bluuebunny/crossref_metadata_2025_split huggingface dataset:
Degeneration patterns on [18F]FDG‐PET predict amyloid deposition in corticobasal syndrome
Authors: Parmera Jacy Bezerra , Coutinho Artur M , Neto Adalberto Studart , Carneiro Camila de Godoi , de Almeida Isabel Junqueira , Aranha Mateus Rozalem , Barbosa Egberto Reis , Buchpiguel Carlos A , Nitrini Ricardo , Brucki Sonia MD 
Published: December 2020

AbstractBackgroundCorticobasal Syndrome (CBS) is a neurodegenerative disease which phenotype is related to multiple pathologies, including 4‐repeat tauopathies ‐ Corticobasal Degeneration (CBD) and Progressive Supranuclear Palsy (PSP) ‐ and Alzheimer’s disease (AD). Previous works with post‐mortem analysis established [18F]FDG‐PET patterns closely related to CBD, PSP or AD pathology.MethodsForty patients with probable CBS were evaluated concerning their movement disorders and cognition. They were underwent [18F]FDG‐PET/CT and, according to their brain metabolic patterns, distributed into two groups: likely related to AD (CBS FDG‐PET AD) (figure 1) and likely unrelated to AD (CBS FDG‐PET nonAD) (figure 2). Twenty‐five patients underwent [11C]PIB‐PET on a hybrid PET/MRI equipment to assess their amyloid status. Both [18F]FDG‐PET and [11C]PIB‐PET were analyzed based on visual and 3D‐SSP semi‐quantitative parameters. Each examination was blind to other modalities.ResultsBased on the patterns at [18F]FDG‐PET, we classified 12 patients (30%) in the CBS FGD‐PET AD group and 28 patients (70%) in the CBS FDG‐PET nonAD group. All patients (100%) previously classified as CBS FDG‐PET AD tested positive for amyloid deposition at [11C]PIB‐PET and 88,9% classified as CBS FDG‐PET nonAD tested negative (p=0,001 for [11C]PIB positive status; sensitivity 77,8%; specificity 100%). There were no significant differences in age, gender, symptoms duration and schooling at CBS FDG‐PET groups or [11C]PIB status. Demography is shown in table 1. Functional and cognitive impairment was markedly more severe in the CBS FDG‐PET AD group, which had worst scores regarding memory, attention and visuospatial domains (table 2). CBS FDG‐PET AD group also presented more frequently myoclonus (100% vs. 53,6%, p=0,004), displayed less frequently dystonia (16,7% vs. 57,1%, p=0,035) and had more neglect syndrome (p =0,041) and hallucinations (p=0,039) (figure 3). Patients with positive status at [11C]PIB also presented worst cognitive performance on memory, attention and visuospatial domains.Conclusion[18F]FDG‐PET was useful to predict CBS variants depicting their degeneration patterns, being able to detect a CBS‐AD group with brain amyloid deposition, worst functional and cognitive decline, also showing high accuracy to exclude AD pathology in the CBS‐nonAD group. Motor and cortical symptoms such as dystonia, myoclonus and neglect syndrome might potentially aid biomarkers in distinguishing pathologic variants.
Validation of the RUDAS for the identification of dementia in illiterate and low‐educated older adults in Lima, Peru
Authors: Caipa Maritza Pintado , Custodio Nilton , Montesinos Rosa 
Published: December 2020

AbstractBackgroundTo evaluate the performance of the Peruvian version of the Rowland Universal Dementia Assessment Scale (RUDAS‐PE) to discriminate between controls and patients with mild cognitive impairment (MCI) and dementia in an illiterate population with low‐levels of education.MethodWe compared the cognitive performance of 187 elderly subjects who were illiterate (controls n=60; MCI n=64; dementia n=63). Neuropsychological measures included the RUDAS‐PE, Mini‐Mental State Examination (MMSE), INECO Frontal Screening (IFS), and Pfeffer Functional Activities Questionnaire (PFAQ). Results were compared to a neuropsychological evaluation (gold standard), including use of Clinical Dementia Rating (CDR) scores.ResultWe found a Cronbach’s alpha was 0.65; Spearman’s correlation coefficient was 0.79 (p < 0.01). The area under the receiver operating characteristics curve for the RUDAS to discriminate dementia from MCI was 98.0% with an optimal cut‐off <19; whereas, to differentiate MCI and controls was 98.0% whit an optimal cut‐off <23.ConclusionBased on its excellent psychometric properties, we find the RUDAS‐PE suitable to aid in the opportune detection of dementia in a geriatric illiterate population with low‐levels of education.
PSMD, a novel marker of small vessel disease, and its association with cognitive function in the community
Authors: Satizabal Claudia L , Beiser Alexa S , Maillard Pauline , Himali Jayandra J , DeCarli Charles , Fornage Myriam , Seshadri Sudha 
Published: December 2020

AbstractBackgroundPeak width of skeletonized mean diffusivity (PSMD) has been proposed as a novel neuroimaging marker for small vessel disease (SVD), which contributes to vascular cognitive impairment and dementia. Although this marker has been related to lower cognitive function in clinical samples with inherited and sporadic SVD, additional research is needed to assess its utility for risk prediction in large, well‐characterized population‐based cohorts.MethodsWe included 929 stroke‐ and dementia‐free participants from the Offspring cohort of the Framingham Heart Study. PSMD was derived from DTI using an automated algorithm, and further log‐transformed to normalize its distribution. To evaluate general cognitive function, we created a composite cognitive score including Logical Memory – immediate and delayed recall, Digit Span Forward and Backward, Category Fluency – animals, Phonemic Fluency – FAS, Trail Making Test A and Test B, and the Boston Naming Test. We used linear regression models to relate PSMD to general cognitive function adjusting for age, sex and educational level. In a secondary model, we additionally adjusted for diabetes, smoking and hypertension. Finally, we included white matter hyperintensity (WMH) volume as percentage of total intracranial volume in the primary and secondary models to assess the contribution of PSMD beyond WMH.ResultsHigher PSMD values were associated with lower general cognitive function (Beta (SE), ‐0.61 (0.10), p<0.001). Results remained virtually unchanged after additional adjustment for vascular risk factors in the secondary model (‐0.60 (0.10), p<0.001). After the inclusion of WMH, associations remained significant in the primary (‐0.58 (0.11), p<0.001) and secondary (‐0.57 (0.11), p<0.001) models, with PSMD explaining an additional 2% of the variance in cognition beyond WMH.ConclusionPSMD was strongly associated with general cognitive function in our sample, suggesting that this novel marker may be suitable for risk prediction for SVD in community‐based samples, and is potentially a better predictor than well‐established markers such as WMH. Additional validation and longitudinal analyses are currently underway in population‐based cohorts and clinical samples in the context of the MarkVCID consortium.
Subfoveal choroidal thickness and choroidal vascularity index on spectral‐domain optical coherence tomography in Alzheimer’s disease
Authors: Robbins Cason B , Grewal Dilraj , Powers James H , Thompson Atalie C , Polascik Bryce W , Agrawal Rupesh , Fekrat Sharon 
Published: December 2020

AbstractBackgroundThe involvement of the retina and its vasculature has previously been demonstrated in Alzheimer’s disease (AD). Choroidal parameters such as choroidal thickness (CT) and choroidal vascularity index (CVI) as measured on spectral‐domain optical coherence tomography (SD‐OCT) have the potential to be used as non‐invasive biomarkers for Alzheimer’s disease.MethodSD‐OCT imaging of 42 participants with AD, 40 with mild cognitive impairment (MCI), and 139 cognitively healthy controls was obtained in a cross‐sectional study (NCT03233646). Exclusion criteria included diabetes, glaucoma, other non‐AD dementias, and any known vitreoretinal pathology. Subfoveal choroidal thickness (CT) was manually measured by two masked graders, with a third grader used as a tie‐breaker for any measurement discrepancy. Total choroid area and luminal area were calculated by automated image binarization techniques. Choroidal vascularity index (CVI) was measured as the ratio of luminal area to total choroid area. Generalized estimating equations were used to assess the difference in parameters between AD, MCI, and controls in univariable and multivariable analyses.ResultChoroidal thickness (p = 0.009), total choroid area (p = 0.02), and luminal area (p = 0.02) were significantly less in AD versus controls in univariable but not in multivariable analysis after controlling for age, sex, and logMAR visual acuity. Choroidal vascularity index was not significantly different between individuals with AD and controls and was significantly different between individuals with MCI and controls only in univariable analysis (p = 0.04). However, CVI was significantly less in AD versus MCI in both univariable and multivariable analyses (p = 0.01).ConclusionSubfoveal choroidal thickness may not be associated with AD independent of aging. However, the choroidal vascularity index was less in AD compared to MCI, suggesting decreased vascularity of the subfoveal choroid in these patients. CVI may be useful as an adjunctive biomarker for the diagnosis of AD.
APOE4 status influences the amyloid and tau relationship
Authors: Dincer Aylin , Gordon Brian A. , Keefe Sarah J. , Flores Shaney E. , Schultz Stephanie A. , Paulick Angela M. , Feldman Rebecca L. , Shady Kristine E. , Hornbeck Russ C. , Zhou Yun , Morris John C. , Benzinger Tammie L.S. 
Published: December 2020

AbstractBackgroundThe apolipoprotein E ε4 (APOE4) allele is a well‐established genetic risk factor for late‐onset Alzheimer disease (AD). There is strong evidence that APOE4 enhances amyloid accumulation and previous research in animal models have demonstrated that APOE4 promotes tau pathology independently of amyloid. In this study, we investigate the relationship between APOE4 and tau to see whether the relationship between APOE4 and tau is mediated by, independent of, or interacts with levels of amyloid.Method347 participants from the Knight Alzheimer Disease Research Center (mean age = 69.7) underwent tau‐PET imaging with [18F]‐flortaucipir and amyloid‐PET with [18F]‐florbetapir within a year. Tau‐ and amyloid‐ PET data were converted to standardized uptake value ratios (SUVRs) for each region of interest. A summary amyloid measure was calculated for statistical analysis using the average of lateral orbitofrontal, medial orbitofrontal, rostral middle frontal, superior frontal, superior temporal, middle temporal, and precuneus regions. APOE4 carrier status was defined by the presence of at least one ε4 allele. We ran three separate linear models for our analysis. First we examined the APOE4‐tau and the amyloid‐tau relationship with model 1 predicting regional tau using amyloid, age, and sex as predictors and model 2 predicting regional tau using APOE4 status, age, and sex as predictors. Next we examined the relationship between tau and both APOE4 and amyloid in concert with model 3 predicting regional tau using amyloid, APOE4 status, an interaction between amyloid and APOE4 status, sex, and age as predictors.ResultWe found that the amyloid‐tau relationship was widespread throughout the brain and the APOE4‐tau relationship was predominately in the inferior parietal and temporal pole regions (figure 1). Most importantly, we found a significant APOE4 status and amyloid interaction that was most prominent in the entorhinal cortex and superior temporal regions (figure 2).ConclusionOur results show that there is a significant effect of APOE4 status and tau deposition that is above and beyond the effect of APOE4 on amyloid. This relationship is synergetic, where E4 carriers have more tau pathology for the same levels of amyloid deposition as non‐carriers.
Relative digit length is associated with cognitive abilities in women and men
Authors: Gatz Margaret , Pike Christian J , Beam Christopher R. , Reynolds Chandra A. 
Published: December 2020

AbstractBackgroundRelative length of the index (second digit; 2D) and ring (fourth digit; 4D) fingers on the right hand (2D:4D) is taken to indicate prenatal hormone levels. Lower 2D:4D (i.e., 4D relatively longer) represents more androgen exposure, with men showing lower 2D:4D on average than women. Women from opposite sex twin pairs have lower 2D:4D compared to women from same sex dizygotic twin pairs. Lower 2D:4D correlates with higher scores on spatial and numerical tasks, while higher 2D:4D advantages verbal tasks. Findings, however, have been quite inconsistent.MethodWe analyzed cognitive scores in a nationally representative internet panel who were asked whether their index or ring finger was longer (or whether they were the same). N=3525 (1521 men; 2004 women), aged 17 – 108, reported a difference in digit length on their right hands. Cognitive tests included IRT‐scored Number Series (NS), Picture Vocabulary (PV), and Verbal Analogies (VA), plus Serial Sevens (SS)–frequently part of mental status testing.ResultMore men (67%) than women (44%) reported relatively longer 4D, consistent with established findings. There were significant interactions by gender, digit length, and age/birthyear on all outcomes. Men outscored women on NS, PV, and VA, and reported higher educational attainment than women. Within women, those with relatively longer 2D reported higher education attainment and scored higher on VA compared to those with relatively longer 4D. However, there was a significant interaction between digit length and age/birthyear for both PV (p=.03) and VA (p=.005): women born more recently had longer 2D associated with higher scores, but older women had longer 4D associated with higher scores, with the crossover around age 65. Within men, those with relatively longer 4D scored higher on NS (p=.0003) and SS (p=.005) than men with relatively longer 2D. Findings were robust to including education as a covariate.ConclusionFindings add to evidence that sex differences in cognitive abilities in adult women and men may be influenced by differences in prenatal levels of sex steroid hormones, indirectly inferred from relative digit length. Results further suggest that prenatal testosterone exposure may confer an advantage in older women. Grant No. RF1 AG058068.
Synaptically preferred anti‐tau antibodies reduce in vitro tau seeding and in vivo neuronal loss
Authors: Tai Chin‐Yin , Ma Haou‐Tzong , Huang Sheng‐Chieh , Li Chung‐Lin , Wu Meng‐Fang , Wu Chia‐Lin , Jang Ming‐Kuei 
Published: December 2020

AbstractBackgroundIn Alzheimer’s Disease (AD) brains, pathological tau species accumulate at the synapses where the cell‐to‐cell transmission of tau has been experimentally demonstrated.MethodA series of assays including: dot‐blot assay of synaptic versus cytosolic fractions, brain immunohistochemistry (IHC), HEK cell‐based tau seeding assay, mass spectrometry‐based epitope mapping and in vivo rTg4510 animal efficacy study were used to identify anti‐tau antibodies for therapeutic purposes.ResultAPRINOIA has characterized 12 anti‐tau antibodies bind to synaptic tau species isolated from AD brain tissues. These synaptic preferred anti‐tau antibodies were not only highly specific to pathological tau species in AD brains, but also exhibited diverse subcellular localization in rTg4510 tau transgenic mouse brains. Among them, we focused on 2 antibodies, APNmAb005 and 037. For 005, it localized at axodendritic compartments in the hippocampi of 3‐mo rTg4510 brains and was found to bind conformational epitopes in the mid‐region of tau protein. On the other hand, 037 localized in the somatic compartments with a conformational epitope in the repeat domain of tau. Moreover, both antibodies could block tau seeding from the rTg4510 mouse brain lysates or from the secreted tau of rTg4510 synaptoneurosomes. A 3‐month efficacy study was performed in rTg4510 animals for 005 and significant reduction of neuronal loss was observed.ConclusionThe therapeutic potentials of anti‐tau antibodies are not judged by the location of epitopes or sub‐cellular localization, but by their abilities to recognize synaptically localized tau in AD brains.
Cognitive results after a FINGER‐like one‐year randomized controlled multidomain intervention: The GOIZ ZAINDU pilot project
Authors: Ecay Mirian , Tainta Mikel , Mugica Justo , Arriba Maria , Ros Naia , Barandiaran Myriam , Iriondo Ane , Garcia‐Sebastian Maite , Estanga Ainara , Aurtenetxe Sara , Saldias Jon , Clerigue Montserrat , Otaegui Ane , Gabilondo Alazne , Arrospide Arantzazu , Martinez‐Lage Pablo 
Published: December 2020

AbstractBackgroundPrevious trials in Europe (FINGER, MAPT and PreDIVA) have shown that interventions on risk and protective factors represent a window of opportunity for dementia prevention, especially in participants with increased risk. To fully understand the potential impact of these interventions, their feasibility and efficacy needs to be explored in contexts worldwide. GOIZ ZAINDU (“caring early” in Basque language) is a pilot study to adapt FINGER methodology in Southern Europe with the aim to evaluate the feasibility of a lifestyle intervention program in this cultural and social context. An additional exploratory aim is to assess the efficacy of the intervention on cognition.MethodGOIZ ZAINDU is a one year controlled, randomized, multimodal intervention. Inclusion criteria were: age 60+; CAIDE dementia risk score of 6 points or higher; no dementia; and below‐than‐expected cognitive performance in at least one of three brief cognitive screening tests. Cognitive status (MCI or normal) and age were accounted for randomization to a multidomain intervention (MI) or to Regular Health Advice (RHA). MI includes cardiovascular risk control, nutritional counseling, physical activity program, and cognitive training. Cognitive outcomes include the modified Neuropsychological Test Battery (mNTB) composite score change, and domain Z score change for executive function, processing speed, and memory. Mixed‐effects regression models with maximum likelihood estimation to analyze change in cognitive scores as a function of randomization group, time and groupxtime interaction will be performed.Result125 participants were recruited. 64 people were assigned to MI and 61 to RHA. The study started in June 2018, last patient first visit was in March 2019. Up to date 94 participants have completed the study that will end in April 2020. Exploratory results of the efficacy analysis of the intervention on cognition change will be presented.ConclusionThe GOIZ‐ZAINDU study has proved that the FINGER methodology is adaptable and feasible in a different socio‐cultural environment. Exploratory efficacy results will support the design of the large‐scale efficacy FINGER‐like trial in the Basque Country.
Mild behavioral impairment is predictive of tau deposition in the earliest stages of Alzheimer's disease
Authors: Johansson Maurits , Smith Ruben , Stomrud Erik , Johansson Per , Janelidze Shorena , van Westen Danielle , Mattsson Niklas , Hansson Oskar 
Published: December 2020

AbstractBackgroundIn Alzheimer´s disease (AD), the emergence of cortical tau deposition has been related to the clinical onset of symptoms. However, associations between tau and Mild Behavioral Impairment (MBI), defined as a neurobehavioral syndrome characterized by late life development of neuropsychiatric symptoms (Table 1), have rarely been investigated. It is unclear if MBI precedes cognitive symptoms, and which manifestation best predicts neuropathology in AD. We cross‐sectionally explored associations between MBI and cortical tau‐pathology in AD and determined if MBI or memory deficit serve as the superior predictor of cortical tau, using Tau PET.MethodsThe study sample (characterized in Table 1), included cognitively unimpaired (CU) (n=50), mild cognitively impaired (MCI) (n= 53) and Aß+ AD dementia cases (n=62) from the Swedish BioFINDER study; all individuals were ß‐amyloid positive (Aß+) according to CSF. Neuropsychiatric assessments included the MBI‐Checklist (MBI‐C) and memory was evaluated using ADAS‐cog Delayed Recall (ADAS‐DR). CSF P‐tau181 was analyzed using ELISA. 18F‐RO948‐PET quantified the level of regional cortical tau deposition. Linear regression models, adjusted for age, sex, level of education and white matter lesions were used to test for associations.ResultsIn the total sample, only tau deposition in the entorhinal cortex was associated with MBI‐C scores (right: b=5.857, p=0.034, left: b=5.592, p=0.034) (Table 2). In Aß+ CU cases, entorhinal tau deposition was predicted by MBI‐C (b=0.338, p=0.010), but not ADAS‐DR. A similar pattern was found for CSF P‐tau181. For the Ab+ subjects with MCI an opposite pattern was observed in which ADAS‐DR (b=0,299, p=0.037), but not MBI‐C, predicted the level of entorhinal tau deposition.ConclusionOur results suggest that MBI is associated with cortical tau deposition only in the entorhinal cortex, a region known to be one of the earliest accumulation sites in AD. MBI, but not memory deficit, also predicted entorhinal tau in Aß+ CU cases. These findings denote MBI as one of the earliest clinical symptoms associated with early tau pathology during the preclinical stages of AD.
Identification and validation of Alzheimer’s disease‐related metabolic pattern in patients with pathologically confirmed Alzheimer’s disease
Authors: Perovnik Matej , Rus Tomaž , Tomše Petra , Jensterle Luka , Emeršič Andreja , Grmek Marko , Jamšek Jan , Kramberger Milica G , Pirtošek Zvezdan , Trost Maja 
Published: December 2020

AbstractBackgroundAlzheimer’s disease (AD) is marked by accumulation of Aβ and tau protein causing neurodegeneration in the brain. AD represents a pathological and clinical continuum, ranging from mild cognitive impairment (MCI) to dementia. A specific metabolic imaging biomarker of AD ‐ Alzheimer’s disease‐related pattern (ADRP) has been previously identified from 2‐[18F]fluorodeoxyglucose positron emission tomography (2‐[18F]FDG‐PET) scans of clinically diagnosed AD patients, using scaled subprofile model based on principal component analysis (SSM/PCA) 1–3. However the clinical diagnosis may be wrong in substantial number of cases 4. We aimed to identify ADRP on patients with Alzheimer’s pathological changes in cerebrospinal (CSF) fluid and to validate it in an independent group of AD and other dementia patients and compare it to the original ADRP 1.Method2‐[18F]FDG‐PET scans from 20 AD1 and 20 normal controls (NC1) were used for pattern identification. Additional 110 scans were analyzed for validation: 68 from AD patients (37 AD2, 13 atypical clinical presentation AD (atAD), 18 MCI), 21 with frontotemporal dementia (FTD), 8 non‐AD MCI and 13 NC2 (Table 1). AD was defined with CSF biomarkers as: Aβ42 < 815 pg/ml, pTau > 60 pg/ml, tTau > 400 pg/ml. Topographic profile rating algorithm was used to prospectively calculate ADRP Z‐scores from subjects scans3. Mini‐mental state examination (MMSE) was performed in all patients.ResultsADRP was identified and voxel weights were found to be stable by bootstrap resampling, Figure 1. Pattern’s expression was significantly higher in AD1 than NC1 (p<0.001) and it strongly correlated (r=‐0.70) with MMSE. Pattern’s expression was also higher in AD2 than NC2 (p<0.001), MCI vs. NC2 (p<0.001), MCI vs. non‐AD MCI (p=0.02) and AD2 vs. FTD (p=0.02), Figure 2. Newly identified pattern moderately correlated (r=0.52) with the original one 1.ConclusionsWe identified ADRP on a cohort of pathologically confirmed AD patients, which was not done before. ADRP has shown to be a reliable metabolic biomarker of AD related neurodegeneration. References: (1) Mattis,PJ. et al. Neurology 87,1925–33(2016); (2) Teune,LK. et al. Curr Alzheimer Res 11,725–32(2014); (3) Spetsieris,PG. & Eidelberg,D. Neuroimage 54,2899–914(2011); (4) Beach,TG. et al. J. Neuropathol. Exp. Neurol. 71,266–273(2012).