bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating changes in gait and activity associated with cognitive impairment using a home‐based technology platform
Authors: Thomas Neil W. , Agarwal Ashi , Ault Laura , Lariviere‐Chartier Julien , Kingstone Lysa Legault , Wallace Bruce , Knoefel Frank , Goubran Rafik , Beattie Zachary , Kaye Jeffrey A 
Published: December 2021

AbstractBackgroundChanges in mobility are associated with cognitive decline in older adults. Mobility is frequently assessed in the clinic setting at episodic intervals. Passive sensors within a home‐based technology platform allow for unobtrusive collection of mobility and gait information over an extended time period. This method of high‐frequency data collection could be sensitive to early changes in mobility associated with cognitive decline.MethodWe present data for a cohort of 32 participants living alone and enrolled in the Collaborative Aging Research Using Technology (CART) Initiative aging study with a pervasive sensing and computing system deployed in their homes. Sixteen individuals with a Clinical Dementia Rating (CDR) scale score of 0.5 were matched by age, sex and education to 16 participants with a CDR of 0; 80% lived in low‐income senior apartments; 6% were non‐white. Mobility and gait data is derived from a gait line, consisting of four ceiling mounted, field‐of‐view restricted passive infrared motion sensors placed 61 cm apart in a line, in each home. The number of walking events, defined as all four sensors being triggered, was analyzed between the two groups.ResultParticipants with a CDR score of 0 had a mean age of 72.1 years and a mean MoCA score of 26.1 (range 21 – 30). Participants with a CDR score of 0.5 had a mean age of 72.2 and a mean MoCA score of 22.1 (range 15 – 27). Fifty‐six percent of participants in each group were female. Preliminary data from the gait line from a combined 1400 days for CDR 0 participants and a combined 1250 days for CDR 0.5 participants is presented here. The mean number of daily walking events detected by the gait line was significantly greater for CDR 0 participants (101.4) compared to CDR 0.5 participants (92.8, p=0.03).ConclusionAmbient sensors are able to collect longitudinal data on gait and activity levels in individuals with a technology platform deployed within their home. This unobtrusive remote mobility assessment methodology identifies individuals experiencing cognitive impairment. Further evaluation of other gait metrics and home‐based activity patterns is ongoing to explore their association with changes in cognition.
Multi‐site neuroimaging analysis across ethnicities: Pilot study from the UNITED consortium
Authors: Evans Tavia E , Adams Hieab H.H. 
Published: December 2021

AbstractBackgroundNon‐Europeans are severely unrepresented in neuroimaging research of neurodegenerative disorders. The uncovering neurodegenerative insights through ethnic diversity (UNITED) consortium was set up to tackle this, aiming to gain insight into the neurodegenerating brain in diverse populations. Large multi‐centre efforts are needed to adequately investigate this, however there are potential hurdles due to multiple sources of heterogeneity in neuroimaging data.MethodThe UNITED consortium currently includes over 95,000 individuals from 64 partners spanning 30 countries on 6 continents [Figure 1]. MRI images were processed through multiple methods extracting millions of imaging markers to characterise the brains morphological architecture at a vertex and voxel level. We performed a pilot analysis using four studies including 25,000 individuals from the consortium to investigate the feasibility of meta‐analysing heterogenous data across multiple processing methods. MRI markers were investigated in relation to Alzheimer’s disease, MCI and apoe4 load. All analyses were stratified by ethnicity and subsequently meta‐analysed.ResultAssociations between clinical markers and MRI were similar across study designs [case‐control vs population‐based]. However, some associations differed significantly across image processing pipelines [FSL vs FreeSurfer], these differences were more pronounced within case‐control samples [Figure 2]. Fine grained imaging markers showed both positive and negative associations within the same brain structure, which was missed with traditional volumetric analysis [Figure 3]. We found subtle differences between ethnic groups [Figure 4].ConclusionMulti‐site analysis can capture a clearer more detailed picture of the neurodegenerating brain. The current pilot highlights the necessity of harmonizing neuroimage processing within meta‐analysis. Our results are promising for wider application to the full consortium and displays the additional insights that can be gained from fine grained imaging markers beyond traditional approaches. While we cannot draw definitive conclusions on the ethnic differences from the current pilot it paves the way for future studies to gain insight into ethnic disparities.
Anomia across the atypical AD phenotypic spectrum
Authors: Eustace Ana , Wong Bonnie , Quimby Megan , Dickerson Brad C. , Putcha Deepti 
Published: December 2021

AbstractBackgroundVisual naming is impaired in AD, most prominently in the typical late‐onset amnestic and logopenic variant Primary Progressive Aphasia (lvPPA) syndromes. However, little is known about how patients with these or other AD syndromes (Posterior Cortical Atrophy; PCA, and early‐onset amnestic dysexecutive) perform on auditory confrontation naming tests that do not rely on visual perception of stimuli. Performance on such tests may be of particular relevance to measuring anomia in PCA, who present with visual cognitive deficits. The present study analyzes Auditory Naming Test (ANT) performance across the atypical AD phenotypic spectrum.MethodFifty‐three patients (19 PCA, 13 lvPPA, 21 amnestic dysexecutive) were administered the ANT. Total uncued correct responses and total correct responses with phonemic cues were analyzed. Performance differences between groups were evaluated using one‐way ANOVA. Independent samples t‐tests were performed to verify between‐group differences.ResultUncued auditory naming was impaired across all atypical AD groups, with group differences observed (F(2,50)=10.31, p<0.001) such that the lvPPA group (60% correct) performed most poorly followed by the amnestic dysexecutive group (77% correct; t=2.09, p=0.04). PCA patients performed best (91% correct; lvPPA < PCA, t=5.5, p<0.001; amnestic dysexecutive < PCA, t=2.5, p=0.02). Auditory naming after phonemic cuing also differed across groups (F(2,50)=6.15, p=0.004): lvPPA (76% correct), amnestic dysexecutive (81% correct), and PCA (97% correct). Performance was still impaired in lvPPA and amnestic dysexecutive groups after cuing, but were comparable to each other (p > 0.6), while PCA patients performed better than lvPPA (t=4.5, p=0.001) and amnestic dysexecutive (t=2.7, p=0.03) groups, falling within normal limits.ConclusionAuditory naming was most impaired in lvPPA but improved with phonemic cues. In contrast, cues did not greatly improve performance in the amnestic dysexecutive group, suggesting either a goal‐directed retrieval deficit or semantic knowledge loss. PCA patients demonstrated mild word retrieval deficits in the absence of visual stimuli, potentially reflecting auditory‐verbal working memory deficits previously identified in the literature. However, the PCA group improved with phonemic cuing, suggesting intact semantic knowledge. We plan to build on these results by next examining the cognitive contributors to and regional atrophy correlates of ANT performance in each group.
Affective factors may play a less important role in subjective cognitive decline symptoms of women than men
Authors: Smith Samantha , Splonskowski Moriah , Jacova Claudia 
Published: December 2021

AbstractBackgroundThe association between subjective cognitive decline (SCD) symptom burden and affective symptoms (i.e., depression and anxiety) is well established, but its interpretation remains elusive: are affective symptoms causally related to SCD or do they reflect independent neurobiological processes? We sought to further the understanding of the SCD/affective symptom association by examining the moderating effects of risk factors for AD/dementia (female gender, older age, and positive family history).MethodA nation‐wide sample of community‐dwelling 483 adults between ages 50 and 79 (66.5% female; 14.5% age > 70; 27% with positive family history) completed an online survey via the crowdsourcing website Amazon Mechanical Turk. Respondents answered demographic questions, completed the Subjective Cognitive Decline Questionnaire (SCD‐Q MyCog) (0‐25, M=4.71, SD=5.77), and the PROMIS anxiety (7‐35, M=13.04, SD=5.68), and depression (8‐40, M=13.18, SD=6.32) measures. Linear regression was conducted to evaluate the interaction of each risk factor with SCD total in the prediction of depression and anxiety (separate models).ResultThe interaction term was statistically significant for gender, both in relation to depression (b=‐0.28, t[479]=‐3.42, p <.001), and anxiety (b=‐0.21, t[479]=‐2.27, p=.02). In both cases, the SCD/affective symptom correlation was lower for females than for males: SCD/depression: female, r=.239; male, r=.543 and SCD/anxiety: females, r=.260; males, r=.445), respectively. There were no significant interactions with age or family history.ConclusionOur finding of gender differences in the association between SCD and depression/anxiety symptoms suggest that affective factors play a less important role in the SCD symptoms of women than men, and raise the possibility that SCD is somewhat different in women than men. We speculate that gender‐specific cognition and affect characteristics rather than differences in AD/dementia risk may be responsible for our findings.
Napping characteristics and cognitive function in older adults
Authors: Leng Yue , Hagen Erika W , Ravelo Laurel A , Peppard Paul E , Yaffe Kristine 
Published: December 2021

AbstractBackgroundBrief naps are considered beneficial for cognition in younger adults, whereas emerging evidence suggests excessive napping may be associated with dementia in older adults. The effects of napping parameters on different cognitive domains remain controversial, and the role of reasons for napping is poorly understood.MethodWe used cross‐sectional data from the Wisconsin Sleep Cohort Study. Participants reported on naps that lasted more than 5 minutes over the past month, nap frequency and length, and reasons for napping. Participants reported nighttime sleep duration and quality, and completed overnight polysomnography to assess sleep apnea. Six neurocognitive tests measured attention, memory, learning and executive function.ResultOf the 686 participants (mean (SD), [range] age 65.0 (7.1), [50‐85] years; 44% women), 500 (73%) reported a nap >5 minutes during the past month and 184 (27%) napped at least four times per week. The average nap length was 41.4 minutes. 187 (27%) napped due to not getting enough sleep at night, 52 (7.6%) napped due to illness or medical reasons, 256 (37%) napped to feel refreshed, 27 (3.9%) napped because they felt unhappy or unwell, and 139 (20%) napped for other reasons. After adjustment for age, sex, body mass index, alcohol intake, smoking, depression, and history of diabetes and cardiovascular diseases, those with more frequent naps performed worse on three neurocognitive tests (P<0.02): Symbol‐Digit Modalities (SDMT) (b=‐1.9, standard error (SE)=0.7), Oral Word Fluency (b=‐2.3, SE=0.9) and Auditory Verbal Learning Test (b=‐1.9, SE=0.8). Those with longer naps performed worse on Grooved Pegboard (b=11.0, SE=2.8), Trails B (b=8.1, SE=2.3), SDMT (b=‐1.9, SE=0.4) and Digit Cancellation (b=14.4, SE=5.6). Further adjustment for sleep duration, quality and sleep apnea did not appreciably alter results. There were no associations between specific reasons for napping and cognition.ConclusionAmong middle‐ to older‐aged adults, more frequent naps were associated with worse attention and memory and learning; longer naps were associated with worse attention and executive function. Longitudinal studies are needed to examine how napping characteristics predict cognition as individuals age and to further explore reasons for napping during this transition.
Transcriptomics, metabolomics, lipidomics, metabolic flux and mGWAS analyses of sphingolipid pathway highlights novel drugs for Alzheimer’s disease
Authors: Baloni Priyanka , Arnold Matthias , Moreno Herman , Nho Kwangsik , Kastenmüller Gabi , Suhre Karsten , Buitrago Luna , Louie Gregory , Kueider‐Paisley Alexandra , Saykin Andrew J. , Ekroos Kim , Meikle Peter J. , Huynh Kevin , Funk Cory C. , Hood Leroy , Price Nathan D. , Baillie Rebecca , Han Xianlin , Kaddurah‐Daouk Rima F. 
Published: December 2021

AbstractBackgroundAlzheimer’s disease (AD) related neurodegeneration has been correlated with metabolic dysfunction. Sphingomyelins (SM), a class of lipids found in the cell membranes especially myelin sheath, have been shown to be disrupted in AD and in other neurodegenerative diseases. Ceramides, the simplest of the sphingolipids, are known to be associated with Aβ production and inflammation. In order to characterize the SM pathway for its molecular links to AD pathogenesis we used complementary multi‐omics approach and identified targets that can be used for intervention.MethodIn this study we used post‐mortem brain transcriptome data of 1000 AD and cognitively normal individuals from ROS/MAP, Mayo clinic and Mount Sinai Brain bank cohort and identified differentially expressed genes in SM pathway. We also used the information derived from metabolic networks of brain and carried out metabolic flux analysis to identify reactions and genes that are altered in SM pathway. We performed multimodal neuroimaging analysis and identified genetic variants linked to genes in SM pathway and associated with AD pathogenesis. Lipidomic analyses and genetic association studies were also carried out to study the SM pathway dysregulation in AD.ResultThe multi‐omics analysis suggested increase in ceramide and depletion of sphingosine‐1‐phosphate that alters sphingolipid homeostasis in AD. To test our hypothesis, we used APP/PS1 mice and modulated S1P activity by targeting the receptor using Fingolimod, an FDA‐approved drug for multiple sclerosis. Our study showed that altering S1P signaling rescues cognitive deficits in the treated mice and Fingolimod and other modulators of S1P metabolism might be potent drug repositioning candidates for AD.ConclusionThis study demonstrates the power of using diverse types of data to inform about underlying mechanisms of AD pathogenesis. It also raises the possibility of employing powerful new approaches to the repurposing of existing drugs used for treatment of other diseases.
Penetrance estimation of SORL1 loss‐of‐function variants adjusted on APOE genotypes suggest a non‐monogenic inheritance
Authors: Schramm Catherine , Charbonnier Camille , Zarea Aline , Wallon David , Lacour Morgane , Alarcon Flora , Génin Emmanuelle , Campion Dominique , Nuel Grégory , Nicolas Gaël ,   CNRMAJ Collaborators
Published: December 2021

AbstractBackground
SORL1 rare loss‐of‐function (LoF) variants are a strong risk factor for Alzheimer disease (AD) with odds ratios above 30 for protein‐truncating variants (PTVs). Accordingly, some pedigrees suggest a high penetrance with individuals developing AD before 65 years. However, the age‐dependent penetrance of these variants is unknown, precluding an accurate use for genetic counselling or inclusion in preventive trials. Importantly, both rarity of these variants and co‐occurrence with other risk factors, including the common APOE4 allele, make penetrance estimations difficult based on classical strategies.MethodWe selected LoF SORL1 rare variants (PTVs and missense variants with a LoF effect following in vitro analyses) from exome sequencing data of >1,300 EOAD cases from France (Rouen‐CNRMAJ). To evaluate the age‐related penetrance of AD associated with SORL1 LoF variants, we first built a model based on family information. To ensure an accurate adjustment for APOE genotypes, our model combines a literature‐based baseline for SORL1 non carriers to an additive effect of SORL1 LoF variants computed from our pedigrees. Since pedigrees include relatives with missing genotypes, we applied an Expectation‐Maximization (EM) algorithm to take full advantage of the available information. Probands’ phenotype information was excluded to avoid ascertainment biases. We applied this first method to 34 pedigrees (69 affected relatives, 270 unaffected relatives, 45 relatives with available genotype information). Additionally, we used sequencing data from 7306 cases and 5852 controls to compute a population‐based estimate of the age‐dependent lifetime risk associated with both APOE4 allele and SORL1 rare PTVs or predicted damaging missense variants.ResultIn both models, 100% penetrance was reached before 75 years for carriers of SORL1 LoF variants who were also homozygous for APOE4. Penetrance remained incomplete for heterozygous E4 carriers, even at age 75, and was lower for non‐E4 carriers. We are providing penetrance estimation curves and 95%IC for the first time for SORL1 rare variants and at the digenic level.ConclusionOur results suggest that SORL1 rare LoF variants should be considered in a non‐monogenic model, different from APP and PSEN1/2 mutations. Such curves appear critical before these variants are used for genetic counseling and preventive clinical trials.
The Women’s Healthy Ageing Project: A pattern of cognitive decline after brain injury
Authors: Bird Stefanie , Faux Noel G , Szoeke Cassandra 
Published: December 2021

AbstractBackgroundIt is well recognised that damage sustained by traumatic brain injury (TBI) initiate injury mechanisms that continue to develop long after insult. Increasing evidence suggests TBI may lead to chronic cognitive decline and the development of dementia later in life. However, due to the low rate of TBI in the general community, there is a paucity of data on the impact of cognitive decline in community TBI. We examined longitudinal cognitive changes over a 12‐year period to determine if there was any relationship with community reported TBI.MethodThe Women’s Healthy Aging Project is an ongoing longitudinal cohort study of community‐dwelling Australian women. Assessments included an extensive range of measures, including neuropsychological testing of multiple cognitive domains and questions relating to head injury. In total, 110 women had complete neuropsychological testing at all three time points; from 2002, 2012 and 2014. Of these women, nine (aged 56‐65 in 2002) had a history of moderate to severe TBI. Composite cognitive scores were compared to 18 healthy controls randomly selected from the complete dataset individually matched for age, education, and APO4‐genotype. Analyses were conducted in five datasets drawn from the complete dataset and results were averaged.ResultMedian scores for executive function were similar for both the TBI group and healthy controls in 2002, lower in the TBI group by 2012 and this difference increased further in 2014. Median scores for verbal episodic memory were slightly lower in the TBI group than controls in 2002 and 2012, and this difference increased in 2014. Although this initial pilot study with small samples in mid‐aged healthy women did not show statistically significant results, the observed relationships were constant over the five datasets, warranting further exploration.ConclusionIn our small pilot study, we observed greater rate of decline of both executive function and verbal episodic memory in women with a history of TBI. Findings warrant a need for larger studies to explore this relationship as it indicates that community‐based reported TBI may impact cognitive performance even in early ageing. Further work will continue to explore cognitive trajectories in women with a mean age 80 at next follow‐up.
Misappraisal of sleep quality is associated with lower cognitive functioning
Authors: Baril Andree‐Ann , Mysliwiec Vincent , Beiser Alexa S , Redline Susan , Seshadri Sudha , Himali Jayandra J , Pase Matthew P 
Published: December 2021

AbstractBackgroundSelf‐reported sleep quality often does not strongly correlate with objective measurements of sleep, and thus, other factors such as cognitive ability might contribute in the self‐awareness of one’s own sleep. Although sleep disturbances are increasingly recognized as risk factor for dementia, individuals with lower cognitive performance might present with an impaired ability to appropriately report their sleep, reducing the importance of self‐reported data. The purpose of this study was to evaluate whether misappraisal of sleep consolidation and quality was associated with poorer cognitive performance.MethodWe studied 265 participants (58.0±8.9 years, 50.2 % men) in the Framingham Heart Study Offspring Cohort who had an overnight in‐home polysomnography and neuropsychological testing 3.5 years later on average. Self‐reported sleep quality regarding the night of the polysomnography was compared to objective sleep efficiency (cut‐off at 85%). Four groups were created representing those with consistent appraisal of good sleep (n=75, good self‐reported and objective sleep); consistent appraisal of poor sleep (n=72, poor self‐reported and objective sleep); misappraisal of poor sleep (n=41, good self‐reported sleep but poor objective sleep); misappraisal of good sleep (n=77, poor self‐reported sleep but good objective sleep). We evaluated global cognition (composite score), verbal memory (Logical Memory immediate and delayed recall), executive function (Trail Making Test B minus A) and visual organization (Hooper Visual Organization Test). Models were adjusted for age, sex, education, time between polysomnography and neuropsychology, APOE4 allele status, body mass index, sleeping pills, depression, and stroke risk.ResultParticipants that misappraised poor sleep, i.e., reported good sleep quality but had lower sleep efficiency, had lower global cognitive performance (β±SE=‐0.34±0.17; p=0.047), worse immediate verbal memory recall (‐1.39±0.67; p=0.039) and poorer executive functioning (‐0.16±0.05; p=0.003) compared to participants with consistent appraisal of good sleep. No other between‐group differences were observed.ConclusionIndividuals with misappraisal of poor sleep had poorer cognitive performance than individuals with consistent appraisal of good sleep. This type of sleep misappraisal could be occurring when cognitive functions are declining and self‐awareness is impaired. Further studies comparing self‐report to objective measures of sleep are required in patients in preclinical stages of dementia and with cognitive impairment.