bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is it possible to implement standard neuropsychological assessment in European memory clinics? An EADC‐ISTAART survey
Authors: Grazia Alice , Monsch Andreas U. , Cappa Stefano , Teipel Stefan J. , Frölich Lutz , Winblad Bengt , Welsh‐Bohmer Kathleen A. , Boccardi Marina 
Published: December 2021

AbstractBackgroundNeuropsychological assessment of mild cognitive impairment (MCI), a gateway for the biomarker‐based diagnosis, should follow a standard operating procedure to enhance the reliability of clinical diagnosis across centers and decrease costs to both patients and health‐care systems. A previous consensus adapted the NACC UDS‐3 for use in European memory clinics (cUDS). Here, we assess its implementability.MethodClinicians from the European Alzheimer’s Disease Consortium (EADC) memory clinics answered an online semi‐structured survey investigating center practices, potential hurdles and facilitators to implement the cUDS. We performed descriptive statistics and content analysis of explanatory comments to investigate the nature and frequency of perceived hurdles and facilitators.ResultFifty out of the 69 EADC memory clinics (72%) answered from 17 countries: 7 Northern, 22 Western, 4 Eastern and 17 from Southern Europe, with heterogeneous national participation (range: 1‐8 centers per country) (Figure).Centers have a variable yearly patient flow (range: 100‐2500), use heterogeneous definitions of MCI and cognitive batteries, and offer variable proportions of neurology (86%), psychology (80%), psychiatry (64%) and geriatrics (62%) services.Thirty‐three centers (66%) expressed propensity to implement the cUDS. Six of the twelve cUDS tests are already frequently used: e.g, the fluency tests are used in 87‐100% of the assessments. Up to 9 of the 12 tests have local norms in different countries, although not systematically. Hurdles for the 17 EADC responders (34%) not inclined to implement the cUDS are organizational‐logistical (7/13 providing explanations) relative to time‐management issues and need for clinicians training, cultural barriers and resistances to change ongoing practices (6/13). Among the latter, availability of previous local harmonization (Germany, Netherlands, Spain, Switzerland and United Kingdom) appears the strongest motive, followed by a preference for patient‐tailored assessment. Economic factors did not seem to hinder implementation, 90% of the centers not in favor having 61‐100% refund for cognitive assessment.ConclusionDespite barriers, our preliminary data denote propensity to standardize neuropsychological assessment. The involved centers of excellence may be not fully representative, especially relative to non‐academic contexts. Next steps may require to collect more detailed information, also from non‐academic clinics, and identify specific country and context requirements.
Assessment of retinal microvascular alterations in individuals with amnestic and non‐amnestic mild cognitive impairment using optical coherence tomography angiography
Authors: Akrobetu Dennis , Robbins Cason B. , Stinnett Sandra , Soundararajan Srinath , Liu Andy , Johnson Kim , Grewal Dilraj S. , Fekrat Sharon 
Published: December 2021

AbstractBackgroundIndividuals with mild cognitive impairment (MCI) can be categorized into amnestic and non‐amnestic subgroups based on the absence or presence of intact working memory. Patients with amnestic MCI have increased likelihood of progressing to Alzheimer’s disease (AD); however, identification of predictive biomarkers distinguishing amnestic and non‐amnestic MCI remains ambiguous. This prospective, cross‐sectional study utilizes optical coherence tomography angiography (OCT‐A) to assess how retinal microvascular density and structure might differ among amnestic and non‐amnestic MCI patients.MethodOne hundred and twelve eyes of 59 amnestic MCI participants, 32 eyes of 17 non‐amnestic MCI participants, and 111 eyes of 56 cognitively healthy controls were included in our study. All participants were imaged using the Zeiss Cirrus HD‐5000 AngioPlex. OCT‐A vessel density (VD) and perfusion density (PD) in Early Treatment Diabetic Retinopathy Study (ETDRS) 3mm and 6mm circles and rings were assessed. Retinal thickness parameters on OCT including retinal nerve fiber layer thickness (RNFL), ganglion cell‐inner plexiform layer (GC‐IPL), and central subfield thickness (CST) were also analyzed. Generalized estimating equations accounting for correlation between two eyes of the same subject were utilized for statistical analysis.ResultAssessment of PD in the 3x3mm inner ETDRS ring revealed a significant decrease in amnestic MCI when compared to non‐amnestic MCI (0.29 ± 0.03 vs 0.34 ± 0.09, p = 0.025), and was significantly lower in amnestic MCI when compared to healthy controls (0.29 ± 0.03 vs 0.39 ± 0.02, p < 0.001), after adjustment for age and sex. Vessel density, subfoveal choroidal thickness, and other retinal thickness parameters (GC‐IPL, RNFL, CST) showed no statistically significant difference among or between diagnostic groups.ConclusionAfter adjusting for age and sex, OCT‐A perfusion density significantly differed among controls, non‐amnestic MCI, and amnestic MCI. Other retinal parameters did not differ between groups after adjusting for covariates. Non‐invasive retinal imaging deserves further study as a potential biomarker for diagnosing and classifying subtypes of MCI.
Duration of life in the three common variants of primary progressive aphasia: A retrospective study in a tertiary memory clinic
Authors: Tastevin Maud , Lavoie Monica , Sablonnière Justine De La , Laforce Robert 
Published: December 2021

AbstractBackgroundPrimary progressive aphasias (PPAs) are a group of neurodegenerative disorders characterized by an insidious and progressive language impairment. Clinical expression and underlying pathology remain highly heterogeneous. To date, there is a lack of knowledge on the natural history of each of the three main variants, particularly mortality. Moreover, advanced stages and end of life issues are rarely discussed with caregivers and families at diagnosis. In turn, this can cause additional psychological distress.We studied the natural history of the three main variants of PPA. More specifically, we focused on mortality and end of life issues in an attempt to better prepare patients and their families.MethodWe retrospectively studied all deceased patients with a diagnosis of PPA that had been followed at our tertiary memory clinic over the past twenty years (n=83). Clinical data included age of onset of symptoms, duration of illness, age at death and specific cause of death.ResultAge at death was similar across all three PPA variants but there was less variability in the non‐fluent variant (nfvPPA) group (M=76.6, SD=6.2) than in the semantic variant (svPPA; M=74.1, SD=8.5) or the logopenic variant (lvPPA; M=76.1, SD=9.1) groups. Age at onset of symptoms was earlier for svPPA participants (M=64.5, SD=8.3) then for the two other variants (lvPPA: M=69.3, SD= 10.7; nfvPPA: M=70.4, SD=6.3). Consequently, duration of the disease (number of years between symptoms’ onset and death) was longer for svPPA participants (M=9.6, SD=3.0) than for nfvPPA and lvPPA participants (respectively M=6.2, SD=2.1 and M=7.0, SD=2.9). Surprisingly, cause of death was unknown for most of the participants. When available (n=15), it included sepsis (n=6), respiratory failure (n=4), neoplasia (n=3) and stroke (n=2), and. There were no differences in causes of death among PPA variants.ConclusionDespite similar age of death across PPA variants, disease duration was longer in the svPPA. Causes of death per se were similar among PPAs. Future studies should include more participants with better emphasis on causes of death. Nonetheless, our study provides useful information about the natural history of the common variants of PPA.
Memory improvement effects of Ganoderma mediosinense in mice via its anticholinergic and antioxidant activities
Authors: Singh Varinder , Arora Sandeep , Kaur Ravneet , Shri Richa 
Published: December 2021

AbstractBackgroundSpecies of the genus Ganoderma are valued both for their medicinal as well as nutritional properties. Traditionally, these are employed in neurological disorders. However, G. mediosinense has not been evaluated for anti‐amnesic effects previously. Therefore the present study is aimed to explore the cognitive improvement effects of the G. mediosinense extract (GME) against mouse model of scopolamine induced amnesia.MethodAnimals were orally administered with GME (200, 400 and 800 mg/kg) for 7 consecutive days and amnesia was induced by scopolamine (1 mg/kg, i.p.) after 30 min of treatment. Cognitive functions were determined by employing passive shock avoidance task and novel object recognition test. Brain AChE and lipid peroxidation were determined to have an insight into the associated neuroprotective mechanism of GME.ResultTreatment with GME showed dose dependent amelioration of cognitive deficit induced by scopolamine in animals. Also, GME reduced the brain AChE activity and oxidative stress.ConclusionThese results indicated the anti‐amnesic effects of GME via decreasing brain cholinergic and oxidative stress.
Pre‐analytical and clinical validation on the highway to implementation of novel dementia blood tests
Authors: Teunissen Charlotte E. 
Published: December 2021

AbstractBackgroundBlood based biomarkers for Alzheimer’s disease and other dementias are now a reality. Results in large well‐defined research cohorts suggest high potential for implementation for diagnosis (pTau, amyloid isoforms, GFAP), prognosis (pTau, GFAP, NfL) or monitoring (pTau, NfL) in clinical practice and treatment development. Implementation of novel blood based biomarkers requires several aspects to be addressed, among which pre‐analytical sample handling, patient heterogeneity and the development of cut‐offs and computer‐assisted tools for interpretation.MethodTo mimic pre‐analytical variations occurring in current practice, systematic experiments were performed and effects on plasma Amyloid beta(42/40), (p)Tau, NfL and GFAP levels were measured using different technologies. To understand patient heterogeneity, these markers are measured in several cohorts of normal aging elderly using Simoa technology. To develop cut‐offs and tools for interpretation, these markers are measured in a retrospective cohort of patients with various dementias. Lastly, prospective analysis of these markers in the memory clinic setting has been started.ResultThe generated knowledge on the most important pre‐analytical factors affecting Amyloidbeta(42/40), (p)Tau, NfL and GFAP levels resulted in the construction of a standardized operating procedure for use in clinical practise and research (Figure). Results in the normal aging population followed longitudinally show that these biomarkers are higher in patients that are proven to be amyloid positive 10 year later. Detailed results of patient biomarker heterogeneity will be presented as well as a decision tool for use in clinical practice. Lastly, pilot data on experience with these novel blood based biomarkers and the decision tools for dementia diagnosis in the memory clinic setting will be presented.ConclusionTogether, the addressed are important steps towards smooth and widespread implementation of blood based biomarkers in clinical practise.
CSF and blood plasma mass spectrometry measures of Aβ, tau, and NfL species and longitudinal relationship to preclinical and clinical staging of amyloid and tau aggregation and clinical stage of Alzheimer’s disease
Authors: Bateman Randall J. , Barthelemy Nicolas R. , Benzinger Tammie L.S. , Bollinger James G. , Fagan Anne M. , Gordon Brian A. , Hansson Oskar , Holtzman David M. , Horie Kanta , Li Melody , Masters Colin L , Mawuenyega Kwasi G. , McDade Eric , Morris John C. , Ovod Vitaliy , Budelier Melissa , He Chloe , Petersen Ronald C. , Mielke Michelle M. , Sato Chihiro , Schindler Suzanne E. , Shaw Leslie M. , Trojanowski John Q , Weiner Mike W. , Xiong Chengjie 
Published: December 2021

AbstractBackgroundRecent advances in the development of novel Alzheimer’s disease (AD) measures of amyloid, tau, and neurodegeneration in cerebrospinal fluid (CSF) and blood have enabled a better understanding of the links between amyloid‐beta (Aβ), tau species and neurodegeneration in the brain, CSF, and blood. The discoveries of novel tau species in CSF and blood, including specific phospho‐tau (p‐tau) and truncated species containing the microtubule binding region of tau (MTBR‐tau) which aggregates in tau tangles, have greatly expanded our understanding of tau biology and tau target development. The longitudinal Aβ, tau, and neurofilament light chain (NfL) changes previously measured in CSF are now being measured accurately in blood, enabling interpretation and understanding of AD progression in much larger and more robust populations.MethodWe analyzed longitudinal CSF and/or blood plasma mass spectrometry measures of Aβ42/Aβ40, multiple p‐tau species (including p‐tau217, 231, 181, 205, etc.), total tau, MTBR‐tau (e.g., MTBR‐tau243, MTBR‐tau299, and MTBR‐tau354), and NfL in sporadic AD and dominantly inherited AD cohorts. Mass spectrometry results were compared to amyloid and tau aggregation measures by Positron Emission Tomography (PET) scans and clinical and cognitive measures in local and international clinical cohorts including ADNI, AIBL, BioFINDER, Mayo Clinic, the Knight ADRC, and the DIAN.ResultThe longitudinal results indicate that a pathophysiological cascade of events begin with altered CSF and blood plasma Aβ42/Aβ40 ratio, followed by increases in amyloid plaques as measured by amyloid PET, associated with increased phosphorylation of specific CSF tau species (e.g., p‐tau217, p‐tau181, etc.), before increases in p‐tau205, NfL, total tau concentrations, hypometabolism, and atrophy. Finally, some species of MTBR‐tau increase before or with tau aggregation by tau PET and onset of clinical symptoms and correlate with longitudinal tau aggregation and clinical progression.ConclusionThese findings indicate that CSF and blood plasma Aβ, p‐tau, MTBR‐tau and NfL measures are highly precise biomarkers of brain amyloidosis, tauopathy, and neurodegeneration and can accurately identify stages of preclinical and clinical AD.
The diagnostic challenge among young onset dementia syndromes and primary psychiatric diseases: Results of a retrospective, 20‐year cross‐sectional study
Authors: Tsoukra Paraskevi , Velakoulis Dennis , Wibawa Pierre , Malpas Charles B , Walterfang Mark , Evans Andrew H , Farrand Sarah , Kelso Wendy , Eratne Dhamidhu , Loi Samantha M 
Published: December 2021

AbstractBackgroundDistinguishing a dementia syndrome from a primary psychiatric disease in younger patients can be challenging and may lead to diagnostic change over time. The aim of this study was to examine diagnostic stability in a cohort of patients with younger‐onset neurocognitive disorders.MethodWe retrospectively reviewed records of patients that were admitted to our unit between 2000 and 2019, were followed‐up for ≥12 months and received a diagnosis of young onset dementia at any time point. Initial diagnosis included Alzheimer disease (AD)‐type dementia (n= 30), frontotemporal dementia (FTD) syndromes (n=44), vascular dementia (VaD, n=7), mild cognitive impairment (MCI, n= 10), primary psychiatric diseases (n=6) and other conditions such as Lewy Body Dementia (n=30).ResultIn a total of n=127 patients, 49 (39%) changed their initial diagnoses during follow‐up. Behavioural variant FTD (bvFTD) was the least stable diagnosis, followed by dementia not otherwise specified and MCI. Compared to patients with a stable diagnosis, those who changed exhibited: a higher cognitive score at baseline, a longer follow‐up period, greater delay to final diagnosis, and no family history of dementia. Patients switching from a neurodegenerative to a psychiatric diagnosis more likely had a long psychiatric history, while those changing from a psychiatric to a neurodegenerative diagnosis had a recent manifestation of psychiatric symptoms.ConclusionMisdiagnosis in younger patients with neurocognitive disorders is not uncommon, especially in cases of behavioural variant FTD. Late‐onset psychiatric symptoms may be the harbinger to a neurodegenerative disease. Close follow‐up and monitoring of these patients are necessary.
Cerebellar atrophy in non‐fluent variant primary progressive aphasia correlates with disease severity and cognitive decline
Authors: Akhmadullina Diliara , Konovalov Rodion , Fedotova Ekaterina , Illarioshkin Sergey 
Published: December 2021

AbstractBackgroundThe role of the cerebellum in cognitive function has been extensively investigated in the last decades. The aim of our work was to characterize cerebellar atrophy in non‐fluent variant primary progressive atrophy (nfvPPA) and to determine whether its atrophy is associated with cognitive impairment.MethodSixteen patients with nfvPPA (mean age 59.6±9.2 years, 7 males) and 10 healthy controls (65.6±11.3 years, 4 males) were included in the study. Disease duration ranged from 12 to 84 months. Notably, the patients had no clinical signs of cerebellar involvement. All participants underwent brain MRI and cognitive assessment. A whole brain VBM analysis between patients and controls was carried out using SPM12. The relationship between clinical data and grey matter atrophy of cerebellum and its distinct areas (anterior lobe, posterior lobe, vermis, left and right hemispheres) was assessed by correlation analysis using the Spearman's rank correlation coefficient.ResultVBM revealed a significant decline in grey matter (GM) volume in the anterior (specifically, 4, 5 and 6 lobules) and posterior (specifically, Crus I and II, 7b and 8 lobules) cerebellar lobes bilaterally compared to controls (Figure 1). Correlation analysis revealed a significant correlation between the posterior lobe GM volume and disease severity and total Addenbrooke Cognitive Examination score (r = ‒0.62, p = 0.01 and r = 0.69, p = 0.028, respectively). No correlations with other clinical manifestations and neuropsychological findings (disease duration, total MoCA and FAB scores, semantic and literal verbal fluency, Trail Making Test part B) were detected.ConclusionThe findings demonstrate that, even in the absence of clinical signs of cerebellar involvement, prominent cerebellar atrophy is characteristic of nfvPPA. This atrophy is associated with disease severity and contributes to cognitive dysfunction.The study was supported by RFBR 19‐015‐00533.
Levels and trajectories of domain‐specific cognition differ across lifestyle engagement subgroups of older adults
Authors: Moored Kyle D , Parisi Jeanine M , Snitz Beth E , DeKosky Steven T , Williamson Jeff D , Fitzpatrick Annette L , Carlson Michelle C 
Published: December 2021

AbstractBackgroundEngagement in lifestyle activities may be neuroprotective, but longitudinal data is needed to best inform health interventions. Characterizing the prospective impact of shared lifestyle activities among older adults may both identify subgroups who could benefit most from intervention and reveal contextual/motivational differences in lifestyle that are relevant to group‐level intervention design. We used latent class analysis to characterize qualitatively distinct lifestyle engagement groups and examined whether they had differential declines in global and domain‐specific cognition.MethodParticipants were 3068 individuals from the Ginkgo Evaluation of Memory (GEM) Study who completed neuropsychological testing up to 8 years (M=5.0, SD=2.4). We assessed 18 physical, intellectual, and social activities using the Lifestyle Activity Questionnaire. Linear mixed effects models adjusted for demographic and health covariates were used to examine lifestyle engagement group differences in cognitive level and changes over time.ResultThe four‐class model fit best (Figure 1). The Variety lifestyle group (22%) had high engagement in both intellectual (e.g., taking classes) and social activities (e.g., concerts, church, social clubs). The Intellectual (18%) group had high engagement in intellectual and some social leisure activities (e.g., concerts). The Social (32%) group had high engagement in social institutional activities (e.g., church). Compared to the Least Active (28%) group, the Variety (B’s=.14‐.25, p’s<.05) and Intellectual (B’s=.10‐.29, p’s<.05) groups had greater levels of cognitive performance across all domains, whereas the Social group was only higher in memory (B=.11, SE=.04, p=.013; Table 1). The Variety group also had attenuated declines in memory (B=.02, SE=.01, p=.035) and attention (B=.02, SE=.01, p=.023) over time.ConclusionHigher lifestyle engagement, especially in intellectual activities, was associated with higher levels of cognition later in life. Yet, only those with the greatest diversity of activities (Variety group) were protected against subsequent declines in memory and attention. These results extend prior findings that these lifestyle groups differ in risk of incident dementia, by suggesting that memory and attention (vs. visuospatial construction) drive this protective relationship. Our findings also highlight subgroup differences in activity types (e.g., primarily social vs. intellectual) that may lead to more targeted interventions to reduce cognitive declines with age.
Clinical and biological heterogeneity in autosomal dominant Alzheimer's disease
Authors: Quiroz Yakeel T. , Aguilar Laura Ramirez , Giraldo‐Chica Margarita , Aguillon David , Baena Ana Y. , Bocanegra Yamile , Vila‐Castelar Clara , Fox‐Fuller Joshua T. , Pluim Celina F. , Aduen Paula , Lopera Francisco 
Published: December 2021

AbstractBackgroundPresenilin‐1 (PSEN1) mutations cause early‐onset autosomal dominant Alzheimer’s disease (ADAD) with nearly 100% penetrance, providing an opportunity to characterize the biological changes associated with preclinical AD. Over 280 different ADAD mutations are currently identified. In Antioquia, Colombia, there are two PSEN1 cohorts, including the world’s largest family with the E280A mutation (consisting of over 1,200 mutation carriers). The clinical phenotype of ADAD is similar to sporadic AD, though some cases have atypical presentations and vary in age at clinical onset and disease course. Here, we reviewed the clinical and biological profiles of these two large families with ADAD.MethodMembers of two large Colombian families with ADAD were included (PSEN1 mutations: 60 E280A carriers, 26 Ile416Thr carriers). All participants underwent a comprehensive clinical and cognitive assessment. Diagnosis of Mild Cognitive Impairment (MCI) and dementia was blind to carrier status. A subset of the E280A (n=35) and Ile416Thr (n=3) mutation carriers also underwent tau and amyloid PET imaging.ResultThe PSEN1 E280A clinical profile is characterized by memory decline beginning in the early 30s, followed by progressive impairment of other cognitive functions. These carriers develop MCI around age 44 and dementia around age 49. There is some phenotypic variability in PSEN1 E280A; some carriers present with epilepsy and ataxia. PET imaging of E280A carriers show a pattern of amyloid and tau pathology similar to that seen in sporadic AD. However, a few cases show distinct patterns of tau accumulation, involving early tau pathology in occipital and parietal regions, absence of tau in medial temporal lobe, and variable cognitive profiles. The Ile416Thr cognitive profile consists of early memory and verbal comprehension impairments. Carriers develop MCI at a mean age of 48 and progress to dementia at age 52. PET imaging of Ile416Thr carriers shows an initial pattern of tau accumulation limited to medial temporal lobe regions.ConclusionThe clinical and biological profiles of ADAD mutations can be heterogenous. Variable cognitive and clinical phenotypes may explain different trajectories of disease progression and response to treatments in clinical trials. Future studies should examine other biological similarities and differences among ADAD mutations.