bluuebunny/crossref_metadata_2025 huggingface dataset:
Obstructive sleep apnea in older adults: Differential cognitive impairment moderated by sex?
Authors: Legault Julie , Thompson Cynthia , Martineau‐Dussault Marie‐Ève , Carrier Julie , Dang‐Vu Thien Thanh , Lorrain Dominique , Gosselin Nadia ,   CIMA‐Q Group
Published: December 2020

Background

Obstructive sleep apnea (OSA) is a risk factor for cognitive decline, but the effect of sex on this association is unknown. This study aims at characterizing the relationship between risk of OSA and cognitive function in older men and women.

Method

We included 152 women (73 ± 6 years) and 89 men (75 ± 6 years) matched for education, age and presence of APOE4 allele. They were part of the Quebec Consortium for Early Identification of Alzheimer’s Disease (CIMA‐Q) and were either cognitively healthy or had subjective cognitive decline or mild cognitive impairment. All participants were tested with a neuropsychological battery measuring cognitive domains typically affected by Alzheimer’s disease. Risk of OSA was determined using a validated questionnaire that considers signs and symptoms associated with OSA such as snoring (S), tiredness (T), observation of apneas (O), high blood pressure (P), high body mass index (B) and larger neck circumference (N), which provides a risk score (STOP‐BN). Multiple linear regressions were performed between STOP‐BN and cognitive scores in men and women separately.

Result

Higher risk of OSA, identified by a higher score on the STOP‐BN, is correlated with slower information processing speed (Stroop, condition 2) in women (β= 0,896, p = 0,006) and men (β= 0,954, p = 0,043). In men, higher risk of OSA correlated with worse performance in short (Digit symbol, incidental learning score: β = 0,982, p = 0,034) and long‐term memory (Face‐name associations, delayed recall: β = 0,318, p = 0,047).

Conclusion

Our results suggest that sex has a moderating effect on the association between OSA and cognitive function. An altered information processing speed has already been reported in apneic patients and does not necessarily reflect a risk of dementia. However, altered memory in men at higher risk of OSA needs to be investigated longitudinally to determine whether OSA could represent an early marker of cognitive decline.
Metabolic syndrome and successful aging: A six‐year cohort study TIGER among community‐dwelling elderly in Taiwan
Authors: Lin Yi‐Hsuan , Chen Yen‐Ching , Chiou Jeng‐Min , Chen Ta‐Fu , Lai Liang‐Chuan , Chen Jen‐Han
Published: December 2020

Background

Metabolic syndrome (MetS) has known to be associated with disability1, 2, cognitive impairment3 and depression4 in the older adults. However, the association between MetS and successful aging, an overall assessment of elders’ status, is unknown.

Method

This study is part of an ongoing prospective cohort study: Taiwan Initiatives for Geriatric Epidemiological Research (TIGER). A total of 605 participants (age 65+) were recruited at baseline (2011‐2013) with 4‐year and 6‐year follow‐ups. After exclusion of participants with missing data of successful aging and metabolic syndrome as well as loss to follow‐up, a total of 202 participants were included for statistical analysis. MetS was assessed at baseline (2011‐2013). Successful aging was evaluated at baseline, 4‐year and 6‐year follow ups. Successful aging was defined by the following variables: cognitive function, numbers of chronic disease, activity of daily living (ADL), instrumental activities of daily living (IADL), gait speed, depression, self‐rated health, the frequency of participating in social and leisure activities, the family support and annual disposable income. Generalized linear mixed‐effects models with random intercept were utilized to assess the association between MetS and successful aging adjusting for time (follow‐up years), age, sex, years of education, smoking, alcohol consumption and the interaction terms with time. A p value of <0.05 (two‐tailed) for individual covariate and <0.1 for interaction with time was considered statistically significant.

Results

At baseline, 33.7% (n=68) older adults had MetS. Compared with older adults without MetS, those with MetS had lower diet quality (the modified Alternative Healthy Eating Index: 34.8 vs. 38.2), higher body mass index (25.7 vs. 22.9 kg/m2), higher mean serum C‐reactive protein level (0.26 vs. 0.17 mg/dL), and more chronic diseases [e.g., hypertension (70.6% vs. 30.6%), diabetes mellitus (27.9% vs. 2.2%), hyperlipidemia (70.6% vs. 35.1%) and cardiac disease (29.4% vs. 15.7%)]. The baseline MetS had a negative effect on the probability of successful aging, and the effect increased as time elapsed [MetS×time interaction: odds ratio=0.87, 90% confidence interval=0.76‐0.98, p‐value=0.06].

Conclusion

MetS is a risk factor of successful aging for community‐dwelling older adults. Prevention of MetS in earlier life will be beneficial to successful aging in their later life.
Global challenges in cognitive assessment: How technology will drive neuropsychologists to the forefront
Authors: Au Rhoda , Christianson Kieffer , McManus Chelsea , Knight Arielle , Karjadi Cody
Published: December 2020

Background

Age remains the strongest risk factor for Alzheimer’s disease (AD). With the number of people over 65 now outnumbering those under the age of 5, the global burden of AD is rapidly increasing. Cognitive decline is the hallmark behavioral symptom of AD. However, accurate cognitive assessment requires consideration of a myriad of factors, including education, language, and culture. In fact, in a majority of low‐to‐middle income countries, as well as many emerging economies, there is no formalized doctoral training in neuropsychology. These circumstances necessitate embracing novel data collection methods in order to preserve the voice of the neuropsychologist. Technological advances can provide the tools to address the global realities of AD and other related disorders.

Method

We have developed a brain health monitoring platform that leverages the relatively ubiquitous use of smartphones across virtually all countries and collects behavioral measures that are inextricably linked to cognitive skills. We are applying machine learning approaches to quantify digital indices into cognitive ones. Importantly, we have strategically selected mobile applications that measure behaviors that are 1) common regardless of age, education, language and culture and 2) can be flexibly customized to circumstances.

Result

We have begun deploying versions of this high tech‐driven platform in the U.S. Further, we are starting to have an impact internationally, particularly in Asia. The health and age demographics in China make its population particularly vulnerable to AD. We present findings that speak to this risk and how our platform, and others like it, will help fill the neuropsychological expertise gap that such countries are currently experiencing.

Conclusion

AD is a rising epidemic. Early and accurate detection is the first step to finding disease modifying interventions and providing the context necessary for maximized efficacy. The coupling of professional neuropsychology skills and digital technology will generate solutions that can sufficiently address the impending challenge of conducting cognitive assessments universally. This potentially includes resolving longstanding health disparities by extending neuropsychologists’ reach into regions with significant economic and/or geographical constraints.
Use‐cases and users' requirements for design of an individualized sensor‐based assistive system for people with dementia in nursing facilities: A user centered design approach using qualitative research
Authors: Köhler Stefanie , Goerss Doreen , Kowe Antonia , Kirste Thomas , Teipel Stefan J
Published: December 2020

Background

Challenging behaviors often cause stress and burden for caregivers of persons with dementia (PwD). Individually tailored assistive devices have the potential to support the persons concerned and reduce caregivers‘ burden, if they are adapted to users’ needs. Therefore, it is an urgent need to focus on values and abilities of prospective users to design suitable technologies. Here, we introduce a user centered design approach in the development process of an assistive technology in institutionalized care for PwD.

Method

We identified three different groups of stakeholders and conducted 28 semi‐structured interviews (9 PwD, 10 relatives, 9 health professionals). Interview categories included daily life of PwD, difficulties in unfamiliar surroundings, presentation of challenging behaviors, previous experiences with technology and perceived use of assistive technologies to be developed. The interviews were transcribed and analyzed using qualitative content analysis according to Mayring.

Result

Results show that the individual set of user values, the global cognitive status, previous experiences with available technology and general interest and curiosity in technology of PwD act as main contributors to the attitude toward using new assistive devices. During the conference we will present resources (i.e. user experience, personal benefit, routine in using technology and autonomous detection of needs) and obstacles/barriers (less support from others, missing time and interest, doubt about usability, complexity) for using technology as well as user values (autonomy, information, privacy). In parallel, we will list use‐cases extracted from the interviews: temporal (i.e. day time, appointments) and spatial disorientation (i.e. pacing, disability to find the right room), aggression and affective disorders, falls and information about (inter‐)national news service. Functional requirements like occupation and cognitive training, communication (caregiver‐relative, caregiver‐PwD), falls and sleep detection, memory function, playing music and spreading fragrance in case of aggression/agitation were named. Further, we will derive design requirements and suitable interventions offered by an assistive device adapted to the users' needs.

Conclusion

We could show that user centered design is applicable even with cognitively impaired people. Qualitative research helps to identify personal key factors that may contribute to usage of assistive devices and should be integrated in future technologies to provide suitable interventions.
The relationship between sleep disturbance and cognitive impairment: A population‐based cross‐sectional study
Authors: Gao Fan , Gao Ling , Wei Shan , Dang Liangjun , Shang Suhang , Chen Chen , Wang Jin , Huo Kang , Deng Meiying , Wang Jingyi , Qu Qiumin
Published: December 2020

Background

Growing evidence suggest that sleep disturbance is a risk factor for Alzheimer’s disease, but the relationship between sleep disturbance and cognitive impairment is not clear.

Method

This was a population‐based cross‐sectional study. A total of 1649 participants from a village in the suburbs of Xi’an, China were enrolled from January 3 to March 26, 2017. Sleep quality was assessed using the Pittsburgh sleep quality index (PSQI). Cognitive function was assessed with the mini‐mental state examination (MMSE). Univariate and multivariate analyses were used to analyze the relationships between sleep disturbance and cognitive impairment.

Result

Among 1649 subjects,110(6.7%) were diagnosed as cognitive impairment, and 960(58.2%) were diagnosed as sleep disturbance. In bivariate analysis, cognitive impairment was associated with insomnia)ρ=0.110; 95%CI=0.060‐0.154 ; P<0.01(, sleep efficiency)ρ=‐0.152; 95%CI=‐0.196‐ ‐0.105; P<0.01(, age)ρ=0.237; 95%CI=0.195‐0.279; P<0.01(and educational level )ρ=‐0.190; 95%CI=‐0.229‐ ‐0.149; P<0.01(. In the binary logistic regression, cognitive impairment was positively associated with the scales of PQSI (OR=1.072; 95%CI=1.016‐1.130; P=0.012). In the internal constitution of PQSI, cognitive impairment was positively associated with the sleep duration (OR=1.567; 95% CI=1.242‐1.979; P<0.01), step disturbances (OR=0.003; 95%CI=0.000‐0.023; P=0.017), and negatively associated with the habitual sleep efficiency (OR=1.068; 95%CI=1.012‐1.127; P<0.01). Cognitive impairment also was negatively associated with patients age (OR=0.130; 95%CI=0.069‐0.244; P<0.01).

Conclusion

Sleep disturbances is associated with cognitive impairment. However, the causal relationships between sleep disturbances and cognitive impairment are not clear and need to be further studied.
Rapidly progressive dementia in Argentina: A multicentric study
Authors: Isa Santiago , Calandri Ismael Luis , Demey Ignacio , Dorman Guido , Couto Blas , Vigo Gabriela , Aleman Alberto , Mellinger Surai , Aldecoa Mayra , Genovese Osvaldo , Sanchez Maria Pilar , O'Neill Santiago , Vazquez Guido , Appiani Franco , Ollari Juan , Acosta Julian , Allegri Ricardo F , Gatto Emilia , Rojas Galeno
Published: December 2020

Background

Rapidly progressive dementia (RPD) is a syndrome caused by different disease entities. Accurate diagnosis is crucial as numerous proportions of these diseases are highly treatable. There are few RPD series published in South America. Knowing regional data may be useful to establish specific diagnostic guidelines based on local information. The main study objectives are to describe the etiological diagnosis of patients with RPD in Argentina and to compare the clinical characteristics and data obtained from complementary studies among patients with Autoimmune Encephalitis (AE), Prion Diseases (PD), Neurodegenerative Diseases (ND) and Other Causes (OC).

Method

A multicenter observational cross‐sectional study was performed with the information obtained from patients referred to the neurology department of the participant centers. Patients with RPD criteria (developing dementia in less than 24 months) were retrospectively included between Dec‐2001 and Jun‐2019. Based on International diagnostic criteria, patients were divided into: AE, PD, ND and OC. We compared baseline clinical data, complementary exams, MRI and serologic characteristics between groups. Parametric or non‐parametric statistic and multivariate analysis was used according to the sample distribution of the available data.

Result

On a sample of 328 patients with a diagnosis of RPD, 54.87% were men (n=180) with a mean age of 60.78±5.57 years at admission. The diagnosis time for dementia was 4.06 (0.83–23.6) months. The three most frequent causes were AE 23.17% (n=76), ND 22.86% (n=75) and PD 15.85% (n = 52). In 15.85% of the patients the diagnosis remained unknown. When comparing AE, ND, PD and OC, statistically significant differences were observed in age (younger age for AE, p=0.0001), higher mortality for PD (p=0.0001) and larger time of evolution in ND (p=0.0001). In the PD group more behavioral symptoms (p = 0.002) and pathological electroencephalogram (p=0.001) were found.

Conclusion

In accordance with similar series, autoimmune etiology was the more frequent cause. This is the first South American RPD multicentric study. These results might supply valuable data for the healthcare system and future epidemiological investigations more focused diagnostic guidelines.
Participation in leisure activities and risk of dementia: Results from Whitehall II study with 18‐year follow‐up
Authors: Sommerlad Andrew , Sabia Séverine , Livingston Gill , Kivimaki Mika , Lewis Glyn , Singh‐Manoux Archana
Published: December 2020

Background

Several studies have reported that participating more frequently in leisure activities protects against dementia, possibly by building cognitive reserve or through better vascular health. However, these studies have been highly susceptible to reverse causation bias due to short follow‐up duration.

We therefore aimed to examine the association of leisure activity participation with incident dementia using data from a cohort study with very long follow‐up.

Methods

We used data from 8,280 participants of the Whitehall II prospective cohort study of London‐based civil servants. A 13‐item scale assessed leisure activities and we ascertained incident dementia status from three comprehensive linked national registers to 2017 (n cases=360). Cox regression models examined the association of leisure activity participation, measured on multiple occasions, and incident dementia, with multiple imputation to account for missing data. We also examined associations of individual activities and subsequent dementia, and examined the association of change in leisure activity participation during late‐middle age and dementia. All models were adjusted for potential confounders.

Results

Participation in leisure activities at mean age 55.8, with 18.0‐year follow‐up, was not associated with dementia (hazard ratio [HR] 0.92, 95%CI 0.79‐1.06) but those with higher participation at mean age 65.7 were less likely to develop dementia with 8.3‐year follow‐up (HR 0.82 (0.69‐0.98)). No individual leisure activities were consistently associated with incident dementia. Decline in leisure activity participation between age of 56 and 66 years was associated with subsequent incident dementia (HR 1.35 (1.10, 1.66) per 1 SD larger activity decline.

Conclusions

Leisure activity participation at 56 years was not associated with incidence of dementia over the subsequent 18 years. Associations were only evident when leisure activity was assessed at older ages, with less than 10 years between assessment of leisure activities and diagnosis of dementia. Decline in leisure activity participation over 10 years was associated with subsequent elevated risk of dementia. No consistent associations were found for participation in specific types of leisure activities. Taken together, these results do not support the hypothesis that leisure activity participation can lower dementia risk, but suggest instead that reduction in activity participation is an indication of possible prodromal dementia.
Stimulation of GLP‐1 signaling enhances protein clearance and reduces Aβ‐mediated toxicity in neuronal cells
Authors: Lin Chih‐Li , Huang Chien‐Ning , Li Hsin‐Hua , Chang Ching‐Chi , Ho Ying‐Jui , Chiu Pai‐Yi
Published: December 2020

Background

Cellular proteostasis failure is proposed to be the major cause of neurodegeneration. The deposition of both extracellular Aβ plaques and intracellular tau‐associated neurofibrillary tangles is central to Alzheimer's disease (AD) pathogenesis. Therefore, development of strategies targeting the removal of misfolded proteins may aid AD treatment. Glucagon‐like peptide‐1 (GLP‐1) is a potent incretin hormone primarily secreted by intestinal L‐cells. It can stimulate pancreatic β‐cells leading to insulin secretion and hence decreasing blood glucose. However, GLP‐1 can also be produced in the brain, and most neuronal cells including neurons and microglia express functional GLP‐1 receptors. Even though it is known for suppressing appetite in hypothalamus, the molecular mechanisms of GLP‐1 signaling are still poorly defined in the other brain regions.

Method

In the present study, we aimed at investigating the exact mechanisms underlying GLP‐1‐mediated neuroprotection, and exploring the potential molecular pathways against Aβ‐induced toxicity based on GLP‐1 signaling by using high‐content analysis (HCA) cellomics techniques.

Result

We found that GLP‐1 receptor agonist (GLP‐1 RA) liraglutide significantly displays anti‐Aβ neuroprotective effects. These effects were likely associated with an restoration of impaired neuronal insulin signaling. In addition, liraglutide also promoted abnormal protein clearance by upregulating autophagy through the AMP‐activated protein kinase (AMPK) pathway, which subsequently restored neuronal insulin signaling and led to upregulation of nuclear factor erythroid 2‐related factor 2 (NRF2)/heme oxygenase 1 (HO‐1) antioxidant signaling. Furthermore, the efficiency of microglial phagocytosis was also stimulated by liraglutide, and may have a beneficial effect on the clearance of extracellular Aβ.

Conclusion

Our results provided the basis for GLP‐1‐based regulatory mechanisms by diminishing Aβ‐related neurotoxicity of neuronal cells. Accordingly, enhanced protein clearance by targeting neuronal GLP‐1 signaling may lead to develop novel therapeutic strategies against AD.
Socioeconomic determinants of dementia in Caribbean Hispanics: An international comparison
Authors: Llibre‐Guerra Jorge J , Li Jing , Harrati Amal , Jiménez‐Velazquez Ivonne Z. , Acosta Daisy , Llibre Juan , Liu Mao‐Mei , Dow William H
Published: December 2020

Background

Hispanics populations in the U.S. are more likely to develop dementia than non‐Hispanic White populations; among Hispanics, those with Caribbean origin seem to carry the higher risk for developing dementia. However, little is known about how various social risk factors for dementia differentially affect non‐Hispanic Whites and Hispanics of Caribbean origin in the U.S., or between those living in the main Caribbean islands. The present study aimed to examine the associations of socioeconomic determinants(SES) with dementia across Puerto Rico, Cuba and the Dominican Republic and compared with similar populations living in U.S.

Method

Using a community‐dwelling population of Caribbean older adults ages 65+ from Puerto Rico, Dominican Republic, and Cuba, enrolled in the 10/66 study we determined dementia prevalence on the main Caribbean Islands using the 10/66 dementia algorithm. Associations between socioeconomic risk factors and prevalent dementia were estimated using linear probability models, stratified by gender and age. We then compared results from the main islands with Hispanic and non‐Hispanic populations living in US enrolled in the U.S. Health and Retirement Study, using the TICS dementia algorithm.

Result

The prevalence of dementia was high: 10.9% in Cuba and 11.7% in Puerto Rico and the Dominican Republic (95% CI, 9.8‐12.1). We found overall weaker associations between education and dementia in the three main Caribbean islands. By contrast, a stronger association between education and dementia was found in the US among non‐Hispanic whites, Mexican Hispanics, and non‐Mexican Hispanics; these persist after controlling for income and wealth(p<0.001). In both the US and in the Caribbean islands, working in a blue collar occupation as opposed to white collar occupation was associated with a higher risk of dementia(p=0.001), and higher income was negatively associated with dementia for both genders(p=0.001), although these associations were stronger in the U.S.

Conclusion

The prevalence of dementia in the older Caribbean population is high, both in the main islands and in US compared to non‐Hispanic‐whites. There were differential associations between SES risk factors, particularly education, and dementia probability between Caribbean islands and the U.S., which may be attributed to differences across societies in risk factors correlated with education.
In‐silico and in‐vitro evaluation of imidazolone fused quinazolinone derivatives as anti‐amyloidal agents in Alzheimer’s
Authors: Sharma Lalit , Kumar Deepak , Bisht Gopal Singh
Published: December 2020

Background

Alzheimer’s disease with a long preclinical period of ∼20 years is a chronic, insidious, and progressive neurodegenerative disease of old age. Neuropathologically AD is characterized by the presence of accumulated Amyloid‐beta in plaques (in extracellular spaces, and walls of blood vessels) and aggregated tau protein in neurofibrillary tangles. Quinazolinone derivatives exhibit inhibition to β‐secretase as well as its core quinazoline moiety prevents the cholinergic system from pathological activities of Aβ by possessing significant amount of inhibition.

Method

In‐silico evaluation was based over computational approaches counting receptor and ligand preparation, grid formation, docking simulation, and its analysis followed by in‐vitro investigation via Thioflavin T‐amyloid binding assay and Protease (Trypsin) digestion assay.

Result

The computational approach provides us with two molecules A and B with higher estimated free energy of binding whereas for the justification of in‐vitro test results one molecule J with lower estimated free energy of binding from top ten docked scored molecules was selected. In‐vitro investigation of these three compounds reveals that compound A cause significant (p<0.005) reduction in fluorescence intensity of ThT as well as Aβ1‐42 peptides resistance to tryptic digestion, when compared with control. Compound B possess lesser amount of reduction (p<0.005) in both the assays as compared to compound A whereas, activity of Compound J was found to be almost negligible.

Conclusion

From the present study we found that our test compound A has shown significant results in modulating the Aβ aggregates i.e. Aβ fibrils. This study strongly suggests the further evaluation of this imidazolone fused quinazolinone derivative.
Flow cytometry detection of inflammatory markers in glial cells and synaptosomes derived from AD cortex
Authors: Melnik Mikhail , Bilousova Tina , Huang Calvin , Cole Emma , Head Elizabeth , Gylys Karen H.
Published: December 2020

Background

Previous research has indicated the involvement of nearly all cell types of the brain (i.e. neurons, microglia, etc.) in progression of Alzheimer Disease (AD). In the case of microglia, increased production of neuroinflammatory markers accompanies AD and has been implicated in the loss of synapses and neurons. In mouse models of AD, gene expression of many inflammatory markers is increased in microglial cells, including genetic risk factors LPL and TREM2, while homeostatic markers are diminished. Intact cells from post‐mortem AD tissue were isolated and used to better explore the relationship of inflammatory markers and AD‐specific pathological species. Further, microglial elements have been found to be associated with synaptosomes (resealed axon terminals) and were further explored to determine if specific inflammatory signals vary with amyloid and tau pathology.

Method

Post‐mortem AD tissue (PMI<6 hours) from late AD patients (Braak V‐VI) and age‐matched controls was enzymatically dissociated, processed and labeled using fluorophore‐conjugated antibodies. The labeled cells were subsequently analyzed by an LSRII flow cytometer using FCS Express v5 software. Synaptosomes were prepared from the same AD patients by homogenizing brain tissue in 0.32 M sucrose with a cocktail of enzyme inhibitors. This preparation, known as P2, then underwent probing using western blotting (10‐20% Tris‐Glycine gel with PVDF membrane) and flow cytometry using the same instrument and software.

Result

Preliminary results show a significant increase in the number of P2ry12+ (homeostatic) microglia in AD patients relative to controls. Further labeling of microglia with CD11b (myeloid marker) and TGFbeta1 (homeostatic marker) showed no significant difference between AD and controls, suggesting a more complex picture of microglial changes compared to mouse models. Preliminary results showed an increase in inflammatory markers TLR4 and IL‐6 in AD P2 samples relative to controls. Further, TLR4 was increased in individuals with at least one APOE4 allele.

Conclusion

Microglial activation in AD mouse models differs from human AD. Human AD microglia demonstrate an increased expression of one homeostatic marker (P2ry12) but not another (TGFB1) while mice show a more uniform decrease of these markers. Further, microglial signals associated with synaptosomes suggests they contribute to neurotoxicity and synaptic loss, a parameter highly correlated with dementia.
Investigating cortical brain volumes three years after ischemic stroke
Authors: Khlif Mohamed Salah , Werden Emilio , Bird Laura J. , Brodtmann Amy
Published: December 2020

Background

Cortical atrophy is associated with cognitive decline and dementia, but few studies have examined cerebral atrophy after ischemic stroke. In this exploratory study, we examined changes in cortical volumes over 3 years in ischemic stroke patients and healthy age‐ and sex‐matched controls.

Method

Participants with first‐ever stroke were sampled from the Cognition And Neocortical Volume After Stroke (CANVAS) study. Cortical volumes were grouped contralesionally and ipsilesionally depending on the stroke side. To avoid any effects from lesions on cortical parcellations, ipsilesional volumes from patients with cortical lesions were excluded. There were 105 and 84 contralesional volumes at the 3‐month and 3‐year post‐stroke timepoints. Ipsilesionally, there were 86 volumes at 3‐months and 68 volumes at 3‐years. Volumes from 40 and 38 controls at same timepoints were used for comparison. Longitudinal cortical volumes were estimated using the ‘Desikan‐Killiany' parcellation atlas in FreeSurfer (version 6.0). A linear mixed‐effect model with random intercept and slope was used to compare volumes between groups and timepoints. Volumes were corrected for age, sex, years‐of‐education, total intra‐cranial volume, and a composite cerebrovascular risk factor coded from the sum of known risk factors: obesity (body mass index ≥30kg/m2), hypertension, cholesterol, smoking (≥1 cigarette/day), and alcohol intake (≥14 units/week). A sum ≥2 was coded as a high risk.

Result

Contralesional volumes: Compared to control, the inferior‐temporal gyrus volume in stroke was significantly lower at both timepoints. Volumes of precentral and rostral‐middle‐frontal gyri were significantly lower at 3 years. Atrophy rates were significantly faster for the entorhinal cortex, paracentral lobule, and frontal pole (see Table 1). Ipsilesional volumes: Several stroke volumes (caudal‐anterior‐cingulate, caudal‐middle‐frontal, inferior‐temporal, and rostral‐middle‐frontal) were significantly lower at both timepoints. Precentral gyrus volume was only significantly lower at 3 years. Atrophy rates were significantly faster for pars‐opercularis, the entorhinal, isthmus‐cingulate, and rostral‐anterior‐cingulate cortices and for postcentral, precentral, and superior‐frontal gyri (see Table 2).

Conclusion

More ipsilesional cortices atrophied at a faster rate within the first 3 years after stroke compared to healthy controls than did contralesional cortices. In particular, volumes of lesion‐free bilateral inferior‐temporal gyrus were greatly reduced in stroke patients and may represent a risk factor for post‐stroke cognitive impairment.
Physical activity and domain‐specific cognitive function: The Shanghai Aging Study
Authors: Wu Wanqing , Ding Ding , Zhao Qianhua , Xiao Zhenxu , Liang Xiaoniu , Luo Jianfeng , Hong Zhen
Published: December 2020

Background

To examine the association of physical activity (PA) and domain‐specific cognitive function among older adults.

Method

This cross‐sectional study analyzed the baseline data of the Shanghai Aging Study, which included 3,507 community‐dwellings aged >=50 years and with >= 6 years of education. The characteristics of the participants were collected via an interviewer‐administered questionnaire. Participants were asked about the average time of doing PAs during the past 12 months. A metabolic equivalent value (MET) was assigned for each type of activity based on the compendium of PAs. We categorized PA into low level (<10.5 METs/week) and medium‐to‐high level (≥10.5 METs/week), based on the tertile of the METs distribution. Each participant was administered a battery of neuropsychological tests including Mini‐Mental State Examination (MMSE); Conflicting Instructions Task(CIT); Stick Test (ST); Modified Common Objects Sorting Test; Auditory Verbal Learning Test (AVLT); and Trail‐making Tests A and B. Impairment in specific neuropsychological test was defined as having test score > 1 SD worse than the mean value in corresponding age‐specific groups. We used multivariate linear regression models to assess the relation between METs (as a continuous variable) and scores of each neuropsychological test. Multivariate logistic regression models were also applied to examine the association between PA levels (as a categorical variable) and domain‐specific cognitive impairment, adjusting for age, sex, years of education, smoking, drinking, hypertension, diabetes, body mass index, and APOE ε4.

Result

Participants with PA ≥10.5 METs/week were significantly younger, more likely to be male, had a lower prevalence of hypertension and diabetes, had a better performance in all the neuropsychological tests. After adjusting for confounders, higher levels of PA was associated with a better performance in MMSE (β=0.09, p=0.020; OR=0.58, 95% CI 0.37‐0.91), conflicting correct tapping in CIT (β=0.06, p=0.056; OR=0.55, 95% CI 0.40‐0.76), recognition in AVLT (β=0.10, p=0.047; OR=0.76, 95% CI 0.60‐0.97), and imitating in ST (β=0.03, p=0.005; OR=0.69, 95% CI 0.48‐0.98) (Table 2, Figure 1).

Conclusion

Medium‐to‐high level of PA was associated with a better performance in global cognition, executive function, visuospatial skill, and memory among older adults. Further prospective studies are required to validate our findings and explore their clinical implications.
Cognitive function, mental decline, and rural‐living effects on brain structure in an elderly Indian population
Authors: Keller Brenton James , Jovicich Jorge , Lee Jinkook , Toga Arthur W. ,   LASI‐DAD
Published: December 2020

Background

Age‐related cognitive decline is widely documented, but with substantial individual differences that are not yet understood (Vaque‐Alcazar et al., 2017). Using the recently collected neuroimaging data from the Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI‐DAD), we investigate the associations between cognitive function (global cognition score), mental decline (JORM IQCODE), and rural‐living on brain structure.

Methods

A total of 103 subjects (female = 46, age = 68 ± 6 years) were studied from three clinical 3T MRI centers using the ADNI 3 MRI protocol (NIMHANS, Bangalore, N = 52, NM Medical, Mumbai, N = 23, and Institute of Kolkata N = 28). Brain morphometry data was studied with Freesurfer using volumetric ROI‐analysis and vertex‐based cluster‐corrected structural analysis. A global cognition score was derived by aggregating all cognitive tests administered, which included a set of common neuropsychological test battery from the Harmonized Cognitive Assessment Project protocol (HCAP) (Weir et al., 2016), as well as additional tests suitable for illiterate and innumerate population in India (Lee et al., 2019).

Results

ROI‐based morphometry analyses identified the hippocampus (subiculum and CA4, 3‐5%) and pars orbitalis (4‐6%) volume as having a positive correlation with global cognition score. Left hemisphere rostal middle frontal gyrus and right hemisphere postcentral gyrus area were also found to be positively associated with global cognition scores. In comparison, healthy status according to JORM IQCODE was positively correlated with right hemisphere rostral middle frontal gyrus thickness. Other significant clusters, including bilateral superior frontal gyrus and superior temporal gyrus thickness were found to be positively associated with JORM IQCODE healthy scores, while also showing colocalized area reductions in those with healthy JORM IQCODE scores. Similar to JORM IQCODE, rural‐living was also found to increase thickness in bilateral superior frontal gyrus.

Conclusions

Through the use of an intensive structural MRI protocol and neuropsychological test battery, we examined factors influencing brain morphometry. Of note, this study is the first to examine the effects of general cognition, respondent‐based memory assessment, and rural‐living on brain structure in an elderly Indian population.
Cross‐sectional and longitudinal analysis of the association between hemogloblin concentrations and depression in older adults: The International Mobility in Aging Study
Authors: Ahmed Tamer , Vasiliadis Helen‐Maria
Published: December 2020

Background

Anemia is a common hematological condition in older adults, with estimated prevalence increasing with age after the fifth decade of life. 1 We examined the cross‐sectional and longitudinal relationships between hemoglobin concentrations and depression in older adults and whether these relationships were modified by sex, social context, or cognitive function.

Method

A total of 1608 community‐dwelling older adults from the International Mobility in Aging Study (IMIAS) aged 65 to 74 years were recruited in Natal (Brazil), Manizales (Colombia), Kingston (Ontario, Canada), and Saint‐Hyacinthe (Quebec, Canada). The study outcome was depression, defined by a score of 16 or over in the Center for Epidemiologic Studies Depression Scale (CES‐D). Poisson regression models were used to estimate prevalence ratios (PR) of depression, while longitudinal associations over four years follow‐up were examined using generalized estimating equations. Hemoglobin concentrations were used either as a continuous measure or categorized according to the severity of anemia. Models reported were adjusted for research sites, alcohol drinking status, body mass index, chronic conditions, activities of daily life disabilities, cognitive function, and polypharmacy.

Result

In multivariate cross‐sectional and longitudinal analyses, for every 1g/dL increase in hemoglobin concentrations there was a significant reduction in the prevalence (PR=0.90, 95% confidence interval (CI): 0.83 ‐ 0.97) and incidence (Odds Ratio (OR)=0.85, 95% CI: 0.77‐0.92) of depression. Moderate anemia was also a strong predictor of depression (OR=8.24, 95% CI: 1.45 ‐ 47.02). None of the multiplicative interactions by sex, research sites, or cognitive function were statistically significant.

Conclusion

In international samples of older adults, hemoglobin concentrations, as well as the severity of anemia, were independent risk factors for depression. References: 1‐ Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. 2004;104(8):2263‐2268.
A story of innovation: Building a national surveillance system for dementia in Canada
Authors: Toews Jennette , Pelletier Catherine , Shaver Larry C
Published: December 2020

Background

Accurately capturing cases of dementia at the population‐level is complex, given the nature of the condition. Over the past decade, Canada has focused on this challenge, evolving and improving dementia surveillance in collaboration with multiple stakeholders.

Method

Originally based on self‐reported data, dementia data in Canada were limited to the prevalence of the condition and were significantly underestimating its burden. Canada sought to develop an innovative and systematic approach to enhance dementia surveillance by, initially, undertaking the National Population Health Study of Neurological Conditions and, then, exploring the feasibility of using linked health administrative data. The Canadian Chronic Disease Surveillance System (CCDSS), a network of provincial/territorial surveillance systems supported by the Public Health Agency of Canada, since became the core platform to support national reporting on dementia.

Result

A validated case definition, incorporating data from hospitalizations, physician claims and drug prescriptions, was developed and applied to the CCDSS linked databases. As a result, since 2016, national and provincial/territorial estimates of dementia incidence, prevalence, and mortality over time (dating back to 2002) are released annually. With the recent adoption of Canada’s National Dementia Strategy in 2019, other innovative methods are being explored to enhance surveillance, including: analysing the trajectory of the condition, with the development of comorbidities and impacts on health outcomes; creating new data linkages to enrich the sociodemographic information on individuals living with dementia; assessing the feasibility to monitor early onset dementia.

Conclusion

Utilizing the unique capacity of the CCDSS, a new national surveillance system for dementia in Canada has been implemented. The evolution and innovation of dementia surveillance over the course of the past decade can provide valuable lessons for the surveillance of dementia and other complex conditions in other countries.
Neuronal trafficking dynamics and regulators
Authors: Feole Monica , Devoto Victorio Martin Pozo , Carna Maria , Stokin Gorazd Bernard
Published: December 2020

Background

Neurons are highly polarized cells continuously relying on intracellular transport, through which they communicate with the external world. Among the somatodendritic and axonal compartments many proteins with different functions are sorted to reach long distances. The relevance of neuronal transport in ensuring cell development and homeostasis maintenance raises a big interest on this topic. Moreover, several neurodegenerative diseases, such as Alzheimer’s or Amyotrophic Lateral Sclerosis, exhibit significant axonal pathology, where transport impairment seems to have a crucial influence. However, the role of this process in neurodegeneration, remains poorly understood. In this study we aim to characterize neuronal transport dynamics of specific proteins, and the molecular machinery regulating this process. Furthermore, we aim to explore transport from the pathological point of view, evaluating the effect that mutant proteins (e.g. TDP43‐related) may have on it.

Method

Human Neural Stem Cells derived neurons were differentiated for 30 DIV. Plasmids encoding for different GFP‐coupled proteins were designed to express those who are involved in main neuronal functions (e.g. synaptic activity) and transfected in neurons. Time‐lapse movies of cargoes were acquired to detect changes in movement. Data analysis was performed using object segmentation and tracking algorithms. Raw data were processed to describe the main motion parameters: average velocity, directionality, track length, and others. Post‐imaging Immunocytochemistry was performed to assess cargoes localization and discriminate between axonal and dendritic transport.

Result

Amyloid Precursor Protein (APP) cargoes with higher velocity in anterograde direction were observed compared with the retrograde one; meanwhile for Synaptophysin, a major population of stationary particles was found. Moreover, sorted data for axonal and dendritic transport description shown faster APP particles in axonal anterograde movement. Relying on the movement dynamics description, we decided to screen for protein‐protein interactions, using GFP‐trap and CoIP approaches followed by Mass Spectrometry analysis, which can shed light on possible partners involved in the transport regulation.

Conclusion

Our work describes an in vitro model for neuronal transport study and highlights the different behavior of proteins with various physiological functions. A complete view will elucidate details about transport regulation and will open a way to understand its role in neuropathological processes.
Circadian rhythm disturbance in agitation of Alzheimer's disease
Authors: Rosenberg Paul B. , Wu Mark N. , Spira Adam P. , Wanigatunga Sarah K. , Zipunnikov Vadim , Outen John D.
Published: December 2020

Background

Agitation in Alzheimer’s disease (AD) is a major cause of distress and burden for AD caregivers and may be driven by disrupted circadian rhythms (often termed “sundowning”) and sleep. In healthy individuals, the circadian clock that generates these rhythms controls patterns in mood, wakefulness, and alertness. We examined the association of activity and sleep with agitation in AD in an observational study using wrist actigraphy, home sleep testing, and measurement of core body temperature.

Method

We studied 13 participants with AD+agitation (AgitAD+) and 7 with AD but without agitation (AgitAD‐) who completed wrist actigraphy for one week (to quantify rest/activity rhythms and sleep); consumed an ingestible, disposable temperature sensor for 1‐2 days (to quantify core body temperature, a marker of the endogenous circadian rhythm); and completed a single night of home sleep testing (HST) using NoxT3. Agitation was measured with the Neuropsychiatric Inventory‐Clinician Version (NPI‐C).

Result

20 participants have completed to date (7 controls/13 agitated, mean age of 68 years, 60% female, 10% African American). There were no statistically significant differences observed in actigraphy‐derived sleep parameters between agitated and non‐agitated participants (2‐group t‐test; see Table 1). However, significant differences between the groups have been observed in the rest/activity rhythms: compared to participants without agitation (AgitAD‐), AgitAD+ participants had lower amplitude in the morning and greater amplitude in the afternoon and evening (Figure 1). We also have performed function‐on‐scalar regression (FOSR) (Goldsmith et al., 2015, Biometrics 71:344‐353) using subject‐specific activity profiles as outcomes and age and Agitation/Controls status as scalar predictors. Figure 2 shows functional effects of age on Rest/Activity Rhythm (left panel) and the functional effect of Agitation status (right panel), the red background shows the pointwise statistically significant (p<0.05) times of the day. Adjusted for age, Agitation was associated with a lower amplitude in the morning period and a trend towards larger amplitude in the afternoon and evening period (not statistically significant).

Conclusion

The collection of multimodal noninvasive data on sleep, activity, and core body temperature is feasible in agitated AD outpatients. We will present HST and core body temperature data at AAIC. Funding: R01AG054771.