bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk prediction of prodromal Alzheimer’s disease using deep learning of MRI scans
Authors: Basha Shaikh , Marizzoni Moira , Frisoni Giovanni B , Jovicich Jorge , Miyapuram Krishna P 
Published: December 2021

AbstractBackgroundDeep learning approaches for classification have the advantage of automatically learning the relevant features but require large amount of data for training. We test the efficacy of deep learning approach for prediction of risk factor for prodromal Alzheimer’s disease from whole brain MRI scans segmented into grey/white matter and CSF images.MethodLongitudinal MPRAGE images were acquired from 146 participants in six month intervals over a period of two years as part of PharmaCog Consortium. Whole brain structural scans were segmented using FreeSurfer pipeline into grey matter (GM), white matter (WM) and cerebrospinal fluid (CSF) images. We used a convolutional neural network architecture with 11 layers to classify individuals with high and low risk based on 3‐dimensional MRI data. The model consisted of 3 convolution layers that performed slice wise convolutions in 2‐dimensions, 3 batch normalization layers, 1 max pooling layer, 1 flatten layer, 2 dense layers and 1 rectified linear unit (ReLU) activation layer. Hyperparameter tuning for the model was done using various combinations of kernel size ([2,3,4]), strides ([1,2,3]), batch size ([5,10,15,20]), epochs ([10,15,20]) and number of neurons in the dense layer ([16,32,64]) to identify the optimized parameters for the model.ResultOut of the 146 subjects available, we chose 97 subjects randomly. The cross‐sectional MRI data at various timestamps was considered for training the model. The rest of the data was considered as the test set. After this separation, we had training size and test size of 436 and 168 images respectively. The training and test sets did not have any common subjects and thus provided relevant results for subject wise classification for unseen subjects.We trained and tested our model with all possible combinations of segmented images separately (GM, WM, CSF, GM+WM, WM+CSF, GM+CSF, GM+WM+CSF). Out of all the combinations, we attained best results using Grey mask (GM) data, with training and test accuracies of 93.62% and 72.02% respectively.ConclusionWe presented a deep learning framework for risk prediction of cross‐sectional whole brain MRI data for unseen subjects. This work combined with classification approaches on longitudinal data can prove effective in early diagnosis of Alzheimer’s disease.
Clinical characterization of Colombian families with frontotemporal dementia due to the MAPT P397S mutation
Authors: Zuluaga‐Castaño Yesica , Aguillon David , Rassi Sofia , Zuluaga Maria , Gómez‐Henck Clara , Lopera Francisco , Quiroz Yakeel T. 
Published: December 2021

AbstractBackgroundMutations in the microtubule associated protein tau (MAPT) gene located in chromosome 17 have been associated with frontotemporal dementia (FTD). The novel mutation Pro397Ser, with an autosomal dominant inheritance pattern has been recently reported in Spain (Borrego‐Écija et al., 2019). The Group of Neuroscience of the University of Antioquia in Colombia has identified several families with mutations leading to FTD. Here we present the initial clinical characterization of individuals carrying the MAPT P397S mutation.MethodA total of 30 family members were included (15 carriers and 15 non‐carriers, 18 – 76 years old). All participants underwent a comprehensive neurological and neuropsychological evaluation. They also completed self‐reported measures of depression and behavioral symptoms. Mann‐Whitney tests were used to test between‐group differences in cognitive measures. Spearman correlations were used to examine associations among outcome measures and age.ResultMean age was 48.7 years (SD 16.4), and mean education was 10.7 years (SD=4.56). Six carriers were classified as cognitively impaired (MCI= 3, moderate/severe dementia= 3). Mean age of clinical was 50 years. Initial symptomatology was predominantly behavioral (disinhibition, aggressiveness, loss of empathy, compulsiveness, dietary changes) followed by loss of executive function, memory, language skills and decline in ADLs in affected individuals. Structural MRIs showed frontotemporal lobar degeneration in all impaired carriers, and additional bilateral hippocampal atrophy with left predominance in two of them. The cognitive profile of carriers was characterized by lower scores in measures of executive function, semantic processing and short‐term memory loss. Cognitively unimpaired carriers had statistically significant worse performance on the INECO Battery, a measure of executive function, compared to non‐carriers, several years prior to their clinical onset.ConclusionInitial findings showed that the clinical profile of Colombian families with the MAPT‐P397S novel mutation is characterized by executive dysfunction, behavioral changes, semantic language alterations and memory loss. Findings suggest that the INECO Battery may be a sensitive tool to detect subtle changes in executive function in cognitively unimpaired carriers of this mutation. Longitudinal follow‐up of these individuals will be important to better characterize the disease progression from preclinical to clinical stages. Future studies should consider adding neuroimaging and other biomarker measures.
In vivo analysis of synaptic degeneration with Aβ plaque and NFT accumulation in cognitive decline
Authors: DiFilippo Alexandra H. , Tullis Tyler , Zammit Matthew D. , Murali Dhanabalan , Kohli Akshay , Ennis Gilda E. , Davenport Nancy J. , Barnhart Todd E. , Engle Jonathan W. , Betthauser Tobey J. , Stone Charles K. , Johnson Sterling C. , Bendlin Barbara B , Christian Bradley T. 
Published: December 2021

AbstractBackground[11C]UCB‐J selectively binds to synaptic vesicle glycoprotein 2A (SV2A) and may be used to measure synaptic density in synaptopathies. Along with the accumulation of amyloid‐b plaques and neurofibrillary tau tangles, neurodegeneration is a hallmark of Alzheimer’s disease (AD) dementia. Synaptic density may be decreased due to AD pathology, resulting in cognitive dysfunction. We examined whether synaptic density was related to the accumulation of protein aggregates characteristic of AD as well as cognitive function.MethodThirty subjects (68.6±6.2 years old, 20F/10M) recruited from the Wisconsin ADRC and the Wisconsin Registry for Alzheimer’s Prevention study underwent [11C]UCB‐J dynamic PET imaging to assess synaptic density, T1w‐MR imaging, and the Rey Auditory Verbal Learning Test (RAVLT). Twenty‐four participants also completed [11C]PiB dynamic imaging to assess amyloid‐b plaque accumulation and [18F]MK‐6240 dynamic imaging to assess neurofibrillary tangle accumulation. T1w‐MRI was used to derive subject‐specific regions of interest (ROIs) as well as to calculate the matrices required to transform images into MNI152 space. Global amyloid burden was ascertained by taking the mean PiB DVR across eight bilateral AAL‐based ROIs. Neurofibrillary tau tangle accumulation in the entorhinal cortex was quantified using the [18F]MK‐6240 SUV ratio. Subject‐specific hippocampus ROIs for [11C]UCB‐J analysis were defined using FreeSurfer (v7) segmentation of the participant’s MR image.ResultUsing data from the n=24 subjects, [11C]UCB‐J binding in the hippocampus was significantly associated with [11C]PiB global DVR (R2 = 0.24, P = 0.01) and [18F]MK‐6240 uptake in the entorhinal cortex (R2 = 0.17, P = 0.04). After correcting for hippocampus volume size, significance decreased for both measures (R2 = 0.28, P = 0.05 for [11C]PiB global DVR; R2 = 0.17, P = 0.05 for [18F]MK‐6240 entorhinal cortex SUVR). [11C]UCB‐J binding in the hippocampus was not significantly related to RAVLT immediate recall (R2 = 0.52, P = 0.08) but was significantly associated with RAVLT delayed recall (R2 = 0.55, P = 0.04).ConclusionFindings suggest that synaptic impairment is related to amyloid‐b and neurofibrillary tau tangle accumulation as well as worse performance on RAVLT delayed recall. Future work will test the longitudinal relationship between accumulation of AD pathology, synapse loss, and cognitive decline.
REACTION: Reducing the effects of aging on cognition with therapeutic intervention of an oral nutrient — A pilot interventional study for age‐related cognitive decline
Authors: Camargo Christian , McInerney Katalina , de Wilde Janneke , Counotte Danielle , Rundek Tatjana 
Published: December 2021

AbstractBackgroundAge‐related cognitive decline (ARCD) refers to the cognitive changes that can occur in individuals as a consequence of aging, distinct from cognitive changes due to a primary neurodegenerative process (e.g., Alzheimer’s Disease), cerebral ischemia (e.g., vascular dementia), or other pathology. However, there is sparse research into direct interventions for ARCD. Recent research suggests that the underlying mechanism behind ARCD is a loss of synaptic plasticity, which is essential for learning, memory, and the formation of memory engrams, in part through its effects on dendritic spine morphology. Therefore, therapies aimed at rescuing dendritic spine density and increasing synaptic plasticity may be viable strategies for decreasing the effects of ARCD. Souvenaid contains Fortasyn Connect, a specific combination of nutrients designed to enhance synapse formation by providing precursors and cofactors for phospholipid synthesis. In prodromal Alzheimer’s disease, Fortasyn Connect showed beneficial effects on memory, cognition, and brain atrophy [1]. In addition, the data from this study suggest a stronger effect would be expected in participants at earlier stages of prodromal AD. Souvenaid has not yet been tested in individuals with ARCD.MethodTowards this end, we present the design of a 6‐month single‐center pilot clinical trial that aims to perform all assessments via a telemedicine platform. The study design specifically factors in local COVID‐19 restrictions. We plan to recruit 60 participants aged 55‐89 with age‐related cognitive decline, who will be screened and randomized to the oral multi‐nutrient combination (Souvenaid) or placebo on a 1:1 basis. The main outcome of this trial is feasibility (recruitment rate and time, adherence rate and retention rate). Other outcomes include memory (e.g. Ray Verbal Learning Task), cognition (e.g. Oral Trail Making Test), and quality of life (e.g. Amsterdam IADL Questionnaire) outcome measures.ResultResults of REACTION will provide insight into the feasibility of a virtual study with Souvenaid in ARCD.ConclusionWith the rapidly growing prevalence of ARCD and no pharmacological interventions currently available, nutritional interventions may potentially play an important role to reduce or delay the effects of ARCD.
Differential measurement of depression by racial group: Findings from an Alzheimer’s Disease Center cohort
Authors: Umucu Emre , Wyman Mary F. , Zuelsdorff Megan , Lambrou Nickolas H. , Summers Marlene , Strong Lois , Martin Wesley , Carter Fabu P , Bouges Shenikqua , Gleason Carey E. 
Published: December 2021

AbstractBackgroundBoth researchers and clinicians require risk screeners that are psychometrically‐sound and culturally‐appropriate in addition to being efficient and low‐burden. Brief versions of the Geriatric Depression Scale (GDS) exist, but there is limited study on the performance of these screeners across historically underserved and underrepresented racial groups. We examined the ability of 10 brief versions of the GDS to detect group differences in depressive symptom endorsement and to predict cognitive status in White, Black, and American Indian/Alaska Native (AI/AN) participants in an ADC‐based cohort.MethodParticipants included 555 cognitively‐normal middle‐aged and older‐adults (Mage
=60.85) enrolled in the Wisconsin ADRC. The majority of participants were female (66.5%). 17.7% of participants were Black and 3.1% were AI/AN. For each GDS version, we used Kruskal‐Wallis tests with post‐hoc‐pairwise comparisons with Bonferroni corrections to compare scores across the three groups.ResultUsing nine of 10 GDS versions, there were significant group differences in total score. Post hoc pairwise comparisons revealed that AI/AN endorsed significantly fewer symptoms of depression than Blacks (p < 0.05) when using the GDS‐4a. Whites and Blacks were not significantly different in GDS‐4a. However, Whites and Blacks were different in eight of 10 versions (i.e., GDS‐1a; GDS‐4b; GDS‐5; GDS‐7; GDS‐8; GDS‐10a; GDS‐10b; GDS‐15). No group differences were found between Whites and AI/AN and Blacks and AI/AN in most versions of the GDS. In the combined sample, all GDS versions showed a significant, moderate positive correlation with CDR score.ConclusionRigorous assessment and detection of depression is an important step to reducing dementia morbidity and possibly risk, but many brief screeners were evaluated in racial homogenous groups. Most GDS short versions were able to detect significant differences in depression score between Whites and Blacks. Interestingly, the GDS‐4a (4 non‐behavioral items) showed significant difference between AI/AN and Blacks, not detected in other versions. These early findings suggest that more research must address culturally‐valid assessment of depressive symptoms in cognitive aging research and geriatric clinic settings. Acknowledgement: Data collection and contributions by author Carey E. Gleason are supported by funding from NIH‐NIA for African Americans Fighting Alzheimer’s at Midlife (AA‐FAIM, R01 AG054059) and the Wisconsin Alzheimer’s Disease Center (P50 AG033514).
Cognitive aging with dementia, mild cognitive impairment (MCI), or no impairment: A comparison of same‐ and other‐sex couples
Authors: Correro Anthony N , Gauthreaux Kathryn , Perales Jaime , Kukull Walter A , Flatt Jason D 
Published: December 2021

AbstractBackgroundChronic stress has harmful effects on cognition, and minority stress is thought to underlie health disparities experienced by lesbian, gay, bisexual, and transgender (LGBT+) older adults. Few studies have compared cognitive trajectories between individuals in same‐ (SSR) versus other‐sex relationships (OSR). We expand on this work by comprehensively examining differences in neuropsychological measurements for individuals in SSR and OSR. We explored whether: 1) SSR have poorer overall cognitive performance at baseline compared to OSR older adults, 2) SSR have steeper cognitive decline relative to OSR, and 3) differences in verbal and visuospatial memory among SSR versus OSR.MethodData were obtained from the National Alzheimer’s Coordinating Center (NACC). Eligibility criteria included 2+ visits in NACC’s Uniform Data Set (UDS) and age 55+ years at baseline. Participants were assigned to normal (N), MCI, or dementia (D) groups based on clinician assessment and CDR® global score. Given neuropsychological tests changed between versions of the UDS, we ran analyses separately using both versions (C1, C2). Multivariable linear mixed‐effects models accounted for center clustering and repeated measures by individual. Models were stratified by baseline cognition and adjusted for baseline age, sex, education, and APOE ɛ4 carrier status.ResultOSR and SSR individuals showed significant decline in CDR® sum of boxes (CDR‐SB) regardless of baseline cognition. Among C1 participants, OSR declined significantly in all cognitive domains regardless of baseline cognition. SSR‐N declined in the attention, executive, and language/semantic memory (SM) domains; SSR‐MCI showed declines in global, attention, and language/SM domains; similar to OSR‐D, SSR‐D declined in all domains. Unexpectedly, SSR‐D declined more slowly than OSR‐D in attention and language/SM domains. Among C2 participants, OSR exhibited greater levels of decline in global cognition relative to SSR.ConclusionWe sought to compare the cognitive changes of older adults in SSR or OSR. SSR declined in attention, language, and semantic memory. OSR had steeper, more global declines. Our results contrast with a recent population‐wide study of SSR versus OSR, suggesting that in our sample, SSR may be resilient to the effects of chronic minority stress on cognition. Additional research regarding LGBT+ related resiliency is necessary.
Updated prevalence estimates of amyloid positivity from cognitively normal to clinical Alzheimer’s disease dementia: The Amyloid Biomarker Study
Authors: Janssen Olin , Jansen Willemijn J , Tijms Betty M , Maserejian Nancy Nairi , Ossenkoppele Rik , Verhey Frans RJ , Visser Pieter Jelle ,   the Amyloid Biomarker Study group
Published: December 2021

AbstractBackgroundWe have updated our previous amyloid positivity prevalence estimates (Jansen, 2015; Ossenkoppele, 2015; Table 1) with data from 19,097 individuals from 85 cohorts. We tested if prevalence estimates differed for positron emission tomography (PET) or cerebrospinal fluid (CSF) amyloid. We calculated data‐driven CSF cut‐points as previous studies suggested a drift in Innotest‐assay performance.MethodWe included 9,908 participants with normal cognition (CN); 1,542 with subjective cognitive decline (SCD); 5,405 with mild cognitive impairment (MCI); and 2,260 with clinical Alzheimer’s disease (AD) dementia. 10,139 participants had an amyloid‐PET measure and 8,958 participants had an amyloid‐CSF measure. Amyloid‐ß aggregation was originally dichotomized as normal or abnormal according to study‐specific cut‐points, and we defined data‐driven CSF cut‐points using Gaussian mixture modelling. Generalized‐estimating‐equations adjusting for within‐study clustering of individuals were used to estimate amyloid positivity prevalence according to age, cognitive status, and biomarker modality and compared original with updated cut‐points.ResultAmyloid positivity prevalence was higher with older age and advancing disease severity. Using original cut‐points as provided by the cohort, the prevalence of amyloid positivity at the median age of 70 was similar for PET and CSF estimates for CN (24%), SCD (26%), and MCI (51%), and was higher in PET (87%) than CSF (79%) for clinical AD dementia. Using the data‐driven CSF cut‐points, the prevalence of amyloid positivity was higher for CSF‐based estimates than PET‐based estimates in CN (CSF 33%, PET 24%), SCD (CSF 36%, PET 27%), and MCI (CSF 60%, PET 49%), but comparable in CSF and PET in clinically diagnosed AD dementia (CSF 83%, PET 87) (Table 1, Figure 1).ConclusionWe provide updated amyloid positivity estimates from the Amyloid Biomarker Study. CSF‐based estimates using a data‐driven approach resulted in higher estimates (up to 11% higher) in people without clinical AD dementia than PET‐based estimates. Whether CSF‐based estimates are more sensitive than PET‐based estimates for amyloid pathology among people without dementia needs to be explored in cohorts that use both modalities. These updated estimates may be useful to understand potential eligible patient population sizes for anti‐amyloid therapies and to inform recruitment strategies for clinical trials investigating anti‐amyloid therapies.
Physical activity and sedentary time in a multimodal lifestyle intervention in prodromal Alzheimer’s disease: The MIND‐ADMINI pilot trial
Authors: Thunborg Charlotta , Rosenberg Anna , Barbera Mariagnese , Coley Nicola , Ekblom Maria , Ekblom Örjan , Levak Nicholas , Solomon Alina , Kivipelto Miia 
Published: December 2021

AbstractBackgroundAlzheimer’s disease (AD) is multifactorial. Interventions simultaneously targeting multiple risk factors are most likely to be effective, as demonstrated in the 2‐year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). While patients with prodromal AD represent a group with high risk of progressing to dementia, no trials have tested the feasibility of multimodal interventions in prodromal AD. The main purpose of the MIND‐ADMINI was to evaluate the overall adherence to such multimodal intervention. This sub‐study focuses on exploratory outcomes which included physical performance and physical activity (PA) levels.MethodMIND‐ADMINI is a 6‐month multicenter (Sweden, Finland, Germany, France) randomized controlled pilot trial. Participants with prodromal AD, between 60 and 85 years were randomized into three groups: usual care (control (C)), multidomain lifestyle intervention combining nutritional guidance, cognitive training, exercise, and careful monitoring of vascular risk factors (ML), or multidomain lifestyle intervention+medical food (ML+MF) (Fortasyn Connect). The multidomain lifestyle intervention was based on the FINGER model and included a progressive aerobic‐ and strength training program. Moderate to vigorous physical activity (MVPA), light activity, step counts, and time (min/day) spent sedentary were evaluated using data from a hip‐worn accelerometer. For each outcome, 6‐month values were regressed on baseline to estimate change.ResultsBaseline accelerometry data was available for 66 of 69 participants in Sweden, Finland, and France. At the 6‐month follow‐up, accelerometry data from 55 participants was included. At baseline mean age (SD) was 72,9 (6,2) years, 50,7% were men, and MMSE score was 27,6 (1,6) points. No significant values were found. At follow‐up, all groups increased their sedentary time, C (8,3%), ML (9,3%) and ML+MF (1,6%). Increased step count (3,4%) time in MVPA (2,8%) and light activity (9,5%) was observed during follow‐up in the ML+MF group.ConclusionsMeasurement of physical activity level using a hip‐worn accelerometer was feasible in this population. The observed increased time in MVPA, light activity and step counts in ML+MF group at the same time as sedentary time increased in all three groups between baseline and 6‐months follow‐up highlight the importance of physical activity as a part of multidomain lifestyle interventions in persons with prodromal AD.
Relationship between resting state alpha electroencephalographic rhythms and aging in cognitively unimpaired seniors and patients with mild cognitive impairment due to Alzheimer’s disease and amnestic mild cognitive impairment
Authors: Del Percio Claudio , Lizio Roberta , Noce Giuseppe , Lopez Susanna , Soricelli Andrea , Ferri Raffaele , Güntekin Bahar , Yener Gorsev , Marizzoni Moira , Frisoni Giovanni B , Babiloni Claudio 
Published: December 2021

AbstractBackgroundThe rsEEG alpha rhythms reflect cortical neural synchronization mechanisms underpinning the inhibition of sensory, cognitive, and motor areas in parietal, temporal, and occipital cortex during a condition of low vigilance. Here we tested the hypothesis that age may diversely affect rsEEG alpha (8‐12 Hz) rhythms recorded in normal elderly (Nold) seniors and patients with Alzheimer’s disease and mild cognitive impairment (ADMCI).MethodClinical and rsEEG datasets in 63 ADMCI and 60 Nold individuals ‐ matched as demography, education, and gender ‐ were taken from an international archive. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands as well as fixed beta (14‐30 Hz) and gamma (30‐40 Hz) bands. Each group was stratified into three subgroups based on age ranges (i.e., tertiles).ResultAs compared to the younger Nold subgroups, the older one showed greater reductions in the rsEEG alpha rhythms with major topographical effects in posterior regions (Figure 1 top). On the contrary, in relation to the younger ADMCI subgroups, the older one displayed lesser reduction in those rhythms (Figure 1 bottom). Notably, the ADMCI subgroups pointed to similar cerebrospinal fluid AD diagnostic biomarkers, gray and white matter brain lesions as revealed by neuroimaging, and clinical and neuropsychological scores.ConclusionThe present results suggest that age may represent a deranging factor for dominant rsEEG alpha rhythms in Nold seniors, while rsEEG alpha rhythms in ADMCI patients may be more affected by the disease variants related to earlier vs. later onset of the AD.