bluuebunny/crossref_metadata_2025_split huggingface dataset:
From brain volumes to subgroup classification in genetic mutation carriers for frontotemporal dementia: A cluster analysis in the GENFI study
Authors: Bocchetta Martina , Todd Emily G. , Nicholas Jennifer M. , Heller Carolin , Swift Imogen J. , Peakman Georgia , Cash David M. , Convery Rhian S. , Russell Lucy L. , Thomas David L. , Iglesias Juan Eugenio , van Swieten John C. , Jiskoot Lize C. , Seelaar Harro , Borroni Barbara , Galimberti Daniela , Sanchez‐Valle Raquel , Laforce Robert , Moreno Fermin , Synofzik Matthis , Graff Caroline , Masellis Mario , Tartaglia Maria Carmela , Rowe James B. , Vandenberghe Rik , Finger Elizabeth , Tagliavini Fabrizio , Mendonca Alexandre , Santana Isabel , Butler Christopher , Ducharme Simon , Gerhard Alexander , Danek Adrian , Levin Johannes , Otto Markus , Sorbi Sandro , Ber Isabelle Le , Pasquier Florence , Rohrer Jonathan D. ,   Genetic Frontotemporal dementia Initiative (GENFI)
Published: December 2021

AbstractBackgroundGenetic frontotemporal dementia (FTD) is highly heterogeneous, with carriers of mutations in the same gene manifesting different phenotypes. Using in vivo MR images from the Genetic FTD Initiative (GENFI), we aimed to identify subgroups within the same genetic group whose brains were affected differently.MethodCortical and subcortical volumes of interest were generated using automated parcellation methods on volumetric 3T T1‐weighted MRI scans for 479 carriers (198 GRN, 202 C9orf72, and 79 MAPT mutation carriers). W‐scores for 85 volumes of interest were computed from a linear regression model carried out on 298 non‐carrier cognitively normal controls adjusting for the effect of age, sex, total intracranial volume and scanner type. Cluster analyses with the Ward agglomerating method were performed on all w‐scores while considering the three genetic groups independently. The identified clusters were then compared for age, estimated years from onset, global and sum of boxes scores of the CDR® plus NACC FTLD (at baseline and after one year), neurofilament light chain (NfL) levels in the plasma and w‐scores in brain regions typically showing early atrophy (Kruskal‐Wallis test).ResultWe identified three clusters among the GRN mutation carriers and four in the MAPT and C9orf72 groups, which were all significantly different for the variables reported in the Table (p‐value<0.003). For all three genetic groups, one cluster was formed by patients with a clinical diagnosis of FTD, with more extensive atrophy and increased disease severity. For the remaining clusters, there seemed to be an association with disease severity for MAPT and GRN mutation carriers but not so for C9orf72 expansion carriers where clinical scores were not clearly associated with a specific cluster.ConclusionBy only looking at regional brain volumes, we were able to detect different clusters within carriers of mutations in the same gene, with C9orf72 expansion carriers being the most heterogenous group. Further investigations with specific cognitive, clinical and biomarkers correlates, including further follow‐up visits, are needed.
Association between bilateral oophorectomy and cognitive decline in older women from the Baltimore Longitudinal Study of Aging
Authors: Reuben Rebekah , An Yang , Resnick Susan M. , Einstein Gillian 
Published: December 2021

AbstractBackgroundNearly two‐thirds of individuals with Alzheimer’s disease (AD) are women, and the lifetime risk for AD is twice as high in women compared to men at age 45 (Alzheimer’s Association, 2019). Despite this increased prevalence, little is known about why more women develop AD. Early life events affecting 17β‐estradiol (E2) may be a potential mechanism behind this sex difference. E2 and/or ovarian loss leads to cognitive decline and neurodegeneration, which is mitigated with E2 (Gervais et al., 2020; Kantarci et al., 2018; Zeydan et al., 2019). Further, women with bilateral oophorectomy have an increased risk of AD in later life (Rocca et al., 2007). However, little is known about the long‐term trajectories of cognitive change post‐oophorectomy.MethodThe current study investigated cognitive decline over time in older women with bilateral oophorectomy (BO; n = 30; total visits = 131) prior to age 45 compared to spontaneously menopausal (SM; n = 61; total visits = 277) women from the Baltimore Longitudinal Study of Aging (BLSA; Shock et al., 1984). All participants were free of any dementia and completed a variety of demographic and cognitive assessments. Each eligible BO participant was age‐matched at a 1:2 ratio with a SM participant. Data were analyzed using linear mixed‐effects models in R 3.6.1 (R Core Team, 2019).ResultParticipants completed an average of four visits over 11‐years, and ranged in age from 52‐91 years. Our analyses revealed the BO group recalled significantly less words on the California Verbal Learning Test and made significantly more errors on the Benton Visual Retention Test over time than the SM group. Additionally, the BO group had poorer Digits Backward and Letter Fluency performance over time compared to the SM group.ConclusionResults demonstrate an association between BO prior to age 45 and greater longitudinal decline in executive function, verbal memory, visual memory, and working memory performance compared to age‐matched, spontaneously menopausal women. This is the first study to evaluate continuous cognitive decline post‐oophorectomy from midlife to older age, and suggests that even in normal aging, the early loss of E2 via BO may confer long‐lasting effects on cognition spanning decades of life.
The neural association between awareness of the self and of others: A brain imaging study of anosognosia and social cognition in early Alzheimer’s disease
Authors: Valera‐Bermejo Jose Manuel , Mitolo Micaela , Cerami Chiara , Dodich Alessandra , De Marco Matteo , Venneri Annalena 
Published: December 2021

AbstractBackgroundA major proportion of patients with Alzheimer’s disease (AD) shows disorders of awareness in the early stages of disease that manifest as lack of/limited self‐awareness of their own cognitive deficits (anosognosia). Additionally, social awareness, i.e. aspects of social cognition, might also be impaired and reflect negatively on the patient’s capacity for self‐appraisal. The present study intends to explain the behavioural, brain structural and functional relationship between the presence of anosognosia and alterations in emotion and intention attribution in early‐AD, to understand the interaction between self/others awareness in the early stages of the disease.MethodsTwenty‐nine early‐AD individuals underwent neuropsychological assessment to detect the presence of anosognosia and alterations in proxies of affective ToM. Additionally, T1‐weighted structural and resting‐state functional MRI scans were acquired and pre‐processed using the Statistical Parametric Mapping (SPM) 12 software. An independent component analysis (ICA) was performed at a group level to isolate and reconstruct four intrinsic connectivity large‐scale brain networks, namely fronto‐parietal, salience, and anterior and posterior default mode networks (DMN). Non‐parametric partial correlations were performed between the neuropsychological proxies of self‐other awareness. Functional and voxel‐based morphometry multiple regression outcome maps of anosognosia and ToM were visually overlapped and brain‐masks were devised to show statistical maps of the intersecting regions.ResultsA significant negative correlation was found between cognitive outcomes of anosognosia with emotion recognition (ρ= ‐.549, p=.004) and Theory of Mind (ρ=‐.671, p=.001). There were significant brain structure intersections between anosognosia and Theory of Mind in relation to grey matter reduction in the right anterior cingulate cortex (ACC) (BA24/32) and left caudate. Anosognosia/ToM functional maps showed only visual intersections of connectivity between the anterior DMN and the inferior occipital gyrus and precentral gyrus (FWE<0.05).ConclusionThere seems to be an association between self and others awareness in early‐AD patients and its impairment appears to be underpinned by loss of neural tissue in the right ACC and subcortical regions. Similarly, the DMN seems to interact with specific occipito‐frontal regions, where visual information and mirror system dynamics might provide valuable resources to achieve self to other awareness in the presence of a neurodegenerative disease such AD.
Differential speech and language characteristics across neurodegenerative disorders
Authors: Robin Jessica , Xu Mengdan , DeSouza Danielle D , Gupta Anoopum S , Kaufman Liam D , Simpson Bill 
Published: December 2021

AbstractBackgroundSpeech and language changes have been reported to occur across a range of neurodegenerative disorders, including Alzheimer’s Disease (AD), Frontotemporal Dementia (FTD) and Parkinson’s Disease (PD). Characterizing and quantifying such changes will enable the development of novel speech‐based measures to identify and monitor disease remotely and non‐invasively. In order to determine if such measures are disease‐specific, it is important to compare speech and language changes across different neurological conditions. In this study, we identify speech and language characteristics that are differentially affected across AD, FTD and PD populations.MethodIn this cross‐study comparison, we pooled data from normative studies of older adults (N = 299), and studies of individuals with a clinical diagnosis of AD (N = 895), FTD (N = 43) or PD (N = 42). In all studies, speech was recorded as participants performed a picture description task, in which they were shown a line drawing of a scene and asked to describe everything they saw in the picture. Speech samples were transcribed and analyzed, producing >500 acoustic and linguistic variables describing the characteristics of the speech sound and content. Speech variables were compared across groups using ANOVAs with a factor of diagnosis group, and significant group effects (p < 0.05) were further examined with pairwise group comparisons.ResultSpeech variables showing common or differential effects according to diagnosis were identified in this exploratory cross‐study comparison. Speech variables relating to the ease of speech production, including speech rate and number of pauses, were affected in all three diseases when compared to control participants. Select acoustic variables, including mean intensity and zero‐crossing rate, showed the greatest differences in PD compared to FTD or AD. Individuals with AD and FTD produced picture descriptions with less relevant information content. Select lexical variables, including pronoun and preposition use, were selectively affected in AD but not FTD or PD.ConclusionThis study indicates that speech and language characteristics, derived from a picture description task, were differentially affected in AD, FTD, and PD. We found evidence for acoustic changes in PD, consistent with motor speech impairments, and linguistic changes in AD and FTD, consistent with cognitive impairments.
Automatic classification of AD versus FTLD pathology using speech analysis in a biologically confirmed cohort
Authors: Cho Sunghye , Shellikeri Sanjana , Ash Sharon , Liberman Mark Y. , Grossman Murray , Nevler Naomi , Nevler Naomi 
Published: December 2021

AbstractBackgroundLogopenic variant primary progressive aphasia (lvPPA) is a non‐amnestic presentation of Alzheimer’s disease (AD). Many studies have proposed automatic classification systems comparing AD to healthy controls (HC), showing an accuracy range of 70%–88%, but have not included lvPPA, nor distinguished patients with AD neuropathologic change (ADNC) from patients with other neurodegenerative changes. We propose automatic classification systems that utilize language features to detect ADNC.MethodUsing automatic language processing tools, we extracted 34 language features from digitized 1‐minute picture descriptions produced by 69 patients with likely ADNC (49 amnestic AD (62.6±7.6y), 28 non‐amnestic lvPPA (63.2±7.1y); confirmed by autopsy or CSF analytes consistent with ADNC), 20 PPA patients with likely FTLD‐tau pathology (67.8±7y), and 35 HC (64.6±7y). Extracted features include part‐of‐speech categories per 100 words, lexical characteristics of content words (e.g. frequency, concreteness), and acoustic properties (e.g. pause rate, articulation rate). Multiple random forest (RF) and support vector machine (SVM) classifiers were built for three binary (ADNC vs. HC; ADNC vs. FTLD‐tau; lvPPA vs. FTLD‐tau) and one three‐way classifications (ADNC vs. FTLD‐tau vs. HC). We performed leave‐one‐out cross‐validation and feature selection with Pearson correlations (r <0.5 to 0.9) and t‐tests/ANOVA (p=0.01 or 0.05) in all models, and reported the best performance after hyperparameter tuning.ResultThe RF classifier of ADNC versus HC (features selected at r<0.7, p=0.01) had 90% accuracy (sensitivity=0.95, specificity=0.8, AUC=0.94) with prepositions, number of phonemes, and pause rate selected as the most important features. The SVM classifier of ADNC versus FTLD‐tau showed 93% accuracy (sensitivity=0.99, specificity=0.7, AUC=0.9), selecting features such as nouns, pronouns, and articulation rate (p=0.05). The RF classifier of lvPPA versus FTLD‐tau showed 85% accuracy (sensitivity=0.93, specificity=0.75, AUC=0.92), selecting features such as nouns, articulation rate, and total words (r<0.6, p<0.05). The RF multiclass classifier had 80% accuracy (sensitivity=0.92, macro‐average recall=0.7, macro‐average AUC=0.88) with word frequency, articulation rate, and number of prepositions selected as the most important features (r<0.6, p=0.01).ConclusionAutomatic classifiers trained with language features extracted from one‐minute picture descriptions using our automatic pipelines showed high accuracy in identifying the pathological grouping of patients, which can potentially be used in the screening stage.
Tracking of the cognitive function and physical fitness in the older population from metropolitan area of Santos: Differences between the sexes
Authors: de Barros Vinícius Lucio , Bomfim Larissa Gomes Peres , Souza Melyssa Alves , Colovati Mileny Esbravatti Stephano , Zanesco Angelina 
Published: December 2021

AbstractBackgroundEpidemiological studies have shown a difference between the sexes in the cognitive dysfunction in the elderly where women are more susceptible to Alzheimer’s disease than men. Evidence has reported that physical activity (PA) is an important strategy for brain health, but the exact mechanism by which PA would promote beneficial effects is not yet clear. The metropolitan area of Santos has the largest proportion of elderly population in Sao Paulo State (22%), but no studies shave examined the prevalence of Alzheimer’s disease in this population or whether there are differences between the sexes in the cognitive function. Therefore, this study aimed to evaluate the differences between the sexes in the cognitive function of the elderly from the metropolitan area of Santos.MethodsThis study was approved by the Ethical Committee Board from Medical School/UNIMES (Number: CAAE 20938619.4.0000.5509). One‐hundred and eleven women and fifty‐seven men were eligible for the study. Inclusion criteria were >65 years‐old, no severe cognitive impairment, preserved activities of daily living. Cognitive function and the level of PA were assessed by the mini‐mental state examination (MMSE) and Baecke questionnaire for older, respectively.ResultsThe mean age of women was 75±3 and for men 73±1.4. There were no differences between the sexes in the MMSE score (27±1 and 27.3±1 for women and men, respectively), and approximately 23% of the participants were below the cut‐off reference values when the educational status was considered. Baecke score shows that the percentage of physically active women is lower as compared to men (44% and 54%, respectively, P<0.05).ConclusionThere were no differences between the sexes in the cognitive function in the elderly even though women are less active than men.Financial Support: Sao Paulo Research Foundation (FAPESP)
Detecting speech and language changes in early AD via automated analysis of clinical interviews
Authors: Robin Jessica , Xu Mengdan , Oday Abdi , Monteiro Cecilia , Liu Kai , Kahn Laura , Hejrati Mohsen , Amora Rainier , Simpson Bill , Teng Edmond 
Published: December 2021

AbstractBackgroundChanges to speech and language patterns in Alzheimer’s disease (AD) may provide sensitive indicators of cognitive decline that could be automatically and objectively detected with speech analysis technology that incorporates natural language processing. In this study, we sought to determine whether analyses of audio recordings of open‐ended Clinical Dementia Rating (CDR) interviews collected as part of a Phase 2 clinical trial in prodromal‐to‐mild AD could identify speech and language characteristics relevant to clinical status.MethodSpeech recordings from baseline CDR interviews were analyzed for 101 English‐speaking AD participants (58F/43M; 30 prodromal/71 mild; mean age = 69 years, range: 53‐80) in the semorinemab (NCT03289143) Phase 2 Tauriel study. Recordings of the CDR interview were analyzed using the Winterlight speech analysis platform, which generates >500 variables describing acoustic and linguistic features of speech. We computed Pearson correlations between the speech variables and five clinical measures (CDR, ADAS‐Cog, RBANS, MMSE, ADCS‐ADL) to identify specific features related to clinical performance.ResultCDR‐SB scores correlated more strongly with linguistic variables (e.g., types of words used, complexity of language) than acoustic variables. Participants with higher CDR‐SB scores (i.e., greater cognitive/functional impairment), used fewer past tense verbs when describing a recent event, a lower proportion of nouns compared to verbs, and shorter and simpler grammatical clauses (all r’s > 0.3, p’s < 0.05, FDR‐corrected). Similar associations were seen with other clinical assessments, and a subset of linguistic variables demonstrated significant (p < 0.05, uncorrected) correlations with all five clinical measures, including clause length, and use of prepositional phrases.ConclusionThese analyses demonstrate that clinical interviews can be analyzed using objective automatic methods to generate speech variables relevant to clinical outcomes in AD. Individuals with greater cognitive and functional impairment used simpler language and fewer content words when describing a recent experience. Future work will include multivariate analyses of speech markers versus cross‐sectional clinical indices.
Characterizing dementia prevalence in the State of Florida: An electronic health record study
Authors: Miller Amber H , Marra David E , Wu Yonghui , Bian Jiang , Shenkman Elizabeth A , Maraganore Demetrius M , Smith Glenn E 
Published: December 2021

AbstractBackgroundAlzheimer’s disease and related dementias (ADRD) are extremely prevalent and expected to significantly rise in the future. However, prevalence rates differ across ADRD sub‐types with Alzheimer’s disease (AD), vascular dementia (VaD), and dementia with Lewy Bodies (LBD) as the three most common. Aside from self‐report surveys, there is minimal research conducted in the state of Florida (USA) examining prevalence rates of ADRD across the lifespan.MethodElectronic health record (EHR) data from the OneFlorida Research Consortium was used to examine prevalence rates of ADRD for individuals across the state. ICD codes were used to identify patients in Florida, aged 45+ years, living with ADRD. Descriptive statistics were calculated to characterize the OneFlorida ADRD population by decade of age, gender, ethnicity, and race.Resultn = 162,356 individuals (5.66%) over the age of 45 with ADRD diagnosis in the EHR were identified. When age was not considered, the overall odds of having an ADRD diagnosis for males was lower than the odds of having ADRD diagnosis for females (Odds Ratio = .693, p < .0001). The unadjusted rate of ADRD diagnosis in the EHR for non‐Hispanic Whites (6.9%), while comparable, was significantly higher than the rates in Blacks (6.2%, χ2(1) = 226.13, p < .0001), Hispanics (6.1%, χ2(1) = 412.22, p < .0001), and other ethnoracial groups. The percentage of ADRD diagnosis increased with each decade of life. Of the ADRD sub‐types, AD was most common (62%), followed by VaD (23%), MCI (21%), LBD (5%), frontotemporal dementia (1%), and primary progressive aphasia (<1%).ConclusionADRD diagnoses are common in patients throughout Florida. Although epidemiology studies suggest ethnic minorities are more likely to develop ADRD, non‐Hispanic Whites were more likely to be diagnosed with ADRD in this sample. This finding suggests a lack of access to diagnostic healthcare in ethnic minorities throughout the state, indicating a “double disparity”. This research will further examine how age, race, gender, and access to healthcare may moderate the rate of ADRD diagnosis. Understanding the trends and prevalence of ADRD may help inform policy makers, healthcare providers, and payers about disease management and may predict future healthcare needs.
Cancer survivors have a lower frequency of dementia in the 95+ oldest‐old
Authors: Lachner Christian , Camsari Gamze Balci , Ertekin‐Taner Nilufer , Thompson E. Aubrey , Petersen Ronald C. , Boeve Bradley F. , Lucas John A. , Reichard Ross R. , Dickson Dennis W , Knopman David S. , Graff‐Radford Neill R. , Murray Melissa E 
Published: December 2021

AbstractBackgroundAdvancing age is an important risk factor for dementia and cancer. An inverse association between these conditions has been described, yet caution from potential biases/confounders is warranted. Dementia and cancer may represent a spectrum of opposing dysregulated degenerative (apoptosis) and growth (proliferative) pathways respectively (Driver, 2014). Risk or resiliency factors affecting these pathways may influence cognitive outcomes in the oldest‐old. We sought to investigate demographics, clinical characteristics, and the impact of medical comorbidity on possible risk‐resiliency factors for neurodegeneration in nondemented and demented oldest‐old who died and underwent autopsy.MethodMedical records of 161 decedents (female n=134) from the Mayo Clinic 95+ year‐old cohort (age range 95‐106 years‐old) were reviewed. Groups consisting of nondemented (n=72) and demented (n=89) decedents were stratified and compared according to demographics and clinical variables, including history of cancer. Autopsy and neuropathologic evaluation was also conducted.ResultAge at death, sex, race, and education showed no differences between nondemented and demented decedents. History of cancer was higher in nondemented (57%) compared to demented decedents (30%) (p=0.002). APOE ε4 allele presence did not differ amongst groups, while APOE ε2 allele was more common in the nondemented group (p=0.026). History of coronary artery disease was higher in the nondemented (p=0.033). No differences were observed in other vascular risk factors, alcohol use, or depression. Smoking history approached significance and was higher in nondemented compared to demented (p=0.068). MMSE scores were higher in the nondemented group (p<0.001). Neuropathology findings included a lower Braak tangle staging in nondemented (median=III) compared to demented (median=V) groups (p<0.001) and less frequent diffuse plaques observed in the nondemented (67%) compared with those demented (93%) (p<0.001).ConclusionDementia is less frequent among cancer survivors in the 95+ oldest‐old. Disease‐related mechanisms associated with malignancy and surviving it may be protective against neurodegeneration in the oldest old.