bluuebunny/crossref_metadata_2025_split huggingface dataset:
Midlife cognitive activity moderates the relationship between brain tau deposition and late‐life cognitive decline
Authors: Ko Kang , Yi Dahyun , Byun Min Soo , Lee Jun Ho , Kim Yu Kyeong , Lee Yun‐Sang , Lee Dong Young 
Published: December 2020

AbstractBackgroundCognitive activity (CA), an important modifiable lifestyle factor, has been related to decreased risk of Alzheimer’s disease (AD) dementia, and reduced cerebral beta‐amyloid deposition and neurodegeneration. The relationship between CA and in vivo tau deposition in brain, however, remains still elusive. Hence, we first aim to examine the direct association of CA, midlife CA in particular, with brain tau deposition. We also investigated the modulation effect of midlife CA on the relationship between brain tau deposition and cognitive decline.MethodOne hundred four elderly subjects from the Korean Brain Aging Study for Early Diagnosis and Prediction of AD (KBASE) cohort underwent comprehensive clinical assessment and 18F‐AV‐1451 positron emission tomography (PET). Brain tau deposition in the inferior temporal (IFT) region on the PET imaging was assessed, and participating frequency of midlife CA was evaluated using a structured questionnaire (Wilson et al., 2005). Mini‐Mental State Examination (MMSE) score was used as a cognitive performance measure.ResultMidlife CA did not show a significant association with IFT tau deposition (Figure 1). We found, however, a significant interaction effect between midlife CA and IFT tau deposition on MMSE score (Table). High midlife CA subgroup showed less steep decline of MMSE score with increase of tau than low CA subgroup (Figure 2).ConclusionThe findings suggest that midlife CA can attenuate the harmful influence of brain tau deposition on late‐life cognition, while it does not directly change brain deposition of tau pathology.
The etiology of long‐term stable mild cognitive impairment
Authors: Sharma Manu J. , Callahan Brandy L. 
Published: December 2020

AbstractBackgroundOf those diagnosed with mild cognitive impairment (MCI), 5‐10% convert annually to dementia (Mitchell & Shiri‐Feshki, 2009). However, 5‐30% can remain cognitively stable (sMCI) for up to 10 years (Alves et al., 2018), suggesting a non‐neurodegenerative etiology in these patients. This study aims to examine the etiological underpinnings of those who remain cognitively stable versus those who decline over time.MethodParticipants from the National Alzheimer’s Coordinating Center were selected if they were nondemented at baseline, had available clinical data ≥5 years following baseline, and had available autopsy data <1.5 years following last visit. They were defined as stable normal controls (sNC; n = 106) or sMCI (n = 28) if cognitive status was unchanged between first and last visit (≥5 years later); declined normal controls (dNC; n = 128) if cognitive status at first visit was normal and MCI or demented by last visit; or declined MCI (dMCI; n = 139) if cognitive status was MCI at first visit and demented by last visit. Neuropathological features were dichotomized to reflect clinically significant levels (≥moderate neuritic plaque density; Braak neurofibrillary degeneration stage ≥4; Thal amyloid plaque phase ≥3; any Lewy bodies; ≥1 large arterial infarct; ≥1 lacune; ≥1 microbleed; ≥1 hemorrhage). Baseline psychiatric symptoms were quantified using the Geriatric Depression Scale (GDS; ≥6 considered clinically significant) and the Neuropsychiatric Inventory Questionnaire (NPI‐Q; grouped into ‘mood’, ‘agitation’ and ‘psychosis’ factors based on previous factor analysis: Aalten et al., 2003, Siafarikas et al., 2018). The groups were compared on frequencies of neuropathological features at autopsy and baseline psychiatric symptoms using chi‐square (χ
2).ResultDemographics are presented in Table 1, with main analysis results in Table 2. Relative to other groups, sMCI had significantly fewer amyloid plaques (χ
2 = 44.2, p < 0.001) and more microinfarcts (χ
2 = 9.9, p = .019). GDS and NPI‐Q showed no significant relationship with sMCI.ConclusionPrevious research indicates microinfarcts are independent of neurodegenerative disease (Launer et al., 2011). In line with this, our results suggest that sMCI may be caused by microinfarcts, rather than frank neurodegenerative disease. This study was limited as only neuropsychiatric symptoms were reported, and future studies should examine sMCI in relation to diagnosed psychiatric disorders.
Acoustic measures in natural speech of progressive supranuclear palsy and corticobasal spectrum disorders
Authors: Parjane Natalia , Ash Sharon , Cho Sunghye , Shellikeri Sanjana , Liberman Mark Y. , Grossman Murray , Nevler Naomi 
Published: December 2020

AbstractBackgroundProgressive supranuclear palsy and corticobasal syndrome (PSP‐CBS) are neurodegenerative disorders involving motor and cognitive deficits. These patients may have slowed and dysfluent speech. However, few studies have investigated specific speech and language deficits in these disorders, although some patients may have non‐fluent/agrammatic primary progressive aphasia (naPPA). In our study, we used novel, automated speech analysis methods to quantify acoustic properties of natural speech in PSP‐CBS. We hypothesized patients would exhibit slowed speech and longer pauses, and predicted that prosodic changes would be related to underlying cognitive and motor impairments. Because PSP and CBS are tauopathies, we related their acoustic performance to cerebrospinal fluid (CSF) analytes associated with Tau pathology.MethodWe obtained digitized samples of natural speech with the Cookie Theft picture description task from PSP‐CBS patients (n = 95), naPPA patients (n = 25) and healthy controls (HC, n = 41). Eight PSP‐CBS patients had concomitant naPPA (PSP‐CBS+naPPA). The groups were matched for age, sex, education, and disease duration. A speech activity detector program automatically segmented the acoustic signal into speech and silent pause segments. We automatically calculated the pitch range by measuring fundamental frequency (f0, semitones), total speech duration, mean speech and pause segment durations, and pause rate (pauses per minute). In a subset of patients with available CSF analytes, we related acoustic markers with levels of phosphorylated tau (pTau).ResultPSP‐CBS without naPPA had shorter mean speech segments (1.42 ± 0.48 sec), shorter total speech durations (31.77 ± 14.66 sec), longer mean pause segments (1.82 ± 1.01 sec) and higher pause rates (45.10 ± 13.43 pauses per minute) compared to HC (2.00 ± 0.57 sec, p < .001; 51.08 ± 21.30 sec, p < .001; 0.93 ± 0.44 sec, p < .001; 31.61 ± 9.51 ppm, p < .001, respectively). PSP‐CBS only differed from naPPA for pause rate (PSP‐CBS, 45.10 ± 13.43 ppm; naPPA, 57.81 ± 19.95 ppm; p = .026). PSP‐CBS+naPPA patients were most impaired for f0 range (3.56 ± 1.21 ST) compared to HC (5.87 ± 1.94 ST, p = .021), paralleling naPPA patients, who had reduced f0 range compared to HC (4.30 ± 1.59 ST, p = .02). f0 range was associated with pTau levels in all patients (r = ‐0.43, p = .004).ConclusionPatients with PSP‐CBS have impaired speech as quantified by automated analysis of acoustic measures of speech. These measures are related to pTau, a marker of likely pathology.
Rural–urban differences in the prevalence and characteristics of mild cognitive impairment in independent community‐dwelling older adults in Taiwan
Authors: Chuang Yi‐Fang , Liu Yi‐Chien , Tseng Hsin‐Yi , Chiu Yen‐Ling , Kuan‐Chia Lin , Shih Ming‐Hsiung 
Published: December 2020

AbstractBackgroundTaiwan is among one of rapidly aging countries and cognitive impairment increases exponentially with age among older adults. Mild Cognitive Impairment (MCI) bears an increased risk of developing dementia later and may represent an early disease stage that is amenable to preventive strategies. There is currently no epidemiological data about the prevalence of MCI in Taiwan.MethodThe data was from the baseline assessment of a community‐based prospective cohort study conducted in one rural and one urban areas of New Taipei City in Taiwan between 2017‐2019. Four hundred and seventy individuals aged 65 years and older, independently living in the community, were recruited and underwent a battery of neuropsychological tests assessing cognitive domains of attention, memory and executive function. Diagnosis of MCI was ascertained through an expert consensus panel based on 2011 NIA‐AA criteria.ResultMean age of participants was 71.1± 5.5 years. Participants from the rural area were older (72.6 vs. 70.6 years), had poorer education (5.5 vs. 8.7 years), higher body mass index (25. 9 vs. 24.6 kg/m2), and higher percentage of hypertension (54.5 vs. 43.6%) The prevalence of MCI was 45/122 (36.6 %) in the rural area and 40/348 (11.5 %) in the urban areas, for a overall 85/470 (18.1 %). The rural area had a significantly higher prevalence of MCI (age‐ ,sex‐, and education‐adjusted odds ratio [OR] = 2.86, 95 % CI: 1.68–4.86) than the urban area. There was no differences in the distribution of subtypes of MCI in two areas. In the rural area, only poorer education was associated higher prevalence OR of MCI whereas in the urban area, being male, poorer education, and higher geriatric depressive scale were associated higher prevalence OR of MCI.ConclusionThe prevalence of MCI was much higher in the rural area relative to the urban area. Different factors were associated with the prevalence of MCI in the rural and urban areas. This regional difference suggests preventive strategies or programs against cognitive impairment should be tailored and modified according to the urbanicity of an area.
Presenilin 1 and APP gene mutations in early‐onset AD families from a southeast region of China
Authors: Peng Guoping 
Published: December 2020

AbstractBackgroundEarly‐onset familial Alzheimer’s disease (EOFAD) has been reported to be associated with presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein (APP) genes. The spectrum of mutations in Chinese patients with EOFAD was rarely investigated. Thus, this study intends to investigate the spectrum of mutations in patients with EOFAD in Chinese population.MethodWe performed a whole‐exome sequencing and described relevant clinical features in a total of 67 patients from 3 families with EOFAD.ResultA splice mutation (p.S290C) in PSEN1 and a missense mutation (p.V717I) in APP were identified.ConclusionThe variant p. S290C (c.869‐2>G) in PSEN1 in Chinese EOAD family revealed different clinical phenotype when compared with that of European.
Predicting activities of daily living in people with dementia of Alzheimer’s type using neurocognitive measures
Authors: Rai Pooja , Singh Tara , Singh Indramani L. , Tiwari Trayambak , Joshi Deepika 
Published: December 2020

AbstractBackgroundCognitive deterioration in neurodegenerative disorders like dementia of Alzheimer’s type affects the overall functioning of daily life activities of a person. Till date, numerous studies have shown correlation between performance on cognitive task and activities of daily living (ADL). Among all the cognitive domains attentional functioning has been the main focus in DAT as it has been the first cognitive domain to be affected.MethodThe present study has an attempt to associate the cognitive functions especially attentional functioning in predicting ADLs in people with DAT. The different ADLs which mainly categories into basic and instrumental ADL have been studied meta‐anatically in relation to its relationship with cognitive functioning in people with DAT. The keywords related with study have been selected and searched on different platforms like Google Scholar, Pubmed etc. The lack of research works in this field narrows the studies related with predictive value of cognitive ability.ResultThe study revealed that out of 11 studies, 7 were related to the assessment of cognitive functioning with ADLs. Out of which 4 were concerning about the cognitive domain related with ADLs whereas 3 studies have shown domains other than attention like visuospatial ability, immediate memory and executive functioning as a predictor to the ADLs in DAT.ConclusionThe relevance of conducting the present study is the emerging life problems of elderly with cognitive impairment. The study suggests how the present approach can be applied to address research issues related with diagnosis and rehabilitation technique for people with DAT.
Physical activity for people with Alzheimer's disease: Are we doing enough?
Authors: Feter Natan , Cassuriaga Júlia , Leite Jayne S , Rombaldi Airton ,   NeuroLaBFEx
Published: December 2020

AbstractBackgroundNational Alzheimer disease (AD) associations are the primary resource of information for AD patients and their caregivers. Physical activity (PA) (i.e. walking) improve quality of life and functional capacity, and preserve cognitive function in patients with AD. We aimed to verify if national AD associations and dementia control plans worldwide recommend PA for this population.MethodWe search for PA mention and recommendation on national dementia control plan in each country in the world. Further, we contacted national Alzheimer’s associations worldwide to verify if it had any mention or recommendation of PA for people with ADResultFrom 224 countries and territories analyzed, 123 had either a national AD association or a national dementia control plan. The sample was compound by 112 countries (loss/refuses: 8.9%). About 50% mentioned PA as a protective factor against AD. Only 19% provided some type of recommendation (i.e. frequency, type, time, intensity) of PA for people with AD. However, all those countries were classified as upper‐middle or high income countries.ConclusionDissemination of benefit from PA for people with AD should be encouraged especially in low and lower‐middle income.
Association of an index of lifespan cognitive reserve with the risk of mild cognitive impairment and its progression to dementia
Authors: Xu Hui , Yang Rongrong , Dintica Christina S , Qi Xiuying , Song Ruixue , Bennett David A , Xu Weili 
Published: December 2020

AbstractBackgroundThe effect of lifespan cognitive reserve (CR) on mild cognitive impairment (MCI) and its progression to dementia remains controversial.MethodWithin the Rush Memory and Aging Project, a community‐based cohort study (mean age, 79 years) with annual follow‐up (median, 5.16 years; maximum, 20 years), a cognitively intact group (n=1182) and an MCI group (n=420) were identified at baseline. During the follow‐up, 611 participants died and underwent autopsies. Neuropathologic evaluations for Alzheimer’s disease (AD) and infarcts were performed in autopsied participants. CR indicator encompassing education, early‐ to late‐life cognitive and social activities was obtained and tertiled.ResultCompared to the lowest CR, the multi‐adjusted hazards ratios (HRs, 95% CI) of the highest CR was 0.78 (0.63–0.98) for incident MCI in the cognitively intact group, and 0.66 (0.45–0.97) for dementia in the MCI group. Among MCI participants with high brain pathologies (including global AD pathology or gross infarcts), the adjusted incident rate of dementia was about 50‐65% lower in people with highest CR compared to lowest CR.ConclusionHigh lifespan CR indicator reduces risk of MCI, and delays its progression to dementia, in the presence of brain pathologies.
Transcranial pulse stimulation in Chinese patients with Alzheimer’s disease
Authors: Au Lisa W.C. , Kwan Pauline , Mok Vincent C.T. 
Published: December 2020

AbstractBackgroundLow‐intensity extracorporeal shock wave therapy (Li‐ESWT) has been used for years to treat musculoskeletal disorders through promoting tissue regeneration. Recently, transcranial pulse stimulation (TPS) with ultrasound, which is a form of Li‐ESWT, was applied to patients with Alzheimer’s disease (AD). The pivotal study using a newly developed TPS system NEUROLITH® showed promising effects on AD. The aim of this study was to investigate the safety and tolerability of TPS in Chinese patients with AD.MethodClinically stable patients with mild cognitive impairment due to Alzheimer’s disease as defined by National Institute on Aging‐Alzheimer’s Association (NIA‐AA) criteria, who had documented abnormal biomarkers including amyloid and tau on positron emission tomography (PET) brain imaging were recruited from an outpatient cognitive neurology clinic in Hong Kong. TPS was performed using NEUROLITH® by trained staffs. Each therapeutic session comprised 6000 shocks at an energy flux density of 0.2 mJ/mm2and pulse repetition frequency of 5 Hz. Stimulation targets include bilateral frontal cortex, bilateral lateral parietal cortex and extended precuneus cortex. The treatment comprised 6 sessions within two weeks. Participants were closely monitored during treatment. Patient’s experience and any adverse reactions were documented. The Clinical Global Impression of Change scale (CGIC) was administered at 4 weeks after treatment.ResultTwo patients underwent TPS treatment using NEUROLITH®. Both were female Chinese patients aged 71 years. Both patients reported satisfactory treatment experience with no adverse reactions. One patient completed follow up at 4 weeks with CGIC showed improvement in behavior/ mood with less agitation.ConclusionTranscranial pulse stimulation is a safe and well‐tolerated treatment for Alzheimer’s disease patients in Hong Kong. Further studies are required to assess the long‐term efficacy of TPS on cognitive, behavioral and psychological symptoms of Alzheimer’s disease patients.
Towards cross‐cohort estimation of cognitive decline in neurodegenerative diseases
Authors: Maheux Etienne , Koval Igor , Archetti Damiano , Redolfi Alberto , Durrleman Stanley 
Published: December 2020

AbstractBackgroundHeterogeneity of cohorts, in terms of inclusion criteria, design of follow‐up visits and batteries of cognitive assessments, hinders any thorough comparisons between them. For that reason, we build a cross‐cohort model of cognitive decline that can be personalized to any patient, allowing to impute partially or totally missing scores. This enables to compare the subjects’ progression across cohorts thanks to common cognitive assessments.MethodBased on a generic framework of disease progression that handles longitudinal data (Schiratti et al. 2015, NIPS) and implemented in the Leaspy Python package, we first estimate the joint progression of a large set of cognitive scores from the ADNI database along a common disease timeline. This group‐average progression is then personalized to individual trajectories of patients from the PharmaCog and AIBL cohorts. In particular, all individuals are characterized by a relative pace of progression and onset age that can be compared across cohorts. To validate our model, we impute missing values of a given score, based on its past and future values together with the dynamics of concurrent scores and compare errors to constant predictions and linear regressions. We finally go further by simulating purposely concealed scores thanks to the progression of the remaining features so to mock reconstruction of scores that are entirely missing in a particular cohort.ResultsFigure 1 shows the relative positioning of all subjects from the 3 cohorts based on their individual pace of progression and their age at disease onset. Such characterization enables to impute missing values of the MMSE or the Immediate/Delayed Logical Memory better than imputing the last known value or fitting a linear regression [Figure 2]. Furthermore, from the multiple measurements of a single score, the model is able to reconstruct the individual progression of the other scores at the corresponding visits [Figure 3], with a controlled error rate.ConclusionOur model enables comparison of patients trajectories from different cohorts. It permits to lessen imputation errors of most cognitive scores in new cohorts and demonstrates a new way to simulate, at any individual visit, scores that have not been measured in practice.
Neurovascular uncoupling of cerebral blood flow and glucose metabolism in APOE4, TREM2, and APOE4.TREM2 mice
Authors: Territo Paul R. , Lin Peter B. , Persohn Scott C. , Bedwell Amanda A. , Eldridge Kierra , Speedy Rachael , Kotredes Kevin P. , Pandey Ravi S. , Oblak Adrian L. , Sasner Michael , Carter Gregory W. , Lamb Bruce T. , Howell Gareth 
Published: December 2020

AbstractBackgroundAlzheimer’s disease (AD) is the most common cause of dementia in the United States, with approximately 95% of patients exhibiting sporadic Late‐Onset AD (LOAD), which lacks an inheritance pattern. Therefore, identifying phenotypic patterns are critical for understanding disease progression. Apolipoprotein E4 (APOE4), the strongest genetic risk factor of LOAD, increases AD risk by 3‐12 fold depending on copy number. Recent GWAS analysis elucidated the LOAD‐associated loci on the triggering receptor expressed on myeloid cell 2 (TREM2). APOE is a known ligand to the TREM2 receptor, and the R47H variant could increase the AD risk by 2‐3 fold. Preclinical studies of these risk alleles and their phenotypes are underway by MODEL‐AD.MethodsUsing PET/MRI and a novel analytical scheme, we established the perfusion‐metabolism profiles across 27 brain regions in both sexes by using 64Cu‐PTSM and 18F‐FDG in the APOE4 (APOE
E4/E4), TREM2 (TREM2
R47H), and double (APOE
E4/E4.TREM2
R47H) knockin (KI) mice, and compared these to blood chemistry and nanoString transcriptomic analysis.ResultsLongitudinal analysis comparing 12mo to 4mo time point revealed that male APOE4 mice and both sexes of TREM2 had hypo‐ perfusion and metabolism, while female APOE4 mice showed an uncoupled hyper‐perfusion and hypo‐metabolism phenotype, and was correlated to human AD pathology. In double KI mice, perfusion and metabolism showed a mixed phenotype which was region dependent. Cross‐sectional analysis of KI compared to C57BL/6J mice at 12mo showed an overall reduced glucose metabolism. Intriguingly, male APOE4, TREM2, and double mice showed hypo‐perfusion and metabolism, while female double mice showed metabolic uncoupling compared to C57BL/6J. Analysis of blood biochemistry in non‐fasted mice revealed no significant difference between genotypes in blood glucose with age. However, APOE4 decreased the blood cholesterol level (LDL, and HDL). RNAseq and immunohistology was peformed, and key genes involved in the regulation of cerebral perfusion, glucose transportation, and metabolism were altered.ConclusionsThese data suggest that the new perfusion‐metabolism strategy may be able to identify AD‐related patterns. Moreover, they replicate clinical manifestations of subjects with the same variants, suggesting additional mechanistic studies are needed to elucidate the mechanisms and etiology of this uncoupling phenomenon.