bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of the 3‐year survival in patients with cognitive impairment based on demographics, neuropsychological data, and comorbidities
Authors: Xing Dianxia , Zhang Wenbo , Yi Qingjie , Hong Huang , Chen Lihua , Wu Jiani , Yu Weihua , Lü Yang
Published: June 2023

Background

To develop and validate a prediction model for the 3‐year survival of patientwith cognitive impairment based on demographics, neuropsychological assessment data, and comorbidities.

Method

Five‐hundred‐and‐eighty‐seven patients with cognitive impairment were included from our memory clinic. Demographic information, comorbidities, the Mini‐Mental State Examination (MMSE), Instrumental Activity of Daily Living (IADL) score, and Neuropsychiatric Inventory Questionnaire sub‐item scores were collected. Survival conditions were obtained by telephone from the caregivers in the third year after the neuropsychological tests. Patients were randomly divided into training set and validation set with a ratio of 7:3. Variables that achieved statistical significance (P < 0.05) in the single‐factor analysis were incorporated in the binary logistic regression model. A nomogram was established according to the multivariate analysis. The receiver operating characteristic curve, area under the curve, C‐index, calibration curve, and the Hosmer–Lemeshow test were performed to validate the nomogram.

Result

Younger age, higher MMSE score, lower IADL score, no symptom of disinhibition, and Charlson Comorbidity Index score equal or less than 1 are associated with 3‐year survival. These predictors yielded good discrimination with C‐indexes of 0.80 (0.73–0.87) and 0.85 (0.77–0.94) in the training and validation cohorts, respectively. The Hosmer–Lemeshow test showed no statistical significance in either cohort, and calibration curves displayed a good consistency between the prediction and the actual observation.
Cognitive function level and chronic disease incidence rate by age of older adults living in the community
Authors: Nam Sanghun , Park Sojung , Bae Suyeong , Hong Ickpyo
Published: June 2023

Background

Research has shown that decline in cognitive function is related to the level of chronic disease in old age. Most studies, however, have either examined limited aspects of cognitive function or used assessment tools with low accuracy. A limited range of cognitive function items and low‐accuracy cognitive function assessment tools may bias the findings. Current literature also has paid little attention to the age‐gradient association between cognitive function and chronic diseases. Utilizing a new cognitive classification method, this study investigated cognitive function‐associated chronic diseases and their relationship with age. Empirical knowledge about the dynamic among cognitive function, changes in chronic diseases, and age may contribute to establishing comprehensive prevention and management programs of diseases in later years.

Method

A total of 6,940 people aged between 55 to 105 years from the 2018 Korean Longitudinal Study of Aging panel data were included in this study. According to the Korean Mini‐Mental State Examination’s total score and instrumental activities of daily living assistance, cognitive status was classified into normal cognition, moderate cognitive impairment, and severe cognitive impairment. The Poisson regression analysis was used to calculate the incident rate ratios (IRR) of cognitive status by age and the incidence of chronic diseases.

Result

The incidence rate of chronic diseases was 1.07 times higher in the moderate cognitive impairment group (n = 4665) than in the normal cognitive group (n = 4665). In addition, it was 1.24 times higher in the severe cognitive impairment group (n = 420) than in the normal cognitive group (Table 1) and the incidence of chronic diseases according to cognitive function increased with age (figure 1).

Conclusion

Applying the new cognitive function classification, we found the incidence rate of age‐related chronic diseases increased with the cognitive status, indicating incidence of chronic diseases increases as the cognitive state decreases and the age increases, leading to complex chronic conditions. This finding points to the importance of an integrated program of cognitive decline prevention and the chronic disease management program, which are currently developed and implanted separately.
Health‐related lifestyle behaviors predict changes in cognitive status in older adults: A latent transition analysis of data from the Mexican Healthy Aging Study 2012‐2018
Authors: Robertson Michael C , Milani Sadaf Arefi , Downer Brian , Samper‐Ternent Rafael , Lyons Elizabeth J , Schulz Paul E
Published: June 2023

Background

Health behaviors, such as exercise, smoking, and alcohol consumption, are potentially modifiable risk factors for cognitive impairment and dementia. The effect of these behaviors on cognitive function is important to examine in Mexico, which faces a rapidly aging population.

Method

Data came from the 2012, 2015, and 2018 waves of the Mexican Health and Aging Study. The final sample included 8,112 participants aged 60 and older. We used latent transition analysis (LTA) to identify latent statuses of cognitive functioning using standardized scores for five cognitive tasks (orientation, visual scanning, verbal learning, delayed verbal recall, and verbal fluency). We evaluated associations between baseline lifestyle behaviors and transition probabilities for latent statuses of cognitive functioning across observation waves.

Result

We identified a three‐status model across the three waves with support for measurement and stationary invariance. Latent statuses were characterized by low (24% at baseline), average (55%), and high cognitive abilities (21%). With probabilities of .66, .78, and .90, respectively, individuals’ statuses tended to stay the same between time periods. The probabilities of an individual with these statuses transitioning to death were .15, .07, and .02, respectively. For individuals with a low cognition status, reporting exercising or doing hard physical work three or more times a week on average during the two years preceding baseline was associated with lower odds of transitioning to either death (OR = 0.551, p<.001) or a high cognition status (OR = 0.006, p<.001), in relation to staying in the same status. Similarly, alcohol use for this group was associated with decreased odds of transitioning to either death (OR = 0.74, p = .040) or a high cognition status (OR = 0.005, p<.001). Finally, for individuals with a low cognition status, reporting reading regularly was associated with increased odds of transitioning to average cognition status (OR = 1.44, p<.046), in relation to staying in the same status.

Conclusion

Findings suggest that individuals tended to stay in the same cognitive status over time and that reading regularly predicted favorable changes in cognition. LTA may be useful for identifying discreet statuses and subsequent transitions in older adults’ cognitive functioning as determined by performance on cognitive tasks.
Assessing the effects of a longitudinal buddy program on mood, knowledge and attitudes toward aging and dementia in university students
Authors: Nambiar Anjali , Neuville Raumin S. , Lee Ariel , Phung Calvin , Grill Joshua D. , Torabzadeh Simin
Published: June 2023

Background

The population of Americans 65 and older is growing rapidly and at risk for Alzheimer’s disease and related disorders (ADRD). As a result, younger generations will be challenged with addressing increasing demand in care for the growing geriatric population. Previous studies have explored the impact of volunteer programs involving geriatric residents and improvements in mood and knowledge of aging in medical and high school students. They underscore the importance of intergenerational relationships, but programs involving university students and individuals with ADRD have not been widely studied.

Methods

Alzheimer’s Buddies at UC Irvine (ABUI) pairs trained university student volunteers with an older individual, or “buddy,” with ADRD. ABUI recruited 30 volunteers total to participate in weekly activities with their buddies for one hour. Considering COVID‐19 safety guidelines, current volunteers have interacted virtually with buddies via phone calls or video conferencing. Volunteers submit reflection journals following each visit describing activities completed, lessons learned, and challenges faced during the visit. Before and after 10 weeks of participating in ABUI, new volunteers’ mood, attitudes toward the elderly, and knowledge of ADRD will be assessed using the following surveys: Dementia Knowledge Assessment Scale, Kogan’s Attitudes Toward Old People Scale, Perceived Stress Scale, and Family Stigma in Alzheimer’s Disease Scale.

Results

We will assess changes in newly recruited volunteers’ mood, knowledge, and attitudes toward ADRD after 10 weeks of participating in ABUI based on the surveys administered. The 160 initial journal submissions from current volunteers demonstrate that volunteers explored shared interests and observed improvement in their buddies’ demeanor over multiple visits. Additionally, volunteers noted difficult situations and strategies developed to adapt and optimize their interactions despite these obstacles.

Conclusion

ABUI provides university students an opportunity to learn more about ADRD and develop their own viewpoints on this unique and growing population. Preliminary findings in volunteer reflection journals provide insight into the program’s effect on volunteers and will be followed by a more rigorous assessment. The results of this study may show that consistent long‐term interaction could be rewarding and provide a better understanding of the experiences of individuals with ADRD for future care providers.
Transfer learning based deep encoder decoder network for amyloid PET harmonization with small datasets
Authors: Shah Jay , Chen Kewei , Reiman Eric M. , Li Baoxin , Wu Teresa , Su Yi
Published: June 2023

Background

The existence of multiple amyloid tracers with varied characteristics poses a significant challenge to standardized interpretation and quantification of amyloid PET data. We previously demonstrated that a deep learning model using a residual inception encoder‐decoder network (RIED‐Net) architecture improved harmonization of florbetapir (FBP) and PiB PET. However, scarcity of head‐to‐head comparison datasets of other amyloid PET tracer may limit the ability to generalize this approach to the other amyloid PET tracers. In this research, we investigate the performance of RIED‐Net model trained on smaller datasets and explore transfer learning (TL) approaches which can leverage multiple different datasets and address the data scarcity issue.

Method

We previously trained our RIED‐Net model using PiB‐FBP data from Open Access Series of Imaging Studies (OASIS) (N = 92) and tested the performance in the independent Global Alzheimer’s Association Interactive Network (GAAIN) (N = 46) dataset. We now use the same procedure to train the RIED‐Net model using the smaller GAAIN dataset and evaluate the model performance. We then examine the feasibility of a TL approach by comparing the model performance between RIED‐Net model directly trained on the PiB‐florbetaben (FBB) from GAAIN (N = 35) and the TL approach in which we started with the optimal RIED‐Net model for PiB‐FBP data and fine‐tuned the network parameters using the GAAIN PiB‐FBB data. A cross‐validation (CV) approach was used to evaluate model performance based on difference before and after harmonization in terms of correlation between mean cortical SUVR (mcSUVR) measurements from different tracers.

Result

RIED‐Net model trained using the smaller GAAIN PiB‐FBP data improved the agreement of mcSUVR measurements as measured by Pearson correlation from r = 0.93 to r = 0.96 (p<0.01) on test‐set. For PiB‐FBB harmonization, the TL approach provided numerically better agreement in mcSUVR from r = 0.96 (direct train) to r = 0.97 (with TL), demonstrating the potential benefits of applying TL based technique to address the issue of smaller sample size.

Conclusion

We demonstrate our RIED‐Net model can achieve improved harmonization even when trained on a relatively small training set. We also demonstrate the potential of transferring knowledge learned from one tracer pairs to improve the harmonization model of other related tracer pairs.
Influence of physical activity and the MIND diet on cognition
Authors: Ahn Sangwoo
Published: June 2023

Background

Physical activity or the Mediterranean‐Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet as a neuroprotective diet is known to be beneficial for cognitive health among older adults, but little is known about the influence on cognition when both behaviors are combined. Therefore, this study was conducted to investigate whether engaging in both behaviors is associated with better cognitive health compared with either behavior alone or neither behavior.

Method

Data were from the Health and Retirement Study for this cross‐sectional, observational study. A total of 3,463 non‐demented participants with the mean age of 68.0 ± 10.0 years were included. Associations of physical activity (PA) and the MIND diet (MIND) with global cognition and odds of cognitive decline were explored using multivariate linear regression and binary logistic regression models with interaction terms between PA and MIND.

Result

Compared with neither behavior (PA−/MIND−), PA only (PA+/MIND−) was not associated with cognitive outcomes. Compared with PA−/MIND−, MIND only (PA−/MIND+) predicted higher global cognition (mean difference, d = 0.81; p < 0.001) and lower odds of cognitive decline (odds ratio, OR = 0.68; p < 0.01). Compared with PA−/MIND−, both behaviors (PA+/MIND+) predicted higher global cognition (d = 0.98; p < 0.001) and lower odds of cognitive decline (OR = 0.69; p < 0.01). Compared with PA+/MIND−, PA+/MIND+ predicted higher global cognition (d = 0.60; p < 0.001), but did not predict a risk of cognitive decline. Compared with PA−/MIND+, PA+/MIND+ did not predict cognitive outcomes.

Conclusion

Adherence to both physical activity and the MIND diet was associated with better cognitive outcomes than non‐adherence to both or adherence to physical activity only. Encouraging both behaviors would be important for the cognitive health of older adults.
Effect of agitation and aggression on quality of life in patients with dementia
Authors: Choudhury Samira , Leventhal Natalie , Soffer Matan , Zarei Shadi , Burhan Amer M. , Colman Sarah , Chu Li , Davies Simon , Derkach Peter , Elmi Sarah , Gerretsen Philip , Graff‐Guerrero Ariel , Hussain Maria , Ismail Zahinoor , Kim Donna , Krisman Linda , Moghabghab Rola , Mulsant Benoit H. , Nair Vasavan , Pollock Bruce G. , Rej Soham , Rostas Aviva , Streiner David , Van Bussel Lisa , Rajji Tarek K. , Kumar Sanjeev
Published: June 2023

Background

Behavioral and psychological symptoms of dementia (BPSD) are highly prevalent in patients with dementia during the course of the disease. Among BPSD symptoms, agitation and aggression are a source of distress for both the patients and their caregivers. In this study, we investigated the impact of agitation and aggression on Quality of Life (QoL) of patients with dementia living in long‐term care homes or admitted to psychiatric inpatient units.

Method

Data were obtained from the Standardizing Care for Neuropsychiatric Symptoms and Quality of Life in Dementia (StaN) study, a multisite trial conducted in Canada. Agitation and aggression were assessed with the Cohen‐Mansfield Agitation Inventory (CMAI) and the Neuropsychiatric Inventory Clinician rating scale (NPI‐C); QoL with the informant‐rated Alzheimer’s Disease Related Quality of Life (ADRQL) tool; stage of dementia with the Functional Assessment Staging Tool (FAST); and burden of physical illness with the Cumulative Illness Rating Scale‐Geriatric (CIRS‐G). Regressions were performed to investigate the associations between agitation or aggression and QoL controlling for demographic factors, FAST score, and CIRS‐G score.

Result

179 participants were included (52.5% female; mean (SD) age = 80.79 (9.45) years. The ADRQL score was correlated with: (1) CMAI total frequency score (Pearson’s r = ‐.333, p<.001); (2) NPI‐C agitation score (Pearson’s r = ‐.209, p = .005); and (3) NPI‐C aggression score (Pearson’s r = ‐.300, p<.001). The associations remained significant for the CMAI total frequency score (β = ‐.235, SE B = 0.054, p<.001), and NPI‐C agitation and aggression composite score (β = ‐.288, SE B = 1.254, p<.001) after controlling for age, sex, current residence, FAST score and CIRS‐G score.

Conclusion

QoL is related to agitation and aggression in patients with dementia. The relationship is independent of demographic factors, stage of dementia, and burden of comorbid physical illness. This suggests that better management of agitation and aggression may be an important factor in improving QoL in patients with dementia.
Sedentary pattern, brain health, and cognitive function in rural‐dwelling older adults: A population‐based study
Authors: Han Xiaolei , Wang Yongxiang , Du Yifeng , Qiu Chengxuan
Published: June 2023

Background

Sedentary behavior is distinct from low moderate‐to‐vigorous physical activity and is associated with a range of adverse health conditions. Population‐based studies have rarely examined the associations of objectively‐measured sedentary parameters, structural brain markers, and cognition among older adults.

Methods

This population‐based study included 2019 rural‐dwelling older adults (age ≥60 years, 59% women) who were free of dementia derived from MIND‐China baseline participants. In 2018‐2020, sedentary behavior parameters were measured using accelerometers. We used a neuropsychological test battery to assess global and domain‐specific cognitive function (memory, language, attention, and executive function). Volumes of total brain tissue, white matter hyperintensities, total grey matter, total white matter, ventricles, and hippocampus were assessed on the magnetic resonance imaging in a subsample (n = 1009). We used the general linear models, restricted cubic splines, and mediation models to examine the associations of sedentary parameters, structural brain markers, and cognitive measures, and the isotemporal substitution models to estimate associations of replacing sedentary time with physical activity.

Results

In the total sample, adjusting for multiple confounders and MVPA, longer mean sedentary bout duration was linearly associated with lower z‐scores of global cognition, memory, and language, whereas the linear association of greater total sedentary time with poorer global cognition, memory, and language existed only among long‐sedentary individuals (>10.2 hours/day); Having more breaks per sedentary hour or replacing 30‐minute sedentary time with the same amount of physical activity was significantly associated with higher cognitive z‐scores (P<0.05). In the MRI subsample, simultaneously or separately entering multiple structural brain markers into the mediation models substantially attenuated the associations between mean sedentary bout duration and cognitive z‐scores.

Conclusion

In the rural‐dwelling Chinese older adults, the association of prolonged uninterrupted sedentary time with poor cognition is largely mediated by structural brain markers and frequent breaks in sedentary time are associated with brain health.
Visual search with finding car task in Alzheimer's Disease and mild cognitive impairment
Authors: Boz Hatice Eraslan , Akkoyun Müge , Koçoğlu Koray , Tüfekci Işıl Yağmur , Ekin Merve , Akdal Gülden
Published: June 2023

Background

We evaluated visual search patterns in finding a car test in Alzheimer’s Disease (AD) and amnestic mild cognitive impairment (aMCI).

Method

29 AD patients (mean age 72,5±7.9 years), 34 aMCI patients (mean age 70,6±6,7 years), and 32 healthy controls (HC) (mean age 68,5±6,2 years) were applied to detailed neuropsychological tests (NT). The visual scan task consisted of 16 pictures divided into 9 parts and the car was hidden in the given pictures. The picture with the car was designated as an area of interest. Participants were asked to find the car hidden in shown pictures. EyeLink 1000 Plus video eye tracker was used to record fixation duration, the number of fixation and saccade and, first fixation duration.

Result

There was no statistically significant difference in demographric features between groups (p<0,05). For the area of interest, fixation durations (p = 0,006), number of fixations, and saccades (p<0,001) were significantly decreased in AD patients than aMCI patients and HCs. Besides, the number of fixations in the area out of interest was significantly decreased in AD patients than HC’s (p = 0,001). The number of saccades was significantly decreased in AD patients compared to aMCI (p = 0,005). Moreover, the visual search was correlated to NT measurements (r = 0,2‐0,4).

Conclusion

Scanning patterns in this visuospatial task‐ car finding were significantly different in AD than aMCI and HC. Visual search is a tool of documenting what and how people look at things in real life which might be used as a valid tool to distinguish AD from aMCI and HCs.
Need assessment of ICT literacy for development of multi‐domain telehealth intervention among cognitive frail (CF) older adults: A preliminary study
Authors: Fadzil Nurul Hidayah MD
Published: June 2023

Background

Telehealth is an alternative platform in managing and delivering health care services to clients using information and communication technologies (ICT). Usage of digital technology among older adults is influenced by many internal and external factors. However, information related to the readiness of tehnology use in developing multi‐domain telehealth among community‐dwelling older adults was still lacking.

Method

This study was part of the screening phase of an ongoing Ageless trial for developing multi‐domain telehealth intervention for CF older adults. This study included community dwelling older adults aged 60 years and above with cognitive frailty assessed using Fried’s criteria. A questionnaire related to digital technology usage was administered to evaluate the need assessement of ICT literacy. Sampling method was purposive sampling. Data was analysed descriptively and using the Chi Square test.

Result

At this preliminary stage, 170 older adults (68.5 year old ± 5.7) living in Kuala Lumpur city participated. Majority of the participants were females (60.6%), from Malay ethnic group (71.2%), married (60.6%), attained upper secondary education level (29.7%) and retired. About one‐third of participants were precognitively‐frail (30.4%) and prefrail (32.8%) and were able to access internet (26.7%) at their homes using smartphones (34.1%), followed by computers or laptops (3.0%) and tablets (2.7%). Older adults with CF used less digital technology and reduced playing games on their phone (4.4%). Therefore, the framework of multi‐domain telehealth intervention designed for older adults must include senior‐friendly specifications for motivating its use among them. Proper training and guidance may boost confidence of older people to use the telehealth. Components in multi‐domain telehealth have to provide more educational talks, assistance during session and design more friendly‐user.

Conclusion

Our preliminary results suggest that older adults with cognitive frailty utilised less digital technology and preferred senior‐friendly and less complex digital technology. Promotion and expansion of the use digital technology among older adults with CF especially in rural area must be emphasized. Framework of multi‐domain telehealth intervention have to be refined in order to be suited among older adults, their cargivers and stakeholders.
Chinese medicine monomers in the treatment of Alzheimer’s disease: Some preclinical findings
Authors: Jia Jianping , Li Yan , Lyu Diyang , Jiao Haishan , Shi Yuqing , Quan Meina
Published: June 2023

Background

Most of the FDA approved drugs for AD are symptom driven and effects are limited. Because AD is a complex disease involving multiple pathological changes, such as senile plaques formed by amyloid‐β (Aβ) deposition, neurofibrillary tangles caused by tau hyperphosphorylation, microglia‐evoked neuroinflammation, synaptic degeneration, and blood‐brain barrier (BBB) disruption. While the current anti‐dementia drugs are mostly single targets, Chinese medicines have great development potential considering their multi‐target anti‐dementia components.

Method

Several Chinese medicine monomers, including cryptotanshinone (CTS), pterostilbene (PTE), Ginsenoside Compound K (GCK), and glabridin (Gla) were selected to test their safety and efficacy in AD cell models, and to further explore their possible molecular mechanisms and target of action. Aβ42 oligomers (AβO) were used to establish AD cell models. The cytotoxicity of AβO as well as protective effects of Chinese medicine monomers on cell models were evaluated using the MTT assay. The molecular mechanisms and pathways were tested using qRT‐PCR, ELISA, Western blot and immunofluorescence.

Result

AβO induced cell injury, apoptosis, and generation of intracellular reactive oxygen species (ROS). In AβO‐induced cell models, CTS significantly reduced tau hyperphosphorylation at Ser202, Ser404, Thr181, and Thr231, and increased the levels of PSD95 and synaptophysin; PTE attenuated cell injury, apoptosis, and ROS generation; GCK diminished inflammatory cytokine production; Gla attenuated cell injury (figure1). Further study found that their mechanisms of action include PI3K/Akt/GSK3β pathway (figure2), BBB permeability and tight junction scaffold protein (figure3), as well as NF‐kB pathway via LRP1 activation (figure4), respectively.

Conclusion

These results provides rational basis for the therapeutic application of Chinese medicine monomers in the treatment of AD, and support further evaluation of these multi‐target action potential in AD treatment.
Coexistence or cooperation? The perspective of people affected by dementia on participation and research‐ a TaNDem study –
Authors: Köhler Stefanie , Scharf Annelie , Raedke Anika , Heppner Marie Marleen , Roes Martina , Michalowsky Bernhard , Hoffmann Wolfgang , Teipel Stefan
Published: June 2023

Background

So far, health services research in dementia has yet led to insufficient transfer of research evidence into healthcare practice or implementation of patient and caregiver perspective into the design of research studies. A strong transdisciplinary network of people with dementia, relatives, researchers, and healthcare service providers is needed to improve research and practice and to speed up the interaction between these stakeholders. Here, we aimed to integrate the perspective of people with dementia and caregivers on health services research into the establishment of a translational network for health services research in dementia (TaNDem, funded by the Federal Ministry of Education and Research).

Methods

We interviewed four people with dementia (mean age: 76.0 years; mean MMSE: 25.5) and 16 family caregivers (15 single interviews, one pair; mean age: 62.6 years). We asked participants about their priorities and expectations in dementia research and their motivation to participate in research projects and networks. The interviews were transcribed and analyzed using qualitative content analysis, according to Mayring.

Results

Most interviewees lacked an idea of how research or researchers work. They could only imagine participating in research projects as consultant, but not as co‐researchers with decision‐making power. Participants were afraid of knowledge gaps and embarrassment in the presence of researchers. However, participating in research projects was perceived as essential to prevent and treat dementia for future affected ones. The interviews elicit five areas of interest that should be addressed by the network: pathogenic themes (e.g., early disease detection; prevention), communication & arrangement (e.g., finding support and supply), disease specific care (specialized staff and facilities), support offers (self‐help; case management) and tasks for policy (plan supply capacities; solve the shortage of staff).

Conclusion

The interviewees identified research gaps that contrasted with the self‐perceived focus of researchers on the research topics. Research must evolve to become more tangible, visible, and understandable for people with dementia and relatives so they can participate actively and on a long‐term basis in research projects. We need case management and a culture of participation to reach people with dementia and their relatives with offers of supply, support, and participation in research.
The effects of 24‐week computerized cognitive training in patients with mild cognitive impairment and Alzheimer’s disease: A single‐blind controlled trial
Authors: Zhang Wenbo , Lü Yang , Yu Weihua
Published: June 2023

Background

Computerized cognitive training (CCT) has been recommended to delay cognitive decline in the healthy elderly. However, little studies have been involved in patients with mild cognitive impairment (MCI) and mild Alzheimer’s disease (AD) to date. The present study thus aimed to investigate the efficacy of CCT intervention on patients with MCI and AD through multimodal evaluation.

Method

A single‐blind active controlled design used multidomain, adaptive, computerized cognitive training. The training program was 40 minutes a day, at least 5 days per week for 24 weeks. Neuropsychological battery was used to assess cognitive function, neuropsychiatric symptoms (NPSs) and activities of daily living (ADL), and brain functional connectivity was also evaluated by functional near‐infrared spectroscopy (fNIRS) .

Result

Forty patients were enrolled from the Memory Clinic, Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University. At the end of the intervention, 30 patients completed the trial, in which 20 patients were in training group (T‐MCI, n = 15; T‐mAD, n = 5), and 10 patients were in control group (C‐MCI, n = 6; C‐mAD, n = 4). Compared to C‐MCI group, T‐MCI showed significant improvement in Alzheimer’s Disease Assessment Scale‐Cognition subscale (ADAS‐Cog) and Neuropsychiatric Inventory (NPI) at the end of intervention (all P<0.05) and presented with improved Instrumental Activities of Daily Living (IADL) at the first month(P<0.05), while T‐mAD group displayed improvement tendency in these scales but with no statistical significance. Importantly, significant increasements were analyzed upon functional connectivity between left primary somatosensory cortex (PSC.L), left supplementary motor area (SMA.L) cortex and right Broca’s area (Broca’s. R) (all P<0.001, FDR corrected) after CCT of 6 months in T‐MCI group (n = 11).

Conclusion

Performances of Cognitive function and NPSs are significantly improved via CCT in patients with MCI, and the neuronal plasticity is enhanced.

aging after age 90.
Multiplex in‐vivo quantification of tau by mass spectrometry: Method optimization for comprehensive detection of tau proteoforms and biomarker identification
Authors: Jacquemin Chloé , Villain Nicolas , Fenaille François , Lamari Foudil , Becher Francois
Published: June 2023

Background

Neurodegenerative diseases diagnosis is still challenging, especially at the early stages. The diagnosis of Alzheimer’s disease (AD) relies on the identification of tau proteoforms (i.e., phosphorylation) in the cerebrospinal fluid (CSF) and plasma. However, pathophysiological fluid biomarkers are still lacking for non‐AD tauopathies. Multiplex liquid chromatography (LC)‐mass spectrometry (MS/MS) offers the opportunity to quantify the vast diversity of tau proteoforms (3R and 4R isoforms, truncations, phosphorylations, acetylations). The current gold standard for tau extraction before LC‐MS/MS analysis of very low concentrations in biofluids relies on immunoprecipitation (IP) approaches. Nonetheless, IP may miss some proteoforms due to its high selectivity. Here, we tested anti‐body free and IP approaches and compared their ability to detect tau proteoforms with LC‐MS/MS.

Method

We analyzed samples of artificial CSF (recombinant tau protein in diluted serum), and human CSF (from AD and non‐AD patients). Fully 15N‐labeled tau was added as an internal standard to the samples. Regarding IP, we first assessed a panel of commercial tau antibodies (in line with the literature) coated on magnetic beads. For the antibody‐free approach, we performed perchloric acid precipitation, followed by micro‐Solid Phase Extraction (Pc‐µSPE) using Oasis hydrophilic‐lipophilic balance sorbent. Purified proteins were digested into peptides using trypsin before multiplex quantitative analysis on reversed‐phase capillary LC, coupled with a qExactive high‐resolution mass spectrometer operated in the Parallel Reaction Monitoring (PRM) acquisition mode.

Result

IP optimization led to a combination of antibodies targeting the central and N‐ter domains of tau. IP and Pc‐µSPE comparison in artificial CSF showed a higher sensitivity of IP: limits of detection decreased up to a factor 5. In the human CSF, Pc‐µSPE allowed for better detection of peptides from the N‐ter to the C‐ter than IP, and a higher signal for tau proteoforms (e.g., 3R and 4R isoforms and phosphorylated tau species).

Conclusion

Despite better performances when dealing with canonical tau, IP was overcome by the antibody‐free sample preparation when identifying tau proteoforms with LC‐MS/MS in human CSF. The protocol is readily applicable to samples of clinical cohorts. This result opens the possibility of better detecting tau proteoforms and identifying pathophysiological biomarkers for non‐AD tauopathies.
Delphi consensus on outcome measures for Alzheimer’s disease in clinical practice
Authors: Frisoni Giovanni B , Ellison Tim S , Cappa Stefano F , Georges Jean , Iwatsubo Takeshi , Lehmann Maryna , Lyketsos Constantine G. , Maier Andrea B. , Merrilees Jennifer , Morris John C , Naismith Sharon L , Nobili Flavio , Pahor Marco , Pond Dimity , Robinson Louise , Soysal Pinar , Vandenbulcke Mathieu , Weber Christopher J. , Visser Pieter Jelle , Weiner Michael W.
Published: June 2023

Background

Previous consensus initiatives on outcomes in Alzheimer’s disease (AD) have focused on clinical trials, may not be applicable to real‐world settings, and did not necessarily consider a comprehensive list or prioritize outcomes. The aim of this initiative was to achieve consensus among experts on priority outcomes and outcome measures for use in clinical practice when caring for patients with symptomatic AD.

Method

The Consensus Group consisted of 20 international voting members and a non‐voting Chair representing diverse specialities relevant to AD. A Delphi approach was used to generate shortlists of the most important outcomes and measures, and to develop consensus statements/recommendations (Figure 1). Initial lists of outcomes/measures were obtained from the ROADMAP project (roadmap‐alzheimer.org), and panel members were given the opportunity to suggest additional ones. The threshold for consensus was predefined as ≥70% voting “agree” or “strongly agree”. Shortlists of outcomes and measures were ranked by priority, their relative importance for mild and moderate disease was indicated, and assessment frequency was recommended. The modified GRADE criteria were used to rate the strength of recommendations and quality of evidence.

Result

Strong consensus was readily reached on 37 statements/recommendations, grouped by ‘General Considerations’ (9) and nine domains (28) (Table 1), as well as on priority shortlists of outcomes and measures across the nine domains; an example of a priority shortlist for the domain ‘Cognitive abilities’ is shown in Table 2. The level of evidence for most items was low; therefore, most statements are based on panelists’ expert opinion. Key recommendations include: patient quality of life (QoL) outcome assessments should measure what the person performs well in addition to deficits, and take into account the values of patients and/or caregivers; there is a need for a more comprehensive measure to assess language and communication; ‘functional ability & dependency’ should include an assessment of motor function.

Conclusion

This Delphi consensus highlights outcomes of highest importance in AD from a professional perspective and includes recommendations regarding the most appropriate measures for use in clinical practice. Further studies are needed to raise the strength of the recommendations and to explore patient/caregiver views.
Yesavage’s Geriatric Depression Questionnaire(GDS‐VE): Analysis of its internal structure inolder adults living in Buenos Aires, Argentina
Authors: Tartaglini María Florencia , Hermida Paula Daniela , Ofman Silvia Deborah , Feldberg Carolina , Heisecke Silvina Lidia , Somale Maria Veronica
Published: June 2023

Background

Depression represents one of the most frequent and disabling mood disorders in the elderly population. To measure it, one of the most used scales is the Geriatric Depression Questionnaire, developed by Yesavage, in its abbreviated version (GDS‐VE). Despite its ample acknowledgment and frequent use, an analysis of these characteristics has not yet been carried out on the Argentine population. Currently, because of the COVID‐19 pandemic and the isolation context, the American Psychological Association recommends adapting face‐to‐face to virtual practices. Given this need, the present work aims to analyze the internal structure of the GDS‐VE, for pencil/paper and Internet modalities examining the metric equivalence between both of them.

Method

A confirmatory factor analysis was carried out and the internal consistency was estimated for both modalities.

Result

Factor invariance between both forms of administration was also examined. A total of 696 older adults participated and responded to the questionnaire, using two modes of administration (50% pencil‐paper and 50% Internet). As a result, an adequate adjustment of the model to the empirical data was verified for both versions (pencil‐paper and Internet), as well as an adequate metric invariance between them.

Conclusion

These findings provide evidence of validity and reliability of the GDS‐VE instrument on the Argentine population.
The results of dementia care policy implementation in Eastern Taiwan
Authors: Tseng Wenting , Wang Naiyen , Lin Chiahui , Wang Chihong
Published: June 2023

Background

Hualien county locates in the eastern part of Taiwan is the biggest county but only 321,358 residents in Taiwan. There are 17.2% of the population over the age of 65, and the middle‐aged population migrated away for job‐seeking . Senile citizens’ health, especially dementia is a critical issue in this area.

Method

Mennonite Hospital Shoufeng Branch undertakes the Dementia Care Center Project of the Ministry of Health and Welfare, which sets up a one‐stop diagnostic and care service to people with dementia. Dementia Care Center provided caregivers with counseling for psychological support, home environmental improvement, problem solving skills for physical caring and behavioral and psychological symptoms of dementia. Case managers link and refer resources such as long‐term care resources, acute medical services, Day‐care center, psychiatric or neurological consultation from hospitals, NGO, or the government. In addition, we provide dementia awareness and health education for ordinary people, volunteers, polices, firefighters, teachers, and students in schools.

Result

1,245 people with dementia were enrolled, and according to CDR classification, Mild Cognitive Impairment (CDR = 0.5) accounted for 1%, mild(CDR = 1) 32%, moderate(CDR = 2) 43%, severe(CDR = 3) 17%.A total of 936 people with dementia were referred to care resources, the first five items of referral care and long‐term care resources are home services(23%), community care stations for dementia(18%), community health stations(11%), day care center (6%)and acute medical care(4%), and 88.3% were satisfied with family services. 6,590 people were educated in the community.

Conclusion

The Dementia Care Center provides accessible care resources to help families with dementia in remote areas, the goal of aging in place of the dementia could be achieved.
Neuropathological correlates of neuropsychiatric symptoms in dementia
Authors: Gibson Lucy L , Grinberg Lea T. , Leite Renata Elaine Paraizo , Rodriguez Roberta Diehl , Ferretti‐Rebustini Renata Eloah de Lucena , Pasqualucci Carlos Augusto , Nitrini Ricardo , Jacob‐Filho Wilson , Aarsland Dag , Suemoto Claudia Kimie
Published: June 2023

Background

Neuropsychiatric symptoms (NPS) are very common in Lewy body dementias (LBD), but their aetiology is poorly understood. In a post‐mortem study we aimed to characterise the contribution of neuropathological substrates to some of the most common NPS in dementia.

Method

Participants who passed away between 2004 and 2021 underwent comprehensive neuropathologic evaluation at the Biobank for Aging Studies. Neuropathological data was collected for Lewy body neuropathology (LBD Braak score), neurofibrillary tangles (NFT Braak score), amyloid‐β burden (CERAD‐NP), TDP‐43, lacunar infarcts, cerebral amyloid angiopathy and hyaline atherosclerosis. Post‐mortem interviews were used to collect information regarding neuropsychiatric and cognitive status using the Neuropsychiatric Inventory (NPI) and Clinical Dementia Rating (CDR). A total of 948 cases were classified according to neuropathological assessment: (1) No pathology (NP) (n = 678); (2) Alzheimer’s Disease (AD) (n = 183); (3) LBD (n = 57); (4) AD+LBD (n = 30).

Result

Multinomial logistic regression models comparing LBD, AD and AD+LBD to NP, adjusted for age, ethnicity, sex, and education level, showed significantly higher odds of hallucination and delusions across all groups compared to NP with the relative risk of hallucinations most elevated in AD+LBD cases (RRR = 19.3,[95%CI = 8.00‐46.3], p<0.001). All groups had increased risk of higher NPI scores relative to NP, but the greatest increase was for AD+LBD (RRR = 1.04, [95%CI = 1.02‐1.06], p<0.001). There were significantly greater risk of agitation and apathy in AD and AD+LBD groups relative to NP. (Table 1) Additionally, hallucinations were associated with higher Lewy body Braak scores (OR = 1.30, 95%CI = 1.13‐1.49, p<0.001). Higher NFT Braak scores were associated with depression (OR = 1.28, 95%CI = 1.09‐1.50, p<0.001), agitation (OR = 1.30, 95% CI = 1.07‐1.57, p = 0.009) and overall NPI score (IRR = 1.15, 95%CI = 1.05‐1.27, p = 0.004). Lacunar infarcts were associated with delusions (OR = 4.68, 95%CI = 1.12‐19.5, p = 0.03). More frequent neuritic plaques was inversely associated with apathy (OR = 0.70, 95%CI = 0.52‐0.93, p = 0.01). Cerebral amyloid angiopathy, hyaline atherosclerosis, and TDP‐43 did not associate with any of the neuropsychiatric symptoms in the multivariable logistic models. (Table 2)

Conclusion

Lewy body pathology was the most significant contributor to the aetiology of hallucinations, while NFT were important contributors to depression and agitation in dementia. Supporting the dual importance of these pathologies, subjects with AD and LBD co‐pathology showed the greatest burden of NPS.
Differences in dynamic functional connectivity across the Alzheimer’s disease spectrum
Authors: Pfeil Julia , Hönig Merle C. , Drzezga Alexander , van Eimeren Thilo
Published: June 2023

Background

To examine differences in dynamic functional connectivity (DFC) in cognitively normal subjects (CN), and patients with mild cognitive impairment (MCI) or Alzheimer’s disease (AD).

Method

Resting‐state functional magnetic resonance imaging (rsfMRI data of 76 participants (40 CN, 24 MCI, 11 AD) from the ADNI database (http://adni.loni.usc.edu/) was used for analysis. Groups were matched according to age, sex and education. rsfMRI data were pre‐processed using the CONN toolbox. For data reduction purposes, spatial independent and principal component analyses were performed on the normalized rsfMRI using GIFT. Resulting meaningful independent components were clustered into 13 functional resting‐state networks. Using GIFT, a sliding window approach was employed to determine dynamic functional connectivity states across the scan period of 9 minutes. Afterwards, non‐parametric t‐tests were performed comparing the groups in measures of DFC such as dwell time (i.e. staying in a state), number of transitions (i.e. switching between states), fraction time (i.e. total time spent in a state), and meta state characteristics.

Result

The DFC analysis resulted in 4 distinct functional connectivity states, which were characterized by either global connectivity patterns or distinct connectivity patterns between certain rs‐networks. Group comparisons yielded that one state was particularly more occupied by the AD group compared to the CN group (p = .02) and the MCI group (p = .001). The AD group showed a lower meta state span and number of meta states compares to the MCI and CN groups.

Conclusion

Network reorganization may influence dynamic functional connectivity patterns in pre‐ and clinical AD.
FLAIR MRI biomarkers of the Normal‐Appearing Brain Matter (NABM) are related to APOE‐4 status and CSF markers Aβ42 and Tau
Authors: Chan Karissa , Fischer Corinne E. , Khosravani Houman , Black Sandra E. , Tyrrell Pascal , Maralani Pejman Jabehdar , Moody Alan R. , Khademi April
Published: June 2023

Background

Reduced amyloid‐beta‐42 (Aβ42) and elevated total tau (t‐tau) protein concentrations in the CSF are characteristic of Alzheimer’s disease (AD) pathology [1]. Aβ42 contributes to extracellular plaque formation between neurons [2]. The total level of tau, a microtubule‐stabilizer in neuron axons [3], is associated with neuronal death [1]. Additionally, presence of ApoE4 (ε4) alleles is an established identifier for increased risk of AD [4]. Non‐invasive imaging‐based correlates of the CSF markers are lacking. This study examines correlations of novel FLAIR texture, intensity, and volume biomarkers, along with white matter lesion (WML) burden, with Aβ42, t‐tau, and ε4 status.

Method

FLAIR volumes (n = 4044) from the ADNI database were used for analysis with CSF biomarkers. A subset (n = 921) was used for ε4 analysis based on available data. Normal‐appearing brain matter (NABM) was obtained by removing CSF and WML. Macrostructural damage (MAD), microstructural damage (MID), and integrity (MII) texture biomarkers [5] were extracted from each NABM volume (Fig. 1), along with median intensity, NABM/ICV ratio, and normalized WML volume [5]. Relationships between FLAIR biomarkers and AD markers were described using parametric statistical analyses. Statistical significance was set at p<0.05.

Result

All FLAIR biomarkers were statistically significantly correlated with CSF Aβ42 levels. All features except MID and WML burden were significantly correlated with CSF t‐tau levels (Table 1). MAD, MID, and WML burden showed negative correlations with Aβ42, while MAD showed a positive correlation with t‐tau. Opposite trends were seen with MII, intensity, and NABM/ICV (Fig. 2). Significant differences between groups without and with one ε4 allele were found in all FLAIR biomarkers except WML burden. Significant differences in MAD, MII and NABM/ICV were found between groups with one and two ε4 alleles (Table 2).

Conclusion

FLAIR biomarkers were inversely associated with CSF Aβ42 concentrations, suggesting they may be surrogate markers of Aβ plaque formation. They were associated with CSF t‐tau concentrations, suggesting they could also be indicators of GM degeneration and neuronal death. They could also be indicators for patients at increased risk of AD, as they demonstrated significant differences with the presence of ε4. Further longitudinal studies are required to establish the exact mechanism of neurodegeneration.