bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of salivary levels of beta amyloid in patients with Alzheimer’s disease
Authors: Santos Gustavo , Pardi Paulo , Vale Francisco , Fazan Valeria
Published: June 2023

Background

Salivary analysis of amyloid beta protein levels in Alzheimer’s disease patients and research participants without Alzheimer’s disease.

Method

This is a case‐control study carried out in patients with a diagnosis of probable AD and cognitively healthy patients without AD. There were 3 groups, totaling 76 people: group 1 with AD; Group 2 without AD (under 59 years old) and group 3 without AD (over 60 years old). Ethics committee opinion n° 3,130,636. Salivary analysis of Ab‐40 and Ab‐42 performed by the ELISA method.

Result

Our investigations for salivary AB42 showed slightly higher levels in male and female AD patients compared to healthy ones. The general AB42 group for AD was superior to the general group of healthy ones, demonstrating the feasibility of using saliva as a diagnostic element for AD.

Conclusion

Amyloid beta protein in fractions 40 and 42 amino acids (Ab1‐40 and Ab1‐42) were expressed in higher concentrations in AD patients and reduced in healthy ones, strengthening the hypothesis of the use of this fluid as an adjuvant in the diagnosis of Alzheimer’s Disease.
Racial/ethnic and sexual orientation disparities in adverse childhood experiences, marijuana use and subjective cognitive decline: A mediational approach
Authors: Brown Monique J
Published: June 2023

Background

Adverse childhood experiences (ACEs) have been shown to be positively associated with substance use and abuse, and have also been linked to subjective cognitive decline (SCD). However, studies examining potential pathways between ACEs and SCD are lacking. In addition, this relationship and related pathways may differ by race/ethnicity and sexual orientation. The aim of this study was to determine the mediational role of marijuana use in the association between ACEs and SCD. The secondary aim was to determine the potential disparities by race/ethnicity and sexual orientation.

Method

Data were obtained from the 2019 Behavioral Risk Factor Surveillance System (N = 14,248). Path analysis was used to determine the mediating role of marijuana use between ACEs and SCD. Overall analyses adjusted for gender, age, income, education, employment and race/ethnicity. Stratified path analyses by race/ethnicity and sexual orientation were also conducted.

Result

Overall, there was a direct association between ACEs and marijuana use (B = 0.102, p = <0.001), marijuana use and cognitive decline (B = 0.119, p<0.001); and between ACEs and cognitive decline (B = 0.047, p<0.001). There was an indirect association where marijuana use mediated the association between ACEs and SCD (B = 0.005, p<0.001). Stratified analyses by race/ethnicity found that marijuana use mediated the association between ACEs and SCD among White (B = 0.003, p<0.001), but not Black, Other or Hispanic respondents. Stratified analyses by sexual orientation found that marijuana use mediated the association between ACEs and SCD among heterosexual (B = 0.002, p = 0.006) but not LGBT respondents.

Conclusion

Disparities by race and sexual orientation existed in the mediating pathway of ACEs and SCD. Intervention programs addressing early trauma and cognitive function should consider these disparities. Future research should examine additional pathways between ACEs and SCD, especially for racial/ethnic and sexual minority populations.
LTD‐inducing low frequency stimulation enhances p‐Tau181 and p‐Tau217 in an age‐dependent manner in live rats
Authors: Hu Neng‐Wei , Zhang Yangyang , Yang Yin , Hu Zhengtao , Zhu Manyi , Qin Shuangying , Rowan Michael J
Published: June 2023

Background

The progressive cognitive decline in Alzheimer’s disease (AD) patients correlates with the extent of tau pathology, in particular tau hyperphosphorylation, which is strongly age‐associated. Although elevation of phosphorylated tau (p‐Tau) on residues Thr181 (p‐Tau181), Thr217 (p‐Tau217), and Thr231 (p‐Tau231) in cerebrospinal fluid or blood are recently proposed to be particularly sensitive markers of early Alzheimer’s disease (AD), the generation of p‐Tau during brain activity is poorly understood. A major form of synaptic plasticity, long‐term depression (LTD), has recently been linked to the enhancement of tau phosphorylation. It is still unknown whether the expression levels of p‐Tau181, p‐Tau217, and p‐Tau231 can be enhanced by physiological LTD induction.

Method

Young adult (2‐3‐months) and aged (17‐18‐months) male Sprague Dawley rats were used in all experiments. Prior to the surgery, animals were anesthetized with urethane (1.5‐1.6 g/kg, i.p.). Field excitatory postsynaptic potentials (EPSPs) were recorded from the stratum radiatum in the CA1 area of left or right hippocampus in response to stimulation of the Schaffer collateral‐commissural pathway. LTD was induced using 1 Hz low frequency stimulation (LFS) consisting of 900 pulses (0.2 ms duration). The rats were sacrificed 30 min post‐LFS. The expression levels of p‐Tau181, p‐Tau217, p‐Tau231, p‐Tau202/205, p‐Tau396, and total tau were analyzed using western blotting and immunofluorescent staining.

Result

Here we show that LFS, used to induce LTD, enhances p‐Tau181 and p‐Tau217 in an age‐dependent manner in the hippocampus of live rats. In contrast, phosphorylation at residues Thr231, Ser202/Thr205, and Ser396 is less sensitive to LFS. Further, blocking either NMDARs or mGluR5 strongly inhibits the elevation of both p‐Tau181 and p‐Tau217. Finally, targeting ageing with a small molecule cognitive enhancer ISRIB (trans‐isomer) prevents the increase of both p‐Tau181 and p‐Tau217 by LFS in aged rats.

Conclusion

Our data provide an in vivo means to uncover brain plasticity‐related cellular and molecular processes of tau phosphorylation in health and ageing conditions.
Supporting the caregiver through the continuum of care
Authors: Renzulli Brenda , Bakkali Leen
Published: June 2023

Background

Caring for Dementia patients is taxing, affecting the caregiver emotionally, physically and financially. Often this results in strained relationships and health issues for the caregiver who becomes known as the ‘invisible patient’.

Method

The Bridgeport Hospital Center for Geriatrics multidisciplinary team engages with our patients and their caregivers in a variety of locations and methods.

We provide a number of educational opportunities, assist in goal setting and in long term planning. We offer LCSW counseling, support groups, and focus on giving a voice to the caregiver through a variety of means.

Result

These engagements have helped our patients and their families as they navigate this difficult journey. Families report through surveys lessened burden, they report being ‘heard’ and being grateful for the 24/7 support.

Conclusion

We found that our multidisciplinary approach and seeing patients and their caregivers at different points within the of the medical system improves outcomes. Both patient and caregiver satisfaction is improved and stress/burden are decreased.
Clinically relevant and explainable feature extraction from remote monitoring data for the prediction of urinary tract infections
Authors: Capstick Alexander , Palermo Francesca , Li Honglin , Barnaghi Payam , Wingfield David , Kolanko Magdalena A , Sharp David J
Published: June 2023

Background

A frequent cause for hospitalisation in people living with dementia (PLWD) is urinary tract infections (UTIs) (Dufour et al., 2015). Early detection aids in avoiding unplanned hospitalisations and machine learning and connected sensors enable development of risk analysis models based on in‐home monitoring data. This work makes use of data from the ongoing Minder study at the UK Dementia Research Institute, including in‐door movement, appliance use, physiology, sleep, and environmental information. Previous work (Li et al., 2020) shows complex models can achieve high accuracy when detecting UTIs, but interpretability and generalisability remain an open issue. This work evaluates how clinically interpretable features and simple models perform.

Method

The engineered features reflect visible symptoms of UTIs in older adults and are daily aggregated and pre‐processed information from PLWD’s homes containing passive sensors. 14 activity, sleep and physiological features were engineered relating to bathroom visits, entropy rate, physiological readings, and sleep behaviour. Raw data consisted of frequencies of the activity sensor firings. Their use in predicting cases of UTIs was compared by evaluating multilayer perceptron models on labelled data (643 negatives and 311 positives, from 39 PLWD), using 5‐fold cross‐validation (80%/20% train/test split), with 5 repeats. Prior to training and testing, the data was z‐normalised using unlabelled data. When evaluating, recall is most essential because reducing false positive rates is crucial in our setting.

Result

The highest performing model achieved the best accuracy, recall, precision and F1 score (85.6%, 69.9%, 81.5%, 74.8%) on combinations of engineered and raw features; though not significantly higher than with raw features alone (83.2%, 63.5%, 80.5%, 70.8%). Full results can be seen in the attached figure.

Conclusion

Our engineered features do not significantly improve results but add interpretability and generalisability to predictions. The models' hidden layers have a high capacity for learning patterns in the raw data, however, may not be clinically interpretable and we hypothesise that engineered features improve generalisation. Engineered features are homogeneous across the cohort and new data, and so create a way of representing the data which is not single device dependent. To verify this, we will continue our data collection and will conduct further experiments.
Long‐term nicotine treatment of mild cognitive impairment (The MIND Study): Baseline characteristics and study progress
Authors: Newhouse Paul A , Raman Rema , Saykin Andrew J. , Dumas Julie , Levin Edward , Kellar Kenneth , Aisen Paul S.
Published: June 2023

Background

Cognitive decline in AD/MCI is related to loss of cholinergic neurons. However, inhibition of acetylcholine degradation has not slowed progression. Treatment directly targeting nicotinic cholinergic receptors may be more helpful. We have shown proof of concept in a 6‐month multicenter trial that transdermal nicotine provides significant improvement in attention, episodic memory, and global ratings of functioning with minimal side effects in MCI. A larger and longer (2‐year) trial is underway to determine the persistence of improvement and attenuation of cognitive decline.

Method

MCI participants were randomized 1:1 to either transdermal nicotine, beginning at 3.5 mg/day, increasing to 21 mg/day or matching placebo by 5 weeks. Participants were assessed at 0, 3, 6, 12, 18, and 24 months, with a subset undergoing MRI scans at 0, 12, and 24 months, and CSF collection at 0 and 24 months. Primary cognitive outcomes included reaction time standard error change‐from‐baseline (Connors CPT) for attention and delayed word recall (Cogstate) for memory. Primary clinical outcome is the CGIC. Secondary clinical measures include behavioral/functional scales and the CDR‐SOB. An MRI substudy is examining possible neural mechanisms.

Result

To date, 663 participants were screened and 309 were randomized including 133 females (43%) and 176 males (57%). Mean age was 73.7±7.1, education 16±2.8 years. Mean MMSE was 27.4±1.8 and CDR Global was 0.5. Randomization of ethnoracial underrepresented populations (URPs) was 9.4% (Black/African‐American 4%, Asian 2%, Hispanic/Latinx 3%). Treatment/Study discontinuations were higher than expected at 29% due in part to pandemic‐related disruptions. There are 87 completers thus far. Baseline MRI scans are 59 and LPs are 37. Safety results show that treatment has been generally well tolerated with no SAEs definitively or probably tied to study participation or investigational product thus far.

Conclusion

If the hypotheses are validated, this will support a novel, broadly available, and inexpensive repurposed intervention for MCI and would encourage early treatment to improve symptoms, attenuate progression of cognitive impairment, and lead to combined trials with agents that interact with Aβ, tau or other mechanisms. Low URP recruitment and higher dropout rate remain challenging and will be specifically addressed in recruitment/enrollment/retention efforts moving forward.
Decoding the gene subnetworks prioritized in prediction with GLRP in Alzheimer’s Disease
Authors: Varathan Pradeep , Xie Linhui , He Bing , Nho Kwangsik , Risacher Shannon L. , Saykin Andrew J. , Yan Jingwen
Published: June 2023

Background

Alzheimer’s disease is the leading cause of brain dementia, along with which substantial failure of organs and mental issues arise. The abundance of AD related data in the current decade has allowed for much advancement in the field using modern machine learning and deep learning techniques to decrypt pathology. Though diagnostic tools have been modeled over such large expanses of data, the black box problem of decoding the significant biological components contributing to the prediction has been overlooked in the research field.

Method

GLRP is a method to decode the final predictions of a deep learning method. Since Graph‐CNN are best suited for using the gene expression data modeled over an established whole human PPI network. The usage of GLRP allows us to build the relevance that we need to interpret how the genes contribute to the prediction based on proven PPI network topology as the basis. From the relevance’s obtained of correctly predicted ROSMAP AD subjects and controls, important genes were extracted to be analyzed for functional annotations and pathway analysis with HPRD PPI.

Result

The graph‐CNN model was able to predict between AD subjects and controls with an AUC of 76.58% and test accuracy of 79.167% while the highest accuracy of machine learning models capped at 75% with an AUC of 72.95% from SVM as seen in Table 1. Having found a threshold of 550 genes to have the highest connected component in graph before noisy genes are added to the network as seen in Fig 1, the average relevance of AD subjects and controls provided us with 214 common genes with 181 genes in the largest connected component as seen in Fig 2.

Conclusion

Along with tackling the black box problem of the deep learning model using GLRP which has allowed us to gather the important genes from the network view at a higher efficiency than the machine learning models. The top 214 common genes and the network relating to the negative regulation of organelle organization, hypoxia and oxygen level response, and cellular response to tumor necrosis factors could have potential impact on the pathology of AD and its progression.
Serum total tau, neurofilament light, and glial fibrillary acidic protein are associated with overall and cardiovascular mortality in a biracial longitudinal population‐based cohort
Authors: Halloway Shannon , Evans Denis A , Desai Pankaja , Rajan Kumar B
Published: June 2023

Background

Serum cytoskeletal biomarkers may indicate greater risk of poor outcomes in age‐related conditions, including mortality. Total tau (t‐tau), neurofilament light (Nf‐L) and glial fibrillary acidic protein (GFAP) are neuronal cytoskeletal biomarkers that are measurable in biofluids. Our objective is to examine separate and combined associations of serum t‐tau, Nf‐L, and GFAP with overall and cardiovascular mortality in a biracial population‐based sample.

Method

Data came from 1,327 older participants who were either of Black or White racial background from the Chicago Health and Aging Project (CHAP), a longitudinal population‐based study of chronic conditions of aging. An ultrasensitive immunoassay was used to measure the concentration of t‐tau, Nf‐L, and GFAP in blood serum. Mortality based on age at death included overall mortality and cardiovascular mortality. A series of Cox proportional hazard regression models were used to examine associations between biomarker(s) and outcomes (overall and cardiovascular mortality), adjusting for age, gender, education, the APOE‐e4 allele, global cognitive function, and physical functioning.

Result

In univariate models, 5‐fold higher concentrations of serum t‐tau (HR = 1.46, 95% CI: 1.28, 1.68), Nf‐L (HR = 2.14, 95% CI: 1.79, 2.57), and GFAP (HR = 1.39, 95% CI: 1.07, 1.81) were separately associated with increased risk of overall mortality, with higher risk in participants of Black race versus White in models with t‐tau or Nf‐L. In combined models with all three biomarkers, t‐tau (HR = 1.38, 95% CI: 1.09, 1.75) and Nf‐L (HR = 3.05, 95% CI: 2.35, 3.95) were associated with risk of overall mortality, with racial differences in t‐tau only. In univariate models, higher concentrations of t‐tau (HR = 1.32, 95% CI: 1.03, 1.68), Nf‐L (HR = 2.11, 95% CI: 1.56, 2.88), and GFAP (HR = 1.74, 95% CI: 1.13, 2.69) were separately associated with risk of cardiovascular mortality, with racial differences in t‐tau or Nf‐L. In combined models, only Nf‐L was associated with cardiovascular mortality (HR = 2.84, 95% CI: 1.84, 4.38).

Conclusion

Serum t‐tau, Nf‐L, and GFAP were associated with increased risk of overall and cardiovascular mortality, with racial differences among associations, in a biracial population‐based sample. Our findings suggest that serum t‐tau, Nf‐L, and GFAP may serve as a potential biomarker for overall and cardiovascular mortality among older adults.
Herpes Simplex Virus‐1 Proteins as Drivers for Alzheimer’s Disease Pathologies
Authors: Shemesh Or A. , Reis Roberta , ` Hyde Vanesa
Published: June 2023

Background

DNA and RNA of Herpes Simplex Virus 1 (HSV‐1) were found in the brains and serological samples of Alzheimer’s disease (AD) patients. Such molecular presence of HSV‐1 in AD patients is especially intriguing as HSV‐1 virions are rarely detected in AD brains.

Method

To follow the molecular footsteps detected, we imaged viral proteins in postmortem human AD brains at superior resolution using expansion microscopy, a tissue manipulation method that physically expands the samples by a factor of 4.5x, allowing a 40 nm imaging resolution, and immunolabeled herpetic proteins, AD pathologies and cell markers.

Result

We found an abundance of herpetic proteins, previously undetectable with standard methods, across large brain areas. Importantly, we found that HSV‐1 proteins strongly co‐localized with AD pathologies. Consequently, we hypothesized that expression of HSV‐1 proteins during latency may be linked to AD pathology. We are now in the process of characterizing the HSV‐1 proteome in AD brains by imaging key proteins in expanded AD brain slices and examining their colocalization with AD pathologies across brain areas and disease stages. As a complementary system to the fixed human brain slices, we are exposing live human brain organoids, to HSV‐1, and imaging the relationships between viral proteins and the formation of AD pathologies via expansion microscopy.

Conclusion

Pathogens may be triggers of immune responses driving AD; this study would shed light on one common pathogen, HSV‐1, while serving as a framework to unveiling molecular causation between infectious agents and AD hallmarks.
A citation network analysis of the rural dementia literature
Authors: Prusaczyk Beth , Huo Rani
Published: June 2023

Background

There are key differences between urban and rural areas in terms of dementia risk, diagnosis, treatment, and service availability and utilization. Despite the unique and important context of rural areas, there has been relatively little research on dementia in rural areas. A broad yet comprehensive understanding of the existing rural dementia literature is an important step in grounding future dementia research in the existing literature and field.

Method

In June 2021, we conducted a citation network analysis of articles on rural dementia. Articles were identified using Web of Science and inclusion criteria included having “rural” and “Alzheimer’s” or “dementia” in the title. The abstracts of articles meeting these criteria were then reviewed manually by two researchers to ensure the primary focus was on rural dementia. Bibliographic data for the final sample of articles was downloaded from Web of Science and imported into VOS Viewer, a software tool for constructing and visualizing bibliometric networks.

Result

Three hundred articles were included for analyses. Using time‐adjusted number of citations as a measure of prominence, 142 (47.3%) articles had been cited more than 10 times. An analysis of these 142 articles revealed twelve clusters. We found no patterns among the clusters based on publication year but found that publications tended to cite others originating from countries in close geographic proximity. Text citation analysis revealed three sub‐themes among the articles based on keywords: long‐term care studies, epidemiological studies, and community‐based and caregiver services studies, with few citations between the last two sub‐themes.

Conclusion

There are three key findings from this analysis that help elucidate the rural dementia literature. First, authors publishing on rural dementia are citing older and newer articles at the same rate, suggesting the field is actively growing. Second, many countries are contributing to the literature base but authors still tend to cite articles originating from their own country or those close to them, suggesting there is a missed opportunity to learn from the global community. Third, there are three sub‐themes dominating the literature with little citations across sub‐themes, which suggests a need for more interdisciplinary research.
Overall and sex‐specific AT(N) biomarker prevalence in a low SES community: A population‐based study
Authors: Shaaban C. Elizabeth , Fang Fang , Cohen Ann D. , Chang Chung‐Chou H , Lopresti Brian J. , Laymon Charles M , Aizenstein Howard J , Klunk William E , Villemagne Victor L , Ganguli Mary , Snitz Beth E.
Published: June 2023

Background

Most previous studies of amyloid[A], tau[T], and/or neurodegeneration[(N)] prevalence have been completed in highly selected samples, leaving low SES older adults from medically underserved areas underrepresented in research. Furthermore, women consistently have greater T and sometimes greater A accumulation than men, but clear characterizations of AT(N) biomarker positivity overall and by sex in different populations are lacking.

Methods

Neuroimaging (NI) sub‐study participants in a population‐representative study of older adults from a low SES, medically underserved US Rust Belt area underwent PET and MRI. We calculated overall and sex‐specific AT(N) biomarker positivity within the NI sub‐study (Table 2) and population‐representative prevalence (Table 3) with inverse probability of selection weighting (IPSW). We calculated age and education adjusted odds ratios (ORs) for women vs men.

Results

The overall sample (N = 1226) was 61% female, 94% white, and 98% dementia‐free. NI study participants (N = 115) were older, likelier to be from the parent study’s original (vs. replenishment) cohort, and less likely to report diabetes than non‐NI participants (N = 1111; Table 1). IPSW based on variables associated with AT(N) biomarkers (age, cohort, sex, race, education, hypertension, diabetes, and number of medications) successfully balanced these characteristics across NI and non‐NI samples. Population‐weighted prevalence of the A‐T‐(N)‐ profile was 18.8%. Based on 2018 NIA‐AA Research Framework terminology, prevalence of AD continuum biomarkers (any A+) was 24.4%; about 2/3 of these cases were specifically due to AD (A+T+ biomarkers). Prevalence of any T+ was 34.7%, and any (N)+ was the most common at 63.0%. Prevalence of A‐ with T+ and/or (N)+ was 56.8%. Any T+ and AD continuum/AD+ biomarkers were non‐significantly more common in women than men (weighted ORs ranging from 1.20 to 1.69, Table 3).

Conclusions

Completely normal AD biomarkers (A‐T‐(N)‐) were comparatively rare in older participants in this community, while any N+ and A‐ with T+ and/or (N)+ were quite common. Women trended toward a greater prevalence of AD+ biomarkers than men. These results are more applicable to other primarily white, low SES, and medically underserved populations than results from highly selected samples. Characterizing brain health across varying cohorts is essential to advance precision medicine and population health.
Cognitive function and brain structure correlates in individuals with subjective cognitive decline: Voxel‐based morphometry results from a lifestyle intervention to prevent Alzheimer’s disease (PENSA study)
Authors: Lorenzo Thais , Cuenca Aida , Operto Grégory , Falcon Carles , Puig‐Pijoan Albert , Forcano Laura , Piera Iris , Boronat Anna , Knezevic Iva , de Toma Ilario , Soldevila‐Domenech Natalia , Fauria Karine , Molinuevo Jose Luis , Gispert Juan Domingo , Torre Rafael de la ,   PENSA Study Group
Published: June 2023

Background

Interventions based on the modification of several lifestyle factors have provided promising results to maintain cognitive function in late/middle‐aged individuals at higher risk of developing Alzheimer’s disease (AD). Framed under the WW‐FINGERS network, the PENSA clinical trial is focused on the prevention of cognitive decline in individuals with subjective cognitive decline who are also APOEε4 carriers. It consists of a 12‐month multimodal lifestyle intervention supplemented with EGCG, a natural flavonoid from green tea. In this study, we looked for the brain structure correlates of cognitive performance for PENSA participants at baseline.

Methods

One hundred thirty‐one (N = 131) participants of the PENSA study at baseline [Table 1] with valid T1w, T2w and FLAIR MRI scans were included. They underwent a neuropsychological assessment battery consisting of the modified Alzheimer Disease Cooperative Study ‐ Preclinical Alzheimer Cognitive Composite (ADCS‐PACC‐Plus‐exe) that includes MMSE, Free and Cued Selective Reminding Test (FCSRT), Delayed Recall Logical Memory (DRLM), Five Digits Test, Digit Symbol Substitution Test, and Stroop. Additional cognitive measurements were obtained from semantic verbal fluency (SVF), Boston Naming Test, digit span subtest, visual puzzle subtest (VPT) and the Montreal Cognitive Assessment. FLAIR images were used to segment white matter hyperintensities and perform a lesion filling procedure in T1w and T2w images. These two later modalities were then entered into a multimodal segmentation in the SPM12 voxel‐based morphometry pipeline. Associations between test scores and grey matter volumes (GMv) were sought (p<0.001) including age, sex, education, and total intracranial volume as confounders.

Results

A positive association was found (p uncorr <0.001; k>200) between GMv and ADCS‐PACC‐Plus‐exe composite [Figure 1] in the bilateral hippocampus, amygdala, entorhinal and parahippocampal gyri. Additionally, positive correlations (p uncorr <0.001; k>200) were found between GMv and FCSRT, DRLM, VPT and SVF tests albeit in less consistent regional patterns. No associations were found between GMv and the remaining tests.

Conclusion

In a sample at high risk of developing AD, the ADCS‐PACC‐Plus‐exe composite is associated with GMv in brain areas known to be affected in AD. These results suggest that the ADCS‐PACC‐Plus‐exe composite might be sensitive to detect subtle cognitive changes in cognitively unimpaired at‐risk individuals.
Longitudinal body weight dynamics in relation to cognitive decline over 18 years: A prospective cohort study
Authors: Zhou Tianjing , Chen Hui , Huang Yuhui , Wang Binghan , Zheng Yan , Wang Liang , Rong Shuang , Ma Yuan , Yuan Changzheng
Published: June 2023

Background

Weight loss and body weight variability have been related to cognitive decline in old adults, respectively. However, the long‐term and independent associations of the two measures of body weight dynamics with cognitive decline remain unclear.

Method

In the Health and Retirement Study (HRS), we included 10,258 participants (58.4% women; mean age ± standard deviation (SD), 68.0 ± 9.8 years) free from memory‐related diseases in 1998. Body weight was reported biennially from 1993/1994 to 2016. Linear regression of the longitudinal body mass index for each individual was used to estimate body weight change (BWC, slope, kg/m2·year) and body weight variability (BWV, root mean squared error, kg/m2). Both measures were categorized by tertiles, with participants being classified as stable weight, weight loss, and weight gain (median = 0.0, ‐0.3, and 0.2 kg/m2·year, respectively), and small, moderate, and large BWV (median = 0.5, 1.1, and 2.0 kg/m2, respectively). Cognitive function was measured biennially from 1998 to 2016 using the Telephone Interview for Cognitive Status (TICS). We investigated the associations of BWC and BWV with annual rate of cognitive decline using linear mixed models.

Result

During a median (IQR) follow‐up of 12 (4‐18) years, the average rate of cognitive decline was ‐0.052 z‐score/year. When adjusted for basic demographics, average BMI, and major lifestyle factors, we observed no significant associations of weight gain and moderate BWV with cognitive decline, whereas both weight loss and large BWV were associated with faster cognitive decline in the same model. Compared to those with stable weight, participants with weight loss experienced faster cognitive decline by ‐0.012 (95%CI, ‐0.015, ‐0.009) z‐score/year. Large BWV was also related to faster cognitive decline (β = ‐0.003, 95% CI: ‐0.006, ‐0.001) compared with small BWV. The associations were similar for both episodic memory and working memory, and across prespecified study subgroups.

Conclusion

Weight loss and large body weight variability were associated with faster cognitive decline in old adults. Our findings suggest the importance of dynamic body weight monitoring and management as a potential strategy to prevent age‐related cognitive decline.
Training caregivers to make meaningful connections with persons living with dementia: Telehealth strategies from the Pacific island of Guam
Authors: Twaddle Iain K. B. , Hattori‐Uchima Margaret Perez , Gutierrez Nikolas Jude , Orallo Rhoda Gaba
Published: June 2023

Background

Alzheimer’s Disease and Related Dementias (ADRD) are not only characterized by a decline in memory and cognition, but also by marked difficulties in language, communication, and social functioning. As ADRD progresses, it becomes increasingly challenging for persons living with dementia to participate in social interactions with family, friends, and caregivers, adversely impacting their well‐being and quality of life. Despite impairment in social functioning, persons with dementia still enjoy interaction with others and respond positively to social contact even in advanced stages. Thus, there is a need to develop effective strategies for interacting with persons living with dementia in a meaningful way.

Method

A telehealth dementia care training initiative was developed in the Pacific island of Guam focused on teaching family and professional caregivers to make meaningful connections with persons with ADRD through a wide range of stimulating, culturally responsive activities adapted to meet their unique needs, interests, and abilities. Activities were designed to provide opportunities for social engagement and simultaneously to help persons with dementia remain mentally and physically active. Examples include: (1) making meaningful connections with persons with dementia during activities of daily living; (2) rediscovering Guam’s history and culture through family‐based virtual museum tours; (3) embracing the oral storytelling traditions of Pacific island cultures by sharing family memories; (4) employing culturally responsive bibliotherapy by reading indigenous stories and picture books together; (5) stimulating the mind through collaborative readings of poetry; (6) soothing the aches and pains that come with aging by providing therapeutic massage; and (7) integrating music, dance, and movement into each day. All trainings were conducted in virtual family caregiver support group sessions as part of a comprehensive telehealth outreach program designed to provide improved access to dementia care support services for persons with dementia and their caregivers in Guam.

Result

Approximately 60‐100 family and professional caregivers participate in the program each month.

Conclusion

Program outcomes indicate that telehealth training in activity‐based dementia care can be an effective way to help caregivers learn to make meaningful connections with persons living with dementia.
Analysing the neuroprotective abilities of Apocynin (APO) & Chlorogenic Acid (CGA) in synergism to treat Alzheimer’s disease (AD)
Authors: Agarwal Vinayak
Published: June 2023

Background

Neurological illnesses accounted for the greatest percentage (6.2%) of Total DALY index among all diseases, according to the World Health Organization (WHO). Alzheimer’s disease (AD) is the second most common neurological illness in the world, after Cerebrovascular disease (12 percent), with epilepsy and migraine accounting for 8% apiece. The cognitive function of people with AD deteriorates over time. It is an irreversible, dynamically changing condition that will afflict approximately 65.7 million people worldwide by 2030. For the treatment of AD, the Food and Drug Administration (FDA) has approved a number of commercial formulations (e.g., donepezil, rivastigmine, galantamine, memantine, and aducanumab). However, they have serious adverse effects and only provide symptomatic relief in people who have the illness. As a result, natural compounds are being investigated in recent years for the treatments of neurodegenerative diseases (NDDs). Picrorhiza kurroa, isolate Apocynin (APO) is a potent inhibitor of NADPH oxidase (NOX) and Chlorogenic Acid (CGA), a product of green coffee beans, has been shown to reduce ROS and NO levels in the brain, which is considered major trigger in AD.

Method

It was possible to execute successful in‐silico validation utilising computational biology, as well as the fabrication of APO‐CGA loaded polymeric nanoparticles using the ionic gelation process. The optimized nano‐formulation (APO – CGA NPs) was characterised by using various techniques to ensure its particle size and physicochemical behaviour along with release kinetics analysis.

Result

The attained results suggested that designed nano formulation will provide enhanced synergistic therapeutic efficacy to treat AD.

Conclusion

The formulation and study of optimal APO‐CGA NPs for effective transport to the target site, their function in synergism, and their anti‐oxidative capabilities to evaluate the neuroprotective efficacy were the emphasis of this research work.
Neuropsychological performance of cognitively healthy older Chinese‐speaking immigrants in U.S.
Authors: Hong Yue , Zeng Xiaoyi , Sano Mary , Zhu Carolyn W , Neugroschl Judith A. , Aloysi Amy , Martin Jane , Huang QiYing , Akrivos Jimmy , Yang Xiao , Li Clara
Published: June 2023

Background

Normative standards for cognitive tests representing the fast‐growing minority aging group of Chinese in the U.S. are rare. Using a cohort of cognitively normal older U.S. Chinese immigrants, this study aims to (1) examine the relationship between demographics and cognitive performance with a Chinese battery, (2) describe neuropsychological performance, and (3) compare performance to published norms from age‐, education‐, and gender‐matched English‐speaking population.

Method

121 Mandarin/Cantonese speaking ≥ 65 years old were recruited at the Alzheimer’s Disease Research Center at Mount Sinai and completed the neuropsychological battery in their preferred language, covering domains of memory (Logical Memory, LM; Philadelphia Verbal Learning Test, PVLT), attention and executive function (Digit Span Forward & Backward, DSF & DSB; Digit Symbol, DS; Similarities; Trail Making Test ‐ Part A & B, TMT‐A & B), and language (Animal & Vegetable Naming; Phonemic Fluency). Participants received a cognitive diagnosis after consensus by qualified clinicians using clinical information other than the neuropsychological scores. Only normal controls (n = 67) were included in the analysis. The relationship between demographic factors and neuropsychological performance was examined using multivariate regression. Independent‐sample t‐test was used to compare neuropsychological performance with the published norms.

Result

Participants were primarily female (69%), Mandarin speaking (61%), and immigrated from China (63%) with 32.4±14.1 years in the U.S. Mean age was 72.7±6.8 years and education was 14.1±3.4 years. Education was positively associated with DSF, DSB, DS, TMT‐A, Animal Naming, and Similarities performance. Age was negatively associated with LM, PVLT, DS, TMT‐A & B, and Similarities performance. Women performed better on Vegetable Naming. Years of living in the U.S. was negatively associated with Vegetable Naming and PVLT delayed recall. Primary language was not found predictive of cognitive performance. Mean/SD/median/range of each test and comparison with published norms were presented in the supplemental table.

Conclusion

Our findings highlight the need to establish neuropsychological norms for older US Chinese immigrants. Cognitive test scores were associated with age and education consistent with existing literature. Factors relating to immigration history may impact cognitive performance and should be investigated further in a bigger sample to provide guidance on norm establishment for immigrant population.
Association between perceived social support and physical activity level of alzheimer family caregivers
Authors: Menengiç Kübra Nur , Bülbül Nazlı Gamze , Doğan Idil Arasan , Kendirli Sude , Şahiner Türker AH , Çınar Nilgün
Published: June 2023

Background

Family caregiving in Alzheimer’s Disease (AD) has been associated with a variety of negative psychological and social processes, including social isolation. Besides, it has been shown that the caregiver’s physical activity level is one of the factors associated with the burden of care. The negative impact of physical inactivity on general health status is well established. This study aimed was investigate relationship between social support and caregiver’s physical acitivity level.

Methods

Participants’ working‐caregiving status and functional independency of their patients was recorded. Physical activity level was assessed with Rapid Physical Activity Assessment (RAPA). Percieved Social Support Questionnary (PSSQ) was used for evaluating of social support. Statistical analysis was performed by Spearman correlation analysis in SPSS 22.0 package program.

Results

Among the 59 participants 88.4% were female and mean age was 54.83±11.9 years. Caregiver’s demographics presented in Table 1. There was a significant correlation was found between RAPA and PPSQ (p = .015, rho = .321). According to RAPA results, 6.7% respondents were reported have no physical activity, 66.7% were underactive, and 13% were active.

Conclusions

Our study was demonstrated that most of the caregivers were physically underactive. Supportive social environment was found related with caregivers physical activity level. It is necessary to be aware of the potential health risks not only for people with AD but also for caregivers. Caregivers should be encouraged to be physically active considering the positive effects on physical and mental health. Policy makers should develop strategies that support caregivers, taking into account all the components that are affect them physically, socially and psychologically.
The mean diffusion propagator model revealed cortical microstructural changes associated with both amyloid‐β and tau pathology and astroglial activation
Authors: Spotorno Nicola , Strandberg Olof , Vis Geraline , Stomrud Erik , Nilsson Markus , Hansson Oskar
Published: June 2023

Background

Markers of downstream events are a key component of clinical trials of disease‐modifying therapies for Alzheimer’s disease (AD). Morphometric metrics like cortical thickness are established measures of atrophy but are not sensitive enough to detect Aβ‐related changes that occur before overt atrophy become visible. We aimed to investigate to what extent diffusion MRI can provide sensitive markers of cortical microstructural changes that could complement morphometric macrostructural measures.

Method

We applied the mean apparent diffusion propagator model (MAP‐MRI) to diffusion MRI data from 492 cognitively unimpaired elderly and patients with mild cognitive impairment from the Swedish BioFINDER‐2 cohort. MAP‐MRI extends diffusion tensor imaging and provides metrics sensitive to subtle changes in the cortex. Participants were stratified in Aβ‐negative/tau‐negative, Aβ‐positive/tau‐negative, and Aβ‐positive/tau‐positive based on Aβ‐ and tau‐PET uptake. Cortical regional values of both MAP‐MRI metrics and CT were compared across groups. Associations between regional values of MAP‐MRI metrics and both Aβ‐ and tau‐PET uptake were also investigated as well as the association between MAP‐MRI metrics and plasma level of GFAP, a marker of astroglial activation (available in 292 participants).

Result

Mean square displacement (MSD) from MAP‐MRI revealed widespread microstructural differences already between Aβ‐negative/tau‐negative and Aβ‐positive/tau‐negative participants with a spatial distribution that closely resembled the pattern of Aβ accumulation. In contrast, differences in cortical thickness appeared to be more limited (figure 1). MSD was also highly correlated with both Aβ‐ and tau‐PET uptake even independently from one another (figure 2). Regional MSD values were associated with GFAP with a pattern that resemble Aβ accumulation, and GFAP partially mediated the association between Aβ and MSD. A sensitivity analysis controlling for cortical thickness revealed that the associations between MSD and Aβ‐PET, tau‐PET and GFAP were largely independent from macrostructural changes (figures 2‐3).

Conclusion

Metrics of cortical microstructural alteration derived from MAP‐MRI are highly sensitive to multiple aspects of the AD pathological cascade. Of particular interest is the link between MSD, Aβ‐PET and GFAP which suggests MSD might reflects microstructural changes related to the astrocytic response to Aβ aggregation. Therefore, MSD could help monitoring the response to anti‐Aβ treatments in clinical trials.

aging after age 90.
Dementia associated disorders, cognitive impairment and impact on social roles activities and participation: Patient centric impact
Authors: Peraza‐Bonilla Sophia , Kaczmarek Olivia , Baek Steven , Sethi Avtej , Bumstead Barbara , Zarif Myassar , Gudesblatt Mark
Published: June 2023

Background

Dementia associated diseases (DAD) refers to several clinical conditions that are characterized by progressive cognitive impairment that interferes with an individual’s ability to function independently. Cognitive impairments (CI) can vary in degree and combination across multiple cognitive domains (CD) that routine care or tests (MMSE, MOCA) might not adequately identify. Therefore, a clinician may not recognize these varied types of CI or change in CD scores effectively. Enhanced recognition of patient centric CI in routine care can be accomplished improved analytics by incorporating a validated, examiner independent computerized cognitive assessment battery (CAB‐NT). Patient self‐reported outcome measures (PRO) are concurrently incorporated with CAB‐NT to gauge associated disability progression. Ability and participation in social roles and activities and communication ability can adversely affect quality of life (QoL) for people with Dementia associated diseases (PwDAD) and are likely related to CI and other factors.

Method

Retrospective review of consecutive PwDAD who completed both CAB‐NT and PRO (SSRA, APSRA, and C‐SF) on the same day in the course of routine care. CAB‐NT included 7 cognitive domains: memory (Mem), executive function (Exe), attention (Att), information processing speed (Inf), visual spatial (Vis), verbal function (Ver), motor skills (Mot) as well as a global cognitive summary score (GCS).

Results

312 PwDaD, 64.74% female, average age 66 +/‐ 17 years. Simple linear regression analyses were performed with significant correlations (p = <0.05): CAB‐NT vs SSRA: GCS r = 0.2, Exe r = 0.3, Mot r = 0.2, and Att r = 0.3. CAB‐NT vs APSRA: Exe r = 0.3, Att r = 0.2. CAB‐NT vs C‐SF: Exe r = 0.2.

Conclusion

Social roles and communication in PwDAD are most impacted by CI associated with executive functioning and attention. Impairment in these domains are associated with increased difficulty for PwDaD to effectively interact with others and may lead to reduced QoL for these patients. Identifying the degree and combination of such CI precisely might allow for early and effective targeted proactive behavioral and/or medicinal intervention to improve QOL of these patients.
Prevalence of cerebrovascular calcifications in indigenous Bolivian Tsimane and Moseten
Authors: Barisano Giuseppe , Sutherland M. Linda , Sutherland James D , Gatz Margaret , Mack Wendy J , Chui Helena C , Law Meng , Rodriguez Daniel Eid , Gutierrez Raul Quispe , Irimia Andrei , Finch Caleb E , Thomas Gregory S , Stieglitz Jonathan , Trumble Benjamin C , Gurven Michael D , Kaplan Hillard
Published: June 2023

Background

Intracranial arteriosclerosis has been increasingly recognized as an etiological factor contributing to cognitive impairment. Indigenous Tsimane and Moseten, Amerindians of the Bolivian Amazon with physically‐active subsistence lifestyle, are reported to have lower prevalence of dementia (Gatz et al., Alzheimer’s Dement, In press) and coronary artery disease (Kaplan et al.,Lancet,2017) than Western populations. We assessed the prevalence of intracranial arteriosclerosis, cerebrovascular calcifications, and leukoaraiosis in these populations and investigated their relationship with brain atrophy and cognition.

Method

155 participants aged ≥60 (60.6% females) underwent a non‐contrast computed tomography scan and cognitive testing. Visual rating scales were used to evaluate global cortical atrophy (GCA, simplified Pasquier), medial temporal atrophy (MTA, Scheltens), internal carotid artery (ICA) calcifications extent and morphology (Babiarz/Kockelkoren), lenticulostriate arteries (LSA) calcifications (de Brouwer), deep and periventricular leukoaraiosis (Fazekas). The maximum density (Hounsfield units) of LSA calcifications and the presence of infarcts and vertebral arteries (VA) calcifications were also evaluated.

Result

Virtually all participants presented vascular calcifications in ICA (99.3%), LSA (87.4%), and VA (98.5%) (Fig.1,2). ICA calcification morphology was continuous in 58.7% and irregular/patchy in 40.5%, indicating medial and intimal pathology, respectively (Fig.3). In 13.2% of cases, the LSA calcifications were surrounded by parenchymal calcifications in the basal ganglia (Fig.4). Most cases showed no radiological sign of infarcts or leukoaraiosis. ICA calcifications correlated with age (P<.0001) while other calcification locations showed little association with age. LSA calcifications were greater in men than women (P<.01) with sex differences minimal for other calcification locations. After controlling for age and sex, ICA, LSA, basal ganglia and VA calcifications were related to greater GCA (all P<.05). LSA calcification density was significantly related to greater GCA and MTA, and to poorer visuo‐constructional ability (all P<.01). Prevalence of ICA and VA calcifications were higher compared to those reported in a population‐based European sample (79% and 16.9%, respectively; Vinke et al.,Neurobiol.Aging,2021). (Fig.5)

Conclusion

Despite the low prevalence of dementia and coronary artery disease, cerebrovascular calcifications are commonly observed in this indigenous Bolivian population, and are associated with greater brain atrophy. Their underlying pathogenetic mechanisms remain unclear, but the high prevalence of infectious and inflammatory disorders might play a role.