bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of plasma extracellular vesicle enrichment for in‐depth lipidomic profiling in Alzheimer’s disease
Authors: Su Huaqi , Fowler Christopher J , Bush Ashley I , Masters Colin L , Barnham Kevin J , Reid Gavin E , Vella Laura J
Published: December 2023

Background

Lipid dyshomeostasis is associated with various disorders including Alzheimer’s disease (AD). The work from our laboratory (Su et al, JEV 2021), and others, suggests that extracellular vesicles (EVs) contain lipid biomarkers that could aid in the diagnosis of AD and diseases associated with impaired lipid metabolism.

Knowing the lipid content of EVs is a key first step to discovering EV‐based lipid biomarkers in blood. Some studies have reported the lipid content of ‘’EVs’’ in blood. However, used EV isolation techniques that are known to co‐isolate free lipid and lipoproteins.

Here we: 1) demonstrate the importance of size exclusion resin size to isolating highly enriched EVs for lipidomic analysis, 2) have developed a reference EV plasma lipidome for the research community and 3) determining if plasma EVs report on lipid dyshomeostasis in Alzheimer’s disease.

Method

Human plasma EVs were isolated using an assortment of commercially available kits or by density fractionation and size exclusion chromatography and characterised by western blot, transmission electron microscopy, and quantitative mass spectrometry based proteomic and lipidome analysis.

Result

Of the high‐throughput EV isolation kits tested, the majority were unable to separate lipoproteins from EVs for the purposes of EV lipidomics. We then relied on comparing labor intensive methods (density gradient and size exclusion) to identify a combination of techniques that isolate the analytes of interest, EV proteins and lipids. Quantitative proteome and lipidome analysis strategies are being applied to highly enriched EVs with the goal of providing the reference lipidome of EVs in plasma and in Alzheimer’s disease.

Conclusion

To enhance the confidence of EV lipid identification and reveal the lipidome of EVs in plasma, our study compared and identified techniques to enrich EVs and deplete non‐EV associated lipid and protein from human plasma. These findings serve as a reference resource and the foundation for research investigating plasma EV lipids as Alzheimer’s disease biomarkers.
Correlates of caregiver burden in African immigrants with personal experiences of dementia
Authors: Nkimbeng Manka
Published: December 2023

Background

Dementia care and caregiving needs of African immigrants are not fully understood. This paper describes the correlates of caregiver burden in a sample of first and second generation African immigrants with personal experiences of dementia. Data comes from the Immigrant Memory Collaborative; a community‐based participatory research project with African immigrants in a Midwestern state in the United States.

Method

We used linear regression modeling to determine whether discrimination and where the person with dementia resides were associated with caregiver burden.

Result

Of the 155 care givers in the sample, 32% (49) were foreign‐born. The mean caregiver burden score in this sample was 6.7(0‐12, range). Compared to those born in the United States, caregivers who were born in Africa were older (31 vs 41) and majority female (20% vs 51%). Older age was associated with a decrease in caregiver burden score (b: ‐0.071 95% CI [‐0.11, ‐0.03]) and higher every day discrimination was associated with higher caregiver burden score (b: 0.22, 95% CI [0.14, 0.29]). The burden score for caregivers of a person living with dementia residing in Africa was lower but this was not statistically significant (b: ‐1.36 95% CI [‐2.72, 0.009]).

Conclusion

In this sample, high discrimination experiences and younger age were associated with greater caregiver burden. Many African immigrants have never heard of dementia prior to migrating to the United States (U.S.) but currently provide care both to persons living with dementia in the U.S. and back home in their countries of origin. There is need for outreach and education towards improved dementia care and caregiving for African immigrants.
Associations of AHA’s Life’s Essential 8 health behaviors with cognitive function among U.S. Black and White midlife adults
Authors: Shen Yuqi , Master Lindsay , Beydoun May A , Zonderman Alan B , Buxton Orfeu M. , Gamaldo Alyssa A. , Evans Michele K
Published: December 2023

Background

Life’s Simple 7 (LS7), originally proposed as the seven most important predictors of heart health, is associated with negative cognitive outcomes (Thacker et al., 2014). The recently updated Life’s Essential 8 (LE8) includes sleep. Limited research has investigated the association between LE8 and cognition, particularly within Black and White adults. We hypothesize that higher composite LE8 scores will be associated with better cognitive performance, particularly within Black adults.

Method

Cross‐sectional analyses were conducted including adults from the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study conducted in Baltimore, MD. Study participants (36‐76 years old; 41% male; 61% Black) completed all LE8 (Lloyd‐Jones et al., 2022) and global cognition measurements in wave 4 data collection (2013‐2017). Cognitive performance on a computerized cognitive battery (Joggle Research) yielded a total global cognition score and individual domains (e.g., working memory, attention). Linear regression analyses were stratified by race and poverty status (below 125% Federal poverty guidelines), education attainment (high school), and reading literacy (median split) respectively. Covariates included age, sex, sleep apnea, and depression. All reported models were fully adjusted.

Result

Among Black adults, higher LE8 scores (better CVH) were associated with better working memory only among individuals living above the poverty level (all b unstandardized; b = 0.008, p = .016), or only with high school education (b = 0.009, p = .027). Among White adults, higher LE8 score was associated with better working memory, particularly among individuals living above poverty level (b = 0.014, p = .002), having an education above high school (b = 0.019, p = .002), or high literacy (b = 0.021, p<.001) . Additionally, higher LE8 scores were associated with better attention, and higher global cognition score among individuals living above poverty (b = 0.015, p = .042; b = 0.039, p = .025) or with a high literacy on (b = 0.023, p = .014; b = 0.049, p = .027).

Conclusion

Higher score of LE8 was associated with better working memory among both U.S. Black and White adults. However, higher LE8 scores were associated with performance across a larger variety of cognitive domains within White adults from diverse socioeconomic indicators. These findings illustrate unique LE8 and cognition associations when disentangling socioeconomic heterogeneity within racial groups.
The role of sleep disturbances in the association between housing conditions and subjective cognitive impairment
Authors: Johnson Dayna A
Published: December 2023

Background

Adverse housing conditions such as crowding, air pollution, or insufficient heat are associated with cognitive impairment. However, the mechanism linking adverse housing conditions and cognitive impairment is not fully understood. Adverse housing can affect sleep – an essential physiologic activity for cognitive function, yet this pathway is understudied. We tested associations between housing condition, sleep disturbances, and cognitive impairment.

Methods

This study utilized data from the Health and Retirement Study, a longitudinal panel study among adults (2020). Participants (n = 2,639) completed questionnaires on housing, sleep disturbances, and cognition. Housing was measured by self‐reported ratings of their homes physical condition (1‐excellent to 5‐poor). Sleep disturbances were self‐reported as trouble falling asleep, trouble waking up during the night, and trouble with waking up too early and not being able fall asleep again, and each item was scored from 0 (rarely/never) to 2 (most of the time). Cognitive impairment was defined as a participant rating of fair or poor regarding their memory at the present time. Logistic regression models were fit to test associations between housing and sleep and cognitive impairment after adjustment for age, sex, and race.

Results

The sample had a mean age of 66.2+10.6 years, and 60% were female, 21.4% Black, 64.6% White, and 11.4% other racial group. The prevalence of cognitive impairment and sleep disturbance was 28.7% and 42.8%, respectively. Individuals living in adverse housing conditions had 32% and 48% higher odds of sleep disturbances [Adjusted Odds Ratio (aOR) = 1.32, 95% confidence interval (1.21, 1.43)] and cognitive impairment [aOR = 1.48 (1.36, 1.62)], respectively. Sleep disturbances were associated with higher odds of cognitive impairment, OR = 2.04 (1.71, 2.44). After adjustment for sleep disturbances, the association between housing condition and cognitive impairment was slightly attenuated, aOR = 1.40 (1.28, 1.54).

Conclusions

Living in adverse housing conditions were associated with greater sleep disturbances and subjective cognitive impairment. Results suggest that sleep may explain a small portion of the association between housing conditions and cognitive impairment, but a formal test of mediation is needed. Housing and sleep may be points of intervention for reducing cognitive impairment.
MIITRA atlas: high resolution FOD template of the older adult brain
Authors: Wu Yingjuan , Ridwan Abdur Raquib , Niaz Mohammad Rakeen , Bennett David A. A , Arfanakis Konstantinos
Published: December 2023

Background

High quality fiber orientation distribution (FOD) template of the older adult brain facilitates white matter studies in older adults. This work compared several methods to construct an FOD template of the older adult brain in the space of the MIITRA atlas(Wu et al.,2022).

Method

T1w and DWI data from 400 non‐demented older adults (50% male;64.9‐98.9 yrs;54% white,43% black)(Bennett et al.,2018;Barnes et al.,2012) participating in the construction of the MIITRA atlas were used.

Method 1: FOD‐based single modality registration(cost function:mean squared difference)(MRtrix3).

Method 2: The nonlinear transformations generated from MIITRA T1w and DTI template construction were applied to the FODs(Wu et al.,2021).

Method 3: Multichannel registration based on T1w, T2w, FA and MD information with equal weights(cost function:cross‐correlation)(ANTs).

Method 4: Multichannel registration based on T1w and FOD information with equal weights(cost function:cross‐correlation)(MRtrix3).

Method 5: Multichannel registration based on T1w, FA and FOD information with weights of 4,3,3 respectively(cost function:cross‐correlation)(MRtrix3).

Method 6: Same as Method 5 followed by FOD registration performed on the FOD data that were already transformed by Method 5(cost function:cross‐correlation)(MRtrix3).

The FOD templates generated with different methods were compared by visual inspection, image sharpness of the total apparent fiber density (AFD) map, precision of spatial normalization of FOD data used in template construction, and spatial matching with the existing MIITRA T1w and DTI templates.

Result

The FOD templates generated with Methods 2, 3 and 6 exhibited higher image sharpness(Fig.1A). Fiber crossings were more clearly defined in the FOD templates generated with Methods 1,4,5,6(Fig.1B). Method 6 allowed higher ACC and lower MSD of spatially normalized FOD data, indicating higher precision in spatial normalization(Fig.2A,B). Method 2 provided the highest spatial matching with the existing MIITRA templates, followed closely by Methods 4,5,6(Fig.2C,D). Overall, the FOD template generated with Method 6 achieved high image quality, was constructed based on precisely matched FOD data, and exhibited high spatial matching to the existing MIITRA templates(Fig.3).

Conclusion

An FOD template of the older adult brain was constructed for the MIITRA atlas. The new template exhibits high image quality, is constructed based on precisely matched FOD data, and exhibits high spatial matching to other existing MIITRA templates.
Understanding Physiotherapy Students’ Perceived Preparedness To Work With People Living With Dementia: A Qualitative Study
Authors: Quick Stephen M , Lawler Katherine , Shannon Michelle M , Soh Sze_Ee , McGinley Jennifer L , Peiris Casey L , Snowdon David A , Callisaya Michele L
Published: December 2023

Background

Dementia is a major cause of disability, and physiotherapists play a vital role in the care of people with this condition. Entry‐to‐professional practice physiotherapy students have been found to be ‘somewhat confident’ in working with this population, however comprehensive data about their practice experiences, their preparedness to care for people living with dementia and any educational gaps have not been previously reported. The aims of this study were to 1) determine physiotherapy students’ experiences in caring for people who have dementia, 2) determine how prepared students were to work with people who have dementia upon graduation and 3) determine if there any areas where students require further education regarding dementia, and how this would be provided.

Methods

This was a qualitative study using an interpretive description approach. Participants were 17 physiotherapy students from entry‐to‐professional practice education programs in three universities in Victoria, Australia, in their final year of study, having completed at least 15 weeks of clinical placements. Students participated in semi‐structured interviews. Thematic analysis was undertaken, with themes/subthemes derived and a qualitative thematic framework generated.

Results

The overarching theme was that students’ experience of providing care for people with dementia was overwhelming. The three sub‐themes were: 1) students experience significant challenges when working with people with dementia, 2) students experience a range of emotions when working with people with dementia, and 3) the quality of dementia learning experiences during entry‐to‐professional practice training was perceived by students as mostly inadequate. Students described the importance of supervisors during clinical placements, and suggested incorporating ‘real‐life’ scenario classroom training to assist them to learn to manage the challenging symptoms of dementia.

Discussion/Conclusion

Physiotherapy students believe that entry‐to‐practice dementia education is currently insufficient. These findings have important implications for the future planning and delivery of physiotherapy dementia education.
The association of Life’s Essential 8 and brain structure integrity in midlife
Authors: Dintica Christina S. , Jiang Xiaqing , Habes Mohamad , Erus Guray , Yaffe Kristine
Published: December 2023

Background

Ideal cardiovascular health has previously been associated with a lower risk of dementia and less cognitive decline in midlife. We investigated if the American Heart Association’s (AHA) “life’s essential 8” (LE8) factors for ideal cardiovascular health are related to brain structure integrity in midlife.

Methods

We included 607 participants from the Coronary Artery Risk Development in Young Adults study with information on LE8 at mean age of 45 (SD = 3.4) and MRI examination ten years later. LE8 factors were dichotomized according to AHA guidelines as yes/no on high blood pressure (≥120 systolic or ≥80 diastolic blood pressure); high BMI (≥25); low physical activity (≤300 exercise units); currently smoking; high cholesterol (≥200); high fasting glucose (≥100); poor diet (<median score on the MedDiet); and poor sleep (≤6 or ≥9 hours per night, and combined into a score ranging from 0 to 8, with higher score indicating worse cardiovascular health. A brain age was derived using previously validated high dimensional neuroimaging pattern analysis, quantifying individual differences in age‐related atrophy. White matter hyperintesities (WMHs) and white matter (WM) microstructural integrity (mean diffusivity [MD] and fractional anisotropy [FA]) were assessed using MRI. Linear regression and structural equation modeling were used to examine the relationships between LE8, brain age, WMHs, FA, and MD, adjusted for age, sex, education, and race.

Results

The range of LE8 was 0‐7 among the participants (median = 2, interquartile range = 2). Having 0‐3 LE8 risk factors was associated with a younger brain age, while having 4+ risk factors was associated with a higher brain age relative to chronological age (Figure 1). Moreover, a higher LE8 score was associated with greater MD (β: 0.16, 95% CI: 0.09 to 0.23), and lower FA (β: ‐0.15, 95% CI: ‐0.22 to ‐0.08), but not with WMHs. The indirect effect of the LE8 score on brain age through MD and FA was (β: 0.50, 95% CI: 0.28 to 0.75), hence the proportion mediated was 75% (Figure 2).

Conclusion

A higher cardiovascular risk as defined by the AHA is associated with a higher brain age in midlife, a majority of which can be explained by markers of early WM deterioration.
End of life in early onset familial Alzheimer’s disease: Bioethical issues and the cognition specialist’s role
Authors: Giordano Ximena , Fernandez Maria Cecilia
Published: December 2023

Alzheimer’s disease (AD) is the most common cause of dementia in the world. Genetic factors are key contributors to all forms of AD, but in some families, it is possible to identify a specific genetic cause for early‐onset familial Alzheimer’s disease (EOFAD). When a genetic cause is identified, it is important that relatives are aware of the implications and alternatives in order to assess how they would like to proceed, based on their values, beliefs, and preferences. This may present ethical challenges for the neurologist due to questions about their decision‐making capacity.

The purpose of this presentation is to report the case of a 66‐year‐old patient diagnosed with EOFAD 11 years ago, in its final stage of the disease, whose husband inquires about the possibility of adopting end‐of‐life measures, and to analyze from it the bioethical aspects and the cognition specialist’s role in this issues.

Given the progressive nature of dementia, it is critical to identify the patient’s social support network early on. The late stage of dementia is associated with a significant decline in a person’s autonomy and will require full‐time assistance. The carers experience sadness and guilt as well, as the realisation that end‐of‐life is approaching and decisions regarding palliative care become imminent, so it is necessary to analyze how far to adopt life support measures, since these will prolong life. Regarding our patient, with the support of a bioethics committee, it was decided to take end‐of‐life measures by stopping enteral nutrition.

Advising on end‐of‐life approach options and especially encouraging the patient to complete advance directives in early stages of the disease, with the fundamental support of a bioethics committee, is the future challenge of the specialist in cognition.

References ‐Gauthier S, Webster C. 2022. World Alzheimer Report 2022: Life after diagnosis: Navigating treatment, care and support. London, England: Alzheimer’s Disease International.

‐M. Congedoa, R. I. Causarano. Ethical issues in end of life treatments for patients with dementia. European Journal of Neurology. 2010; 17: 774‐779.
Deletion of microRNA‐21 exacerbates multiple phenotypes associated with Alzheimer’s disease through the RECK and ADAM10 pathway in a mouse model of Aβ amyloidosis
Authors: Kim Byungwook , Tate Mason , Wijeratne H.R. Sagara , Karahan Hande , Philtjens Stéphanie , Sharify Ahmad Daniel , Al‐Amin Mamun Md , Kim Jungsu
Published: December 2023

Background

microRNAs have emerged as a new class of therapeutic targets that regulate the expression of target genes by binding their 3’‐untranslated regions. Growing evidence suggests that dysregulation of microRNAs may contribute to the onset and/or progression of various diseases. However, the functional and therapeutic implications of microRNA dysregulation in Alzheimer’s disease (AD) remain largely unclear. To gain insight into the roles of microRNAs in AD pathogenesis, we recently performed unbiased microRNA profiling with entorhinal cortices of AD and age‐matched non‐demented subjects. We found that miRNA‐21 (miR‐21) expression was markedly increased in AD patients. In addition, miR‐21 levels were increased in oligomeric amyloid‐beta (Aβ)‐treated neurons, suggesting that miR‐21 induction is directly associated with Aβ pathology. Therefore, we investigated the pathogenic/therapeutic potential of miR‐21 in AD.

Method

To investigate the role of miR‐21 in amyloid pathology in vivo, we crossed APP/PS1 mice with mir‐21−/− mice to generate APP/PS1;mir‐21+/+, APP/PS1;mir‐21+/− and, APP/PS1;mir‐21−/− mice. We evaluated the changes in the pathological features of AD, such as Aβ levels, amyloid plaques, and gliosis in these mice. Moreover, to investigate the effects of miR‐21 deletion on spatial learning and memory functions, we performed the Morris Water Maze (MWM) and Contextual fear conditioning (CFC) tests.

Result

Deletion of miR‐21 increased the levels of insoluble and soluble Aβ40 and Aβ42 levels, as well as increased Aβ‐positive and X‐34‐positive plaque deposition in the cortex and hippocampus. CD45‐positive, IBA1‐positive microgliosis, and GFAP‐positive astrogliosis were also increased in the brain of APP/PS1;mir‐21+/− and APP/PS1;mir‐21−/− mice compared to APP/PS1;mir‐21+/+ mice. Mechanistic studies identified RECK as a potential target gene of miR‐21. miR‐21 deficiency upregulated the RECK protein level, leading to the inhibition of ADAM10 activity. This finding was also corroborated by the decrease in the soluble APPα level. Furthermore, we demonstrated that miR‐21 deficiency decreased spatial learning and contextual memory in MWM and CFC tests, respectively in APP/PS1 mice.

Conclusion

Taken together, our results demonstrated that miR‐21 may regulate multiple AD‐associated pathologies. Therefore, modulation of miR‐21 may represent a novel potential therapeutic strategy for AD.
Association of mild cognitive impairment, dementia and vitamin B12 levels in older adults
Authors: Aguilar‐Navarro Sara Gloria , Gutiérrez Lidia Antonia , Hernandez Maria Duadalupe Palacios , Mimenza Alberto Jose
Published: December 2023

Background

Vitamin B12 deficiency has been associated with the development of multiple pathologies. However, it is still controversial if the deficiency is associated with cognitive impairment. Objective: To determine the association between cognitive performance and the vitamin B12 levels.

Method

Cross‐sectional study including 241 adults aged 60 or older, treated as an outpatient at a tertiary care hospital, who had serum levels of vitamin B12. Participans underwent a cognitive assessment and assigned to one of three groups: normal cognition (NC), mild cognitive impairment (MCI), and dementia. Vitamin B12 levels were classified in three categories: sufficiency (>400 pg/ml), subclinical deficiency (201‐400 pg/ml), and absolute deficiency (≤200 pg/ml). Univariate and multivariate linear regression analyzes were used to assess the association between cognitive performance and vitamin B12 levels

Result

Mean age was 81.4 ± 8.0 years and 68% were women. The prevalence of absolute and subclinical B12 deficiency was 17.8% and 39.8%, respectively. Eigthy participants (33%) had MCI and 70 (29%) dementia. Those with MCI and dementia had lower vitamin B12 levels compaired with NC after adjusting for age, sex and education level (p = 0.019).

Conclusion

This study suggests a statistically significant association between global cognitive performance and serum levels of vitamin B12 in older adults
Interaction between Oligomeric Amyloid‐β and Cardiovascular Risk Factors is Associated with Executive and Dorsal Attention Network Dysfunction in Pre‐dementia
Authors: Kumar Dilip , Soo See Ann , Sandhu Gurveen Kaur , Zailan Fatin Zahra , Leow Yi Jin , Vipin Ashwati , Koh Chen Ling , Lee Faith Phemie Hui En , Ghildiyal Smriti , Kandiah Nagaendran
Published: December 2023

Background

Oligomeric amyloid‐β(OAβ) accumulation within brain tissue has been shown to be associated with major AD neuropathological features including tau pathology, synaptic loss, inflammation and oxidative damage; as well as cognitive impairment in dementia cohorts (Celine.E.N et.al.,2018). However, association of OAβ with functional connectivity (FC) and cardiovascular risk factors is not clearly known in the pre‐dementia stage. We aimed to examine association of FC with OAβ and other dementia risk factors in a pre‐dementia cohort to understand the underlying mechanisms related to OAβ.

Methods

We included 98 age and sex matched participants and classified them into OAβ+(28) and OAβ‐(70) subgroups using a OAβ cut‐off ratio of ≥ 0.9 (MDS‐ OAβ Test Kit, PeopleBio Inc, South Korea). Participants completed resting‐state functional MRI, clinical and lifestyle history questionnaires, blood, and neuropsychological assessments for global cognition on Montreal cognitive assessment and Visual Cognitive Assessment at Dementia Research Centre (Singapore). The Cardiovascular Risk Factors, Aging and Dementia (CAIDE) risk score was computed, and independent sample or chi‐squared analysis were performed to evaluate group‐level participant characteristics. Region‐of‐interest based FC analysis for 19 seeds from executive control (ECN), default‐mode, salience and dorsal‐attention networks (DAN) was performed to examine the network‐based FC differences in OAβ+ and OAβ‐ groups in association with CAIDE using ANCOVA model.

Results

Mean age of OAβ+ and OAβ‐ were 62.04±8.84, and 62.05±8.07 (Table‐1). No significant FC differences were observed between OAβ+ vs OAβ‐ subjects. There were no significant FC differences related to CAIDE score in OAβ+ and OAβ‐ groups. Nonetheless, the OAβ*CAIDE interaction showed significant FC changes. The OAβ+*CAIDE interaction analyses showed reduced FC within ECN and DAN (Figure‐1a). Whereas OAβ‐*CAIDE interaction showed reduced FC only within ECN (Figure‐1b). Furthermore, OAβ interaction with apolipoprotein‐ε4 (OAβ*APOE4) was found to further influence FC trends in ECN and DAN (Figure‐1c,1d).

Conclusion

While no FC differences were observed between OAβ+ vs OAβ‐ subjects, the interaction between CAIDE and APOE4 moderated FC changes within the ECN and DAN. These observations in a pre‐dementia cohort suggest that the presence of cerebrovascular risk factors may result in differential FC dysfunction in ECN and DAN depending on APOE4 status.
Results from the Australian PITCH study: a national stepped‐wedge cluster RCT evaluating a dementia training program for home care workers
Authors: Dow Briony , Dang Christa , Doyle Colleen , Savvas Steven , Batchelor Frances , Ames David , Winbolt Margaret , Malta Susan , Clarke Philip , Panayiotou Anita , Cooper Claudia , Livingston Gill , Lyketsos Constantine G. , Burton Jason , Loi Samantha M , Low Lee‐Fay , Wise Erica , Scherer Sam , Fairhall Anne , Goh Anita M Y
Published: December 2023

Background

The NHMRC‐funded Promoting Independence Through quality Care at Home (PITCH) project aimed to improve outcomes for people living with dementia and their paid and family carers via an evidence‐based dementia specialist training program for home care workers (HCWs). PITCH training was co‐designed with HCWs, family carers and people with dementia, consisting of 2×3.5 hour sessions, delivered face to face (F2F) or on‐line.

Methods

Stepped‐wedge cluster RCT including 18 home care services in rural and urban VIC, NSW, and SA cluster‐randomised into one of two arms. Data collection from 18 July 2019 to 12 May 2022. Analyses included linear mixed models with intention to treat.

Results

N = 213 HCWs completed baseline measures, N = 144 completed 6‐month follow‐ups, and N = 120 completed 12‐month follow‐ups. 172 HCWs completed the training program. N = 148 (86%) completed all training sessions; N = 81 F2F and 67 online.

Primary outcome measure

HCWs' Sense of Competency in Dementia Care Staff (SCIDS) was higher after training (p = 0.04). This was driven by F2F training: SCIDS for HCWs completing F2F training was higher vs no training (p = 0.003) and online training (p = 0.015). There was no difference between online training and no training (control condition).

Secondary outcome measures

Overall, HCW scores on the Dementia Attitudes Scale (DAS) showed no difference between training and no training. However, F2F training was associated with higher DAS compared to no training (p = 0.05) and online training (p = 0.05).

Training improved scores on the Dementia Knowledge Assessment Scale (DKAS, p = 0.03). This was also driven by F2F training (F2F vs no training p = 0.024; F2F vs online p = 0.026).

There was no difference between online training and no training for DAS and DKAS. Training had no effect on Strain in Dementia Care Scale (SDCS) scores.

Discussion/Conclusion

Receiving F2F PITCH training improved dementia attitudes, dementia knowledge, and sense of competence in delivering dementia care for HCWs versus no training and online training.

The HCW workforce has unique challenges to accessing and completing training and education to deliver evidence‐based dementia care. Minimising these challenges is critical to the delivery of quality home care. PITCH training now has evidence for its efficacy but only when delivered face‐to‐face.
Diagnostic of Novel Plasma Biomarkers in Controls, SCD and MCI Subjects
Authors: Boutajangout Allal , Masurkar Arjun V. , Ahmed Wajiha , Debure Ludovic , Vedvyas Alok , Links Jon , Faustin Arline , Osorio Ricardo S , Marsh Karyn , Wisniewski Thomas
Published: December 2023

Background

Alzheimer’s disease (AD) is the most common cause of dementia, and a challenging disease for the development of plasma biomarkers. Blood samples are the most easily collectable samples for medical diagnosis. This study evaluates the potential of plasma biomarkers in identifying early stages of AD.

Method

189 participants were recruited at the NYU Alzheimer Disease Research Center. This cohort includes n = 75 with normal cognition (NL), n = 77 with subjective cognitive decline (SCD), n = 37 with mild cognitive impairment (MCI). Comprehensive neuropsychological and magnetic resonance imaging evaluations were conducted for all patients. Plasma biomarkers assays (total tau [t‐tau], neurofilament light [NfL], glial fibrillary acid protein [GFAP], ubiquitin carboxyl‐terminal hydrolase L1 [UCH‐L1], Aβ1‐42, Aβ1‐40 and pTau181) were measured using the SIMOA SR‐X, a novel technology that employs highly sensitive immunoassays with a limit of detection (LOD) under 100 fg/ml.

Result

The levels of NfL, t‐Tau, GFAP and UCH‐L1 were measured using the Neurology 4‐plex A. NfL levels showed a significant difference between NL and SCD (one tailed t‐ test p = 0.0459). GFAP showed statistically significant differences between NL and MCI, (one tailed t‐test p = 0.0369). Aβ1‐42 showed a significant difference between SCD and MCI (one tailed t‐test p = 0.0493). pTau181 levels showed a significant difference between NL, SCD and NL, MCI (p = 0.0447 and p = 0.0439, respectively). The ratio of pTau181/Aβ1‐42 shows a significant difference between NL and MCI (one tailed t‐test p = 0.0187). Correlation of these biomarkers with brain imaging and cognitive measures is underway.

Conclusion

Biomarker levels of NfL, GFAP, Aβ1‐42, pTau181 and Ratio pTau181/Aβ1‐42 in plasma samples showed several significant differences between the three groups of subjects. Plasma biomarkers can be useful for the diagnosis of AD related pathology at early stages.
Plasma phosphorylated tau 181 in relation to Alzheimer’s prevalence and cognition in the Thai community
Authors: Hemachudha Pasin , Thanapornsangsuth Poosanu , Saraya Abhinbhen Wasontiwong , Luechaipanit Watayuth , Hemachudha Thiravat
Published: December 2023

Background

The identification of biomarkers for Alzheimer’s disease (AD) in blood samples has the potential to facilitate early diagnosis and improve the accuracy of AD diagnosis. Plasma phosphorylated tau (p‐tau) is a promising biomarker for AD; however, its utility in estimating the prevalence of AD and screening for cognitive impairment in non‐demented populations has yet to be explored in Thailand.

Method

The study recruited 110 non‐demented participants over the age of 40 from the family members of patients attending a neurology clinic. Plasma p‐tau 181 levels were measured, and AD prevalence was estimated using a pre‐defined cut‐off derived from an independent cohort with biomarker‐defined AD status according to the current framework (Jack et. al., 2018). The correlation between plasma p‐tau 181 levels and. neuropsychological data were also evaluated.

Result

The median age of participants was 66 years, and the median mini‐mental state examination score was 29. The estimated prevalence of AD was 20.0% (95% CI 13.6‐28.4) in preclinical and mild cognitive impairment patients when using p‐tau as a biomarker, which was lower than the prevalence estimated using amyloid abnormalities of 30.1% (95% CI 29.2‐31.1)(Jansen et. al., 2022) (X
2 [N = 8944] = 5.28, p = .022). Plasma p‐tau 181 levels also showed a negative correlation with neurocognitive test scores (Rho = ‐0.24, P .013).

Conclusion

The results of this study suggest that plasma p‐tau 181 is a promising biomarker for the estimation of AD prevalence in non‐demented populations in Thailand and may represent those at risk of clinical onset. However, further studies are needed to investigate its utility in risk stratification, public health preparedness, and cognitive performance assessment.
Tau pathology is associated with neuropsychiatric symptoms in a cohort of individuals of predominantly Mexican descent at risk for autosomal‐dominant Alzheimer’s disease
Authors: Ortega Nancy E , Pa Judy , Shi Yonggang , Sagare Abhay P , Zlokovic Berislav V , Chui Helena C , Ringman John M
Published: December 2023

Background

Neuropsychiatric symptoms are common in Alzheimer’s disease (AD), causing significant suffering and diminished quality of life for both individuals and caregivers. The goal of this study was to investigate the relationship between tau pathology in vivo and neuropsychiatric symptoms within a cohort of individuals of predominantly Mexican ancestry at risk for fully penetrant autosomal dominant AD (ADAD) caused by mutations in PSEN1 and APP genes (Figure 1).

Method

Participants from the Estudio de la Enfermedad de Alzheimer en Jalisciences (EEAJ) cohort were selected based on availability of demographic variables, mutation carrier status, tau PET scans (flortaucipir), and completion of the neuropsychiatric inventory (NPI). Linear regression models were used to investigate whether regional tau PET standard uptake value ratio (SUVR) predicted total score on the NPI. Models were adjusted for age, sex, and mutation carrier status. Participants were characterized as carriers if they possessed one of the following ADAD mutations: PSEN1 A431E, PSEN1 I180F, or APP V717I. Analyses were done with and without outliers. The 12‐item total NPI score was used for all analyses. The primary brain regions of interest (i.e., medial orbitofrontal, caudal anterior cingulate, rostral anterior cingulate, parahippocampal, precuneus, and lateral occipital) were selected based on previous findings. Additional analyses were conducted only on individuals who were carriers of 1 of the ADAD mutations.

Result

The sample consisted of 31 participants (45% women, mean age±SD = 37.1±11.7 years, 71% ADAD mutation carriers [81% PSEN1 A431E, 16% PSEN1 I180F, and 3% APP V717I carriers]). A significant relationship was found between regional tau pathology and neuropsychiatric symptoms for all six brain regions (Table 1), all p’s < 0.01. Within all regression models, regional tau pathology explained between 24% to 49% of the variance in neuropsychiatric symptoms. Sub‐set analyses completed on the ADAD mutation carriers sample exhibited similar results (Table 2). No significant results were found for non‐carriers.

Conclusion

Regional tau pathology within six distinct brain regions is strongly associated with neuropsychiatric symptoms in a cohort of individuals of predominantly Mexican ancestry at risk for fully penetrant ADAD caused by mutations in PSEN1 and APP genes.
Biomarkers of Alzheimer’s disease pathology in atypical non‐amnestic clinical phenotypes
Authors: Nevzorova Kseniya , Shpilyukova Yuliya , Shabalina Alla , Fedotova Ekaterina , Illarioshkin Sergey
Published: December 2023

Background

Alzheimer’s disease (AD) is most commonly presented with memory loss features. However, there are atypical clinical phenotypes including predominant visual, language, executive, behavioural, or motor dysfunction. The goal of our study was to estimate the prevalence of Alzheimer’s pathology in non‐amnestic clinical variants.

Method

We examined 40 patients (17 males, 23 females, 66.1±8.3 yrs) with atypical phenotypes of AD (Table 1). Seven patients had the phenotype of logopenic variant of primary progressive aphasia (lvPPA), 3 patients had the diagnosis of posterior cortical atrophy (PCA), 19 had corticobasal syndrome (CBS), and 11 cases met research criteria of clinical behavioral variant of AD (bvAD). All patients underwent lumbar puncture. CSF biomarkers Abeta‐42 (cutoff 150 pg/mL) and p‐tau181 (cutoff 600 pg/mL) were analyzed. According to the recommendations of International Working Group (2021) we defined probable and possible AD based on clinical phenotype and studied CSF biomarkers.

Result

The overall prevalence of AD pathology in the studied groups was 42.5% (20% for probable diagnosis and 22.5% for possible). All results are presented in Table 1. The highest prevalence of AD pathology in atypical clinical phenotypes was found in the group of PCA (66.7%), the lowest ‐ in the group of bvAD (36.4%). Almost a half of patients in both lvPPA and CBS groups had AD pathology based on biomarkers – 42.9% and 42.2%, respectively.

Conclusion

The results showed the importance of verifying AD pathology biomarkers in common (PCA, lvPPA) and uncommon (CBS) phenotypes. Behavioral variant, considered as a rare AD phenotype, in our studied cohort was characterized by relatively high occurrence of positive AD biomarkers. Increasing the use of AD biomarkers in clinical practice and greater recognition of atypical phenotypes can ensure early diagnosis, treatment and care for these patients.
Metformin use and stroke risk in Hispanic and non‐Hispanic veteran men with type 2 diabetes
Authors: Imran Noor , Vasquez Eliana A , MacCarthy Daniel , Jacob Mini Elizabeth , Espinoza Sara , Hazuda Helen , Seshadri Sudha , Satizabal Claudia L. , Wang Chen‐Pin
Published: December 2023

Background

Stroke is a strong risk factor for dementia in the elderly. Traditional stroke risk factors such as hypertension and diabetes are also associated with the incidence and progression of dementia. There is a lack of data characterizing the effect of metformin use on stroke in racially/ethnically diverse cohorts. We sought to evaluate the impact of metformin as a preventative treatment in reducing the incidence of stroke risk in a cohort of older US veteran men with type 2 diabetes (T2D).

Method

Our cohort included men with T2D, ≥65 years old, insulin/thiazolidinediones naïve, and without stroke history. Metformin use was defined as ≥180 days of prescription during 2002‐2003. Stroke incidence was identified by ICD9 codes 430‐438 (excluding TIA, 435) from inpatient/outpatient visits every year during 2004‐2012. Generalized estimating equations were used to estimate the odds ratios (OR) of stroke diagnosis over time associated with metformin use, where inverse propensity score weights (IPSW) for metformin use were incorporated to minimize confounding. Furthermore, the generalizability method was used to compare IPSW adjusted ORs between race/ethnicity groups after calibrating covariates between groups. Finally, inverse probability weights for survival were incorporated to project the adjusted ORs among the survivors.

Result

Among 19,705 men with T2D, 81.3% were non‐Hispanic White, 5.3% Hispanic White, and 13.4% were non‐Hispanic Black. Overall, 26.7% used metformin (35.2% of Hispanic Whites, 27% of non‐Hispanic Whites, and 21.4% of non‐Hispanic Blacks). Metformin use was associated with attenuating the temporal increase in stroke risk during 2009‐2012 (vs. 2004‐2008) among Hispanic White (log(aOR) = ‐0.05, p‐value = 0.02), This stroke risk attenuation effect by metformin use was marginally different between Hispanic White with non‐Hispanic Black (p = 0.056) and significantly different between Hispanic White and non‐Hispanic White (p = 0.02). The stroke risk attenuation effect of metformin was not significant conditioned on survival.

Conclusion

Our study suggests that metformin use is associated with a reduced distal stroke risk amongst men of Hispanic ethnicity compared to non‐Hispanics. Further studies are needed to elucidate the putative biological or pharmacological mechanism for this difference and to uncover the impact on dementia risk.
A Study on the effects of seasonal variations in cognitive function on driving behaviour.
Authors: Suzuki Mio
Published: December 2023

Background

The population in Japan is ageing, and approximately 30% of the elderly are said to have Alzheimer’s disease. On the other hand, however, there are areas with insufficient transport services due to the declining birth rate, and the elderly have to drive cars. In order to reduce accidents caused by drivers with dementia, it is necessary to know the relationship between cognitive function and driving, but cognitive function is said to fluctuate daily. The aim of this study is to obtain knowledge that contributes to the prediction of accidents by observing the seasonal variation in cognitive function and driving using the same subjects.

Method

A cognitive function test, a driving skill test at a driving school and an observation 1‐month survey of driving behaviour on public open roads were conducted on 40 drivers aged 70 years or older who drive their cars daily. The survey was conducted twice on the same subjects, once between April and June and once between October and December. From the data obtained, seasonal differences were verified.

Result

It is said that elderly drivers often drive short distances in their neighbourhood, but in reality they also make long trips. Comparing spring/summer and autumn/winter, autumn/winter drivers are more likely to be in a state of cognitive decline and drive more unevenly.

Conclusion

Cognitive function and driving behaviour of older drivers differ depending on the season. As the passage of time and more short‐term fluctuations may have an impact, it is important to systematise the fluctuating changes in various cycles and link them to safe driving support.
Ameliorative effect of β‐pinene targeting mitochondrial dysfunction and oxidative stress in Alzheimer’s disease
Authors: Dahiya Mini , Kumar Anil , Yadav Monu
Published: December 2023

Background

Sporadic Alzheimer’s disease (sAD) is the most common type of dementia, characterized by the deposition of extracellular senile plaques, neurofibrillary tangles (NFTs), and neurodegeneration, leading to memory impairment and dementia. Intracerebroventricular (ICV) streptozotocin (STZ) mimics sporadic Alzheimer’s disease (sAD) characterized by neurodegeneration arising from oxidative stress, and mitochondrial dysfunction. β‐pinene is a monoterpene having antioxidant properties interlinked with mitochondrial functioning. To study the neuroprotective and cognitive enhancement properties of β‐pinene on mitochondrial dysfunction, oxidative stress, and histological changes in an animal model of Alzheimer’s disease induced by ICV‐STZ.

Method

To establish the sAD model, intracerebroventricular (ICV) streptozotocin (STZ) at a dose of 3 mg/kg was administered bilaterally in rats on a stereotaxic apparatus. Behavioral tests such as Morris water maze (MWM), novel object recognition (NOR) and Actophotometer were performed to evaluate spatial & recognition memory and locomotor functions. Three treatment doses (50mg/kg, 100 mg/kg and 200mg/kg) of Beta pinene (β‐pinene) and Galantamine (2 mg/kg) as a reference drug were given orally to ICV‐STZ induced rats for 21 days. Cortical and hippocampal tissues were dissected. Estimation of oxidative stress, mitochondrial dysfunction as complex I, II, III, IV activity and acetylcholinesterase activity were performed for cholinergic function. Moreover, histopathology was evaluated by hematoxylin and eosin (H&E) staining.

Result

β‐pinene treatment attenuated ICV‐STZ‐induced cognitive impairment in MWM and NOR. There is no significant effect revealed on locomotor activities. Moreover, in the cortex and hippocampal area of the brain, Mitochondrial enzyme complex I, II, III, and IV, and acetylcholinesterase (AchE) activities were normalized. Furthermore, reduced glutathione (GSH), catalase, superoxide dismutase (SOD), and (Lipid peroxidation) LPO were also reversed. β‐pinene prevents neurodegeneration as examined in histopathology.

Conclusion

In the ICV‐STZ rat model, β‐pinene was found to be neuroprotective by reducing oxidative stress and mitochondrial dysfunction, consequently enhancing cognitive functions indicated in the behavioral outcomes.
Clinical and neuroimaging predictors of Alzheimer’s Dementia Conversion in patients with mild cognitive impairment using 18F‐Florapronol amyloid PET by quantitative analysis over 2 years
Authors: Kim Seon Jeong , Chung Hye‐in , Yoon Daye , Jeong Young Jin , Kang Do‐Young , Park Kyung Won
Published: December 2023

Background

Patients with mild cognitive impairment(MCI) are a clinically important group because of the increased risk for the progression to Alzheimer’s dementia(AD). Amyloid positron emission tomography(PET) was useful as a predictor for identifying AD pathology in the pre‐dementia stage. We determined the rates of conversion to AD in MCI patients based on amyloid positivity by visual and quantitative analysis over 2 years. We also investigated the clinical and neuroimaging predictors for conversion to AD.

Method

Individuals aged 50 and above with MCI according to Petersen’s criteria were eligible. Subjects underwent laboratory tests including APOE genotyping, neuropsychological tests, brain magnetic resonance imaging(MRI), and amyloid PET assessed by 18F‐FC119S. Amyloid positivity was determined in each lobe of the brain and quantitatively analyzed. The follow‐up period was at least 2 years. Cox regression analysis was performed to identify prognostic factors which are independently related to time to AD conversion.

Result

We recruited 50 patients and 39 subjects were enrolled. 5 patients dropped out at 2 years, so 34 subjects were finally included. 13 of 34(38.2%) by visual analysis and 12 of 34(35.3%) by quantitative analysis of 18F‐FC119S PET showed amyloid positive. The basic demographics were not significantly different between the groups except for Korea‐Instrumental Activities of Daily Living(K‐IADL) at baseline(p = 0.004) and 1 year(p = 0.001), Mini‐mental State Examination(MMSE) at 2 years(p = 0.047) and Global Deterioration Scale(GDS) at 2 years(p = 0.029). 4 of 13(30.8%) by visual analysis, 4 of 12(66.7%) by quantitative analysis amyloid‐positive MCI patients converted to AD. Amyloid positive in posterior cingulate was marginally significant(p = 0.066). AD conversion group had a higher Clinical Dementia Rating‐Sum of box(CDR‐SOB) at baseline(p = 0.002) compared with remained MCI group. In multivariate cox regression, CDR‐SOB at baseline, MMSE at 1 year and K‐IADL at 2 years were included.

Conclusion

Amyloid‐positive MCI group was more likely to progress to AD. But long‐term follow‐up was required. By quantitative analysis of 18F‐FC119S PET, amyloid deposition in posterior cingulate was highly associated with the AD conversion group. CDR‐SOB at baseline, MMSE at 1 year and K‐IADL at 2 years were considered as clinically valuable prognostic predictors of disease progression. Especially, CDR‐SOB is important as a predictive biomarker in the pre‐dementia stage.