bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cross‐cultural issues in AD risk factors and assessment: A Nigerian perspective
Authors: Ucheagwu Valentine A 
Published: February 2022

AbstractBackgroundRoles of demographics, anthropometry and metabolic syndrome (Mets) on cognition in mid adults from rural part of Nigeria were examined to determine their contribution to dementia.MethodOne hundred and seventy two (172) middle aged adults from a rural community in Anambra state Nigeria were recruited for the study. Their age range were between 50 – 70 years with a mean age of 57.48 and SD age of 5.48. The Montreal Cognitive Assessment (MoCA) Symbol Digit Modality Test (SDMT) and Digit Symbol Test (DST) were used to assess the participants’ cognition. The anthropometric measures assessed were the body mass index (BMI), height, weight and waist circumference while the Mets assessed were blood sugar level and total cholesterol and blood pressure. Gender, occupation and education were included as demographic factors assessed in the study.ResultFindings show the BMI, weight and waist circumference as predictors of general cognition, but the blood pressure and height were not significant predictors. Equally, mixed findings were got on processing speed. The variables measured were not significant predictors of SDMT as a measure of processing speed while they to significant extent predicted processing speed when DST was used.ConclusionContrary to findings from western world blood pressure as a cardiovascular marker did not predict general cognition and processing speed while mets had significant contribution on general cognition and processing speed.
Subthreshold amyloid pathology and changes in functional brain networks in patients with delayed cognitive decline after stroke
Authors: Lim Jae‐Sung , Lee Jae‐Joong , Woo Choong‐Wan , Shin Dong Woo , Lee Keon‐Joo , Kim Hang‐Rai , Yang Mi Hwa , Jang Myung Suk , Baek Min Jae , Kim Beom Joon , Kim Sangyun , Bae Hee‐Joon 
Published: February 2022

AbstractBackgroundIn clinical practice, some of the stroke survivors who have normal cognitive function until three to six months after index stroke, develop cognitive decline gradually after then. Although amyloid deposits and advanced small vessel disease are reported to be the possible predictors, pathogenesis for delayed cognitive decline has not been identified yet. Thus, we aimed to explore the brain network characteristics in those with delayed cognitive decline after stroke compared to those without.MethodUsing a prospective stroke registry, we identified patients with ischemic stroke who had undergone the cognitive evaluations including mini‐mental state examination (MMSE) twice or more after index stroke. We included patients whose baseline cognitive evaluation (between 1 and 12 months after stroke) was normal and who had one or more follow‐up evaluations after more than 6 months from the baseline evaluation. Among 222 eligible patients, decliners were defined as having a decline in 3 or more per year or an absolute decline of 5 or more between baseline and follow‐up MMSE, while non‐decliners as having a decline of 1 point per year or less and an absolute decline of less than 3 points. Brain network attributes were analyzed using resting‐state functional MRI, and superimposed amyloid positivity was assessed using 18F‐florbetaben PET.ResultEleven patients (5%, 11/222) met the criteria for decliners, and ten matched non‐decliners were enrolled. For about 5.7 years of follow‐up, the mean change of MMSE scores was ‐9.1 points in the decliners, while ‐0.2 point in the non‐decliners. Ten (10/11) decliners were amyloid‐negative on the amyloid PET, and the APOE e4 allele was identified in one decliner. However, the global SUVR value showed a negative correlation with the final MMSE scores as well as the amount of MMSE change. Normalized transitivity was lower in decliners compared to non‐decliners. Mean connectivity strengths were averaged based on the seven canonical functional networks, and the intra‐network connections within the frontoparietal network showed the considerable differences between groups. (Figure)ConclusionThis study suggests that alteration of brain networks may explain the pathogenesis of the delayed post‐stroke cognitive decline independent of amyloid PET positivity and APOE genotype.
Data‐driven cut‐off values for 18‐F‐AV‐45 tau PET staging in AD
Authors: Quattrini Giulia , Ferrari Clarissa , Pievani Michela , Frisoni Giovanni B. , Marizzoni Moira 
Published: February 2022

AbstractBackgroundThe identification of unbiased cut‐off for amyloid and tau positivity is fundamental to early AD classification. While cut‐offs for amyloid markers are relatively established, tau markers cut‐off definition is controversial as they are influenced by the reference population. Moreover, several not modifiable risk factors (i.e., Apolipoprotein E ε4 allele [APOE4], age, and sex) may affect tau pathology. The aim of the present study is to define data‐driven cut‐off values for cortical tau staging and to assess the effect of APOE4, age, and sex.MethodData were derived from the Alzheimer's Disease Neuroimaging Initiative consortium (ADNI). Amyloid‐PET (18‐F‐AV‐45) standardized uptake value ratio (SUVR) was used to classify subjects as amyloid positive (A+) or negative (A‐). Tau PET (18‐F‐AV1451) SUVR, APOE4, age, sex and clinical information were then collected. For 18‐F‐AV1451 SUVR, we applied a staging system according to Braak. Data‐driven stage‐specific 18‐F‐AV1451 cut‐offs were computed by applying Gaussian mixture model (GMM) to the subsample including A‐ cognitively normal (CN‐A‐) and AD dementia (AD‐A+) (n=194). We also investigated the effect of age, APOE4 status, and sex on 18‐F‐AV1451 SUVR distribution and cutoff extraction applying the GMM to 18‐F‐AV1451 SUVR distribution adjusted for these covariates. Finally, the cut‐offs sensitivity was assessed in preclinical AD (CN‐A+; n=45), prodromal AD (MCI‐A+; n=22), and AD‐A+ (n=19) subjects.ResultIn tau stage regions I–VI, 18‐F‐AV1451 cut‐off values for positivity ranged between 1.21‐1.35. The cut‐offs sensitivity increased from CN‐A+ to MCI‐A+ and AD‐A+ in all tau stages regions: from 20% to 64% and 90% for tau stage I‐II, from 16% to 46% to 90% for tau stage III, from 11% to 46and 90% for tau stage IV, from 0% to 18% and 53% for tau stage V, and from 0% for CN‐A+ and MCI‐A+ to 32% for tau stage VI. A similar sensitivity progressive pattern was detected within each tau stage region. Finally, APOE4, age, and sex significantly impacted 18‐F‐AV1451 regional SUVR of each tau stage.ConclusionData‐driven 18‐F‐AV1451 SUVR cut‐offs for in‐vivo tau staging could be useful to index regional tau deposition. The impact of APOE4, age, and sex should be also considered.
Cerebral white matter microstructure in superagers: A diffusion MRI study of a population over the age of 80 with youthful episodic memory
Authors: Pascual Marta Garo , Zhang Linda , Strange Bryan A. 
Published: February 2022

AbstractBackgroundSuperagers are people over the age of 80 who possess the episodic memory function of a person 20‐30 years younger. We have recently identified the grey matter signature of this population, with preserved volume in episodic memory‐related areas and motor thalamus. Here we extend these observations by characterising superagers’ cerebral white matter microstructure using diffusion MR imaging.MethodA sample of 64 superagers (mean age 81.9 years ± 1.9 std, 59.4% women) and 55 age‐matched controls (mean age 82.4 years ± 1.9 std, 63.6% women) from the Vallecas Project cohort in Madrid, Spain, were selected according to their episodic memory score in the Free and Cued Selective Reminding Test. Superagers scored at or above the mean value of a 50‐56yo person, whereas controls scored within one standard deviation for their age. Differences across groups in two measures derived from DTI data were tested, comprising fractional anisotropy (FA), and mean diffusivity (MD). Voxelwise analyses were carried out using TBSS (Tract‐Based Spatial Statistics, [Smith 2006]), in FSL software.ResultSuperagers showed higher FA than controls in bilateral frontal tracts and the anterior thalamic radiation (p < 0.05, FWE‐corrected). Lower MD were found in superagers compared to controls in an extensive network comprising the forceps major and minor, superior and inferior longitudinal fasciculus, inferior fronto‐occipital fasciculus, anterior thalamic radiation, corticospinal tracts and cingulum bundle (p < 0.05, FWE‐corrected).ConclusionHigher FA and lower MD can be indicative of preserved white matter microstructure. Superagers exhibit higher FA in frontal tracts and lower MD across the main cerebral white matter tracts relative to healthy controls with normal‐memory‐for‐age. These results suggest an association between preservation of white matter microstructure and extraordinary memory function in old age.
Cognitive resilience to tau and amyloid burden in a memory clinic population
Authors: Ribaldi Federica , Altomare Daniele , Quattrocchi Lara , Tomczyk Szymon , Garibotto Valentina , Frisoni Giovanni B. 
Published: February 2022

AbstractBackgroundCognitive resilience (CR) is defined as the capacity to sustain a better‐than‐expected cognitive performance based on pathological burden. There is high variability in the individuals’ CR, and it has been demonstrated that individuals with high resilience develop symptoms later than those with low CR. The aim of this study it to investigate the association between demographic and clinical features and individual CR.Method144 subjects from the Geneva memory center cohort (N=37 cognitively unimpaired, N=84 mild cognitive impairment, N=23 dementia) that underwent amyloid PET, tau PET and an extensive neuropsychological battery were included. A linear regression model between amyloid and tau global standardized uptake value ratio (SUVr) vs Mini‐Mental State Examination (MMSE) was performed, and the residuals of the model were used as a measure of individual CR. A multivariate linear regression was used to assess the association between CR and age, sex, education, and white matter hyperintensities.ResultMean age was 72.2 (sd = 7.8), 72 were female (50%), and mean years of education was 13.9 (4.1). Greater CR was associated with better education (β = 0.26, p = 0.001), older age (β = 0.25, p = 0.002) and low white matter hyperintensities (β = ‐0.17, p = 0.037). No associations were observed between CR and gender (gender, β = 0.06, p = 0.455).ConclusionWe confirmed in our population that education is strongly associated with CR. Future development of this study will be to investigate brain resilience (BR), defined as the relationship between atrophy and amyloid and tau, and the longitudinal cognitive trajectory of the individuals with high BR and/or CR compared to those with low BR and/or CR. the definite article More (Definitions, Synonyms, Translation)
Brain architecture changes across the FTLD spectrum
Authors: Cividini Camilla , Agosta Federica , Basaia Silvia , Spinelli Edoardo Gioele , Castelnovo Veronica , Canu Elisa , Riva Nilo , Magnani Giuseppe , Caso Francesca , Filippi Massimo 
Published: February 2022

AbstractBackgroundTo explore structural/functional MRI connectomic features of the motor neuron disease (MND) and behavioral variant of frontotemporal dementia (bvFTD) spectrum.Method115 MND (including amyotrophic lateral sclerosis [ALS] and primary lateral sclerosis), 35 bvFTD patients and 61 controls underwent clinical/cognitive and MRI evaluations. MND patients were divided in 79 pure‐motor (MND‐motor) and 36 cognitive/behavioral impaired (MND‐ci/bi). A sub‐analysis was performed on ALS patients only (54 ALS‐motor, 21 ALS‐ci/bi and 8 ALS‐FTD). Graph analysis and connectomics assessed structural/functional topological network properties at global, lobar and regional level.ResultGlobally, bvFTD showed altered structural and functional network properties compared to all other groups. At lobar level, bvFTD showed altered structural and functional network properties within the frontotemporal and basal ganglia areas relative to all groups. Structural alterations in the parietal lobe discriminated bvFTD from controls and MND‐motor only. MND groups showed altered structural properties within sensorimotor and basal ganglia areas relative to controls. Regionally, bvFTD showed widespread structural damage and decreased functional connectivity relative to all groups. MND showed disrupted structural architecture and enhanced functional connectivity within sensorimotor, basal ganglia and frontotemporal areas relative to controls. Similar results have been found in ALS sub‐analysis.ConclusionThe disruption of the structural architecture in MND worsens in relation with cognitive deficits. Functional changes are characterized by enhanced functional connectivity in presence of exclusive motor impairment that intensifies with the occurrence of cognitive impairment in MND. The Italian Ministry of Health (GR‐2011‐02351217; GR‐2013‐02357415; RF‐2011‐02351193), AriSLA (ConnectALS), European Research Council (StG‐2016_714388_NeuroTRACK).
Use of graphical markers for the differential diagnosis of primary progressive aphasia subtypes
Authors: Plonka Alexandra , Macoir Joel , Robert Philippe , Manera Valeria , Gros Auriane 
Published: February 2022

AbstractBackgroundPrimary Progressive Aphasia (PPA) brings together a group of neurodegenerative pathologies whose principal characteristic is to start with a progressive language disorder. Three main PPA subtypes were established, depending on the affected brain regions and the type of language disorder: the logopenic subtype (lvPPA), the non‐fluent/agrammatic subtype (nfavPPA) and the semantic subtype (svPPA) (Gorno‐Tempini et al., 2011). PPA diagnosis is often delayed in non‐specialised clinical settings. With the development of technologies, new diagnostic tools can be used, such as writing on a touch pad (Plonka et al., 2020). We have already highlighted differences between patients with typical Alzheimer's Disease (AD) and healthy controls (Gros et al., 2019), but the kinematic writing parameters are still understudied in the differential diagnosis of PPA subtypes.Method29 subjects with Primary Progressive Aphasia (lvPPA N= 18; nfavPPA N=6; svPPA N=5) were included in this study. They performed ten graphical markers tasks (2 non‐cognitive and non‐linguistic tasks, 4 cognitive and non‐linguistic tasks and 4 linguistic tasks) on an I‐Pad® tablet. Different writing parameters were extracted: writing pressure, velocity, jerk and stroke.ResultPreliminary results revealed a main effect of diagnosis in linguistic tasks on average velocity (p= 0,041) and on average stroke (p= 0,029). The two‐by‐two comparison of different variants of PPA also showed significative differences: 1) lvPPA vs nfavPPA: significant differences in the average velocity, jerk and stroke were found, with lvPPA participants showing a higher velocity (p= 0,037), jerk (p= 0,046) and stroke (p= 0,014) than nfavPPA participants in linguistic tasks. 2) lvPPA vs svPPA: significant difference in velocity was found in linguistic task (p=0,037). 3) nfavPPA vs svPPA: significant difference in maximum pressure was found in linguistic task (p= 0,044), with nfavPPA participants showing a lower maximum pressure than svPPA participants.ConclusionThese preliminary results suggest that the use of graphical markers can be helpful in the differential diagnosis of PPA subtypes. A longitudinal study is ongoing to collect a bigger and more balanced PPA sample by including these markers within an already existing screening test battery.
Neuroinflammation in medial temporal regions predicts cognitive decline in dementia with Lewy bodies
Authors: Malpetti Maura , Savulich George , Mak Elijah , Nicastro Nicolas , Jones P. Simon , Surendranathan Ajenthan , Su Li , Passamonti Luca , Chouliaras Leonidas , Fryer Tim D. , Hong Young T. , Aigbirho Franklin I. , Rowe James B. , O'Brien John T. 
Published: February 2022

AbstractBackgroundNeuroinflammation is implicated in the pathogenesis of neurodegenerative disorders including dementia with Lewy bodies (DLB), but its relationship with disease progression, including cognitive decline, is less well understood. We investigated the predictive value of microglial activation, assessed in vivo using positron emission tomography (PET) imaging with [11C]PK11195, on the rate of annual cognitive decline in patients with DLB. We hypothesised a detrimental effect of inflammation on cognition over time.MethodNineteen patients with DLB underwent baseline assessment, including [11C]PK11195 PET and cognitive tests from the Neuroimaging of Inflammation in Memory and Related Other Disorders (NIMROD) study. Cognitive performance was then assessed at an average of 1.1‐year intervals (standard deviation (SD) ± 0.03 years) up to 3.4 years (average ± SD = 3.20 ± 0.16) using the revised Addenbrooke's Cognitive Examination (ACE‐R) and Cambridge Neuropsychological Test Automated Battery (CANTAB). Regional [11C]PK11195 binding potential values were included in a principal component analysis (PCA). Linear mixed effects models were applied to the longitudinal ACE‐R scores. Individual component scores were included in analysis of interaction with time to test for associations between [11C]PK11195 uptake at baseline and longitudinal cognitive performance scores. Age and sex were included as covariates in the models.ResultPatients showed a mean 8.8‐point loss per year on the ACE‐R total score (p<0.001) (Figure 1, left panel). The PCA identified five components, explaining >80% of variance. Annual rate of change in the ACE‐R total score (estimate=‐2.90, p=0.0226) (Figure 1, right panel), memory (estimate=‐1.14, p=0.004) and attention/executive function (estimate=‐0.80, p=0.022) sub‐scores was negatively associated with increased microglial activation in component #4, which was mainly loaded onto the hippocampus, amygdala and pallidum but also parahippocampal cortex and the pre‐subgenual frontal area.ConclusionHigher levels of neuroinflammation in medial temporal regions and pallidum predict faster cognitive decline in patients with DLB, particularly in the domains of memory and attention/executive function. Our results encourage the application of [11C]PK11195 PET in DLB to inform prognosis, and to improve patient stratification for clinical trials.
Longitudinal clinical, cognitive and neuroanatomical changes over five years in GBA‐positive Parkinson’s disease patients
Authors: Leocadi Michela , Agosta Federica , Canu Elisa , Donzuso Giulia , Basaia Silvia , Piramide Noemi , Stojkovic Tanja , Stankovic Iva , Tomic Aleksandra , Markovic Vladana , Petrovic Igor , Stefanova Elka , Kostic Vladimir S. , Filippi Massimo 
Published: February 2022

AbstractBackgroundGlucocerebrosidase gene (GBA) mutations are the greatest genetic cause of Parkinson’s disease (PD). The aim of this study was to monitor the longitudinal disease course of PD patients with GBA mutation (GBA‐positive) at diagnosis compared to PD noncarriers (GBA‐negative) along a 5‐year follow‐up, evaluating changes in clinical and cognitive outcomes, cortical thickness, and subcortical volumes.Method10 GBA‐positive and 20 GBA‐negative PD at diagnosis underwent clinical, neuropsychological and brain MRI assessments at study entry and once a year for 5 years. At baseline and at the last visit, each group of patients was compared in terms of cortical thickness and subcortical volumes to a group of 22 age‐matched healthy controls (HC). Clinical, cognitive and cortical/subcortical MRI features were compared between groups at baseline and over time.ResultAt baseline, GBA‐positive and GBA‐negative patients had similar clinical and cognitive profiles. Compared to GBA‐negative and HC, GBA‐positive patients showed cortical thinning of left temporal, parietal and occipital gyri. Over time, compared to GBA‐negative, GBA‐positive worsened significantly in motor and cognitive symptoms, and showed a greater pattern of bilateral cortical thinning involving also frontal cortices. After 60 months, compared to HC, GBA‐negative PD patients showed a pattern of cortical thinning similar to that shown by GBA‐positive at baseline. The two groups of patients showed similar patterns of subcortical volume loss over time.ConclusionCompared to GBA‐negative patients, GBA‐positive PD showed a greater and earlier cortical thinning which worsened over time. GBA‐negative PD patients reached the pattern of cortical thinning of GBA‐positive at the baseline only after 5 years, reflecting a slower disease progression. This study highlights the importance of the early detection of GBA mutation in PD patients. Funding: This study was supported by the Ministry of Education and Science of the Republic of Serbia (Grant #175090).
Topographic distribution of MRI‐visible enlarged perivascular space (ePVS) in Alzheimer's disease: Role of ePVS located at the temporal lobe
Authors: Na Han Kyu , Baek Min seok , Kim Han‐Kyeol , Cho Hanna , Lyoo Chul Hyoung 
Published: February 2022

AbstractBackgroundAccumulating data suggests that MRI‐visible enlarged PVS (ePVS) may serve as an imaging marker of glymphatic dysfunction. Until now, ePVS in various regions such as basal ganglia (BG‐ePVS) or centrum semiovale (CS‐ePVS) have been introduced and their topographic distributions are recognized as a marker to differentiate the underlying etiologies, although they failed to predict amyloid‐positivity. As the conventional classification of ePVS was insufficient to predict Alzheimer pathologies, we developed a new grading system for ePVS located at the temporal lobe (T‐ePVS), a strategic region where both amyloid and tau overlaps in their early stages. We investigated whether amyloid‐positivity or tau‐positivity is associated with T‐ePVS along with other conventional ePVS markers.MethodePVS were manually counted on magnetic resonance (MR) images obtained from 272 participants (cognitively normal, n=96; cognitively impaired, n=176) who underwent dual PET scans (18F‐flortaucipir and 18F‐florbetaben). T‐ePVS and BG‐ePVS were defined as “extensive” when the counts in any hemisphere were >10, while the cutoff of CS‐ePVS was >20. Subjects were grouped based on the combinations of the severity of region‐specific ePVS and their relationship with amyloid‐/tau‐positivity were investigated. Moreover, logistic regression models were constructed to investigate whether severity of region‐specific ePVS were predictive of amyloid‐ or tau‐positivity.ResultCompared to those with low T‐ePVS burden (21/136, 15.4%), subjects with high T‐ePVS burden were more likely to show amyloid‐positivity (89/136, 65.4%). Among the 8 groups based on region‐specific ePVS burden, subjects with high T‐/CS‐ePVS but low BG‐ePVS burden showed highest amyloid‐positivity (46/56, 82.3%). Furthermore, high T‐ePVS burden (Odds ratio [OR]=7.458; 95% confidence interval [CI]=3.387‐16.419), low BG‐ePVS burden (OR=0.238; 95% CI=0.108‐0.524), and APOE ε4 allele presence (OR=5.175; 95% CI=2.444‐10.959) were significantly associated with amyloid‐positivity. Similar results were reproduced when the analyses were performed within subjects with cognitive impairment. Within the amyloid‐positive subjects, subjects with high CS‐ePVS but low BG‐ePVS burden were likely to exhibit tau‐positivity, while the severity of each region‐specific ePVS were not independently predictive of tau‐positivity.ConclusionOur findings suggest that investigating the load and topographic distribution of ePVS based on MR images may be useful for predicting amyloid‐ and tau‐positivity, suggesting that glymphatic dysfunction may contribute to Alzhiemer’s pathogenesis.