bluuebunny/crossref_metadata_2025 huggingface dataset:
Risks and mitigating factors in psychosocial adjustment of spousal caregivers of people with dementia
Authors: Ho‐yin Lai Frank
Published: June 2023

Background

We are living in an era when the world’s aging population is rapidly expanding. The importance of family caregivers has been receiving increasing attention since last decade. With longer lifespans and limited caregiving resources from the affected ones’ own children, some of whom are even childless, caregiving for older adults has become the main responsibility of their spouses. Caring for older adults with dementia has always been a family endeavor and spousal caregivers play a crucial role in caring for people affected by dementia in the community

Method

By applying the Stress Process Model to examine the characteristics of people with dementia and their spousal caregivers, this study aims to identify the potential risk and mitigating factors of psychosocial adjustment among the spousal caregivers. We recruited 80 care recipient‐caregiver couples in Hong Kong and examined the relationships of socio‐economic, care recipient’s, and caregiver’s factors with spousal caregivers’ psychosocial adjustment through the use of questionnaire survey.

Result

It was found that care recipients’ cognitive functions were associated with caregivers’ reported frequencies of their behavioral and psychological symptoms of dementia (BPSD) (r = .30, p = .008), and caregivers’ perceived burden of caregiving (r = ‐.54, p = .008). Caregivers’ quality of life was associated with their perceived caregiving burden (r = ‐.82, p = .001) and self‐efficacy (r = .32, p = .001). Upon further examining the caregiving model with these parameters, a significant multivariate general linear model was found with (F (1, 12) = 13.06, p = .001, partial eta square = .70, observed power = .99). Moreover, female caregivers reported higher sense of caregiving stress and poorer quality of life than male caregivers.

Conclusion

This study found that the cognitive functions and BPSD of care recipients with dementia and perceived level of caregiving burden are strongly associated with degrees of psychosocial adjustment among their spousal caregivers. The self‐perceived caregiving role in a family is also a possible confounding factor contributing to the perceived caregiving burden. To support in‐home caregiving of people with dementia, strategies to empower spousal caregivers to execute their caregiving roles are recommended.
Individualized and ecological analyses of the needs of family caregivers of older adults with dementia: The phenomenological approach
Authors: Ho‐yin Lai Frank
Published: June 2023

Background

Dementia is a worldwide public health challenge. Caring for a person with dementia affects their caregivers in different ways.

Objectives

Using an integration of the Model of Human Occupation (MOHO) and Bronfenbrenner’s ecological systems theory (EST), this study aimed at exploring the needs of and stress arising in family members who are caregivers of people with dementia and identifying the coping strategies these family members use in caring.

Methods

Using the purposeful sampling strategy and a blend of closed‐and‐open‐ended questions, four focus groups were conducted in four different districts. A phenomenological explanation approach was used to examine participants’ caring experience and their needs.

Results

Eighty family caregivers (FCGs) of people with dementia, who are their family members, were recruited. Seeking understanding, stabilization, preparation, implementation, and adaptation are the themes that were identified for analysis. The results indicated caregiving is a demanding task, both mentally and physically.

Conclusion

Being older, having a lower socioeconomic status and having lower levels of informal support were related to higher levels of care stress and poorer coping strategies in FCGs. Moreover, active service provision can be started in the early stages of caring and this should accompany with the active involvement of service in the volitional aspects of the FCGs.
Clustering patients with vascular cognitive impairment using quantitative magnetic resonance imaging data and a finite mixture model
Authors: Murtagh Ryan D , Schultz Susan , Kindy Mark Stephen , Taheri Saeid
Published: June 2023

Background

Blood‐brain barrier (BBB) leakage is a marker of vascular cognitive impairment and dementia (VCID). The advance of in vivo imaging enabled us to quantify the degree of BBB transfer rates in VCID patients. However, a consensus has not been reached on the role of BBB in the differential diagnosis of VCI subtypes. The objective of this work was to use neuroinflammatory and in vivo imaging data on BBB health to identify clusters of VCID patients with distinct underlying pathologies.

Method

Patients included were on average 61 (SD = 15.94, M/F = 27/34) years old. The MRI data were collected by using a 1.5 Tesla Siemens Sonata scanner. Pixel‐by‐pixel BBB transfer rate (Ki) was calculated using Patlak compartmental analysis on dynamic contrast‐enhanced T1 maps. The mean BBB transfer rate was calculated for the brain section above the ventricular zone (sampled by six consecutive slices). MR Spectroscopy was used to investigate N‐Acetylaspartate (NAA), Creatine (Cr), and Choline (Cho) levels. Moreover, Active MMP3 data were used in patients clustering. Thirty‐eight patients enrolled in the study have all data for three entities; NAA, mean Ki, and active MMP3 used for clustering. A multi‐parametric model‐based classification method was used to blindly classify VCID data based on Ki, NAA, and active MMPs.

Result

BBB leakage increased by age, which is more pronounced in patients diagnosed with cognitive impairment when compared with 17 controls, r2 = 0.060, P = 0.021. Statistical classifiers identified three clusters in VCID patients. Identified VCID clusters are similar to the distinction that was made on this VCID cohort based on the clinical scores and psychological entities that we have published earlier.

Conclusion

The results suggest that a statistical combination of imaging and inflammatory attributes renders a tool to blindly separate VCID patients into distinct groups that may have different underlying pathology.
Terminalia catappa fruit extract effect on biochemical parameters of the brain like oxidative stress, amyloid beta and Acetylcholinesterase
Authors: Joshi Ankur , Malviya Neelesh
Published: June 2023

Background

The present research deals with the assessment of Anti‐Alzheimer affect Terminalia catappa fruit extracts (TCFE) in Alzheimer diseased (AD) rat and also propose its probable mechanism of action.

Method

Alzheimer disease was induced by administering streptozotocin i.e. STZ (3 mg/kg) by Intracerebroventricular injection (i.c.v. injection) day 1st and 3rd day, after surgery. Stereotaxic apparatus was used for surgery. Anesthetized rats were used for surgery. Streptozotocin induced Alzheimer diseased rats were treated with hydroalcoholic extract of TCFE (100 and 200 mg/kg, p.o.) for 14 days. Effects of TCFE in Alzheimer diseased rats were assessed for biochemical parameter in the brain tissue oxidative stress parameters (SOD, CAT, GSH and TBARS), amyloid β peptide (Aβ) and acetylcholinesterase (AchE)

Result

TCFE significantly (p<0.01) decreases the Aβ1‐40, Aβ1‐42 peptides. Acetylcholinesterase level in the rats brain tissue reduced compared to Alzheimer diseased rats. TCFE significantly decreases the oxidative stress level in Alzheimer diseased rats.

Conclusion

Effect of TCFE on superoxide dismutase, catalase, reduced glutathione and Thiobarbituaric acid reactive species in the brain tissue of STZ treated AD rats were shown in Table 1.TCFE significantly increased level of antioxidants in brain tissues ((P< 0.01)). β amyloid level of Aβ1‐40 and Aβ1‐42 in the brain tissue decreased significantly (p<0.01) in TCFE treated group compared to AD rats (Negative control group)(Table 2) STZ administration produced significant elevation in brain AchE activity compared to control group of rats. However, TCFE significantly inhibited (P< 0.01) of AchE activity in brain tissue as compared with the negative control group of rats.
Cognitive, clinical and genetic characterization of dementia in Cali, Colombia: A pilot study in a diverse population
Authors: Zapata‐Restrepo Lina Maria , Ibanez Agustin , Allen Isabel Elaine , Kosik Kenneth S. , Possin Kate L
Published: June 2023

Background

The aging population and the prevalence of dementia are rapidly growing in Latin America. People with dementia are underdiagnosed and not well characterized in this region. The scenario is complicated by limited options for culturally proper testing and Latinos' socio‐biological and phenotypic diversity, which affect dementia presentation. In Cali, frontotemporal dementia (FTD) is misdiagnosed as a psychiatric disorder in >70% of cases. Delay in the accurate diagnosis and misdiagnosis of dementia affects genetic counseling, treatment, prognosis, and caregiver burden. Furthermore, most of the discovery efforts in genetics are based on data from populations of European ancestry. This bias in representation can exacerbate existing disease and healthcare disparities. Innovative technology for neuropsychological assessment could help make an early and accurate diagnosis. Genetic analysis is novel in this region, and the proposed work lays the basis for the genomic studies we advocate for.

Method

We will evaluate the accuracy of the TabCAT cognitive tests for the identification of cognitive impairment in participants previously diagnosed with FTD (N = 20), AD (N = 20), and healthy controls (N = 40). We also will assess the NPI. In addition, we will collect family history information for neurodegenerative diseases, genome sequencing of the sample.

Result

We hypothesize that the TabCAT evaluation will show sensitivity and specificity >.80 for detecting cognitive impairment, exceeding the accuracy of standard cognitive screenings, such as the Montreal Cognitive Assessment (MoCA). The assessment will be similarly accurate for detecting cognitive impairment in AD and bvFTD, each separately compared to controls. For participants with bvFTD, the NPI will improve the classification of bvFTD from controls and AD, above and beyond the cognitive tests. We hypothesize that 10‐20% of the participants will have a family history of dementia and be identified with genetic risk for neurodegenerative diseases.

Conclusion

This pilot lays the groundwork to establish a new site for ReDLat, a consortium of multiple partners to expand dementia research in Latin America and the Caribbean. Assessing this underrepresented population, we will contribute to an accurate characterization of dementia in Colombia, which will improve dementia diagnosis and reduce health inequities in this region.
Sleep parameters might affect the attrition of leukocyte telomere length
Authors: Kwon Hyuk Sung , Koh Seong‐Ho , Park Hyun‐Hee , Lee Eun‐Hye , Hwang Min A , Baek Jeong Min , Lee Eun Ji , Ryu Ye Jin
Published: June 2023

Background

The relationship between sleep parameters and longitudinal shortening of telomere length is unclear. This study aimed to investigate the relationship between sleep parameters and the shortening of leukocyte telomere length (LTL) over two years.

Method

Among the participants in the validation cohort of the Korea Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease, participants who measured both baseline and follow‐up (two years later) of LTL were analyzed. They were dichotomized according to the degree of LTL attrition. Clinical characteristics, including sleep duration, sleep latency, Pittsburgh Sleep Quality Index (PSQI), Stanford Sleepiness Scale, and Epworth Sleepiness Scale scores were compared between the two groups.

Result

A total of 238 patients were analyzed in current study. Participants with faster LTL shortening had a shorter duration of sleep (P = 0.013) and longer sleep latency (P = 0.007). Among the components of the PSQI, subjective measures of sleep quality, sleep latency, sleep duration, and sleep efficiency were significantly worse in participants with faster LTL shortening. Multivariate logistic regression analysis showed that sleep latency (odds ratio [OR] = 1.015, confidence interval [CI] = 1.001–1.029, P = 0.029), global PSQI score (OR = 1.130, CI = 1.017–1.256, P = 0.023), shortest sleep duration (OR = 5.057, CI = 1.189–21.502; P = 0.028), and lowest sleep efficiency (OR = 8.598, CI = 1.584–46.672, P = 0.013) were independently associated with faster LTL shortening.

Conclusion

Poor sleep quality, specifically long sleep latency, less than 5 hours of sleep, and low sleep efficiency were associated with faster longitudinal shortening of the LTL.
The Endophenotypic Effect of the SORL1 Variant rs2298813 on Regional Brain Volume in Patients with Alzheimer’s Disease
Authors: Fuh Jong‐Ling , Chen Chun‐Yu , Lin Yung‐Shuan , Lee Wei‐Ju , Yang Albert C.
Published: June 2023

Background

Two common variants of sortilin‐related receptor 1 gene (SORL1), rs2298813 and rs1784933, have been associated with late‐onset Alzheimer’s disease (AD) in the Han Chinese population in Taiwan. However, neuroimaging correlates of these two SORL1 variants remain unknown. We aimed to determine whether the two SORL1 polymorphisms were associated with any volumetric differences in brain regions in AD patients.

Methods

We recruited 200 patients with late‐onset AD from Taipei Veterans General Hospital. All patients received a structural magnetic resonance imaging brain scan and completed a battery of neurocognitive tests at enrollment. We followed up to assess changes in Mini‐Mental State Examination (MMSE) scores in 155 patients (77.5%) at an interval of 2 years. Volumetric measures and cortical thickness of various brain regions were performed using FreeSurfer. Regression analysis controlled for apolipoprotein E status. Multiple comparisons were corrected for using the false discovery rate.

Result

The rs2298813 and rs1783933 genotypes were not associated with cognitive test performance or clinical progression. The homozygous major allele of rs2298813 was associated with larger volumes in the right putamen (p = 0.0442) and right pallidum (p = 0.0346). There was no link of the rs1784933 genotypes with any of the imaging measures. In the rs2298813 homozygous major allele carriers, the right putaminal volume was associated with verbal fluency (p = 0.008) and clinical progression (p = 0.020). In the minor allele carriers, the right putaminal and right pallidal volumes were not significantly related to cognitive test scores or clinical progression.

Conclusion

The major and minor alleles of rs2298813 had differential effects on the right lentiform nucleus volume and distinctively modulated the association between the regional volume and cognitive function.
Contributions of macrostructural and microstructural white matter damage to apathy in people with Alzheimer’s disease
Authors: Manca Riccardo , Venneri Annalena ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: June 2023

Background

Apathy is the most common neuropsychiatric symptom in Alzheimer’s disease (AD) that affects patients’ quality of life and prognosis. Previous functional neuroimaging studies have found multiple cerebral alterations suggesting a conceptualisation of apathy as a symptom resulting from a communication breakdown among functional neural networks involved in motivational‐affective processing. To test this hypothesis, this study investigated the association between white matter (WM) structural connectivity and apathy in AD.

Method

Sixty‐one patients with (AD‐AP) and 61 without apathy (AD‐NA) were identified from the ADNI database and matched for diagnosis, cognitive status, age and education. A group of 61 matched healthy older adults (HOA) was also included. Data on cognitive performance, cerebrospinal fluid (CSF) biomarkers, brain volumes and mean DTI indices of 50 WM tracts were extracted for all participants. Cognitive profiles and volumetric/DTI data were compared across groups using general linear models including sex as a covariate. Post hoc analyses were performed to investigate pair‐wise differences in all outcome measures.

Result

Both patient groups showed widespread cognitive deficits and neural alterations, lower amyloid beta and higher phosphorylated tau CSF levels compared to the HOA group. The direct AD‐AP vs AD‐NA comparison showed no significant differences in CSF biomarkers and MRI outcomes, but the AD‐AP group had more severe neuropsychiatric symptoms, lower scores on the Clock Test – copy and relied more on cues in the Logical Memory test – delayed recall. When the patient groups were compared to the HOA independently, the AD‐AP group had more extensive WM damage: 1) reduced WM and larger WM hyperintensity volume; 2) increased radial diffusivity and reduced fractional anisotropy primarily in the cingulum, superior longitudinal and inferior fronto‐occipital fasciculi and genu of the corpus callosum.

Conclusion

AD‐AP patients had WM damage mildly more severe than that observed in AD‐NA, especially in associative tracts in the frontal lobes and the cingulum. Such disruption in structural connectivity might affect crucial functional inter‐network communication resulting in motivational deficits and worse cognitive decline. These findings warrant further investigations to ascertain the relationship between WM damage and disruption of functional brain network dynamic interactions in AD patients with apathy.
Mitochondrial dynamic modulators improve cognitive function in rats with myocardial infarction
Authors: Jinawong Kewarin , Apaijai Nattayaporn , Piamsiri Chanon , Maneechote Chayadom , Arunsak Busarin , Pintana Hiranya , Chattipakorn Nipon , Chattipakorn Siriporn C
Published: June 2023

Background

Cognitive impairment is the most frequent mental health problem among people with heart failure (HF). Brain pathologies in HF‐induced cognitive impairment are possibly associated with the imbalance of brain mitochondrial dynamics. Therefore, therapeutic interventions targeting mitochondrial dynamics by mitochondrial fission inhibition or mitochondrial fusion enhancement would provide beneficial outcomes to the brain of HF subjects. This study aimed to test whether modulating mitochondrial dynamic improves cognitive function in HF rats via reduced brain mitochondrial dysfunction, and dendritic spine loss.

Method

Rats underwent either sham surgery or permanent left anterior descending coronary artery ligation‐induced myocardial infarction (MI). MI rats developed HF with reduced ejection fraction (%LVEF <50%) at 1‐week post‐operation. Then, MI rats were assigned to receive one of four following interventions: (1) DMSO as a vehicle, (2) enalapril (a positive control, 10 mg/kg/day, orally), (3) mitochondrial division Inhibitor (Mdivi‐1, 1.2 mg/kg/day, intraperitoneal (IP) injection), (4) mitochondrial fusion promotor (M1, 2 mg/kg/day, IP injection). All rats were received the intervention for 4 weeks, then, the cognitive function via NOL was assessed, and were sacrificed. Brain mitochondrial function and dendritic spine density were determined.

Result

HF rats developed cognitive impairment, when compared to the sham group, and it was associated with increased brain mitochondrial oxidative stress, and dendritic spine loss in hippocampus (Figure). Treatment with Mdivi‐1 and M1 improved cognitive function similar to enalapril, as indicated by increasing %preference of NOL. Furthermore, all treatments effectively reduced brain mitochondrial ROS levels and hippocampal dendritic spine loss in HF rats (Figure).

Conclusion

Mitochondrial fusion inhibitor and mitochondrial fusion improved cognitive function in HF rats through a reduction of mitochondrial ROS levels and preserved dendritic spine density.
Association of blood pressure and cognitive function based on MoCA‐INA and MMSE scores among ischemic stroke patients at Atma Jaya Hospital in 2014‐2019
Authors: Roliadi Yefin , Wreksoatmodjo Budi Riyanto
Published: June 2023

Background

Cognitive impairment is a common finding among stroke patients and causing significant decline in survivors’ quality of life. Hypoperfusion is one of the mechanism of transient or permanent ischemia and cause of cognitive deficit. Hypertension causes right shift on cerebrovascular autoregulation, causing brain to be more vulnerable to hypoperfusion in hypotensive state. However, studies assessing the association of blood pressure on acute phase of stroke and cognitive function are still scarce.

Method

A cross‐sectional study using secondary data from Atma Jaya Hospital Stroke Registry in 2014‐2019. Total sampling method resulted in 144 eligible samples. Blood pressure measurement was done at the time of admission, cognitive function was assessed at the time of discharge using MoCA‐INA and MMSE questionnaires. Data analysis was performed using Kruskall‐Wallis comparative test.

Result

No significant association of systolic blood pressure and cognitive function based on MoCA‐INA (p = 0,569) and MMSE (p = 0,147) scores. No significant association of diastolic blood pressure and cognitive function based on MoCA‐INA (p = 0,818) and MMSE (p = 0,184) scores.

Conclusion

No significant association of blood pressure on acute phase of stroke and cognitive function based on MoCA‐INA and MMSE scores among ischemic stroke patients at Atma Jaya Hopital in 2014‐2019.
Development of an instrument to elicit patient preferences for Person‐Centered Dementia Care – insights from a formative pilot study to design a dementia‐friendly Analytic Hierarchy Process‐Survey
Authors: Mohr Wiebke , Raedke Anika , Afi Adel , Michalowsky Bernhard , Hoffmann Wolfgang
Published: June 2023

Background

Person‐Centered Care (PCC) requires knowledge about patient preferences for multiple components (criteria) of care. The Analytic Hierarchy Process (AHP) is one approach to measure the importance of individual criteria from the patient perspective and to identify quantitative preferences for PCC. The AHP is expected to be suitable for People living with Dementia (PlwD) due to its simple pairwise comparisons with individual criteria of a complex decision problem. The aim of this pilot study was to design a dementia‐friendly assisted AHP‐survey with PlwD.

Method

We conducted two expert panels with n = 4 Dementia Care Managers and n = 4 physicians to ensure content validity, as well as individual “thinking aloud”‐interviews with n = 11 PlwD and n = 3 informal caregivers (CGs) to ensure face validity. Interviews followed a semi‐structured interview guide. Participants were asked to assess the survey’s appropriateness, coherence, and to provide information about the motivation for their answers. Main source of data were field notes. Interviews were recorded and partially transcribed. To follow an iterative constant comparative approach, data were analyzed and patient’s feedback incorporated on a continuous basis by two reviewers until the patients had no further comments and no struggles with completion of the survey. Survey data were analyzed with Microsoft®Excel and ExpertChoice Comparion®, to i.a. assess consistency ratios (CRs).

Result

Three main categories with several sub‐categories emerged from data analysis: 1) content including clear introduction, description of (sub)criteria, homogeneity of criteria, appropriateness of (sub)criteria, inclusion of re‐test questions, sociodemographic questions to consider heterogeneity of respondents, 2) format including structure of an AHP‐survey for PlwD, sequence of pairwise‐comparison questions, length of survey, visual formatting (incl. AHP‐scale), explanation of survey procedure, assistance during survey, perspective during completion of survey, and 3) layout including easy wording, avoidance of long sentences, and use of ICONs as visual aids. Individual CRs ranged from 0.08 to 0.859, whilst the consolidated CR was 0.038.

Conclusion

Our study provides insights from a formative pilot study to design a dementia‐friendly AHP‐Survey. Consideration of our findings may contribute to content‐ and face validity, acceptability, feasibility and internal consistency, as well as reproducibility in future dementia‐focused quantitative preference research.
MAC28 Attenuates Neurodegeneration and Restores Cognitive Function via Reducing Peripheral Insulin Resistance, Neuroinflammation, Brain Oxidative Stress, Amyloid‐β Deposition, and Loss of Dendritic Spines in High‐Fat Diet‐induced Obese Rats
Authors: Oo Thura Tun , Sumneang Natticha , Nawara Wichwara , Arunsak Busarin , Chunchai Titikorn , Apaijai Nattayaporn , Pratchayasakul Wasana , Liang Guang , Chattipakorn Nipon , Chattipakorn Siriporn C
Published: June 2023

Background

Long‐term high‐fat diet (HFD) consumption induces not only peripheral insulin resistance with low‐grade systemic inflammation, but also neuroinflammation and subsequent brain pathologies including neurodegeneration, which can lead to cognitive impairment (1). MAC28, a novel mono‐carbonyl analogue of curcumin, was recently identified as a novel MD‐2 inhibitor, and has been shown to attenuate systemic inflammation (2). However, the effects of MAC 28 on the neuroinflammation, neurodegeneration and cognitive function in the HFD‐induced obese rats have never been studied.

Method

Male Wistar rats were fed either a normal diet (ND; n = 8) or HFD (n = 40) for 16 weeks. At week 13, ND‐fed rats were orally administered a vehicle for 4 weeks, while HFD‐fed rats were randomly divided into 5 groups (n = 8/group). Each subgroup was orally administrated either vehicle, 10mg/kg/day of MAC 28, 20mg/kg/day of MAC 28, 40mg/kg/day of MAC 28 or 300 mg/kg/day of metformin for 4 weeks. At the end of experimental protocol, the novel object location (NOL) test was examined in each rat. Brains were rapidly removed to determine brain TLR4‐MD‐2 signaling pathway, inflammatory cytokines, brain oxidative stress, dendritic spine density, amyloid and tau pathology.

Result

HFD‐fed rats developed obesity with peripheral insulin resistance. Neuroinflammation was observed in HFD‐fed rats, as evidenced by increased expressions of hippocampal MD‐2, TLR4 and TNF‐α levels. In addition, HFD‐fed rats not only increased the levels of brain MDA, hippocampal amyloid‐β/APP ratio, but also reduced hippocampal dendritic spine density, resulting in cognitive decline. Although all doses of MAC 28 and metformin attenuated peripheral insulin resistance, brain pathologies and cognitive impairment, MAC 28 (20mg/kg/day and 40mg/kg/day) and metformin had the highest efficacy in attenuating peripheral insulin resistance, brain inflammation, brain oxidative stress, amyloid‐β deposition and improving dendritic spines, resulting in restoring cognitive function (P < 0.05, Figure 1).

Conclusion

These findings suggest that an obvious neuroprotective effect of MD‐2 inhibitor may be the potential strategy for attenuating neurodegenerative disorders in the obese‐insulin resistant condition.
Cross‐species evidence of differential expression of S100A6 and SLC11A1 in the hippocampus of Alzheimer’s disease patients and mouse models
Authors: De Bastiani Marco Antônio , Bellaver Bruna , Carello‐Collar Giovanna , Zimmermann Maria , Kunach Peter , Forner Stefania , Martini Alessandra Cadete , Lima‐Filho Ricardo A S , Lourenco Mychael V. , Rosa‐Neto Pedro , Pascoal Tharick A. , Zimmer Eduardo R.
Published: June 2023

Background

The evaluation of similarities and differences between mouse models and human Alzheimer’s disease (AD) provides invaluable insights on disease pathophysiology. We compared hippocampal transcriptomic profiles of human late‐onset AD (LOAD) and early‐onset AD (EOAD) individuals with three mouse models (hAβ‐KI, APP/PS1 and 5xFAD) in an exploratory analysis. Afterwards, we validated the intersection of genes consistently altered in all groups using hippocampal tissue from APP/PS1 mice, and EOAD and LOAD patients.

Methods

Five publicly available human AD/cognitively unimpaired (CU) transcriptomic profiles were collected from GEO (https://www.ncbi.nlm.nih.gov/geo/), merged and submitted to differential expression analysis (DEA) using R. APP/PS1 mouse model RNAseq data from two datasets (GSE149661 and GSE145907) were also collected. Finally, RNAseq data of 5xFAD and hAβ‐KI mouse models were obtained from AMP‐AD Knowledge Portal (https://www.synapse.org/) using synapser and synapserutils packages. All animal models were also submitted to DEA. Validation of selected genes was performed by qRT‐PCR. Target mRNA levels were normalized using β‐actin as a housekeeper gene. The results were expressed relative to wild‐type (WT) animals or CU controls using the 2−ΔΔCt method.

Results

DEA identified 1164, 3261 and 1782 differentially expressed genes (DEGs) for the comparisons between hAβ‐KI, 5xFAD and APP/PS1 mutants versus WT controls, respectively. hAβ‐KI, APP/PS1, and 5xFAD mice exhibited more DEGs in common with LOAD than with EOAD patients. Interestingly, APP/PS1 and 5xFAD mice also presented more DEGs in common with LOAD than with EOAD patients. However, 5xFAD showed significantly higher DEGs intersection with EOAD than with hAβ‐KI and APP/PS1. Additionally, we identified S100A6, C1QB, SST, CD14, CD33, SLC11A1 and KCNK1 genes altered in both EOAD and LOAD as well as the three mouse models evaluated. qRT‐PCR analysis of these genes in EOAD, LOAD and APP/PS1 model revealed S100A6 and SLC11A1 consistently altered in human pathology and mouse model.

Conclusion

Animal models seek to better simulate AD pathology, making the evaluation of their molecular overlap with human disease greatly important. S100A6, a calcium‐binding protein modulating several biological activities, and SLC11A1, a metal transporter associated with inflammatory processes, were consistently altered in our transcriptomics exploratory analyses and experimental validation, making them promising targets for further investigation.
Beta‐amyloid plaque accumulation comparison in down syndrome and non‐down syndrome cohorts
Authors: McVea Andrew K , DiFilippo Alexandra H , McLachlan Max , Murali Dhanabalan , Xin Yangchun , Johnson Sterling C. , Betthauser Tobey J , Converse Alexander K , Stone Charles K , Tudorascu Dana L. , Laymon Charles M , Klunk William E , Cohen Ann D. , Handen Benjamin L. , Christian Bradley T.
Published: June 2023

Background

Down syndrome (DS) is characterized by earlier beta‐amyloid (Aβ) plaque accumulation and an increased prevalence of Alzheimer’s disease (AD) due to trisomy 21 and triplication of the amyloid precursor protein (APP) gene. While the age of AD onset is earlier in DS, AD pathology progression in non‐DS populations follows similar trends to the DS cohort. This study compares the accumulation rate of Aβ between DS and non‐DS populations measured with [C‐11]PiB at same site using the same scanning procedures.

Methods

Individuals with at least one Aβ+ [C‐11]PiB scan (Global SUVR>1.40), and at least one Aβ‐ scan from our site at the University of Wisconsin were selected for this study. 12 out of 58 DS participants in the Neurodegeneration in Aging DS (NiAD) study and 14 out of 246 non‐DS subjects from the PREDICT study fit this criteria. All images were collected on an ECAT HR+ scanner from 50‐70 minutes injection (i.d. = 15mCi). Reconstructed PET images were aligned and summed before being normalized into MNI‐152 space and converted into an SUVR image using cerebellar grey matter as a reference region. We determined rate of Aβ accumulation as the change in global SUVR per year, defined as the average of grey matter regions in the anterior cingulate, frontal cortex, parietal cortex, precuneus, temporal cortex, and striatum, and focused on the period when participants became Aβ+.

Results

Plotting global [C‐11]PiB SUVR and age (Fig 1) there is no age overlap between the two groups. The average rate of amyloid accumulation per year when becoming Aβ+ in the DS group was 0.058±0.026 compared to 0.059±0.028 for the non‐DS sample. The two groups have notably similar mean values, although when organized into box plots (Fig 2), the interquartile range of the DS subjects is 0.044 compared to a tighter 0.019 for non‐DS.

Conclusions

The pattern of Aβ accumulation in DS and non‐DS groups becoming Aβ+ have similar distributions. While we might expect a higher rate in the DS population due to the additional APP gene, our findings do not support this hypothesis. However, considerable variability in the rate of accumulation is observed requiring further investigation towards understanding this process.
Anti‐amyloid beta and anti‐acetylcholinesterase activity of Anaphalis neelgerriana leaves extract in streptozotocin induced Alzheimer rats
Authors: Malviya Dr Sapna , Malviya Dr Neelesh , Joshi Ankur
Published: June 2023

Background

Alzheimer is associated with neuronal degeneration, characterized by memory loss and altered behaviour. Many pathological conditions like increased amyloid β (Aβ) plaque formation, and acetylcholinesterase neuroinflammation results in AD. Due to excess of reactive oxygen species (ROS) oxidative stress develops which overexpress Aß in the neuron which modifies the cellular function and thereby activates the neurodegeneration.

Method

AD was induced by streptozotocin i.e. STZ (3 mg/kg, ICV) day 1st and 3rd day after surgery. Surgery was done on anesthetized rats by the help of stereotaxic apparatus. STZ induced AD rats were treated with ethanolic extracts of Anaphalis neelgerriana leaves (ANLE) (100 and 200 mg/kg, p.o.) for 14 days. Effects of ANLE in Alzheimer diseased rats were assessed for amyloid β peptide (Aβ) and acetylcholinesterase (AchE)

Result

ANLE significantly (p<0.01) decreases the Aβ1‐40, Aβ1‐42 peptides. Acetylcholinesterase level in the rat’s brain tissue reduced compared to Alzheimer diseased rats.

Conclusion

The present study reveals that the ANLE produces Anti‐Alzheimer’s effect in Alzheimer diseased rats by decreasing Aβ protein level and Acetylcholinesterase level in the brain tissue.
Patterns matter: differential effects of stress‐inducing and novelty‐associated locus coeruleus firing on pretangle tau pathophysiology in a rat model
Authors: Omoluabi Tamunotonye , Torraville Sarah , Maziar Aida , Ghosh Abhinaba , Power Kyron , Rinhardt Camila , Harley Carolyn , Yuan Qi
Published: June 2023

Background

The brainstem locus coeruleus (LC), the main source of brain norepinephrine (NE), is critically involved in several functions including wakefulness, vigilance, attention, learning and memory. LC functioning is firing pattern‐dependent. Phasic pattern promotes novelty and learning, while high tonic activity associates with stress and anxiety. LC has been identified as a key structure in Alzheimer’s disease (AD) development. Braak and colleagues propose that soluble abnormally phosphorylated tau (pretangle tau) originates in the LC early in life. The spreading of pretangle tau to other neuromodulatory areas and transentorhinal cortex constitutes Braak’s pretangle AD stages. Pretangle stages appear to be universal in human, however, only a portion of us develop AD. The selective vulnerability of individuals for AD is not understood. We hypothesized that differential LC activity patterns, influence the pretangle tau pathophysiology and the development of AD.

Method

In this study, an AAV carrying pseudo‐phosphorylated human tau (AAV9‐DIO‐EGFP‐htauE14) was infused into the LC of 2‐3 month‐old TH‐CRE rats, mimicking the onset of tauopathy during puberty in humans. Another AAV containing ChR2 opsin (AAVdj‐DIO‐ChR2‐mCherry) was co‐infused with htauE14. Chronic light stimulation of the LC of either a 10 Hz phasic pattern or a 25 Hz tonic pattern was carried out for 6 weeks. The performance of ChR2 rats in a battery of behavioral assays was compared with control groups without ChR2 (AAVdj‐DIO‐mCherry), 10 months following the AAV infusion. This was followed by immunohistochemistry and Western blotting comparing different biomarkers.

Result

Phasic LC activation improved spatial and olfactory discrimination of the htauE14 rats, while chronic tonic activation increased stress level of the rats and led to anhedonia. Phasic pattern rescued axonal degeneration observed in the control htauE14 rats, showing higher density of LC fibers in the piriform cortex and hippocampal dentate gyrus. Tonic LC activation did not rescue LC fiber degeneration, instead, worsened LC neuronal health indexed by elevated level of active caspase 3. The learning performance was positively correlated with the LC fiber density.

Conclusion

These results argue that variations in environmental experiences associated with differing LC activity patterns may account for individual susceptibility to development of AD in humans.
A case of early‐onset familial Alzheimer’s disease caused by PSEN1 gene Y115C mutation in a Chinese pedigree
Authors: Zhang Yuan , Jia Ziyan , Suen Mengfan , Jiang Jiwei , Xu Jun
Published: June 2023

Background

Alzheimer’s disease is the most common cause of dementia, with approximately 0.9% associated with known genetic mutations. Presenilin 1(PSEN1) gene is one of the most common genes associated with early‐onset familial Alzheimer’s disease (EOFAD). We reported a case of EOFAD with Y115C mutation of PSEN1 gene which was the first report in China.

Method

An early‐onset Alzheimer’s patient from Beijing Tiantan Hospital, Capital Medical University and her family were enrolled as the research object. The clinical and imaging data of the proband were collected. The genomic DNA from peripheral venous blood of the proband was screened.

Result

There were 6 members with memory and working competence loss in this pedigree. The proband, whose age of onset was 42 years old, was manifested as memory loss for more than 1year. She became apathetic, lazy in housework but without abnormal mood and behavior. She was healthy in the past, denied smoking and drinking history. Her grandmother, mother, aunt, uncle and brother all showed memory loss. Her brother is now unable to complete the driver’s work. The physical examination showed poor memory, calculation, orientation, executive functions, slow reaction and poor comprehension. The MMSE score was 11, MoCA‐Beijing score was 5, ADL‐20 score was 28, HAMD score was 2, HAMA score was 1 and PSQI score was 5. Head MRI of the proband showed whole cerebral cortical atrophy and bilateral hippocampal atrophy, obviously on the left side. The arterial spin labeling finding showed significantly reduced blood perfusion in the left cortex and hippocampus. A c.344A > G (p. Tyr115Cys) pathogenic mutation in the exon 5 of PSEN1 gene was found, proving the diagnosis.

Conclusion

We reported this EOFAD case caused by Y115C mutation of PSEN1 gene in a Chinese family to enrich the genetic and clinical phenotypic characteristics in China. Gene detection plays an important role in the diagnosis of the early‐onset Alzheimer’s disease.
Determining feasibility for use of geriatric cognitive screening tools by medical case managers (MCM) serving older (50+) people living with HIV (PLWH)
Authors: Maly Monica , Burk‐Leaver Erin
Published: June 2023

Background

The advent of antiretroviral therapy (ART) has led to improved life expectancy of people living with HIV (PLWH) that is nearing that of populations living without HIV. In the United States, 51% of PLWH are 50 years or older and have unique pathophysiology contributing to accelerated and accentuated aging when compared to older adults living without HIV. Cognitive impairment (CI) is a significant age‐related risk and is exacerbated by HIV. Currently, geriatric cognitive screening tools are not calibrated for older PLWH, and have not been effectively translated for use within AIDS Service Organization (ASOs) where older PLWH often seek HIV‐related care and supportive services. In partnership with the Colorado Health Network Inc., this study examined feasibility for use of cognitive screening tools by medical case managers (MCM) working with clients aging with HIV at Colorado‐based ASOs.

Method

MCMs were recruited from 11 Colorado‐based ASOs. MCMs completed an anonymous, self‐administered questionnaire measuring baseline knowledge related to risks of CI in older PLWH, and evaluated their familiarity with, screening of, and response to signs of CI within this client population. The questionnaire also evaluated perceived limitations and barriers to use of cognitive screening tools within MCM workflow.

Result

Data was collected from 28 MCMs who confirmed barriers and limitation to use of cognitive screening tools. While MCMs reported, on average, 50% of their clients were 50+, 71.4% of respondents reported not receiving training on complications related to aging with HIV, signs and symptoms, or on warning signs and risk factors (WS/RF) of CI. All (100%) respondents reported not screening for CI. MCMs indicated important elements of cognitive screening questions, including ease of administration, clear instructions, and information on referral. Table 1 provides a list of warning signs and Table 2 provides a list of screening questions.

Conclusion

MCMs working with older PLWH identified a need and desire for use and implementation of cognitive screening tools within their workflow. Training MCM on WS/RF, signs, and symptoms of CI, and implementing cognitive screening tools and referral systems will lead to improved continuity of care provided by medical case managers, and ASOs, serving older PLWH.
Effects of aerobic exercise on plasma AT(N) biomarkers
Authors: Yu Fang , Han SeungYong , Salisbury Dereck , Pruzin Jeremy J. , Geda Yonas E. , Caselli Richard J. , Li Danni
Published: June 2023

Background

Physical activity is associated with reduced risk for Alzheimer’s disease (AD). Aerobic exercise produced modest‐to‐moderate cognitive gains in older adults with mild cognitive impairment or AD dementia. In animal models, aerobic exercise modifies AD’s AT(N) biomarkers of Amyloid‐beta (Aβ), hyperphosphorylated Tau, and Neurodegeneration. However, most observational studies didn’t find significant associations between physical activity and AT(N) biomarkers. Few exercise trials included biomarkers, partially attributable to the prohibitive cost and invasiveness of cerebrospinal fluid or PET biomarkers and reported mixed effects on central AT(N) biomarkers. Plasma Aβ42/40 ratio, phosphorylated tau 181 (p‐tau181), and total tau (t‐tau) demonstrate robust correlations with central amyloid and tau levels and offer an opportunity for inclusion in exercise trials.

Method

This pilot study examined the preliminary effects of 6‐month aerobic exercise on plasma Aβ42/40 ratio, p‐tau181, and t‐tau in older adults with mild‐to‐moderate AD dementia. Twenty‐six participants were eligible, and all consented to enroll (8 in stretching, 18 in cycling). Plasma Aβ42/40 ratio, p‐tau181, and t‐tau were measured using Simoa™ assays at baseline, 3, and 6 months. Data were analyzed using Cohen’s d, multilevel model, and intention‐to‐treat.

Result

The sample averaged 77.58±6.99 years old, 15.44±3.00 years of education, 65% male, and 96.2% carrying an APOE e4 allele. The 6‐month within‐group trajectories of changes in outcomes trended differently but were not statistically significant. Aβ42/40 ratio (mean ± standard deviation) increased by 0.001±0.012, p‐tau181 increased by 0.609±1.417 pg/ml, and t‐tau decreased by 0.020±0.279 ng/ml in the stretching group, while Aβ42/40 ratio decreased by 0.001±0.010, p‐tau181 increased by 0.101±1.579 pg/ml, and t‐tau decreased by 0.075±0.215 pg/ml in the cycling group. Between‐group differences were not significant. Effect sizes for 6‐month within‐group changes were small except for p‐tau181 in stretching (d = 0.43 [‐.65, 1.45]) and t‐tau in cycling (‐0.35 [‐0.87, 0.17]). Most 6‐month between‐group effect sizes were also small except for p‐tau181 (d = .40 [‐.70, 1.51]) and t‐tau (d = .53 [‐.40, 1.46]), a trend favoring cycling.

Conclusion

Blood biomarkers are highly feasible and tolerable. Exercise modalities may affect AD plasma biomarkers differently. Aerobic exercise may reduce p‐tau181 levels and stretching exercise may improve Aβ42/40 ratio, which need to be validated in future trials.
Increased spatial extent of cerebral tau PET elevations in former NFL and college football players from the DIAGNOSE CTE Research Project
Authors: Chen Kewei , Reiman Eric M. , Luo Ji , Protas Hillary D. , Cummings Jeffrey , Shenton Martha E , Stern Robert A , Su Yi
Published: June 2023

Background

We previously found greater spatial extent of flortaucipir (tau) PET elevations in Arizona‐Boston (DETECT) Study of 26 former National Football League (NFL) players than in 31 normal controls—using a voxel‐based Majority Count Statistics (MCS) algorithm which enabled us to detect tau PET abnormalities in the player group free from the inflated Type 1 error associated with voxel‐wise multiple comparisons (Stern et al, NEJM 2019). We now confirm this finding in a larger group of former NFL players, former college football players and asymptomatic controls without exposure to repetitive head impacts from the DIAGNOSE CTE Research Project.

Method

Flortaucipir PET images were acquired in 106 former NFL players, 51 former college players, and 53 unexposed controls, 57.71+8.37 years of age. An automated algorithm (SPM12) and co‐registered MRIs were used to spatially normalize PET images into Montreal Neurological Institute template, and compute statistical brain maps of group differences in regional cerebral‐to‐cerebellar crus1 standard uptake value ratio (SUVR), controlling for the participants’ age and race with P≤0.005, uncorrected for multiple comparisons. Our MCS was then applied with 1,000 iterations to test the hypothesis that there would be a greater number of cerebral voxels with SUVR elevations in each and combined player group versus control group, as well as between the NFL versus college player groups.

Result

As predicted, the NFL, college player and aggregate player groups each had significantly more cerebral voxels with flortaucipir SUVR elevations than in the control group (postulated vs opposite directions: 53,879 vs 79, 79,552 vs 89 and 100,837 vs 86 voxels), respectively, MCS P<0.001, but not between former NFL and former college players (482 versus 306, p = 0.305).

Conclusion

Using a voxel based MCS analysis, former NFL and college football players have a greater spatial extent of elevations in tau PET measurements than asymptomatic controls. Additional work is needed to clarify the biological nature of these small but spatially extensive elevations, the extent to which they are related to symptom severity, cognitive performance, repetitive head impact exposure, and other risk or resilience factors, and the extent to which they are associated with subsequent clinical decline.