bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal validation of Cognigram™ in mild cognitive impairment (MCI): First year of data
Authors: Frank Andrew R. 
Published: December 2020

AbstractBackgroundIt is estimated that 10‐16% of patients with mild cognitive impairment (MCI) transition to dementia each year[1], though it has been difficult to predict which patients are at highest risk of deterioration[2]. CognigramTM is a computerized card game that measures cognition, with results relatively unaffected by language, educational level, and cultural background[3]. Our three‐year longitudinal study aims to assess the capacity of Cognigram to predict future cognitive decline in MCI and cognitively normal (CN) subjects.MethodOne year data is presented here for the first 7 MCI (mean age 76.0, mean MoCA 21.0) and first 6 CN (mean age 69.5, mean MoCA 27.5) participants. Cognigram testing was performed at baseline, 3, 6, 9, and 12 months. Cognigram captured performance scores related to card detection, identification, one‐back, and card learning. Clinical change was assessed using blinded neuropsychological evaluations performed at baseline and 12 months.ResultBased on the neuropsychological testing, MCI and CN participants were classified as either clinically “stable” (4 MCI and 5 CN) or “declining” (3 MCI, 1 CN). On Cognigram card learning accuracy, clinically declining participants showed an accuracy drop of ‐0.14 (0.89 to 0.75) compared to clinically stable participants who showed an accuracy increase of +0.05 (0.89 to 0.94) (p=0.013). There were no clear patterns in the other Cognigram sub‐tests.ConclusionThe Cognigram card learning accuracy test may distinguish between clinically stable and declining participants. The stable participants’ improvement may be explained by a learning effect, which is absent in the decliners. This analysis is limited by the small number, and data will be reviewed with more participants over three years. At the conclusion of our longitudinal study, we hope to determine if Cognigram can identify early cognitive changes in CN and MCI which predict which patients eventually convert to dementia. References: (1) Moon Y, Oh‐Park M, Lee J.(2013). http://www.sciencedirect.com/science/article/pii/B9780323544542000133; (2) Brooks, L.G., Loewenstein, D.A. Alz Res Therapy 2, 28 (2010); (3) Cogstate Healthcare, LLC (2017). https://www.cognigram.us/cognigram/about/index/index0.
Derivation of a tau‐PET based pathology accumulation index to estimate global tau‐load
Authors: Leuzy Antoine , Lilja Johan , Ossenkoppele Rik , Palmqvist Sebastian , Janelidze Shorena , Stomrud Erik , Strandberg Olof , Smith Ruben , Hansson Oskar 
Published: December 2020

AbstractBackgroundAs cortical tau pathology in Alzheimer’s disease (AD) has been shown to correlate closely to neurodegeneration and onset of cognitive impairment, there is a growing interest in the further refinement of tau‐PET methods for clinical use. Similar to amyloid‐PET, tau‐imaging will likely be approved for visual‐read supported by quantification (i.e. standardized uptake value ratio [SUVR]). Recently, we showed that a spatial normalization‐based weighting‐parameter (w, termed Aβ‐index) derived from amyloid‐PET was highly correlated to SUVR. As this measure carries several advantages over SUVR (e.g. no need to define ROIs and no need for an MRI), we here aimed to extend this method to tau‐PET.MethodPreliminary findings are based on 245 subjects with and without cognitive impairment scanned with [18F]flortaucipir as part of the Swedish BioFINDER study. The relationship between w (termed Tau‐index) and SUVR (temporo‐parietal target‐ROI (Vogels et al.,2018) and inferior cerebellar cortex as reference) was assessed via linear regression and coefficient‐of‐determination (R2). Additional analyses are ongoing with a larger cohort (AVID AO5 and Expedition‐3), including cases with antemortem [18F]flortaucipir and post‐mortem tau immunohistochemistry for neurofibrillary tangle pathology. Findings will also be validated in BioFINDER‐2 (n=800, scanned with the second‐generation tau tracer [18F]RO948). Both cohorts will also include longitudinal data. Diagnostic performance of Tau‐index and SUVR will be assessed against visual‐read and post‐mortem tau‐histopathology using area‐under‐the‐curve (AUC) values from receiver‐operating characteristic analyses. These results will be presented at AAIC2020.ResultStrong associations were observed between [18F]flortaucipir Tau‐index and SUVR (R2=0.933, P<0.001;Figure 1). No significant difference was seen between AUC‐values from Tau‐index and SUVR for the separation of AD from CU controls (Tau‐index=0.913, SUVR=0.920;Figure 2).ConclusionThe proposed Tau‐index is simpler to implement clinically and may also facilitate the comparison of tau‐PET across different tracers/processing approaches. The proposed Tau‐index showed a clear association to SUVR and carries an advantage over the latter in that it does not require ROI definition nor the use of an MRI, which is important considering that many elderly subjects have contraindications for MRI. The findings require replication in the larger data sets as well as against neuropathology, which will be presented at the conference.
Detection of attenuated dynamic cerebrovascular function in aging and cognitive decline using a novel neuroimaging approach
Authors: Yew Belinda , Dutt Shubir , Li Yanrong , Ho Jean K , Jang Jung Yun , Blanken Anna E , Sible Isabel J , Marshall Anisa J , Gaubert Aimee , Shao Xingfeng , Wang Danny JJ , Nation Daniel A 
Published: December 2020

AbstractBackgroundCerebrovascular contributions to aging and cognitive decline have been increasingly recognized, yet the impact of changes in dynamic cerebrovascular function remain unclear. Breath holding and hyperventilation elicit alterations in end‐tidal carbon dioxide (etCO2) and cerebrovascular functions underlying cerebral blood flow (CBF). Manipulation of breathing during neuroimaging may therefore enable assessment of dynamic cerebrovascular changes implicated in cognitive decline.MethodCommunity‐dwelling younger (n=15) and older (n=40) adults performed guided 15‐second breath holds to induce hypercapnia and paced breathing (alternating between 5‐second inhalation and exhalation) to induce hypocapnia, while undergoing pseudo‐continuous arterial spin labelling (pCASL) MRI. Continuous blood pressure and end‐tidal carbon dioxide (etCO2) were simultaneously collected. Cerebrovascular resistance index (CVRi), was estimated by dividing mean arterial blood pressure by pCASL‐derived CBF. Carbon dioxide reactivity (CO2R) was calculated by dividing change in CBF by change in etCO2. Older adults also underwent neuropsychological assessment of global and domain‐specific cognition. Relationships between dynamic cerebrovascular function, aging, and cognition were analyzed, controlling for hypertension and education.ResultAcross age groups, paced breathing decreased etCO2, CBF, and CO2R, while increasing CVR. Breath‐holding increased etCO2, CBF, and CO2R, while decreasing CVR. Older adults demonstrated attenuated cerebrovascular autoregulation (i.e. changes in CBF, CO2R, and CVR) in response to hypo‐ and hypercapnia, despite equivalent changes in etCO2 and blood pressure. Among older adults, weaker cerebrovascular response was associated with worse performance on measures of global cognition, memory, and executive function. Effects were preserved even after controlling for hypertension.ConclusionThrough instigation of mild hypercapnia and hypocapnia during MRI, cerebrovascular reactivity deficits were detected in community‐dwelling older adults. Hemodynamic response was attenuated in older relative to younger individuals, suggesting that acute autoregulatory capacity may diminish with aging, above and beyond changes associated with hypertension. Reduced hemodynamic response was also associated with poorer global cognition and performance on tests of executive function and memory. Results suggest that age‐related vascular changes may hamper the proficiency with which changes in blood pressure and CO2 are met with cerebrovascular responses, potentially compromising CBF and neuronal function. This noninvasive method may therefore enable detection of cerebrovascular changes characterizing the earliest stages of cognitive decline.
Levels of amyloid β in cerebrospinal fluid predicts cognition five years later: A population‐based study of 70‐year‐olds
Authors: Skoog Johan , Bodin Timothy Hadarsson , Zetterberg Henrik , Kern Jurgen , Zettergren Anna , Blennow Kaj , Kern Silke , Thorvaldsson Valgeir , Skoog Ingmar 
Published: December 2020

AbstractBackgroundFew studies have investigated the relationship between cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and later cognitive function in the general population. The aim of this study was to study the association between Aβ42/40‐ratio, total‐tau (t‐tau) and phosfo‐tau (p‐tau) at age 70 and cognition at age 75 in a population‐based sample without dementia at baseline.MethodThe sample was derived from the population‐based Gothenburg H70 Birth Cohort Studies. A representative sample of 70‐year‐olds (N=1203, response rate=72%) were examined between 2014‐2016. A subsample of 316 individuals (26%) consented to a lumbar puncture and were free from dementia at age 70. Data have so far been collected on 72 individuals with CSF‐measures at age 70 and cognitive data at the follow‐up at age 75. CSF measures included Aβ42/Aβ40‐ratio, T‐tau and P‐tau, while cognitive tests comprised the Ray Auditory Verbal Learning Test (RAVLT), Semantic Fluency (animals) and Trail Making Test (TMT) A and B.ResultAt age 70, the prevalence of amyloid pathology was 22.8%, total tau pathology 33.2%, and phosphorylated tau pathology 6.9% in cognitively unimpaired individuals. Lower Aβ42/Aβ40‐ratio at age 70 was associated with lower verbal learning score (p<0.01), lower delayed recall (<0.0001) and lower verbal fluency score (p<0.05) at age 75. Aβ42/Aβ40‐ratio was not significantly associated with TMT, and T‐tau and P‐tau was not significantly related to any of the cognitive measures.ConclusionOur findings indicate that amyloid pathology precedes decline in cognition with at least five years while T‐tau and p‐tau does not.
Genome‐wide gene‐based analysis of episodic memory trajectories in the Mexican Health and Aging Study (MHAS)
Authors: Barral Sandra , Gao Yizhe , Arango Silvia Mejia , Obregon Alejandra Michaels , Samper‐Ternent Rafael , Wong Rebeca , Mayeux Richard , Reyes‐Dumeyer Dolly , Rentería Miguel Arce , Tosto Giuseppe 
Published: December 2020

AbstractBackgroundUnderstanding genetic modulation of memory will yield insight into the biological mechanisms underlying memory decline and dementia. The cognitive genetics field has largely focused on populations of European descent. Including genetically diverse populations, such as the Mexican population, the largest USA minority group, will increase our understanding of the genetic architecture of memory function.MethodThe analysis sample consisted of 17,650 participants from the Mexican Health and Aging Study for whom socio‐demographic and longitudinal scores on episodic memory were available. Adjusted trajectories of memory performance were estimated using Latent Class Mixed Models. Genome‐wide gene‐based analyses were carried out in the sub‐sample of participants (n = 2,433) with imputed genotyped data (Haplotype Reference Consortium reference). The slope of episodic memory scores was used as the outcome in gene‐based analyses adjusted for sex, age, education, kinship matrix and principal components. Secondary analyses were restricted to participants with Native‐American ancestry (n = 1,842).ResultThe majority of the participants (77%) clustered as Stables, those who maintained their memory performance over time. Compared to those classified within the Stable memory trajectory, the prevalence of dementia was higher among Decliners. Zinc metabolism appear to be essential for neurogenesis, and neural migration and dietary zinc deficiency has been associated with memory impairment. The Zinc Finger CCHC Domain‐Containing Protein 2 (ZCCHC2) gene yielded the strongest association (p = 4.1 × 10−5). A less strong association with ZCCHC2 was also observed (p = 0.003) in the Native‐American ancestry sub‐sample. However, among the Native‐American participants, a different gene yielded the strongest association (p = 1.3 × 10−4), the Intraflagellar Transport 74 (IFT74) gene. The gene is a member of the IFT complex implicated in the vesicular trafficking to axons and dendrites. Sequence variants in IFT74 have been linked to a form of amyotrophic lateral sclerosis accompanied by progressive cognitive impairment.ConclusionGenetic variation influence longitudinal changes in episodic memory in a sample of Mexican population. Our results suggest that the indigenous Native American ancestry of Mexican population harbors novel and unique genetic variation underlying memory decline. Future work will include a larger sample (approximately 10,000 participants) and trans‐ethnic meta‐analysis with additional Caribbean‐Hispanics, African‐Americans and non‐Hispanic Whites cohorts.
OWOW! Six years on, what have we learned? Experience and perspectives on a cognitive interventional programme for persons with dementia
Authors: Choong Tanya‐Marie Yuen Oi , Yong Ting Ting , Satish Vaynii , Wilbur Koh Zhi Hao , Mei Nyu Mei , Lim Levinia , Silva Eveline , Kandiah Nagaendran 
Published: December 2020

AbstractBackgroundCognitive stimulation is an effective non‐pharmacological intervention shown to support cognitive function in persons with dementia (PwD). In 2014, we initiated the OWOW! programme as a multidisciplinary platform to address the physical and cognitive needs of our patients and offer opportunities for proactive behavior and social interaction. In this study, we draw further insights to the programme by examining staff experience and perspectives.MethodSemi‐structured interviews were conducted with past and existing facilitators of the OWOW! programme (n=8). Questions were pertained to facilitators’ (1) rationale for programme participation, (2) personal experiences and emotions, and (3) feedback regarding organizational and administrative efficiency, and areas of improvement. Responses were examined and analyzed using a systematic thematic analysis approach.ResultThree main themes were identified from preliminary thematic analysis: (1) gaining fresh insight into the level of personhood retained in PwD, (2) relevance of facilitators’ competency and skill, and (3) challenges with respect to programme logistics and organization. All facilitators also emphasized the need to incorporate PwDs' autonomy and personhood in the programme.ConclusionOur findings demonstrate that empowering PwD and reinforcing their personhood is the driving factor behind the effectiveness of the OWOW! programme. The various issues brought up by facilitators will also direct the team to better prepare for future runs of OWOW!
Association of brain copper with Alzheimer’s disease neuropathology: A community‐based neuropathologic study
Authors: Agarwal Puja , Dhana Klodian , Schneider Julie A. , Ayton Scott , Wang Yamin , Agrawal Sonal , Bennett David A. , Barnes Lisa L. , Leurgans Sue E. , Bush Ashley I. , Morris Martha Clare 
Published: December 2020

AbstractBackgroundCopper (Cu) is an essential element for brain health. There is increasing recognition that altered Cu homeostasis is related to the development of Alzheimer’s disease (AD). Neuropathologic findings of amyloid plaque and neurofibrillary tangles are the hallmarks of Alzheimer's disease process. Whether brain Cu is associated with AD neuropathology in humans is unknown. This study examines the relationship between brain Cu levels and AD neuropathology in autopsies from a community sample of older adults.MethodThe study was conducted in 679 deceased participants from the Rush Memory and Aging Project, a cohort study. Brain Cu levels were measured using ICP‐MS in gray matter from inferior temporal, mid frontal, anterior cingulate, and cerebellum. Diffuse and neuritic plaques and neurofibrillary tangles were assessed in multiple brain regions and summarized as standard measures of AD pathology, including Braak, CERAD, NIA‐Reagan, global AD pathology. Linear regression analyses were used to evaluate the associations of brain Cu (grouped in tertiles) with the AD pathology in models controlled for age at death, sex, education, and APOE‐ ε 4 status.ResultThe mean age at death was 90.2 (±6.2) years, 70% were women, and 25% carriers of the APOE4 allele. Higher brain Cu levels were associated with less AD neuropathology. Participants in the middle and highest tertile of overall brain Cu levels had less global AD pathology (T3 vs. T1:β = ‐0.10; T2 vs. T1 = ‐0.11; p trend = 0.007) and Braak stage (T3 vs. T1: β = ‐0.31; T2 vs. T1 = ‐0.22; p trend = 0.005) when compared to those in the lowest tertile. Similar associations were found between inferior temporal brain Cu levels and AD neuropathology: global AD pathology (T3 vs. T1: β = ‐0.17, p = <0.0001); Braak (T3 vs. T1: β = ‐0.42, p = 0.0001); CERAD (T3 vs. T1: β = ‐0.17, p = 0.008); NIA‐Reagan (T3 vs. T1: β = ‐0.21, p = 0.002)). Brain Cu levels in mid‐frontal and cerebellum had a marginal association, whereas anterior cingulate Cu levels had no association with AD neuropathology.ConclusionHigher brain copper levels are associated with fewer AD neuropathology, suggesting that brain Cu levels either may reflect the severity of the disease or may indicate its potential beneficial effect on the disease process.
Comparison of static and dynamic analysis techniques for longitudinal analysis of amyloid PET
Authors: Cash David M , Markiewicz Pawel J , Jiao Jieqing , Coath William , Modat Marc , Lane Christopher A , Parker Thomas D , Keuss Sarah E , Buchanan Sarah M , Burgos Ninon , Dickson John , Barnes Anna , Cardoso Jorge , Alves Isadora Lopes , Barkhof Frederik , Thomas David L , Beasley Daniel , Wong Andrew , Schöll Michael , Richards Marcus , Ourselin Sebastien , Fox Nick C , Schott Jonathan M 
Published: December 2020

AbstractBackgroundAmyloid PET is a robust biomarker of cortical β‐amyloid accumulation and a candidate endpoint for Alzheimer’s prevention trials. Quantification typically uses Standard Uptake Value Ratio (SUVR) measures acquired over 10‐20 minutes at steady‐state. SUVR may be more susceptible to altered blood flow than modelling of dynamic uptake data from injection to steady state. This may influence quantification, particularly change over time. Here we compared cross‐sectional measures and longitudinal rates of β‐amyloid change from static and dynamic analyses in individuals free of dementia.MethodAll participants were from Insight46, a sub‐study of the British 1946 birth cohort. Florbetapir PET scans were acquired on a single Biograph mMR PET/MR scanner and reconstructed using pseudo‐CT attenuation maps. Static SUVR images were acquired 50‐60 minutes post‐injection. Distribution Volume Ratio (DVR) was obtained from the Simplified Reference Tissue Model (SRTM) over 0‐60 minutes post‐injection. Both analyses used the same reference (cerebellar grey) and target (composite cortical grey) regions with no partial volume correction. Amyloid positivity was determined from a Gaussian Mixture model of the baseline data, taking the 99th percentile of the amyloid negative distribution. Amyloid accumulators were individuals with annual rates of change above 1.8%/year, representing the mean annualised rate of change in 37 cognitively normal CSF Aβ42 positive ADNI participants (doi:// 10.2967/jnumed.114.148981).Result390 participants had suitable PET data for cross‐sectional static and dynamic analysis; 195 participants had longitudinal data. DVR and SUVR exhibited high agreement cross‐sectionally (r2=0.79) with similar cut‐points (Table 1) and amyloid positivity rates (94% concordant classification, Figure 1). Longitudinal DVR resulted in more converters and accumulators in the amyloid negative group (Figure 2 and 3). However, comparing baseline amyloid positive/negative groups, longitudinal SUVR provided a larger effect size (Cohen’s d=1.02) than longitudinal DVR (d=0.28) (Table 1), with a sample size of 241 needed to detect a 25% reduction in SUVR per arm (compared to amyloid negatives) at 95% significance, 80% power.ConclusionStatic and dynamic PET measures provide similar “state measures” at baseline, but have different longitudinal properties. SUVR may be more sensitive for quantifying accumulation in amyloid positive individuals; dynamic measures may be better at detecting earlier accumulation and conversion.
Diagnostic lumbar puncture in people with Down syndrome: The experience of the Jerome Lejeune Institute
Authors: Rebillat Anne‐Sophie , Hiance‐Delahaye Anne 
Published: December 2020

AbstractBackgroundPeople with Down syndrome (DS) face an extremely high risk to develop dementia due to Alzheimer’s disease (AD) (Ballard C et al., 2016). The diagnosis of dementia in this population is complex given the pre‐existing intellectual disability, behaviour and co‐morbidities (Esbensen AJ et al, 2018). Contribution of biomarkers is crucial. However there are many reservations on the feasibility of lumbar puncture in this population. Nethertheless, this medical procedure should be accessible for people with DS (Carmona‐Iragui M., 2017)MethodDescription of the procedure performed at the Jerome Lejeune Institute using standard guidelines, pictograms and nitrous oxide analgesiaResultAbout a third of the patients refused the procedure. For the others, the puncture was very well tolerated but sometimes made difficult by the anatomical particularities of the patientsConclusionIt is a well accepted and well tolerated procedure, requiring time.