and reach of this approach specific for aging African American adults.
Amyloid burden was associated with worse memory performance but no associated with conversion to mild cognitive impairment in SuperAgers
Authors: Neto Adalberto Studart , Coutinho Artur Martins , Carneiro Camila de Godoi , Moraes Natália Cristina , Aranha Mateus Rozalem , Spera Raphael Ribeiro , Parmera Jacy Bezerra , Yassuda Monica Sanches , Brucki Sonia Maria Dozzi , Leite Claudia da Costa , Buchpiguel Carlos A , Nitrini Ricardo 
Published: December 2023

AbstractBackgroundThe term “SuperAgers” (SA) was proposed to define older adults with 80 years or more who have a memory equivalent to 20‐30 years younger. The study aimed to investigate cortical amyloid deposition and follow‐up in a cohort of SA.MethodWe identified eleven SA seniors from an initial sample of 66 older adults who sought the study because they believed they had exceptional memory. Nine were evaluated in two time points (enrollment and 1 year follow‐up). PET with Pittsburgh Compound‐B labeled with carbon‐11 (11C‐PIB) was acquired on a hybrid PET/MR equipment and analyzed individually using semiquantitative analyses with 3D‐SSP. SPM8 software was used for group comparisons.ResultFour SA (36.4%) were PIB‐PET positive, without significant differences compared to the age‐matched healthy controls. Three out of four SA with PIB‐PET positive had subjective cognitive decline (SCD). Another three SA with SCD were negative PIB‐PET. A negative association between memory tests and the amyloid burden was found in the SA group. At one year of follow‐up, three of the nine SA evolved as non‐amnestic MCI, and six (66.7%) remained cognitively unimpaired. No SA group participant converted to amnestic MCI. There was no association between conversion rate to MCI and amyloid status (p = 0.583). Only one SA classified as MCI on the second visit had PIB‐PET positive. We found no association between the presence of memory complaints and conversion rate to MCI in SA group (p = 0.524).ConclusionAmyloid burden was associated with worse performance on memory tests and SCD but was not associated with conversion to MCI at a one‐year interval. SCD was also not associated with cognitive decline in SA.
The role of cerebrovascular pathology in the association between amyloid‐β and tau in cognitively unimpaired and impaired individuals
Authors: Coomans Emma M. , van Westen Danielle , Binette Alexa Pichet , Strandberg Olof , Spotorno Nicola , Palmqvist Sebastian , Stomrud Erik , Ossenkoppele Rik , Hansson Oskar 
Published: December 2023

AbstractBackgroundAlthough cerebrovascular pathology often co‐exists with Alzheimer’s disease pathology, it remains incompletely understood to what extent it can contribute to the progression of Alzheimer’s disease pathology. We investigated whether cerebrovascular pathology (white matter lesions [WML] and microbleeds) modified the association between amyloid‐β (Aβ) and both cross‐sectional and longitudinal tau in cognitively unimpaired (CU) and cognitively impaired (CI) individuals.MethodWe included 1240 participants from the Swedish BioFINDER‐2 cohort including 402 Aβ‐negative CU, 147 Aβ‐positive CU, 257 Aβ‐negative CI (MCI and non‐AD dementia) and 434 Aβ‐positive CI participants (MCI and AD dementia) (Table 1). All underwent baseline [18F]RO948 (tau)‐PET, and a subset (n = 678) underwent longitudinal tau‐PET (2.6±1.0‐years). We extracted tau‐PET SUVr in a temporal meta‐region‐of‐interest. For Aβ, we used global [18F]flutemetamol‐PET SUVr for CU and Aβ‐status (+/‐) for CI participants. Global WML volume was calculated using the SPM lesion segmentation tool, corrected for intra‐cranial volume and log‐transformed. Presence of microbleeds was dichotomized into absent or present (≥1) by visual read. Primary analyses included age‐, sex‐ and APOE ε4‐corrected linear mixed models between tau‐PET (outcome) and interactions between time, Aβ and WML volume/microbleeds (predictors).ResultUpon correcting for age, sex and ε4‐carriership, Aβ‐positive CU and CI participants showed significantly more microbleeds compared to Aβ‐negative participants of the same cognitive stage (both p<0.05), but no differences in WML volume was observed (both p>0.05). In CU, we observed a significant interaction effect between ≥1 microbleed and higher Aβ‐load with both greater cross‐sectional tau (β = 0.67 [CI: 0.45‐0.89], p<0.001) and longitudinal tau (β = 0.11 [CI: 0.07‐0.16], p<0.001) (Fig‐1, Table‐2). In CU, we also observed a significant interaction effect between larger WML volumes and higher Aβ‐load with greater cross‐sectional tau (β = 0.14 [CI: 0.06‐0.22], p = 0.001). When including both microbleeds and WML volume in the same model, only effects of microbleeds remained significant (Table‐2). No significant effects were observed in CI participants.ConclusionIn CU (but not CI) individuals, cerebrovascular pathology may modify the association between Aβ and tau by accelerating tau accumulation in the presence of Aβ. These results might suggest an early effect of cerebrovascular pathology on the interplay between Aβ and tau.
Loneliness and social isolation association with incidence of disability, dementia and mortality in Mexican older adults: three follow‐up years
Authors: Sánchez Brenda Sarai Miranda , Acosta‐Castillo Gilberto Isaac , Sosa‐Ortiz Ana Luisa 
Published: December 2023

AbstractBackgroundLoneliness is defined as the feeling of being alone and can be considered as persistent, unavoidable and unpleasant. Social isolation is characterized by low frequency of contact with the social network, which may or may not include family members. The study of each of these entities is important because of their high frequency in OA and their association with negative outcomes as disability, dementia even mortality.MethodWe performed a secondary analysis of 1,668 adults aged 65 years or older, evaluated within Dementia Research Group 10/66 protocols in Mexico, after 3‐year follow‐up. Loneliness presence was assessed based on three questions included in the Geriatric Mental State Inventory (GMS): do you feel lonely, does this feeling of loneliness generate discomfort or sadness, can you avoid feeling lonely. Social isolation was identified by assessing friends, relatives and neighbors contact frequency; co‐residence; church attendance and social gatherings. Association of loneliness with and without emotional discomfort, as well as social isolation with incidence of disability, dementia, and mortality after three years of follow‐up was estimated using multivariate competing risk models.ResultLoneliness without emotional discomfort was about 35.4%, 24.0% reported loneliness with emotional discomfort, meanwhile social isolation prevalence was 41.1%. A differential distribution of loneliness with and without emotional discomfort, age groups and education by catchment area was observed (Table 2). After three years of follow‐up loneliness was found to be associated with incident dementia subHR = 1.5 (95%CI:1.1‐2.1), and social isolation with mortality, subHR = 1.5 (95%CI:1.1‐2.0).ConclusionAfter three years follow‐up one out 3 OA reported feeling lonely without emotional discomfort, 1 out 4 felt lonely with emotional discomfort, while 2 out 5 reported social isolation. Loneliness without emotional discomfort showed an association with dementia development, meanwhile social isolation was associated with mortality. Finally, no association was found between loneliness with emotional discomfort with disability, dementia or mortality in the analyzed sample.
The association between 73 Alzheimer’s disease risk variants and white matter microstructural decline in aging
Authors: Archer Derek B , Shashikumar Niranjana , Jasodanand Varuna , Moore Elizabeth E. , Murray Sydney , Pechman Kimberly R. , Bilgel Murat , Beason‐Held Lori L , An Yang , Risacher Shannon L , Landman Bennett A. , Jefferson Angela L. , Saykin Andrew J. , Resnick Susan M. , Hohman Timothy J. 
Published: December 2023

AbstractBackgroundAlthough several prior diffusion MRI studies have indicated a role of medial temporal lobe (MTL) white matter microstructural decline in Alzheimer’s disease (AD), it is unclear which AD risk genes are associated with this decline. The goal of this study is to leverage multi‐site harmonized diffusion MRI data to investigate the relationship between 73 AD risk variants and microstructural decline in MTL tracts.MethodThe dataset used in this study was collated from three longitudinal cohorts of aging [Alzheimer’s Neuroimaging Initiative (ADNI), Baltimore Longitudinal Study of Aging (BLSA), Vanderbilt Memory & Aging Project (VMAP)]. In total, this dataset included 1,308 participants (70% cognitively unimpaired, 27% MCI, 3% AD) aged 50+ who had both diffusion MRI and genotype data and includes a total of 3,442 imaging sessions (mean number of visits: 2.68 ± 1.66, interval range: 1 ‐ 12 years). Genotype data was preprocessed using a standardized approach, and the dosage of the 73 AD risk variants was extracted. Diffusion MRI data was preprocessed using the PreQual pipeline and free‐water (FW) correction was conducted to obtain FW and FW‐corrected fractional anisotropy (FAFWcorr) maps. FW and FAFWcorr were quantified within 5 MTL tracts, including the cingulum, fornix, uncinate fasciculus, inferior longitudinal fasciculus, which were subsequently harmonized using the Longitudinal ComBat package. Linear regression was conducted to investigate the association between AD risk variants and MTL microstructure at baseline, while linear mixed effects regression was used for longitudinal analysis. All models were corrected for age at baseline and sex and corrected for multiple comparisons using the FDR approach.ResultAt baseline, APOE‐ε4 dosage was strongly associated with MTL FW in all tracts, with additional associations for TMEM106B and CR1 dosages with fornix FW (Table 1). Longitudinally, APOE‐ε4 dosage was a strong predictor of MTL FW decline in all tracts, and KAT8, CR1, and TMEM106B dosages exhibited significant associations with fornix microstructural decline (Table 2 and Figure 1).ConclusionThis study suggests that although APOE‐ε4 is the strongest predictor of white matter microstructural decline, several other AD risk genes (i.e., CR1, SPI1, TMEM106B, KAT8) contribute to decline, particularly in the fornix.
Burden of cerebral small vessel disease modifies relationship between some plasma Abeta 42/40 assays, but not p‐tau181 assays, with amyloid PET
Authors: Lesman‐Segev Orit H. , La Joie Renaud , Rozen Yael , Leibovici Anat , Livny Abigail , Yaffe Kristine , Weiner Michael S. W. , Silbert Lisa C , Shaw Leslie M. , Gardner Raquel C. 
Published: December 2023

AbstractBackgroundWe aimed to determine if burden of cerebral small vessel disease (CSVD) modifies the relationship of plasma amyloid‐beta (Abeta) 42/40 ratio and/or plasma p‐tau 181 with amyloid PET.MethodWe studied N = 100 participants from the Alzheimer’s Disease Neuroimaging Initiative with 1) Abeta‐42/40 biomarker levels using Quanterix SIMOA (Quanterix), Washington University Mass Spectroscopy (WashU), Simoa HD‐X 4Plex, Roche Elecsys, Shimadzu Mass Spectroscopy, and Gothenburg Mass Spectroscopy, 2) p‐tau181 plasma biomarker levels using Lumipluse G, Roche Elecsys, Simoa p‐tau181V2 Advantage (Simoa Advntage), Simoa p‐tau181, 3) MRI brain, and 4) amyloid‐PET. We stratified by CSVD bruden tertile (calculated from total white matter FLAIR hyperintensity volume). Amyloid positivity was defined as standardized uptake value ratio ≥ 1.11 for florbetapir PET scans. We used box plots to visualize plasma Abeta‐42/40 and p‐tau181 levels stratified by Amyloid‐PET positivity and CSVD tertile. Using logistic regression models, we tested for an interaction between CSVD and plasma Abeta‐42/40 ratio or p‐tau181 on amyloid PET positivity in unadjusted models and models adjusted for age, Clinical Dementia Rating, and presence of ≥1 apolipoprotein E4 allele (ApoE4+).ResultThe cohort had an average age of 77 years, was 56% female, 50% cognitively normal, and 42% ApoE4+ (Table1). We found significant interactions between CSVD and plasma Abeta‐42/40 ratio on amyloid‐PET positivity for Quanterix (raw/adjusted: p = 0.035/p = 0.049), Simoa HD‐Plex (p = 0.047/p = 0.047), and Gothenburg assays (p = 0.026/p = 0.030), with worst discrimination between amyloid‐PET positivity among participants with highest CSVD burden (Figure1A). The Quanterix and Gothenburg assay demonstrated near total overlap between amyloid‐PET positive vs. negative groups at the highest tertile of CSVD. No significant interaction was found between CSVD and any plasma p‐tau181 assay on amyloid‐PET positivity (all p>0.2, Figure1B).ConclusionOur findings suggest that individuals with a high burden of CSVD are at risk for incorrect Abeta‐42/40 ratio on certain assay platforms but not others. No interaction was found between CSVD and any plasma p‐tau181 assay on amyloid‐PET positivity. Further research in diverse cohorts with a high burden of CSVD is warranted to inform appropriate use of these blood assays and unravel mechanisms of this unexpected finding.
Reports of responses to coconut oil and medium‐chain triglyceride oil in 288 persons with Alzheimer’s and other cognitive impairment
Authors: Newport Mary T 
Published: December 2023

AbstractBackgroundGlucose hypometabolism is an early key feature of AD. Ketones provide alternative fuel to glucose during fasting, ketogenic diet (KD), and ketogenic oil consumption, and are taken up normally in the AD brain (Croteau J Alz Dis 2018). RCTs of KD ± MCT oil or CO (in program recipes) report improvement in people with cognitive impairment (reviewed in Cunnane NRDD 2020; Phillips Alz Res Therapy 2021), usually attributed to generation of ATP by circulating ketones. Ketones are also anti‐inflammatory (Kim Frontiers Immunol 2022) and reduced beta‐amyloid plaques and tau tangles in animal models (Kashiwaya PNAS 2000; Wu FASEB 2020). While blood ketones from CO are lower than from MCT oil, lauric acid (50% of CO) potently stimulated ketone production in cultured KT‐5 astrocytes (Nonaka J Oleo Science 2016), suggesting a more direct effect. Virgin CO also contains antioxidants and substances that inhibit amyloid plaque formation (Chatterjee Mech Ageing Devel 2020).MethodResponse/non‐response to CO ± MCT oil from all communications about persons with AD and other memory impairment collected by the author from 2008 to mid‐2014 were analyzed. Respondents were not prompted regarding expected improvements. Verbatim phrases allowed further categorization of improvements.Result288 reports were tabulated (33‐94yo; 48% male/52% female; 55% AD, 25% other dementia, 6% Parkinson’s, 2.4% MCI, 12% other memory complaints). 72% consumed only CO, 26% CO+MCT, and 2% MCT only. 89.2% reported improvements overall, further categorized as Memory/Cognition (72.6%), Social/Behavior/Mood/Personality (37.4%), Speech/Conversation (37.7%), Resumption of Self‐Care/Other Activities (28.4%), Physical Symptoms (20.7%), and Sleep (3.9%).ConclusionJust a few targeted FDA‐approved drug therapies claim slowing of cognitive decline. However, nutritional ketosis broadly addresses important pathological changes in the AD brain, including insulin resistance, glucose hypometabolism, and inflammation. A growing number of RCTs of KD ± MCTs/CO with positive cognitive outcomes and improvement in biomarkers add weight to this large collection of communications reporting meaningful improvements while consuming CO and/or MCT oil in cognition, social interaction, self‐care, and other areas important to daily life. Nutritional ketosis deserves more attention from funding organizations and greater public awareness for the potential to improve the lives of people with AD and other neurological impairments.
Longitudinal Cognitive Associates of the ATN Model in Down Syndrome
Authors: Peven Jamie C 
Published: December 2023

AbstractBackgroundIndividuals with Down syndrome (DS) are genetically at risk of Alzheimer’s disease (AD) due to the triplication of the amyloid precursor protein, resulting in overproduction of amyloid‐beta. In autosomal dominant AD (ADAD) and late‐onset AD (LOAD), the cascade of pathology begins with amyloid‐beta (A) accumulation, followed by tau (T) accumulation, and finally neurodegeneration (N), known as the ‘ATN model.’ The goal of this study was to understand the relationship between ATN and cognitive functioning in DS.MethodData on two time points (16 months apart) from a subset of adults with DS (N = 93) in the Alzheimer’s Biomarkers Consortium for Down Syndrome were analyzed. Participants completed a cognitive battery at both time points including the modified Cued Recall Test (mCRT) to measure episodic memory. Change scores were calculated subtracting baseline from cycle 2 performance. Baseline PET imaging assessed A+ and T+ defined by previously published regional cutoffs. Baseline hippocampal volume was extracted from structural MRI and N+ was defined as one standard deviation below the mean controlling for intracranial volume. General linear models examined follow‐up cognitive performance and total change by baseline ATN group controlling for age, premorbid intellectual disability, and, when appropriate, baseline scores using Bonferroni correction.ResultParticipants were 39.15 years old (SD = 8.99) and 55.9% male. Participants were classified as: A‐T‐N‐ (65; 69.9%), A+T‐N‐ (15; 16.1%), A+T+N‐ (8; 8.6%), A+T+N+ (5, 5.4%). At follow‐up, the A‐T‐N‐ and A+T‐N‐ groups produced significantly fewer mCRT intrusions than the A+T+N‐ and A+T+N+ groups (F(3,86) = 4.41, p = .006). ATN status was not associated with any other follow‐up or change score. However, patterns of change reflect greater decline with conversion to T+ for recall, switching, visual construction, and overall cognitive ability.ConclusionAdults with DS with greater AD biomarkers, and particularly the presence of T+, show poorer memory functioning compared with those who have lower neuropathological burden. At follow‐up, only intrusions were significantly associated with baseline ATN status. Adults with DS show similar trends of neuropathology and related cognitive decrements as have been reported in both ADAD and LOAD, although individuals with DS may require greater accumulation of neuropathology to detect more subtle impairments.